Professional Documents
Culture Documents
Rheumatology Masud
Rheumatology Masud
De nnis W. Boulwa re , MD
Professor of Medicine
University of Ala ba ma a t Birmingha m
Chief of Rheuma tology
Ha wa ii Perma nente Medica l Group
Honolulu, HI
Prin t e d in Ch in a
ISBN-13: 978-1-60913-808-0
ISBN-10: 1-60913-808-2
Ca r e h a s b e e n t a k e n t o c o n fir m t h e a c c u r a cy o f t h e in fo r m a t io n p r e s e n t e d a n d t o
d e s cr ib e ge n e ra lly a cce p t e d p ra ct ice s . How eve r, t h e a u t h o rs , e d it o rs , a n d p u blis h e r a re
n ot re s p on s ible for e rrors or om is s ion s or for a n y con s e q u e n ce s from a p p lica t ion of t h e
in for m a t io n in t h is b oo k a n d m a k e n o w a r ra n t y, e xp re s s e d o r im p lie d , w it h re s p e ct t o
t h e cu rre n cy, co m p le t e n e s s , o r a ccu ra cy o f t h e co n t e n t s o f t h e p u blica t io n . Ap p lica t ion
o f t h e in fo r m a t io n in a p a r t icu la r s it u a t io n re m a in s t h e p ro fe s s io n a l re s p o n s ib ilit y o f
t h e p ra ct it ion e r.
Th e a u t h o r s , e d it o r s , a n d p u blis h e r h a ve e x e r t e d eve ry e ffo r t t o e n s u re t h a t d r u g
s e le ct ion a n d d os a ge s e t fort h in t h is t e xt a re in a ccord a n ce w it h cu rre n t re com m e n d a -
t io n s a n d p ra ct ice a t t h e t im e o f p u b lica t io n . How e ve r, in vie w o f o n go in g r e s e a rch ,
ch a n ge s in gove r n m e n t re gu la t io n s , a n d t h e co n s t a n t flow o f in fo r m a t io n r e la t in g t o
d ru g t h e ra p y a n d d ru g re a ct ion s , t h e re a d e r is u rge d t o ch e ck t h e p a cka ge in s e rt for e a ch
d ru g for a n y ch a n ge in in d ica t ion s a n d d os a ge a n d for a d d e d w a rn in gs a n d p re ca u t ion s .
Th is is p a r t icu la r ly im p o r t a n t w h e n t h e re co m m e n d e d a ge n t is a n ew o r in fre q u e n t ly
e m p loye d d ru g.
Som e d ru gs a n d m e d ica l d evice s p re s e n t e d in t h e p u blica t ion h a ve Food a n d Dru g
Ad m in is t ra t io n (FDA) cle a ra n ce fo r lim it e d u s e in re s t r ict e d re s e a rch s e t t in gs . It is t h e
re s p o n s ib ilit y o f t h e h e a lt h ca re p rovid e r s t o a s ce r t a in t h e FDA s t a t u s o f e a ch d r u g o r
d evice p la n n e d for u s e in t h e ir clin ica l p ra ct ice.
Vis it Lip p in cot t Willia m s & W ilkin s o n t h e In t e rn e t : a t LW W.com . Lip p in cot t W illia m s &
Wilkin s cu s t om e r s e rvice rep re s e n t a t ive s a re a va ila ble from 8:30 a m t o 6 p m , EST.
10 9 8 7 6 5 4 3 2 1
Dedica tion
iii
Contributors
Sarah L. Morgan , MD, RD, FADA, FACP, CCD Te rry Sh an eyfe lt, MD, MPH
Profe s s or of Nu t rit ion Scie n ce s a n d Me d icin e Ch ie f, Ge n e ra l Me d icin e
Me d ica l Dire ct or, UAB Os t e op oros is Preve n t ion a n d Birm in gh a m VA Me d ica l Ce n t e r
Tre a t m e n t Clin ic As s ocia t e Profe s s or of Me d icin e
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m UAB Dep a rt m e n t of Me d icin e
Birm in gh a m , AL Birm in gh a m , AL
Con t ribu t ors vii
1. Book: Th e book con t a in s bot h bu lle t e d p oin t s for q u ick look-u p a cce s s
w h e n you n e e d a n a n sw e r righ t aw a y, a s w e ll a s lon ge r t e xt for t h e
occa s ion s w h e n you n e e d a lit t le m ore in form a t ion .
Ad d it io n a lly w e h a ve in clu d e d p e d a go gy t o h igh ligh t ce r t a in
a s p e ct s of t h e t e xt . Th e s e e le m e n t s in clu d e :
2. We bs ite t h a t in clu d e s :
• Fu lly s e a rch a ble t e xt of t h e book
• Im a ge ba n k t h a t ca n be d ow n loa d a ble in t o Pow e rPoin t for
p re s e n t a t ion s
• PDF d ow n loa d a ble Pa t ie n t In form a t ion Sh e e t s
We ce rt a in ly h op e t h is p rod u ct is u s e fu l a n d m e e t s you r n e e d s .
ix
Prefa ce
De n n is W. Bou lw a re , MD
Gu s t a vo R. He u d e be rt , MD
xi
Acknowledgments
x iii
Contents
CHAPTER 4 : Sh o u ld e r Pa in 30
Dennis W. Boulw are
CHAPTER 5: Pa in fu l Fe e t 37
Dennis W. Boulw are and Gustav o R. Heudebert
CHAPTER 7: Hip Pa in 55
Carol Croft
xv
x vi Con t e n t s
CHAPTER 10 : Th e Se ro n e ga tive
Sp o n d y lo a rth ro p a th ie s 95
Dennis W. Boulw are
CHAPTER 12: Ra y n a u d ’s Ph e n o m e n o n a n d Sy s te m ic
Scle ro s is 111
Laura B. Hughes and Barri Fessler
INDEX 297
SECTION
1
Introduction to the
Rheuma tic Disea ses
1
CHAPTER
1 Evaluation of Patients
with Rheumatic Diseases
Carlos A . Estrada and Gustav o R. Heudebert
Appro a ch to the
A 24-ye ar-o ld f e m ale co m e s
s
Pa tie nt w ith Articula r
e
s
t o t h e Em e rg e n cy De p art m e n t
a
Co mpla ints
e
s
w it h a 3-d ay h ist o ry o f p ain in
i
D
CLINICAL PRESENTATION
c
t h e rig h t k n e e t h at re so lve d
i
t
a
Th e clin ica l p re s e n t a t ion of rh e u m a t ic
m
in 48 h o u rs, f o llo w e d b y p ain
u
d isea ses is fra m ed on t h e u n iq u e p a tien t’s
e
in h e r le f t w rist (m ig rat o ry
h
R
ba ckgrou n d in clu d in g a ge, ge n d e r, e t h -
art h rit is). Sh e h as also n o t ice d
e
n icity, a s s ocia t ed con d it ion s , fa m ily h is -
h
t
dif culty holding to atw are on her right hand (tenosynovitis). tory, a n d h abits. Su ch ch a ra cteris tics ca n
o
t
p rovid e u sefu l clu es for p a tien ts p resen t-
n
She not ice d onse t of sym pt om s short ly af te r he r m e nse s (se e n
o
i
in g w it h s ign s or s ym p t om s con s is t e n t
t
c
in d isse m in at e d g o n o co ccal in f e ct io n ). Ph ysical e xam in at io n
u
w it h a rh e u m a t ic d is e a s e. We w ill con -
d
o
re ve als p ain w it h m o t io n o f t h e le f t w rist w it h a t h ick e n e d s id e r t h e s e ch a ra ct e ris t ics s e p a ra t e ly,
r
t
n
I
syn o viu m ; e xio n o f d ig it s is t e n d e r at t h e rig h t h an d con sid er m ostly a d u lt p a tien ts, orga n ize
1
N
(t e n o syn o vit is), h o w e ve r, w rist e xio n is n o t p ain f u l. Th e re on th e ba sis of etiologic ca u ses, a n d p ro-
O
vid e exa m p les. We recogn ize th a t typ ica l
I
T
are a f e w p u st u le s n o t e d in t h e le f t f o re arm an d rig h t f o o t
C
p a t t e r n s o c c u r in a fe w in s t a n ce s ;
E
(art h rit is–d e rm at it is syn d ro m e ).
S
h ow eve r, w e p re s e n t a fra m ew o r k t o
e f cie n t ly re cogn ize d is e a s e p a t t e rn s .
Ta ble 1.1 su m m a rizes th e p a tien t’s ba ck-
grou n d a n d com m on clin ica l en tit ies.
PATIENT ASSESSMENT
Patie nt’s Backg ro und
• De t e rm in e t h e p a t t e rn o f Ag e
jo in t in vo lve m e n t : Crys t a l-in d u ce d a rt h rop a t h ie s (gou t a n d p s e u d ogou t ) ca n p re s e n t a t a n y a ge ;
• Nu m b e r o f jo in t s
a lt h ou gh , p s e u d ogou t u s u a lly p re s e n t s in t h e ft h or s ixt h d e ca d e of life. Gou t
in vo lve d : m o n o a rt icu la r, d ia gn os e d in t h e t w e n t ie s s h ou ld ra is e t h e s u s p icion of le a d e xp os u re (s a t u r-
o lig o a rt icu la r, p o lya rt ic- n in e gou t ), in cre a s e d e n d oge n ou s p rod u ct ion of u ric a cid (e.g., lym p h op rolif-
u la r ( 3 jo in t s) e ra t ive d is ord e r), or a n in h e re n t d e fe ct of p rod u ct ion or e xcre t ion of u ric a cid .
• Evolution of involvement: Os t e oa rt h rit is (OA) u s u a lly p re s e n t s in in d ivid u a ls old e r t h a n 50 ye a rs of
a d d it ive , m ig ra t o ry a ge. OA ca n be d ia gn os e d in you n ge r p a t ie n t s w it h p a s t t ra u m a (e.g., gym n a s t s )
• An a t o m ic lo ca t io n : a xia l,
or in t h e fa m ilia l form of t h e d is e a s e.
p e rip h e ra l Th e in fe ct iou s e t iology of a rt h rit is va rie s ba s e d on a ge. H. in uenz a a rt h rit is
p re s e n t s a lm os t e xclu s ive ly in ch ild re n , w h e re a s gon ococca l a rt h rit is is d ia g-
• Sym m e t ry: sym m e t ric,
a sym m e t ric
n os e d a lm os t e xclu s ive ly in s e xu a lly a ct ive in d ivid u a ls 40 ye a rs of a ge. Old e r
p a t ie n t s a re m ore like ly t o h ave com orbid it ie s or u n d e rlyin g a rt icu la r d is e a s e s
• De t e rm in e p re se n ce o f s u ch a s OA o r jo in t re p la ce m e n t . Th e a ffe ct e d jo in t s a re m o re vu ln e ra ble t o
in a m m a t io n :
s yn ovia l in va s ion , e s p e cia lly in t h e p re s e n ce of ba ct e re m ia .
• Jo in t s, t e n d o n in se rt io n , An kylos in g s p on d ylit is , p s oria t ic a rt h rit is , Re it e r’s s yn d rom e, a n d re a ct ive
syn o viu m a r t h r it is (s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s ) a re m o re co m m o n ly s e e n in
(Con t in ue d ) 3
4 Se ctio n 1 In t rod u ct ion t o t h e Rh e u m a t ic Dis e a s e s
PATIENT ASSESSMENT (Co n t in u e d) Table 1.1 Pat ient ’s Background and Diagnosis of Pat ient s
Present ing wit h Art icular Complaint s
• De t e rm in e p a t t e rn o f
m u scle in vo lve m e n t :
AFRICAN–
• Pro xim a l ve rsu s d ist a l FEMALE MALE AMERICAN WHITES
• Pa in fu l ve rsu s p a in le ss Ag e 40 y Ta ka ya su ’s Reiter’s syndrome, Sa rco id o sis Reiter’s syndrome,
a rt e rit is, SLE, SS AS AS
• Ca re fu l n e u ro lo g ica l
e xa m in a t io n fo r p a t ie n t s Ag e 50 y RA, OA, GCA Gout, pseudogout OA, GCA
w it h m u scu la r co m p la in t s
AS, a n kylo sin g sp o n d ylit is; GCA, g ia n t ce ll a rt e rit is; OA, o st e o a rt h rit is; RA, rh e u m a t o id a rt h rit is; SLE,
• Ca re fu l a sse ssm e n t o f t h e syst e m ic lu p u s e ryt h e m a t o su s; SS, syst e m ic scle ro sis.
skin , e ye s, a n d m u co u s
m e m b ra n e s
Sympto mato lo g y
Pa t t e rn o f Jo in t In vo lve m e n t
A s u m m a ry of t yp ica l p a t t e rn s of join t in volve m e n t a n d ce rt a in d ia gn os is is
in clu d e d in Ta ble 1.2 . Th e n u m be r of join t s in volve d , evolu t ion of join t in volve -
m e n t , a n a t om ic loca t ion of join t s , a n d s ym m e t ry a re im p ort a n t fe a t u re s in t h e
h is t ory a n d p h ys ica l e xa m in a t ion of p a t ie n t s w it h join t com p la in t s .
Ch a p te r 1 Eva lu a tion of Pa tien ts w ith Rh eu m a tic Disea ses 5
AS, a n kylo sin g sp o n d ylit is; OA, o st e o a rt h rit is; RA, rh e u m a t o id a rt h rit is; SLE, syst e m ic lu p u s e ryt h e m a t o su s; SS, syst e m ic scle ro sis.
s
e
in volvem en t is ch a ra cteristic of ba cteria l in fection s, crysta l-in d u ced d isea se, a n d
s
a
tra u m a . Oligoa rticu la r in volvem en t is seen in p a tien ts w ith seron ega tive sp on dy-
e
s
i
D
loa rth rop a th ies a n d ju ven ile RA. Fin a lly, p olya rth ritis is typ ica l in p a tien ts w ith
c
a d u lt on set RA a n d freq u en tly seen in p a tien ts w ith SLE a n d system ic sclerosis.
i
t
a
Th e evolu t ion of join t in volve m e n t ca n be a d d it ive or m igra t ory. Ad d it ive
m
u
refers w h en a secon d join t becom es a ffected w h ile th e rst on e is still in volved —
e
h
R
ch a ra ct e ris t ic of RA a n d Re it e r’s s yn d rom e. Migra t ory re fe rs w h e n a n ot h e r join t
e
be com e s a ffe ct e d a ft e r re s olu t ion of t h e la s t on e —ch a ra ct e ris t ic of gon ococca l
h
t
a n d vira l a rt h rit is .
o
t
Th e a n a t om ic loca t ion of join t s ca n be broa d ly d ivid e d a s a xia l or p e rip h -
n
o
i
e ra l. Th e jo in t s o f t h e a x ia l s ke le t o n in clu d e t h e s p in e , s a cro ilia c, s t e rn o cla -
t
c
u
vicu la r, a crom ioclavicu la r, s h ou ld e r, a n d h ip join t s . Se ron ega t ive s p on d yloa r-
d
o
t h rop a t h ie s a n d os t e on e cros is t yp ica lly in volve t h e a xia l s ke le t on . Th e join t s of
r
t
n
I
t h e p e rip h e ra l s ke le t o n in clu d e t h e join t s d is t a l t o t h e e lb ow s a n d k n e e s —
1
N
ch a ra ct e ris t ic of RA a n d m a n y of t h e con n e ct ive -t is s u e d is e a s e s . Fu rt h e rm o re,
O
d is t in ct jo in t s ca n h e lp in t h e d iffe re n t ia l d ia gn o s is . Fo r e x a m p le , b ila t e ra l
I
T
C
h a n d in vo lve m e n t o f t h e m e t a ca r p o p h a la n ge a l (MCP) a n d p ro x im a l in t e r-
E
S
p h a la n ge a l (PIP) join t s is ch a ra ct e ris t ic of RA, w h e re a s in volve m e n t of t h e d is -
t a l in t e rp h a la n ge a l (DIP) join t s is m ore com m on in OA a n d p s oria t ic a rt h rit is .
Th e co m bin a t ion o f a n e n t h e s it is (e .g., Ach ille s t e n d on it is , p la n t a r fa s ciit is )
w it h s a croiliit is s h ou ld ra is e t h e s u s p icion of Re it e r’s s yn d rom e.
Jo in t s a ffe ct e d ca n be s ym m e t ric o r a s ym m e t ric. Mo n oa rt icu la r a n d o li-
goa rt icu la r d is e a s e s a re by d e n it ion a s ym m e t ric. Bila t e ra l in volve m e n t , s ym -
m e t ric, of t h e DIP join t s is s e e n in p s oria t ic a rt h rit is a n d in occa s ion a l p a t ie n t s
w it h p olya rt icu la r gou t . Of t h e p olya rt icu la r e n t it ie s , RA a n d t h e con n e ct ive -
t is s u e d is e a s e s a re m ore like ly t o p re s e n t in a s ym m e t ric fa s h ion .
Pre se n ce o f In a m m a t io n
De t e rm in in g t h e p re s e n ce of in a m m a t ory ch a n ge s is on e of t h e m os t im p or-
t a n t a s p e ct s in t h e eva lu a t ion of p a t ie n t s w it h join t com p la in t s . Th e h is t ory is
h e lp fu l, a s p a t ie n t s ca n a ccu ra t e ly d e s cribe if a join t h a s be e n or is cu rre n t ly
w a rm , re d , sw olle n , or s im p ly p a in fu l.
Crys t a l d ep os it ion d is e a s e u s u a lly p re s e n t s w it h in a m m a t ion . Gou t t e n d s
t o b e a n a cu t e m o n o a r t h r it is t yp ica lly a ffe ct in g t h e r s t m e t a t a r s a l jo in t
(p od a gra ), follow e d by t h e kn e e (gon a gra ), or t h e w ris t (ch in a gra ). Occa s ion a lly,
gou t ca n m im ic RA w it h p olya rt icu la r in volve m e n t . Us u a lly, p a t ie n t s w it h gou t
h ave t op h i e ls ew h e re. Ps e u d ogou t ca n m im ic gou t in t e rm s of a cu t e n e s s a n d
d egre e of in a m m a t ion ; t h e join t s m os t com m on ly a ffe ct e d in p s e u d ogou t a re
t h e kn e e, s h ou ld e r, a n d w ris t .
De t e rm in in g t h e d u ra t ion of m orn in g s t iffn e s s is a ls o ve ry h e lp fu l. Ch a ra c-
t e ris t ica lly, p a t ie n t s w it h RA a n d ot h e r in a m m a t ory a rt h rop a t h ie s e xp e rie n ce
6 Se ctio n 1 In t rod u ct ion t o t h e Rh e u m a t ic Dis e a s e s
s
like ch a n ge s ) a re d u e t o in lt ra t ion of t h e s kin a n d n ot d u e t o t h a t of t h e s yn o-
e
s
via l s p a ce.
a
e
Pa t ie n t s w it h s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s ca n m a n ife s t jo in t
s
i
D
in volve m en t in va riou s w ays : t h os e w it h p s oria t ic a rt h rit is ca n h ave a s ym m e t ric
c
i
t
p olya rt h rit is in d is t in gu is h a ble from t h a t in p a t ie n t s w it h RA; t h e m os t s eve re
a
m
form of p s oria t ic a rt h rit is p rod u ce s a cla s s ic d e s t ru ct ion of t h e d is t a l p h a la n x
u
e
k n ow n a s a r t h r it is m u t ila n s . Pa t ie n t s w it h a n kylo s in g s p o n d ylit is u s u a lly
h
R
p re s e n t w it h lit t le or n o evid e n ce of a p e rip h e ra l a rt h rit is ; t h e s e in d ivid u a ls
e
h
h a ve p re d om in a n t in volve m e n t of t h e a xia l s ke le t on . In d ivid u a ls w it h in a m -
t
o
m a t ory bow e l d is e a s e ca n p re s e n t w it h e it h e r oligoa rt h rit is or, m ore com m on ly,
t
n
oligoa rt h ra lgia s .
o
i
t
c
u
d
Appro a ch to Pa tie nts w ith Muscle Diso rde rs
o
r
t
n
I
1
CLINICAL PRESENTATION
N
O
Ce r t a in d e m ogra p h ic ch a ra ct e ris t ics ca n b e lin k e d t o s p e ci c in a m m a t o ry
I
T
C
m u s cle d is o rd e r s . Fo r e x a m p le , in clu s io n b od y m yos it is is ch a ra ct e r is t ica lly
E
s e e n in e ld e rly m e n ; p olym yos it is /d e rm a t om yos it is (PM/DM) occu r m ore com -
S
m o n ly in fe m a le s . Age is a n im p o rt a n t cr it e rio n fo r d iffe re n t ia t io n b e t w e e n
in a m m a t ory a n d n on in a m m a t ory m yop a t h ie s . Ad u lt p a t ie n t s w it h p olym y-
os it is a n d d e rm a t om yos it is a re u s u a lly d ia gn os e d in t h e ft h d e ca d e of life ;
p a t ie n t s w it h p a ra n e op la s t ic PM p re s e n t a t a rou n d 60 ye a rs of a ge. Th e n on in -
a m m a t ory m yop a t h ie s of glycoge n or lip id s t ora ge d is e a s e s p re s e n t in ch ild -
h ood or in e a rly a d u lt h ood ; t h e m yop a t h ie s a s s ocia t e d w it h con n e ct ive -t is s u e
d is e a s e u s u a lly p re s e n t in t h e s e con d or t h ird d e ca d e of life.
Th e p a t ie n t w it h m yop a t h y m a y p re s e n t w it h : (a ) p a in le s s w e a kn e s s t h a t is
d iffu s e (s u ch a s in p olym yos it is ) or loca lize d (d is t a l, s u ch a s in clu s ion bod y
m yo s it is ); (b ) p a in fu l w e a k n e s s (s u ch a s in p o lym ya lgia r h e u m a t ica ); a n d
(c) p a in w ith ou t w ea kn ess th a t ca n be gen era lized (in u en za , system ic in fect ion s)
or loca lize d ( brom ya lgia ).
PHYSICAL FINDINGS
Dis t in gu is h in g m u s cle w e a kn e s s of a n e u rop a t h ic ve rs u s m yop a t h ic e t iology
ca n be d if cu lt . We a kn e s s d u e t o u p p e r m ot or n e u ron d is e a s e t yp ica lly p re s e n t
NOT TO BE MISSED w it h a s ym m e t r ic w e a k n e s s (s u ch a s h e m ip a re s is ), h yp e r re e x ia , p o s it ive
Ba bin s ki’s s ign , a n d u lt im a t e ly, s p a s t icit y. Pa t ie n t s w it h low e r m ot or n e u ron
• Se p t ic a rt h rit is d is e a s e m igh t be m ore ch a lle n gin g t o d iffe re n t ia t e from p a t ie n t s w it h a p ri-
m a ry m yo p a t h ic p ro ce s s ; t h ey p re s e n t w it h d is t a l w e a k n e s s , fa s cicu la t io n s ,
• In a m m a t o ry
a rt h ro p a t h ie s h yp ore e xia , a n d u lt im a t e ly, d e cre a s e d m u s cle t on e. Pa t ie n t s w it h d is ord e rs
a ffe ct in g t h e n e u ro m u s cu la r ju n ct io n a re ch a lle n gin g t o d iffe re n t ia t e fro m
8 Se ctio n 1 In t rod u ct ion t o t h e Rh e u m a t ic Dis e a s e s
CLINICAL POINTS: PHYSICAL Table 1.3 Demographic and Clinical Charact erist ics of Pat ient s
FINDINGS Present ing wit h Muscular Complaint s
• Like lih o o d o f ce rt a in
d ia g n o se s is a sso cia t e d MALE FEMALE PROXIMAL DISTAL
w it h a g e a n d g e n d e r.
Ag e 50 y CTD En d o crin e , CTD LMN (?)
• Pa t t e rn o f in vo lve m e n t
Ag e 50 y In clu sio n b o d y PM/DM PM/DM e n d o crin e In clu sio n b o d y
(p ro xim a l vs. d ist a l) is
m yo sit is m yo sit is
im p o rt a n t fo r t h e
d iffe re n t ia l d ia g n o se s.
CTD, connective-tissue disorder; DM, dermatomyositis; LMN, lower motor neuron disease; PM, polymyositis.
• Co n sid e r m e t a b o lic a n d
n e u ro lo g ica l co n d it io n s
ca re fu lly w h e n a sse ssin g
p a t ie n t s w it h m u scle
co m p la in t s. p a t ie n t s w it h m yop a t h ic p roce s s e s , a s t h ey s h a re s im ila r ch a ra ct e ris t ics (p roxi-
m a l d is t ribu t ion , n orm a l re e xe s , n o Ba bin s ki’s s ign , a n d n orm a l m u s cle t on e ).
Not u n com m on ly, clin icia n s re s ort t o e le ct rom yogra p h ic s t u d ie s (EMG/NCV) a n d
S
E
m u s cle biop s ie s t o d is t in gu is h be t w e e n t h e s e la t t e r t w o grou p s of p a t ie n t s . Ta ble
C
T
1.3 s u m m a rize s t h e p a t ie n t ’s d e m ogra p h ics a n d com m on m u s cu la r d is ord e rs .
I
O
Th e p a t t e rn of m u s cle in volve m e n t ca n be h e lp fu l in t h e d iffe re n t ia l d ia g-
N
1
n os is of p a t ie n t s w it h w e a kn e s s . Proxim a l m u s cle w e a kn e s s of in s id iou s on s e t
I
n
is m ore ch a ra ct e ris t ic of p olym yos it is . In d ivid u a ls w it h in clu s ion bod y m yos it is
t
r
o
t e n d t o h ave bot h p roxim a l a n d d is t a l m u s cle w e a kn e s s . Proxim a l w e a kn e s s is
d
u
ch a ra ct e ris t ic of t h e m e t a bolic m yop a t h ie s (h yp oka le m ia , h yp e rca lce m ia ) a n d
c
t
i
o
t h e m yop a t h ie s a s s ocia t e d w it h e n d ocrin e d is ord e rs (t h yroid d is ord e rs , h yp e r-
n
t
ca lce m ia ). Pa t ie n t s w it h p e riod ic h yp oka le m ic p a ra lys is ca n p re s e n t w it h p ro-
o
t
fou n d ge n e ra lize d w e a kn e s s of ra t h e r a cu t e on s e t ; a s e a rch for h yp e rt h yroid is m
h
e
is w a rra n t e d in s u ch p a t ie n t s , e s p e cia lly if t h ey a re of As ia n d e s ce n t .
R
h
In d ivid u a ls p re s e n t in g w it h re gio n a l p a in a n d / o r w e a k n e s s n e e d t o b e
e
u
m
a p p roa ch e d in a d iffe re n t m a n n e r. Pa t ie n t s w it h cle a r regio n a l m u s cle p a in
a
s h ou ld be ca re fu lly q u e s t ion e d for a h is t ory of t ra u m a . Occa s ion a lly, in fe ct ion s
t
i
c
m igh t be re s p on s ible for t h e region a l n a t u re of t h e p a in . Pyom yos it is , a re la -
D
i
s
t ive ly u n u s u a l d is ord e r ou t s id e of t h e t rop ics , s h ou ld be s u s p e ct e d in p a t ie n t s
e
a
w it h kn ow n h u m a n im m u n od e cie n cy viru s w h o p re s e n t w it h feve r a n d loca l-
s
e
s
ize d m u s cle p a in . On occa s ion t h e s e p a t ie n t s m igh t a ls o h a ve a s s ocia t e d w e a k-
n e s s . Th e p re s e n ce of glu t e a l m u s cle w e a kn e s s a n d a t rop h y a m on g d ia be t ics
s h ou ld a le rt t h e clin icia n t o t h e p os s ibilit y of d ia be t ic a m yot rop h y. Dia be t ics
w it h lon g-s t a n d in g, p oorly con t rolle d d ia be t e s ca n p re s e n t w it h loca lize d p a in
a n d w e a kn e s s d u e t o d ia be t e s m yon e cros is . More com m on , h ow eve r, is t h e
p a t ie n t w it h brom ya lgia w h o p re s e n t s t o t h e clin icia n w it h com p la in t s of p ro-
fou n d ge n e ra liz e d fa t igu e a n d d iffu s e m u s cle p a in s . Diffe re n t ia t in g fa t igu e
from w e a kn e s s ca n be ch a lle n gin g. In t h e s e p a t ie n t s d ocu m e n t a t ion of n orm a l
m u s cle s t re n gt h a n d t on e is of gre a t im p ort a n ce. Elicit a t ion of p a in fu l t rigge r
p oin t s m igh t h e lp t h e clin icia n t o m a ke t h is d ia gn os is .
Additio na l Re a ding
1. Bow e n JL. Ed u ca t io n a l s t ra t e gie s t o p ro m o t e clin ica l d ia gn o s t ic re a s o n in g . N Engl J Med 2006 ;355 :
2217 –2225 .
2. Ch ew FS. Ra d iologic m a n ife s t a t ion s in t h e m u s cu los ke le t a l s ys t e m of m is ce lla n e ou s e n d ocrin e d is ord e rs .
Radiol Clin North A m 1991 ;29 :135 –147 .
3. De Gow in RL. DeGow in & DeGow in’s Diagnostic Exam ination . New York : McGraw -Hill, In c , 1994 .
4. McClu s key P, Rich a rd J, Pow e ll RJ. Th e eye in s ys t e m ic in a m m a t ory d is e a s e s . Lancet 2004 ;364 :2125 –2133 .
5. Na s ch it z JE, Ros n e r I, Roze n ba u m M , e t a l. Rh e u m a t ic s yn d rom e s : clu e s t o occu lt n e op la s ia . Sem in A rthritis
Rheum 1999 ;29 :43 –55 .
6. Sa p ira JD. The art and science of bedside diagnosis . Ba lt im o re –Mu n ich : Urba n & Sch w a rze n be rg , 1990 .
SECTION
2
Sport-Rela ted,
Occupa tiona l, a nd Other
Regiona l Pa in Syndromes
Chapter 2 Ne ck Pain
Jerom e Van Ruisw yk
Chapter 5 Pain fu l Fe e t
Dennis W. Boulw are and
Gustav o R. Heudebert
9
10 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
s
ca re s e t t in gs . St u d ie s s u gge s t
e
m
forearm and up into the head; he does ad- t h a t u p t o t w o t h ird s of in d i-
o
r
m it som e associated num bness in the left vid u a ls e x p e r ie n ce n e ck p a in
d
n
a t le a s t on ce d u rin g t h e ir life -
y
hand and occasionally in the right hand.
S
t im e . Th e p reva le n ce of n e ck
n
He denies bow el or bladder incontinence
i
p a in in cre a s e s w it h a ge a n d is
a
P
but feels that his sense of balance has m ore com m on in w om e n t h a n
l
a
n
been off for years. He has a history of prior in m e n . Alt h ou gh u p t o 10% of
o
i
t h e a d u lt p op u la t ion h a s n e ck
g
lum bar decom pression for lum bar spinal stenosis and radiculopathy.
e
R
p a in a t a n y o n e t im e , m o s t
On e xam in at io n , h e h as d im in ish e d lig h t t o u ch se n sat io n o n t h e
2
n e ck p a in is s e lf-lim it e d . Con -
N
d o rsu m o f t h e le f t f o re arm an d h an d . St re n g t h in t h e arm s is 5 /5 in t h e s e q u e n t ly, p a t ie n t s s e e k in g
O
I
T
d e lt o id s, b ice p s, t rice p s, an d h an d g rip . De e p t e n d o n re e xe s in t h e ca r e fo r n e ck p a in t e n d t o
C
E
arm s an d le g s are n o rm al e xce p t t h e le f t b ice p s is 3 . Ho ff m an ’s re e x h a ve m ore s eve re p a in , ot h e r
S
a s s o c ia t e d s y m p t o m s , o r
is n e g at ive . Th e re is n o an k le clo n u s.
ch ro n ic s ym p t o m s t h a t h a ve
A m agnetic resonance im aging of the cervical spine show s severe m ul- n ot re s p on d e d t o re s t or ove r-
tilevel degenerative disc disease w ith broad-based disc protrusion at C3-C4 t h e - c o u n t e r a n a lg e s ic s ; o r
resulting in spinal cord deform ity (see im age), severe foram inal narrow ing t h ey re p ort n e ck p a in a s a s e c-
o n d a ry s ym p t o m o f a m o re
at bilateral C5, left C7, and bilateral C8 nerve roots. Electrom yogram
ge n e ra liz e d co n d it io n . Th o s e
show s a chronic neurogenic lesion affecting the left C7 nerve root. p a t ie n t s s e e k in g ca r e w it h
He is in it ially m an ag e d co n se rvat ive ly. Ho w e ve r, 3 m o n t h s lat e r h e n e ck p a in a s a p rim a ry com -
p re se n t s w it h a w o rse n in g o f sym p t o m s w it h n u m b n e ss an d t in g lin g in p la in t t e n d t o h ave s ym p t om s
b o t h e rs o m e e n o u gh t o ca u s e
b o t h arm s an d h an d s t h at is e xace rb at e d b y m o ve m e n t o f h is n e ck . He
fu n ct io n a l lim it a t io n s . Fu n c-
co n t in u e s t o d e n y b o w e l o r b lad d e r in co n t in e n ce . His n e u ro lo g ic e xam - t io n a l cla s s i ca t io n s ys t e m s
in at io n is u n ch an g e d e xce p t t h at h e n o w h as a p o sit ive Ho ff m an ’s s u ch a s t h e Wo r ld He a lt h
re e x in t h e rig h t arm . Orga n iz a t io n ’s In t e r n a t io n a l
Cla s s i ca t io n of Fu n ct io n in g,
Because of progression of sym ptom s and subtle signs of m yelopathy,
Dis a bilit y, a n d He a lt h (ICF) ca n
he undergoes posterior cervical decom pression and fusion. Postoperatively, be u s e d t o m ore fu lly d e s cribe
his neurologic sym ptom s abate, but his pain continues, and his neurologic p a t ie n t im p a irm e n t s .
exam ination continues to show dim inished light touch sensation on the Mu lt ip le -r is k fa ct o r s fo r
n e ck p a in h a ve b e e n id e n t i-
dorsum of the left hand and 5/5 m otor strength in both arm s except for
e d (1 ) in clu d in g in cre a s in g
4 /5 m otor strength in the left w rist extensors and triceps. a ge, obe s it y, s m okin g, u n u s u a l
p os t u re s , a n d h e a vy lift in g or
11
12 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Dorsal View
Dens Superior
articulate facet
Transverse
POSTERIOR foramen
Superior View Transverse
Posterior tubercle process
Posterior arch Vertebral
foramen
Location of Inferior articular Lamina
transverse process
ligament Spinous process Dens
Transverse Lateral View
Articular surface foramen
for dens of axis Articular facet for anterior arch of atlas
Superior articular facet
Lamina
Transverse
process Superior
Lateral
s
articular
e
mass facet POSTERIOR ANTERIOR
m
Location
o
Groove for vertebral of dens
r
Spinous
d
artery and first cervical
Anterior tubercle
n
spinal nerve process
y
S
Anterior arch Inferior articular Transverse Transverse
n
process process foramen
i
a
A ANTERIOR B
P
l
a
n
Posterior
o
Anterior
i
g
e
Pedicle
R
Superior articular facet
2
Lamina
N
Vertebral body
O
Spinous process
I
Spinous process
T
Intervertebral disk
C
E
Superior Inferior articular
S
Lamina facets facet Nerve root
Posterior
Transverse process
Spinal nerve
Pedicle
Anterior
Vertebral body
Figure 2.1 (A) Ana tomy of a tla s; (B) a na tomy of a xis; a nd (C) a na tomy of typica l vertebra . All illustra tions from Oa tis CA. Kinesiology. The Mecha nics a nd
Pa thomecha nics of Huma n Movement. Ba ltimore: Lippincott Willia ms & Wilkins; 2003.
s
e it h e r a p rim a ry u n d e rlyin g m u s cu los ke le t a l a bn orm a lit y or a re e x s p a s m of
e
d e t e rm in e d b y t h e w o rk-
m
in g d iffe re n t ia l d ia g n o sis t h e p os t e rior n e ck m u s cle s . In e it h e r ca s e, s p on t a n e ou s m ove m e n t of t h e h e a d
o
r
a ft e r a ca re fu l h ist o ry a n d is t yp ica lly re d u ce d . It is im p ort a n t t o obs e rve for a s p a s t ic ga it t h a t m a y origi-
d
n
p h ysica l e xa m in a t io n . n a t e from ce rvica l s p in a l cord d ys fu n ct ion .
y
S
Exa m in a t ion s h ou ld t h e n focu s on in s p e ct ion a n d p a lp a t ion o f t h e n e ck
n
• Pa t ie n t s w it h a xia l n e ck
i
a
p a in w it h o u t n e u ro lo g ic w it h s p e cia l a t t e n t ion t o t h e a re a of m a xim a l s ym p t om s . It is oft e n h e lp fu l t o
P
sym p t o m s o r sig n s a n d h a ve t h e p a t ie n t s p oin t t o t h e s p e ci c a re a w h e re t h ey a re e xp e rie n cin g s ym p -
l
a
w h o a re n o t su sp e ct e d
n
t om s a n d h a ve t h e m p oin t ou t a n y a bn orm a lit ie s t h a t t h ey h a ve p e rce ive d .
o
o f h a vin g a n e m e rg e n t
i
Ra s h e s or bru is e s m ay s u gge s t zos t e r or p rior t ra u m a , re s p e ct ive ly. For p a t ie n t s
g
o r se rio u s u n d e rlyin g
e
R
co n d it io n d o n o t re q u ire re p or t in g a n t e rio r n e ck p a in , rs t in s p e ct t h e a n t e rior ce rvica l t ria n gle bor-
2
in it ia l im a g in g . d e re d by t h e s t e rn ocle id om a s t oid m u s cle, m a n d ible, a n d s t e rn a l n ot ch on e a ch
N
s id e lookin g for d e form it ie s a n d a s ym m e t ry; a n d t h e n bot h p os t e rior ce rvica l
O
• An u n d e rst a n d in g o f
I
T
ce rvica l sp in a l a n a t o m y t ria n gle s bord e re d by t h e s t e r n ocle id o m a s t oid , cla vicle , a n d t ra p e ziu s . Bo t h
C
E
is re q u ire d t o a llo w in t e r- a re a s s h ou ld t h e n be p a lp a t e d for loca lize d t e n d e rn e s s . Th e m u s cle bod ie s a n d
S
p re t a t io n o f im a g in g t h e ir u n d e rlyin g s t ru ct u re s s h ou ld be p a lp a t e d a n d t h e p re s e n ce of lym p h a d -
n d in g s a n d re p o rt s. e n op a t h y or m a s s e s d e t e rm in e d . For p a t ie n t s w it h re s p ira t ory s ym p t om s or
d ys p h a gia , t ra ch e a l loca t ion , a n d t h yroid s ize, s h a p e, loca t ion , a n d m ove m e n t
w it h sw a llow s h ou ld be n ot e d . Th e ve s s e ls of t h e n e ck s h ou ld be obs e rve d a n d
t h e ca rot id p u ls e p a lp a t e d . A s cre e n in g ca rd iop u lm on a ry e xa m in a t ion s h ou ld
a ls o be d on e s in ce n e ck p a in m a y be re fe rre d from in t ra t h ora cic s t ru ct u re s .
For p a t ie n t s w it h p os t e rior n e ck p a in , begin t h e e xa m in a t ion w it h in s p e c-
t ion of t h e ce rvica l s p in ou s p roce s s e s by lookin g a t t h e ir a lign m e n t a n d n ot in g
a n y d e form it ie s . Als o look for d e form it y or a s ym m e t ry of t h e p a ra ce rvica l m u s -
cle s , s ca p u la , a n d s u rrou n d in g m u s cle s . Th e n p a lp a t e t h e s p in ou s p roce s s e s a n d
p os t e rior n e ck s oft t is s u e s a n d m u s cu la t u re from t h e occip it a l in s e rt ion s t o t h e
in fe rior a n gle of t h e s ca p u la a n d la t e ra lly ou t t o t h e s h ou ld e rs lookin g for p oin t
t e n d e rn e s s a n d s p a s m . Th e a s s ocia t e d leve l of a n y s p in ou s t e n d e rn e s s , d e form -
it y, or s t ep -off s h ou ld be n ot e d ; t h e p rom in e n t C7 s p in ou s p roce s s ca n be u s e d
a s a p oin t of re fe re n ce ; p oin t t e n d e rn e s s a t a p a rt icu la r leve l w a rra n t s fu rt h e r
in ve s t iga t ion w it h im a gin g. For p a t ie n t s w it h m ore t h a n on e p oin t of m u s cu la r
t e n d e rn e s s , a s e a rch for a n y t rigge r p oin t s in ot h e r body a re a s is w a rra n t e d .
Th e a ct ive a n d p a s s ive ra n ge s of m ot ion of t h e n e ck s h ou ld t h e n be obs e rve d .
Fu ll ce rvica l s p in e ra n ge of m ot ion in you n g a d u lt s is 60 d egre e s of e xion ,
75 d egre e s of e xt e n s ion , 45 d egre e s of la t e ra l be n d t o e a ch s id e, a n d 90 d egre e s
of rot a t ion t o e a ch s id e. In p a t ie n t s old e r t h a n 50 ye a rs , ext e n s ion is re d u ce d t o
60 d egre e s a n d la t e ra l be n d is re d u ce d t o 30 d egre e s (4 ). Pos it ion s t h a t a ggrava t e
or a llevia t e t h e n e ck p a in or it s ra d ia t ion s h ou ld be n ot e d . Ne ck m u s cle s t re n gt h
t e s t in g s h ou ld t h e n be d on e. Th e s t e rn ocle id om a s t oid s a re t h e m a in exors a n d
rot a t ors of t h e n e ck, w h ile t h e m a in e xt e n s ors a re t h e p a rave rt e bra l m u s cle s
16 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
C1
C2
C3
C4
C5
T1
T2
C6
C7 C8
C6
C7
C8
S
T1
E
C
T2
T
I
O
N
2
Figure 2.2 Derma tomes of the cervica l spine.
R
e
g
i
o
n
a n d t h e t ra p e zii. Th e exors a re t e s t e d by p u t t in g a h a n d be low t h e ch in ; t h e
a
l
e xt e n s ors a re t e s t e d by p la cin g a h a n d on t h e occip u t w h ile t h e ot h e r h a n d
P
a
h old s t h e s h ou ld e r, a n d t h e rot a t ors a re t e s t e d by p u t t in g a h a n d on t h e s id e of
i
n
t h e ch in ; t h e t ra p e zii ca n be t e s t e d by a s kin g t h e p a t ie n t t o s h ru g h e r s h ou ld e rs
S
y
a ga in s t re s is t a n ce. Rep rod u ct ion or a ggrava t ion of s ym p t om s d u rin g s t re n gt h
n
d
t e s t in g s u gge s t s a p os s ible m u s cu los ke le t a l e t iology of t h e p a in .
r
o
m
A d e t a ile d n e u rologic e xa m in a t ion of t h e u p p e r e xt re m it ie s s h ou ld t h e n be
e
d on e t o h e lp d e t e ct a n a s s ocia t e d ra d icu lop a t h y or m ye lop a t h y. For p a t ie n t s
s
w it h a re a s of s e n s ory d e cit s , d e rm a t om e ch a rt s ca n be u s e d t o d e t e rm in e t h e
m a t ch of t h e n d in gs t o a n a s s ocia t e d corre s p on d in g ce rvica l n e rve root leve l
(Fig. 2.2 ). W h e n t e s t in g for m ye lop a t h y, in clu d e ligh t t ou ch a n d p rop riocep t ion
t e s t in g t o a s s e s s p os t e rior s p in a l cord fu n ct ion a n d t e m p e ra t u re a n d p in p rick
t e s t in g t o a s s e s s a n t e rola t e ra l s p in a l cord fu n ct ion . Alt h ou gh t h e m a t ch of ce r-
vica l n e rve root s t o in d ivid u a l m u s cle s is ve ry n on s p e ci c, s e le ct e d m ot or t e s t -
in g ca n h e lp loca lize a n in volve d ce rvica l n e rve leve l, e s p e cia lly if t h e p a t t e rn
co r ro b o ra t e s a d e r m a t o m a l p a t t e r n o f s e n s o ry lo s s (s e e Ta ble 2.1 ). Mu s cle
s t re n gt h s h ou ld be gra d e d on t h e s t a n d a rd 0 t o 5 s ca le :
0. No con t ra ct ion
1. Vis ible t w it ch bu t n o join t m ove m e n t
2. Able t o m ove join t w it h gravit y e lim in a t e d
3. Join t m ove m e n t a ga in s t gravit y bu t n ot a ga in s t re s is t a n ce
4. Join t m ove m e n t a ga in s t s om e re s is t a n ce
5. Join t m ove m e n t a ga in s t fu ll re s is t a n ce
Bra ch iora d ia lis , bicep s , a n d t ricep s d e ep t e n d on re e xe s s h ou ld be ch e cke d
a n d gra d e d u s in g t h e s t a n d a rd s ca le :
0. Abs e n t
1. Tra ce
2. Norm a l
3. Bris k
4. 3 be a t s clon u s
5. Su s t a in e d clon u s
Ch a p te r 2 Ne ck Pa in 17
Table 2.1 Localizing Neurologic Sympt oms and Signs Associat ed wit h Cervical
Nerve Root s
s
4t h , 5t h d ig it s 5t h d ig it s
e
m
o
a
Wrist e xt e n so r t e st in g : Fle x n g e rs t o e lim in a t e w rist e xt e n sio n b y n g e r e xt e n so rs a n d t h e n e xt e n d w rist in ra d ia l d ire ct io n . Fle xo r ca rp i ra d ia lis
r
d
t e st in g : Ext e n d n g e rs t o e lim in a t e w rist e xio n b y n g e r e xo rs a n d t h e n e x w rist in ra d ia l d ire ct io n .
n
y
b
Fle xo r d ig it o ru m su b lim is t o rin g n g e r t e st in g : St a b ilize lo n g , in d e x, a n d lit t le n g e rs in e xt e n sio n a n d e x n g e rs.
S
n
i
a
P
l
a
n
o
W h e n s e n s ory a n d m ot or a bn orm a lit ie s a re fou n d bu t t h e ir p a t t e rn s d o n ot
i
g
NOT TO BE MISSED t w e ll w it h a s p e ci c ra d icu la r p a t t e rn , com m on u p p e r e xt re m it y p e rip h e ra l
e
R
n e u rop a t h ie s s h ou ld be e xp lore d a s a p ot e n t ia l e t iology for t h e n d in gs . Te s t s
2
• Sp in a l in st a b ilit y d u e t o
N
for u p p e r m ot or n e u ron s ign s s u ch a s Hoffm a n ’s a n d Ba bin s ki’s re e xe s a n d a n
fra ct u re s o r so ft t issu e
O
e xa m in a t ion of low e r e xt re m it y m ot or s t re n gt h a n d t on e s h ou ld a ls o be d on e
I
T
in ju ry d u e t o t ra u m a o r
C
in a m m a t o ry co n d it io n s t o s cre e n for ce rvica l m ye lop a t h y.
E
S
su ch a s rh e u m a t o id Seve ra l s p e cia lize d m a n e u ve rs a re oft e n re com m e n d e d t o fu rt h e r eva lu a t e
a rt h rit is. for p os s ible ra d icu lop a t h y or m ye lop a t h y. Sp u rlin g’s t e s t in volve s p la cin g t h e
• Sp in a l co rd co m p re ssio n n e ck in p o s it io n s t h a t re d u ce t h e d ia m e t e r o f t h e ce r vica l in t e r ve r t e b ra l
o r im p e n d in g co m p re ssio n fora m in a w h ich m a y ca u s e com p re s s ion of t h e s p in a l n e rve ; t h e t e s t is con s id -
d u e t o in fe ct io n , ca n ce r, e re d p o s it ive if ra d icu la r s ym p t o m s a re e licit e d w h e n t h e p a t ie n t ’s n e ck is
a n d d e g e n e ra t ive o r e xt e n d e d a n d rot a t e d t ow a rd t h e s ym p t om a t ic s id e. Th e com p le m e n t a ry t e s t
co n g e n it a l co n d it io n s.
t h a t a t t e m p t s t o m a xim iz e t h e fo ra m in a l op e n in g is ca lle d t h e “d is t ra ct io n
• Pa in t h a t is a risin g fro m t e s t .” Th e p a t ie n t is p la ce d s u p in e a n d t h e e xa m in e r t h e n ge n t ly p u lls on t h e
visce ra l o rg a n s su ch a s h e a d ; re lie f o f s ym p t o m s s u gge s t s u n d e r lyin g ce r vica l ra d icu lo p a t h y. Th is
t h e h e a rt , va scu la t u re ,
lu n g s, o r g a st ro in t e st in a l m a n e u ve r s h ou ld n ot be d on e in p a t ie n t s w h o m igh t h ave u n d e rlyin g s p in a l
t ra ct t h a t is re fe rre d t o in s t a bilit y. Bot h t e s t s h a ve low s e n s it ivit y, bu t fa ir s p e ci cit y, yie ld in g a p os it ive
t h e n e ck. like lih ood ra t io of 3 a n d a n ega t ive like lih ood ra t io of 0.6 (5 ). A la n cin a t in g p a r-
• Syst e m ic in fe ct io u s e s t h e s ia w it h n e ck e xion , t e rm e d “Lh e rm it t e ’s s ign ,” m a y be s e e n w it h com -
(e .g ., m e n in g it is) o r p re s s ion of t h e s p in a l cord in p a t ie n t s w it h s p in a l s t e n os is .
in a m m a t o ry (e .g .,
t e m p o ra l a rt e rit is)
co n d it io n s t h a t m a y
p re se n t w it h n e ck p a in
Studie s
a s a n e a rly sym p t o m . Fu rt h e r d ia gn os t ic t e s t in g is n e e d e d w h e n t h e h is t ory or p h ys ica l e xa m in a t ion
• Pro g re ssive n e u ro lo g ic u n cove rs p os s ible e m e rge n t o r s e riou s u n d e rlyin g con d it ion s ; w h e n t h e p a t -
co n d it io n s t h a t m a y t e rn or s eve rit y of p a in or a s s ocia t e d s ym p t om s s u gge s t t h e n e e d for t re a t -
p ro d u ce sym p t o m s t h a t m e n t s ot h e r t h a n a n a lge s ics , re s t , or p h ys ica l t h e ra py; or w h e n t h e re m ay be
a re sim ila r t o t h o se e xt e n u a t in g n on m e d ica l is s u e s s u ch a s w or k, a ccid e n t , or d is a bilit y-re la t e d
se e n w it h sp in a l co rd
cla im s . Im a gin g s h ou ld be obt a in e d in p a t ie n t s w it h a h is t ory of t ra u m a , con -
co m p re ssio n o r sp in a l
n e rve co m p re ssio n . s t it u t ion a l s ym p t om s , u n d e rlyin g s ys t e m ic illn e s s e s in clu d in g ca n ce r or in fe c-
t ion , or n e u rologic s ym p t om s , a n d s h ou ld be con s id e re d in p a t ie n t s old e r t h a n
18 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
50 ye a rs w it h n ew on s e t of p a in a n d in p a t ie n t s w it h ch ron ic p a in p e rs is t in g
m ore t h a n 6 w e e ks d e s p it e con s e rva t ive t h e ra p ie s .
Th e t yp e of t e s t in g d ep e n d s on t h e w orkin g d iffe re n t ia l d ia gn os is a ft e r t h e
h is t ory a n d p h ys ica l e xa m in a t ion , e s p e cia lly for p a t ie n t s p re s e n t in g w it h a n t e -
rior n e ck p a in , s in ce a n t e rior s ym p t om s a re n ot t yp ica lly ca u s e d by s p in a l-
re la t e d con d it ion s . In a d d it ion t o t e s t in g re la t e d t o s p e ci c d ia gn os e s s u gge s t e d
by t h e h is t ory a n d p h ys ica l e xa m in a t ion , if a n u n d e rlyin g s ys t e m ic illn e s s is
s u s p e ct e d , a s cre e n in g CBC w it h d iffe re n t ia l, ESR a n d /or C re a ct ive p rot e in , a n d
a lka lin e p h os p h a t a s e s h ou ld be obt a in e d .
Ne ck p a in p a t ie n t s w h o re p or t a h is t ory of t ra u m a s h o u ld h a ve fu rt h e r
eva lu a t io n w it h im a gin g. For p a t ie n t s w it h m ild or m od e ra t e t ra u m a , h igh -
q u a lit y ce rvica l s p in e p la in ra d iogra p h s h ave a d e q u a t e s e n s it ivit y t o e xclu d e
s e riou s u n d e rlyin g fra ct u re, bu t it is im p ort a n t t o re m e m be r t h a t s e n s it ivit y for
fra ct u re d e t e ct ion ca n be re d u ce d in p a t ie n t s w it h os t e op e n ia or p rior ce rvica l
s p in e s u rge rie s . Th e fu ll ce rvica l s p in e s e rie s in t h e n e u t ra l p os it ion in clu d e s
la t e ra l a n d PA view s a n d a n od on t oid view w h ich is obt a in e d w it h t h e m ou t h
op e n t o e lim in a t e t e e t h ove rlyin g t h e a re a of C1-C2 a n d a llow a d e q u a t e vis u -
a liza t ion of t h e od on t oid p roce s s . If fra ct u re is ru le d ou t , le ft a n d righ t obliq u e
S
view s a re obt a in e d t o com p le t e t h e s e rie s . In s om e p a t ie n t s , it m ay be d if cu lt
E
C
t o ge t a d e q u a t e view s of e it h e r C1 or C7; in fa ct , in a d e q u a t e vis u a liza t ion of C7
T
I
O
is t h e m o s t co m m o n e r ro r m a d e in t h e x -ra y a s s e s s m e n t o f ce rvica l s p in e
N
in ju ry. PA a n d la t e ra l view s s h ow t h e h om oge n e it y, h e igh t , a n d a lign m e n t of
2
t h e ve rt e b ra l bo d ie s a n d t h e in t e r ve r t e bra l d is cs , a n d t h e la t e ra l view a ls o
R
e
s h ow s t h e s p in ou s p roce s s e s a n d fa ce t join t s a n d a llow s e s t im a t ion of t h e p re -
g
i
o
ve rt e bra l s oft t is s u e w id t h w h ich m ay be in cre a s e d in p a t ie n t s w it h a re la t e d
n
a
ve rt e bra l fra ct u re or p reve rt e bra l s oft t is s u e in ju ry; obliq u e view s a re be t t e r for
l
P
vis u a liz in g t h e in t e r ve r t e b ra l fo ra m in a . If t h e re a re co n ce r n s a b o u t s p in a l
a
i
in s t a bilit y d u e t o s oft t is s u e in ju ry or a n u n d e rlyin g in a m m a t ory con d it ion
n
S
s u ch a s rh e u m a t oid a rt h rit is , t h e n la t e ra l e xion a n d e xt e n s ion view s ca n be
y
n
obt a in e d if t h e n e u t ra l p os it ion view s e xclu d e fra ct u re. In ge n e ra l, it is d if cu lt
d
r
o
t o fu lly eva lu a t e a ll e le m e n t s of t h e p os t e rior ve rt e bra l a rch w it h p la in lm s
m
be ca u s e of s u m m a t ion e ffe ct s of ove rlyin g s h a d ow s . For p a t ie n t s w it h a h is t ory
e
s
of p os s ibly s eve re t ra u m a or t ra u m a p a t ie n t s w it h a n y n e u rologic s ign s s u gge s -
t ive of ra d icu lop a t h y or m ye lop a t h y, t h e h igh e r s e n s it ivit y of ce rvica l com p u t e d
t om ogra p h y (CT) or m a gn e t ic re s on a n ce im a gin g (MRI) is n e e d e d t o ru le ou t
occu lt fra ct u re s a n d ce rvica l s p in a l cord or s oft t is s u e in ju rie s .
For p a t ie n t s w it h p os t e rior n e ck p a in , t h e p a t t e rn of s ym p t om s a n d n d in gs
ca n d ire ct t h e t yp e of s u bs e q u e n t t e s t in g. Im a gin g of ch ron ic p a in t h a t h a s n ot
re s p on d e d t o con s e rva t ive m e a s u re s a n d is loca lize d t o t h e a xia l a n d p a ra s p i-
n a l a re a w it h ou t a n y ra d ia t ion or a s s ocia t e d s ym p t om s s u gge s t ive of ra d icu -
lop a t h y or m ye lop a t h y s h ou ld s t a rt w it h a ce rvica l s p in e s e rie s . X-rays w ill fre -
q u e n t ly s h ow s ign s of d ege n e ra t ive d is e a s e of t h e in t e rve rt e bra l d is cs or fa ce t
join t s a n d /or n a rrow in g of t h e in t e rve rt e bra l fora m in a . In fa ct , in a s ym p t om a t ic
p a t ie n t s old e r t h a n 40 ye a rs , ce rvica l d ege n e ra t ive ch a n ge s (s p on d ylos is ) a re
com m on , a n d a ft e r t h e a ge of 50 ye a rs , ce rvica l s p on d ylos is is p re s e n t in m ore
t h a n 90% of in d ivid u a ls (6 ). Th e re fore, t h e s e d ege n e ra t ive ch a n ge s a re re leva n t
on ly if t h ey s p e ci ca lly t w it h t h e re s t of t h e p a t ie n t ’s s ym p t om s a n d s ign s .
For p a tien ts w ith ra d icu la r sym p tom s a n d con sisten t p h ysica l exa m in a tion
n d in gs, fu rth er testin g cou ld be d eferred d u rin g a p eriod of in itia l con serva tive
m a n a gem e n t sin ce sym p tom s te n d to a ba t e over tim e; h ow ever, fu rt h er in itia l
eva lu a tion is w a rra n ted if th ere is sign i ca n t w ea kn ess. W h en w ea kn ess is p resen t,
w orku p w ith electrom yogra m ca n con rm th a t th e etiology of th e w ea kn ess is d u e
to cervica l ra d icu lop a th y a n d ca n h elp con rm th e su sp ected n erve root; h ow ever,
electrom yogra p h ic testin g w ill be n orm a l in p a tien ts w ith ou t in volvem en t of th e
m otor p a rt of th e sp in a l n erve. For p a tien ts w ith in con sisten t or u n clea r n eu ro-
logic exa m in a tion n d in gs in th e u p p er extrem ities, electrod iagn ostic testin g ca n
h elp u n cover a n u n d erlyin g p erip h era l or en tra p m en t n eu rop a th y.
Ch a p te r 2 Ne ck Pa in 19
s
la t e d w it h t h e h is t o ry, p h ys ica l e x a m in a t io n , a n d o t h e r d ia gn o s t ic t e s t in g
e
m
be fore m a kin g a clin ica l d ia gn os is of ce rvica l m ye lop a t h y.
o
r
Bon e s ca n is ra re ly d on e in t h e eva lu a t ion of p a t ie n t s w it h n e ck p a in , s in ce
d
n
bot h CT a n d MRI h ave e xce lle n t s e n s it ivit y for in fe ct ion a n d t u m or. Th e p h ys i-
y
S
ologic in form a t ion of bon e s ca n ca n s om e t im e s be h e lp fu l t o con rm a s p e ci c
n
i
fa ce t join t a s a n u n d e rlyin g p a in ge n e ra t or; a d ia gn os t ic in je ct ion of loca l a n e s -
a
P
WHEN TO REFER t h e t ic in t o t h e s u s p e ct join t ca n t h e n be d on e t o s e e w h e t h e r t h e p a t ie n t ’s p a in
l
a
n
is e lim in a t e d . Com bin e d bon e a n d ga lliu m s ca n s a re s om e t im e s n e ce s s a ry t o
o
i
• Pa t ie nt s w it h sp in a l co rd eva lu a t e for p os s ible in fe ct ion in p a t ie n t s w it h s p in a l h a rd w a re, w h ich d is t ort s
g
e
co m p re ssio n o r in st a b ilit y
R
com p u t e d t om ogra p h ic a n d MR im a ge s .
should be urge ntly re fe rre d
2
to a spina l surge on.
N
Tre a tme nt
O
• Pa t ie n t s w it h ce rvica l
I
T
C
ra d icu lo p a t h y w it h w e a k-
E
n e ss o r p e rsist e n t sym p - In it ia l t re a t m e n t of n e ck p a in d e p e n d s on t h e re m a in in g d iffe re n t ia l d ia gn os is
S
t o m s a ft e r a co u rse o f co n - a ft e r h is t o ry, p h ys ica l e xa m in a t ion , a n d in d ica t e d d ia gn os t ic s t u d ie s . Tre a t -
se rva t ive t h e ra p y ca n b e m e n t is d ire ct e d a t t h e u n d e rlyin g con d it ion for p a t ie n t s w it h a s p e ci c con -
re fe rre d fo r e p id u ra l in je c- rm e d d ia gn os is . For e xa m p le, p a t ie n t s fou n d t o h ave in t e rve rt e bra l d is cit is or
t io n s o r sp in a l su rg e ry.
ce rvica l s p in a l os t e om ye lit is a re t re a t e d w it h a p p rop ria t e a n t ibiot ics a ft e r cu l-
• Pa t ie n t s w it h ce rvica l st ra in t u re s a re o b t a in e d . Pa t ie n t s w it h s p in a l co rd co m p re s s io n d u e t o e p id u ra l
ca n b e re fe rre d t o p h ysica l a bs ce s s or ca n ce r s h ou ld be e m e rge n t ly re fe rre d t o n e u ros u rge on s , a n d in t h e
t h e ra p y fo r in st ru ct io n in
ca s e of m a lign a n t t u m ors a p p rop ria t e ca n ce r s p e cia lis t s , t o h e lp p reve n t w ors -
h o m e e xe rcise s, p o st u re ,
e rg o n o m ics, a n d p o ssib le e n in g of m ye lop a t h y. Pa t ie n t s w it h ce rvica l s p in a l fra ct u re s or in s t a bilit y d u e t o
a ct ivit y m o d i ca t io n s. t ra u m a s h ou ld a ls o be e m e rge n t ly re fe rre d t o n e u ros u rge on s for p os s ible s p i-
n a l s t a biliza t ion . Pa t ie n t s w it h s p in a l cord com p re s s ion d u e t o ce rvica l s p on d -
• Pa t ie n t s w h o a re fe lt t o
h a ve p a in a risin g fro m a ylos is or s p in a l s t e n os is s h ou ld a ls o be re fe rre d t o s p in e s u rge on s w h o ca n
d e g e n e ra t ive fa ce t jo in t p re s e n t t h e p a t ie n t w it h t h e be n e t s a n d ris ks of s u rgica l d e com p re s s ion .
w h o h a ve p e rsist e n t p a in In it ia l t re a t m e n t for p a t ie n t s w it h ou t a n u n d e rlyin g e m e rge n t or s e riou s
d e sp it e co n se rva t ive co n d it io n is o ft e n a im e d a t s ym p t o m co n t ro l. Pa t ie n t s w it h ce rvica l ra d icu -
m e a su re s ca n b e re fe rre d
lop a t h y a re t yp ica lly t re a t e d con s e rva t ive ly for 6 t o 8 w e e ks . Th e n on p h a rm a -
fo r d ia g n o st ic fa ce t jo in t
in je ct io n , m e d ia l b ra n ch cologic con s e rva t ive m od a lit ie s m os t fre q u e n t ly u s e d a re avoid a n ce of a ggra -
b lo ck, a n d /o r p e rcu t a n e o u s va t in g a ct ivit ie s a n d t h e n p ro gre s s ive m o b iliz a t io n a n d p h ys ica l t h e ra p y
n e u ro t o m y. e xe rcis e s on ce p a in is t ole ra ble. Ce rvica l colla rs m ay be u s e d in t h e s h ort t e rm
• Pa t ie n t s fo u n d t o h a ve if t h ey p rovid e s om e s ym p t om a t ic re lie f, bu t lon g-t e rm u s e s h ou ld be avoid e d ,
syst e m ic co n d it io n s p re - s in ce it ca n con t ribu t e t o d is u s e a t rop h y of t h e ce rvica l m u s cu la t u re.
se n t in g w it h n e ck p a in Ph a rm a cologic t re a t m e n t of ce rvica l ra d icu lop a t h y t yp ica lly in clu d es a n a l-
m a y n e e d t o b e re fe rre d t o ge s ics s u ch a s n on s t e roid a l a n t i-in a m m a t orie s d ru gs a n d m ay a ls o in clu d e
a p pro p ria t e sp e cia list s fo r
m u s cle re la xa n t s in p a t ie n t s w it h p a ra s p in a l m u s cle s p a s m d e t e ct e d on exa m i-
d ia g n o st ic co n rm a t io n
and management. n a t ion ; n e u rop a t h ic p a in m e d ica t ion s s h ou ld be con s id ere d in p a t ie n t s w h os e
ra d icu la r s ym p t om s a re n ot con t rolle d w it h s im p le a n a lges ics . Th e s e le ct ion of
20 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Clinica l Co urse
Pa t ie n t s p re s e n t in g w it h n e ck p a in ca n re p re s e n t a d ia gn o s t ic ch a lle n ge
be ca u s e of a n e xt e n s ive d iffe re n t ia l d ia gn os is t h a t in clu d e s e m e rge n t a n d s e ri-
ou s u n d e rlyin g con d it ion s a n d t h e p oor corre la t ion of d ia gn os t ic t e s t n d in gs
t o clin ica l s ym p t om s in p a t ie n t s w it h ch ron ic, n on u rge n t con d it ion s . Pa t ie n t s
w it h a h is t ory of m a jor n e ck t ra u m a , or m a jor blu n t t ra u m a w it h a lt e re d m e n -
t a l s t a t u s , or “d is t ra ct in g” in ju rie s (w h os e p a in m a y s u p e rs e d e p a in from a con -
cu rre n t n e ck in ju ry) n e e d ce rvica l s p in e im m obiliza t ion a n d e m e rge n t im a gin g
t o ru le ou t s p in a l fra ct u re or ot h e r s p in a l cord t h re a t e n in g s oft t is s u e in ju ry.
In fe ct ion m u s t be ru le d ou t w it h im a gin g a n d blood t e s t s in p a t ie n t s w it h IV
d ru g a bu s e, va s cu la r a cce s s d evice, or im m u n ocom p rom is e d s t a t e, or w h o h ave
con s t it u t ion a l s ym p t om s or feve r on e xa m in a t ion ; a n d m e t a s t a t ic ca n ce r m u s t
be ru le d ou t in p a t ie n t s w it h a h is t ory of m a lign a n cy. Pa t ie n t s w it h n e u rologic
s ym p t om s or p h ys ica l e xa m in a t ion s ign s of m ye lop a t h y n e e d u rge n t im a gin g
Ch a p te r 2 Ne ck Pa in 21
s
p e rs is t e n t p a in a n d p oore r fu n ct ion a l ou t com e s .
e
m
Alt h ou gh d e ge n e ra t ive d is c d is e a s e a n d d ege n e ra t ive fa ce t join t d is e a s e
o
r
a re fre q u e n t ly fou n d on im a gin g in a s ym p t om a t ic p a t ie n t s , t h e s e s t ru ct u re s
d
n
a re fe lt t o be t h e p a in ge n e ra t ors in m a n y p a t ie n t s w it h n e ck p a in . In p a rt icu la r,
y
S
a xia l n e ck p a in w it h ou t n e u rologic s ym p t om s t h a t h a s a n a cu t e on s e t is t yp i-
n
i
ca lly a t t rib u t e d t o a n o b s e rve d co rre s p o n d in g d is c h e rn ia t io n —e s p e cia lly in
a
P
you n ge r p a t ie n t s , a n d ch ron ic n e ck p a in is oft e n a t t ribu t e d t o obs e rve d corre -
l
a
n
s p o n d in g fa ce t d ege n e ra t ive jo in t d is e a s e —e s p e cia lly in o ld e r p a t ie n t s . Th e
o
i
m a jorit y of p a t ie n t s d ia gn os e d w it h a cu t e d is c h e rn ia t ion im p rove ove r a few
g
e
R
w e e ks . Pa t ie n t s d ia gn os e d w it h d ege n e ra t ive fa ce t a rt h rit is t e n d t o h ave ch ron ic
2
s ym p t o m s t h a t ca n b e co n t ro lle d w it h co n s e r va t ive t h e ra p ie s . Fo r t h o s e
N
p a t ie n t s w it h s eve re s ym p t om s d e s p it e con s e rva t ive t re a t m e n t s , a d ia gn os t ic
O
I
T
fa ce t join t in je ct ion w it h loca l a n e s t h e s ia ca n be u s e d t o con rm t h a t it is t h e
C
E
p a in ge n e ra t or. If t h e p a t ie n t obt a in s re lie f w it h t h e t a rge t e d d ia gn os t ic in je c-
S
t ion , fu rt h e r m e a s u re s s u ch a s p e rcu t a n e ou s ra d iofre q u e n cy n e u rot om y of t h e
m e d ia l b ra n ch o f t h e co r re s p o n d in g s p in a l n e r ve m a y p rovid e lo n ge r t e r m
re d u ct ion of s ym p t om s (10 ).
Sim ila rly, a lt h ou gh fa ce t join t os t e op h yt e s , in t e rve rt e bra l d is c h e rn ia t ion s ,
a n d t h icke n in g of t h e p os t e rior lon git u d in a l liga m e n t a n d liga m e n t u m avu m
a re o ft e n s e e n o n co m p u t e d t o m ogra p h ic o r MR im a ge s in a s ym p t o m a t ic
p a t ie n t s , t h ey a re fre q u e n t ly fou n d t o ca u s e s p in a l cord or n e rve com p re s s ion
in p a t ie n t s w it h ce rvica l m ye lop a t h y or ra d icu lop a t h y, re s p e ct ive ly. Dege n e ra -
t ive ch a n ge s of t h e ve rt e bra l bod y a n d a s s ocia t e d s oft t is s u e s t r u ct u re s a re
re fe rre d t o by t h e n on s p e ci c t e rm “s p on d ylos is .” Th e s e d ege n e ra t ive ch a n ge s
a re s e e n m ore fre q u e n t ly in t h e low e r ce rvica l ve rt e bra e. Con s e q u e n t ly, ce rvica l
m ye lo p a t h y a n d ra d icu lo p a t h y m o re fre q u e n t ly o ccu r a t t h e s e leve ls . Ma n y
p a t ie n t s w it h ce rvica l s p on d ylit ic m ye lop a t h y h a ve cord com p re s s ion a t m ore
t h a n on e leve l. Th e m a jorit y of p a t ie n t s w ill im p rove a ft e r s u rgica l d e com p re s -
s ion , bu t p oore r ou t com e s a re s e e n in old e r p a t ie n t s w h o h ave lon ge r d u ra t ion
of a n d m ore s eve re s ym p t om s be fore s u rge ry. Sim ila rly, t h e m a jorit y of p a t ie n t s
w ill im p rove a ft e r s u rgica l d e com p re s s ion o f ce rvica l ra d icu lop a t h y. Ce rvica l
ra d icu lop a t h y p a t ie n t s h avin g s u rgica l d e com p re s s ion h ave q u icke r im p rove -
m e n t of p a in a n d m ore im p rove m e n t in s t re n gt h t h a n p a t ie n t s m a n a ge d con -
s e rva t ive ly, bu t by 1 ye a r p a in s ym p t om s of con s e rva t ive ly m a n a ge d p a t ie n t s
a re s im ila r t o t h os e p a t ie n t s w h o h a d s u rgica l d e com p re s s ion .
In n e ck p a in p a t ie n t s w it h n e u rologic s ym p t om s , it is im p ort a n t t o con s id e r
ot h e r e t iologie s for t h e obs e rve d n e u rologic s ym p t om s or n d in gs . Dia gn os e s
t o con s id e r in t h e d iffe re n t ia l for p a t ie n t s w it h ra d icu la r s ym p t om s in clu d e
p e r ip h e ra l o r u p p e r e x t re m it y e n t ra p m e n t n e u ro p a t h ie s ; b ra ch ia l p le x u s
in ju rie s , d ege n e ra t ion , or in a m m a t ion ; h e rp e s zos t e r; a n d ot h e r in fe ct iou s ,
22 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Co nclusio ns
In p a t ie n t s w it h a n t e rior n e ck p a in , t h e d iffe re n t ia l d ia gn os is ca n be ve ry broa d ,
s in ce t h is is a com m on s it e for re fe rre d vis ce ra l p a in . Tre a t m e n t a n d clin ica l
ou t com e s w ill d ep e n d on t h e s p e ci c d ia gn os is u n cove re d .
Sim ila rly, in p a t ie n t s w it h n e ck p a in d u e t o ot h e r s ys t e m ic con d it ion s s u ch
a s rh e u m a t oid a rt h rit is , a n kylos in g s p on d ylit is , or p olym ya lgia rh e u m a t ica , t h e
s p e ci c t re a t m e n t a n d eve n t u a l clin ica l ou t com e is d ep e n d e n t on t h e u n d e rly-
in g con d it ion .
Re fe r to Patie nt Education
ICD9
S
E
C
723.1 Ce rvicalg ia
T
I
De g e ne ratio n, de g e ne rative
O
N
722.4 ce rvical, ce rvico t h o racic
2
722.71 w it h m ye lo p at h y
R
e
Displace me nt, displace d
g
i
722.0 ce rvical, ce rvico d o rsal, ce rvico t h o racic
o
n
729.2 Radiculitis (p re ssu re ) (ve rt e b ro g e n ic)
a
l
723.4 ce rvical NEC
P
a
756.11 Spo ndylo lysis (co n g e n it al)
i
n
S
738.4 acq u ire d
y
n
756.19 ce rvical
d
r
721.90 Spo ndylo sis
o
m
721.0 w it h ce rvical, ce rvico d o rsal
e
s
721.1 w it h m ye lo p at h y
Ste no sis (cicat ricial)
723.0 ce rvical
Re fe re nce s
1. Rin d e is ch JA. Ne ck p a in . In : Integrativ e Medicine, 2n d e d . Ph illa d e lp h ia , PA: W B Sa u n d e rs Com p a n y ;
2007 ,697 –708 .
2. Ca m e ro n ID, Re b be ck T, Sin d h u s a ke D, e t a l. Legis la t ive ch a n ge is a s s ocia t e d w it h im p rove d h e a lt h
s t a t u s in p e op le w it h w h ip la s h . Spine 2008 ;33 :250 .
3. Obe lie ie n e D, Sch ra d e r H , Bovim G, e t a l. Pa in a ft e r w h ip la s h : a p ros p e ct ive con t rolle d in cep t ion coh or t
s t u d y. J Neurol Neurosurg Psychiatr 1999 ;66 :279 –282 .
4. Devin C, Sillay K, Ch e n g J. Ne ck p a in . In : Kelley’s Textbook of Rheum atology , 8t h e d . Vol. 1. Ph ila d e lp h ia , PA:
W B Sa u n d e rs Com p a n y ; 2008 ;571 –584 .
5. Ch ild s JD, Cle la n d JA, Elliot t JM , e t a l. Ne ck p a in : clin ica l p ra ct ice gu id e lin e s lin ke d t o t h e In t e r n a t ion a l
Cla s s i ca t ion of Fu n ct ion in g, Dis a bilit y, a n d He a lt h from t h e Ort h op e d ic Se ct ion of t h e Am e rica n Ph ys i-
ca l Th e ra p y As s ocia t ion . J Orthop Sports Phys Ther 2008;38 (9):A1 –A34 .
6. Elia s F. Roe n t ge n n d in gs in t h e a s ym p t om a t ic ce rvica l s p in e . N Y State J Med 1958 ;58 :3300 .
7. Te re s i LM , Lu fkin RB, Re ich e r MA, e t a l. As ym p t om a t ic d ege n e ra t ive d is k d is e a s e a n d s p on d ylos is of t h e
ce rvica l s p in e : MR im a gin g . Radiology 1987 ;164 :83 .
8. Ma n ch ika n t i L, Ca s h KA, Pa m p a t i V, e t a l. Th e e ffe ct ive n e s s of u oros cop ic ce rvica l in t e rla m in a r e p i-
d u ra l in jection s in m a n agin g ch ron ic cervica l d isc h ern ia tion a n d ra d icu litis: p relim in a ry resu lts of a ra n -
d om ized , d ou ble -blin d , con t rolle d t ria l . Pain Physician 2010 ;13 :223 –236 .
9. Pe lo s o P, Gros s A, Ha in e s T, e t a l. Me d icin a l a n d in je ct ion t h e ra p ie s for m e ch a n ica l n e ck d is ord e r s .
Cochrane Database Syst Rev 2007 ;2:CD000319 .
10. Nie m ist o L, Ka lso E, Ma lm iva a ra A, et a l. Ra d iofreq u e n cy d en e rva t ion for n eck a n d ba ck p a in . A s ys t em a t ic
review of ra n d o m ize d con t rolle d t ria ls . Cochrane Database Syst Rev 2003 ;3:CD004058 .
CHAPTER
3 Low Ba ck Pa in a nd
Lumba r Stenosis
Lisa L. W illett
s
w it h co m p lain t s o f lo w e r b ack
e
m on re a s on s t h a t p a t ie n t s s e e k m e d ica l
m
p ain and n um bne ss in he r fe e t ,
o
a t t e n t ion . It is e s t im a t e d t h a t t w o t h ird s
r
d
int e rm itt e n tly f or 8 m o nt hs. o f a d u lt s h a ve e x p e r ie n ce d low b a ck
n
y
S
Pain is w o rse at t h e e n d o f p a in a t le a s t o n ce, a n d a p p roxim a t e ly
n
7% h a ve h a d a t le a s t on e s eve re ep is od e
i
d ay an d g e t s b e t t e r w it h
a
P
w it h in a 1 ye a r p e riod . Th e t yp ica l a ge of
l
re cu m b e n cy; p ain is also m o re
a
o n s e t o f low b a ck p a in is b e t w e e n 30
n
o
n o t ice ab le w it h am b u lat io n a n d 50 yea rs, w ith m en a n d w om en bein g
i
g
e
an d g e t s b e t t e r w h e n n o eq u a lly a ffected (1,2). Low ba ck p a in orig-
R
in a tes from m a n y sp in a l s tru ctu res, a n d
2
lo n g e r w alk in g . Th e re is n o
N
in clu d es liga m en t stra in , d egen era tion of
O
h ist o ry o f f e ve r, ch ills, an d w e ig h t lo ss. Th e re is n o h ist o ry fa ce t join t s , h e rn ia t e d d is cs , a n d s p in a l
I
T
C
o f t rau m a o r an u n u su al act ivit y t h at p re ce d e d t h e o n se t s t e n o s is (Figs . 3.1A, 3.1B). Sym p t o m s
E
S
o f t h e se sym p t o m s. Th e re is n o h ist o ry o f m alig n an cy o r ra n ge from m ild , s e lf-lim it in g p a in , t o
severe, in ca p a cita tin g p a in w ith ra d icu la r
in t rave n o u s d ru g u se .
sym p t om s , n e u rologic com p rom is e, a n d
ch ron ic m orbid ity.
Be ca u s e of t h e com p le xit y of t h e s p in e a n a t om y, a p re cis e a n a t om ica l d ia g-
n os is for p a t ie n t s w it h low ba ck p a in is d if cu lt . It is e s t im a t e d t h a t on ly 15%
of p a t ie n t s w it h low ba ck p a in a re a ble t o be d ia gn os e d w it h a p re cis e s p in a l
CLINICAL POINTS a bn orm a lit y or s p e ci c e t iology (1). In a n e ffort t o a ch ieve a ccu ra t e d ia gn os is
• Pa t ie n t s w it h lo w b a ck a n d e ffe ct ive t h e ra py, cos t ly im a gin g a n d s u rgica l re fe rra l is p u rs u e d . De s p it e
p a in sh o u ld b e cla ssi e d w id e va ria t ion s in t h e clin ica l eva lu a t ion a n d m a n a ge m e n t of low ba ck p a in ,
in t o a risk ca t e g o ry b a se d ove ra ll ou t com e s a re s im ila r for p a t ie n t s . Pu blis h e d gu id e lin e s e xis t t o gu id e
o n n o n sp e ci c lo w b a ck
t h e clin icia n on t h e be s t a p p roa ch t o eva lu a t e a n d m a n a ge a cu t e a n d ch ron ic
p a in , p a in a sso cia t e d w it h
ra d icu lo p a t h y (in clu d in g low ba ck p a in in t h e p rim a ry ca re s e t t in g.
h e rn ia t e d d isc o r sp in a l W h e n t a kin g t h e m e d ica l h is t o ry, clin icia n s s h o u ld a t t e m p t t o p la ce t h e
stenosis), and pain associated p a t ie n t in t o a ca t egory of ris k (2). Th e t h re e a re a s of ris k a re : (a ) n on s p e ci c low
w it h syst e m ic d ise a se . b a ck p a in , (b ) p a in a s s o cia t e d w it h ra d icu lo p a t h y o r s p in a l s t e n o s is , a n d
• Mo t o r w e a kn e ss, fe ca l (c) p a in from a s ys t e m ic ca u s e. In a d d it ion t o t h e p a in loca t ion , s eve rit y, a n d
in co n t in e n ce , a n d u rin a ry d u ra t ion , a p rior h is t ory of ba ck p a in a n d t h e clin ica l cou rs e is a ls o im p ort a n t .
re t e n t io n a re sym p t o m s o f Th e r s t p r io r it y is t o r u le o u t n e u ro lo gic co m p ro m is e . Qu e s t io n s s h o u ld
ca u d a e q u in a syn d ro m e
in clu d e t h e p re s e n ce of low e r e xt re m it y m ot or w e a kn e s s , fe ca l in con t in e n ce,
a n d re q u ire im m e d ia t e
su rg ica l e va lu a t io n . a n d u rin a ry re t e n t ion w it h ove r ow in con t in e n ce. Of t h e s e, u rin a ry re t e n t ion
is t h e m os t fre q u e n t s ym p t om of ca u d a e q u in a s yn d rom e.
• Pa t ie n t s w it h p sych o so cia l
Th e n e xt leve l of q u e s t ion s s h ou ld eva lu a t e for s ys t e m a t ic d is e a s e s , e s p e -
st re sso rs a re m o re like ly t o
d e ve lo p ch ro n ic p a in . cia lly ca n ce r w it h s p in a l m e t a s t a s is , fra ct u re s from os t e op oros is or s t e roid u s e,
a n d s p in a l in fe ct io n s . Ris k fa ct o rs fo r ca n ce r, in clu d in g m u lt ip le m ye lo m a ,
23
24 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Bone spur
impinging
on spinal
nerves
S
E
C
Compression
T
fractures
I
O
N
2
R
e
g
i
o
Herniated disc
n
N ote: discs can be herniated and not be painful
impinging on
a
l
spinal nerve,
P
causing pain
a
i
n
S
y
n
d
r
o
m
e
s
A B
Figure 3.1 A: Sa gitta l view of the norma l spine. Ima ge provided by Ana tomica l Cha rt Co. B: Ca uses of low ba ck pa in. From Nettina SM. Lippincott Ma nua l
of Nursing Pra ctice , 9th ed. Phila delphia : Wolters Kluwer Hea lth; 2010.
a ge o f 60 ye a r s a n d h a ve a h is t o ry o f ch ro n ic low b a ck p a in fo r m o n t h s t o
PATIENT ASSESSMENT ye a r s . Th e p a in is w o r s e w it h w a lk in g o r s t a n d in g, im p rove d w it h b e n d in g
fo r w a rd , a n d , a t t im e s , in d u ce d w h e n b e n d in g b a ck w a rd (3,4). In a s t u d y o f
• Ph ysica l e xa m in a t io n
sh o u ld e va lu a t e fo r fe ve r, p a t ie n t s p re s e n t in g t o a n o r t h o p e d ic s u rge o n w it h p a in o r n u m b n e s s in t h e
ve rt e b ra l t e n d e rn e ss, a n d le gs , t h e m o s t s p e ci c s ym p t o m s fo r lu m b a r s p in a l s t e n o s is w e r e a h is t o ry
n e u ro lo g ic d e cit s o f u r in a r y s y m p t o m s , im p r o ve m e n t w it h b e n d in g fo r w a rd , a n d b ila t e r a l
• Ra d icu la r sym p t o m s a re p la n t a r n u m b n e s s (5). He r n ia t e d lu m b a r d is cs ca n a ls o p re s e n t w it h s cia t ica ,
se e n w it h h e rn ia t e d d iscs b u t ca n b e d is t in gu is h e d fro m s p in a l s t e n o s is by a n a cu t e o n s e t o f p a in a n d
o r sp in a l st e n o sis e x a m in a t io n fe a t u r e s , s u ch a s a p o s it ive s t ra igh t le g-ra is in g, w h ich is s u g-
• He rn ia t e d d iscs ca u se ge s t ive o f a h e r n ia t e d d is c.
a cu t e se ve re b a ck p a in , Fin a lly, a s s e s s m e n t o f p s ych os o cia l d is t re s s is im p o rt a n t . Pa t ie n t s w it h
involve L4/L5 and L5/S1, d e p re s s ion , s om a t iza t ion d is ord e r, s u bs t a n ce a bu s e, job d is s a t is fa ct ion or d is -
a n d h a ve a p o sit ive a bilit y com p e n s a t ion , a n d t h os e in volve d in lit iga t ion a re m ore like ly t o h a ve
st ra ig h t le g -ra isin g t e st p rolon ge d ba ck p a in a n d p e rs is t e n t u n e xp la in e d s ym p t om s (5).
• Sp in a l st e n o sis o ccu rs in
e ld e rly p a t ie n t s w it h a
h ist ory of chronic low b ack
p ain, w orse with walking
Exa mina tio n
o r stan ding, improve d w ith As w it h t h e h is t ory, t h e p h ys ica l e xa m in a t ion for p a t ie n t s w it h low ba ck p a in
s
b end ing forward, ind uce d
e
s h ou ld focu s on t h e n e u rologic e xa m in a t ion a n d s h ou ld e n s u re t h a t t h e re a re
m
w hen be nding backward,
o
and has bilateral pla nta r n o d e cit s . Aft e r a s s e s s in g for feve r a n d t h e p re s e n ce of ve rt e bra l t e n d e rn e s s
r
d
n umb ness w it h p a lp a t ion , a focu s e d n e u rologic e xa m in a t ion s h ou ld be p e rform e d . More
n
y
t h a n 90% of h e rn ia t e d d is cs occu r a t t h e L4/L5 a n d L5/S1 leve ls a n d t h e n e u ro-
S
n
lo gic e x a m in a t io n fo cu s e s o n t h e s e n e r ve ro o t s , a n d in clu d e s t h e s t ra igh t
i
a
P
leg-ra is in g t e s t (Fig. 3.2 ), a n d t h e m ot or a n d s e n s ory fu n ct ion t e s t s (2).
l
A s t ra igh t leg-ra is in g t e s t in volve s h a vin g t h e p a t ie n t s u p in e on t h e e xa m -
a
n
o
in a t ion t a ble. Th e e xa m in e r h old s t h e leg s t ra igh t w it h on e h a n d a n d cu p s t h e
i
g
h e e l w it h t h e ot h e r. Th e s t ra igh t leg is lift e d off t h e e xa m in a t ion t a ble from t h e
e
R
h e e l in a n e ffo rt t o re p rod u ce t h e p a t ie n t ’s s cia t ica . A p os it ive t e s t p ro d u ce s
2
p a in t h a t ra d ia t e s be low t h e kn e e be t w e e n 30 a n d 70 d egre e s of e leva t ion . A
N
O
p os it ive t e s t on t h e ip s ila t e ra l s id e h a s a s e n s it ivit y of a p p roxim a t e ly 90% for a
I
T
C
h e rn ia t e d d is c, w h e re a s a p os it ive t e s t w h e n t h e op p os it e leg is ra is e d (a cros s e d
E
t e s t ) h a s a s p e ci cit y of a p p roa ch in g 90% (2). Fu rt h e r n e u rologic eva lu a t io n
S
in clu d e s s e n s o ry a n d m o t o r n d in gs o f t h e L4 t h ro u gh S1 n e r ve ro o t , a n d
in clu d e s a s s e s s in g kn e e s t re n gt h a n d re e xe s (L4), gre a t t oe a n d foot d ors i e x-
ion (L5), foot p la n t a r e xion a n d a n kle re e xe s (S1).
Studie s
Fin d in gs on ra d iologic im a gin g corre la t e p oorly w it h
t h e s eve rit y of s ym p t om s in p a t ie n t s w it h low ba ck
p a in . Th ere fore, rou t in e im a gin g is n ot clin ica lly u s e fu l
for p a t ie n t s w it h n on s p e ci c low ba ck p a in . Im a gin g is
re com m e n d e d for p a t ie n t s w it h con ce rn s for ca n ce r,
fra ct u re, or in fe ct ion , a n d for p a t ie n t s w it h n e u rologic
n d in gs. Gu id e lin es re com m en d p la in ra d iogra p h y for
p a t ie n t s w it h a p os s ible s ys t e m ic illn e s s , in clu d in g
p a tien ts w ith fever, u n exp la in ed w eigh t loss, a h istory of
ca n cer, a lcoh ol or d ru g in jection , tra u m a , foca l vertebra l
ten d ern ess on p a lp a tion , a n d age old er th a n 50 yea rs.
Pla in ra d iogra p h y is n ot s e n s it ive for ea rly ca n ce r or
in fe ct ion . Th u s , if t h e clin ica l s u s p icion is h igh , fu rt h e r
t es t in g s u ch a s a n e ryt h rocyt e s ed im e n t a t ion ra t e (ESR)
or C-re a ct ive p rot e in (CRP), a com p le t e blood cou n t
(CBC), a n d a com p u t e d t om ogra p h y (CT) or m a gn e t ic
Figure 3.2 The stra ight leg-ra ising test. MediClip ima ge copyright © re s on a n ce im a gin g (MRI) s h ou ld be p e rform e d . Pa t ie n t s
2003 Lippincott Willia ms & Wilkins. All rights reserved. w it h s eve re or p rogre s s ive n e u rologic d e cit s s h ou ld
26 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Tre a tme nt
Tre a t m e n t fo r low b a ck p a in rs t in vo lve s e d u ca t in g t h e p a t ie n t a b o u t t h e
e xp e ct e d clin ica l ou t com e. Ove ra ll, t h e p rogn os is is good , a n d m os t p a t ie n t s
S
w ill im p rove w it h in 4 w e e ks . For p a t ie n t s w it h n on s p e ci c low ba ck p a in , evi-
E
C
d e n ce is lim it e d bu t s u gge s t s t h a t con s e rva t ive m a n a ge m e n t is e ffe ct ive for
T
I
O
s ym p t om re lie f. Pa t ie n t s s h o u ld re s u m e n orm a l a ct ivit ie s w h e n a ble t o, a n d
N
s h ou ld a void be d re s t . He a t in g p a d s a n d bla n ke t s m a y p rovid e re lie f, bu t t h e re
2
is in s u f cie n t evid e n ce t o re com m e n d lu m ba r s u p p ort s or ice p a cks . He a vy lift -
R
e
in g a n d t w is t in g s h ou ld be avoid e d .
g
i
o
Me d ica l t h e ra p y h a s be e n s h ow n t o p rovid e s h ort t e rm re lie f t o p a t ie n t s
n
a
w it h a cu t e low ba ck p a in (1,2). Pa t ie n t s s h ou ld be p re s cribe d n on s t e roid a l a n t i-
l
P
in a m m a t ory d ru gs (NSAIDS) a n d m u s cle re la xe rs a s rs t lin e t h e ra p y, u n le s s
a
i
n
t h e re is a con t ra in d ica t ion s u ch a s re n a l in s u f cie n cy or a ris k of ga s t roin t e s -
S
t in a l ble e d in g. Ace t a m in op h e n is le s s e ffe ct ive t h a n NSAIDS bu t a s a fe a n d
y
n
re a s on a ble rs t -lin e op t ion for p a t ie n t s w h o ca n n ot t a ke NSAIDS. Th e re is n o
d
r
o
d a t a t o gu id e clin icia n s on t h e d os e a n d d u ra t ion of t h e ra p y.
m
For p a tien ts w it h severe p a in , u n relieved w ith NSAIDS a n d m u scle rela xa n t s,
e
s
op ioid a n a lgesics a n d tra m a d ol ca n be con s id ered , w eigh in g th e risk of ch ron ic
u sa ge a n d a bu se p oten tia l. Tricyclic a n tid ep ressa n ts a re effective for ch ron ic low
ba ck p a in ; s elective seroton in reu p ta ke in h ibitors (SSRIs) a n d t ra zod on e a re n ot.
NOT TO BE MISSED Ga ba p en tin h a s lim ited d a ta sh ow in g s m a ll s h ort-term ben e t in p a tien ts w it h
ra d icu lop a th y; system ic corticosteroid s h ave n ot been sh ow n to be effective a n d
• Ne u ro lo g ic co m p ro m ise
a re n ot recom m en d ed for p a tien ts , w ith or w ith ou t scia t ica .
a n d ca u d a e q u in a
Mu lt ip le in t e rve n t ion s s u ch a s s p in a l m a n ip u la t ion , p h ys ica l t h e ra p y, m a s -
• Meta sta t ic ca n ce r, fra ctu re, s a ge t h e ra p y, a n d a cu p u n ct u re h a ve b e e n u s e d t o t re a t a cu t e low b a ck p a in
o r spin a l infe ct ion
(1,2). Alt h o u gh evid e n ce is la ck in g, ce r t a in p a t ie n t s m a y d e rive re lie f w h e n
• Fo ca l ve rt e b ra l t e n d e rn e ss u s e d a s s e con d lin e t h e ra p y. Tra ct ion , fa ce t -join t in je ct ion s , a n d t ra n s cu t a n e -
t o p a lp a t io n o u s e le ct r ica l n e r ve s t im u la t io n a ls o la ck s u p p o r t in g evid e n ce o f e f ca cy.
• Fe ve r Be ca u s e t h e m a jorit y of low ba ck p a in im p rove s w it h in 4 w e e ks , re fe rra l for
s u ch a lt e rn a t e in t e rve n t ion s s h ou ld be d e la ye d u n t il t h e n .
• Un e xp la in e d w e ig h t lo ss
Th era py op tion s for p a tien ts w ith h ern ia ted d isks a re th e sa m e a s for n on sp e-
• Hist o ry o f ca n ce r, a lco h o l, ci c low ba ck p a in . Un less th ere is ca u d a eq u in a syn d rom e or p rogressive n eu ro-
o r d ru g in je ct io n
logic d e cits , t h e m a jorit y of p a t ien ts im p rove. Th e p a in m ay be m ore s evere,
• Tra u m a req u irin g n a rcotic a n a lgesia , a n d ep id u ra l corticosteroid s m ay p rovid e a d d ition a l
• Ag e o ve r 50 ye a rs relief; system ic corticosteroid s h ave n ot been sh ow n to p rovid e ben e t. Pa tien ts
w ith severe p a in , d esp ite th era py, a n d th ose w it h p ersisten t n eu rologic d e cit s
• Pa in d u ra t io n 6 w e e ks
sh ou ld be eva lu a ted w ith a n MRI or CT a n d referred for su rgica l eva lu a tion .
• Life -t h re a t e n in g Evid e n ce t o gu id e n on s u rgica l t h e ra py for p a t ie n t s w it h lu m ba r s p in a l s t e -
co n d it io n s o u t sid e t h e n os is is la ckin g, a n d t h e re is w id e va ria t ion in t h e m e t h od s u s e d . Alt h ou gh d a t a
sp in e , su ch a s a o rt ic
s u p p ort t h e be n e t of s u rgica l d e com p re s s ion , t h e be n e t of s u rge ry com p a re d
a n e u rysm , p a n cre a t it is,
a n d e n d o ca rd it is t o n on s u rgica l a p p roa ch e s is u n kn ow n . Me d ica l t h e ra p y is re com m e n d e d for
p a t ie n t s w it h h igh s u rgica l ris k a n d m ild -t o-m od e ra t e s ym p t om s (3,4).
Ch a p te r 3 Low Ba ck Pa in a n d Lu m ba r St e n os is 27
s
h e m ila m in e ct o m y a n d t e ch n iq u e s t o p re s e r ve t h e in t e r s p in o u s liga m e n t s .
e
m
Alt h ou gh s t u d ie s s h ow lon g t e rm ou t com e s t o be s u cce s s fu l in p a t ie n t s w it h
o
r
a d va n ce d a ge, eve n in t h e ir 80s , op e ra t ive ris k m u s t be w e igh e d ca re fu lly a s
d
n
s u rgica l com orbid it ie s a re oft e n p re s e n t in t h e e ld e rly (4).
y
S
n
i
a
P
Clinica l Co urse
l
a
n
o
In p a t ie n t s w it h a cu t e low ba ck p a in , it h a s be e n rep ort e d t h a t 90% im p rove
i
g
w it h in 2 w e e ks (1). Th e m a jorit y of p a t ie n t s w it h n on s p e ci c low ba ck p a in , a n d
e
R
eve n t h os e w it h a h e rn ia t e d d is c, im p rove w it h in 4 w e e ks w it h con s e rva t ive
2
t re a t m e n t . Th e re fore, p a t ie n t s w it h p a in t h a t p e rs is t s lon ge r t h a n 4 t o 6 w e e ks ,
N
O
d e s p it e con s e rva t ive t h e ra p y, s h ou ld be re eva lu a t e d a n d h ave im a gin g t o ru le
I
T
C
ou t a s ys t e m ic p roce s s . Som e cros s -s e ct ion a l s t u d ie s of p a t ie n t s follow e d in
E
p rim a ry ca re s h ow t h a t m ore t h a n 60% of p a t ie n t s im p rove d w it h in 7 w e e ks ,
S
bu t re cu rre n ce w a s com m on , a ffe ct in g 40% of p a t ie n t s w it h in 6 m on t h s (1).
Mos t p a t ie n t s w it h s p in a l s t e n os is w h o a re m a n a ge d m e d ica lly d o n ot h ave
s ign i ca n t clin ica l p rogre s s ion ove r t h e cou rs e of a ye a r. Sym p t om s a n d n e u ro-
logic e xa m in a t ion s h ou ld n ot a cu t e ly w ors e n ; likew is e, d ra m a t ic s ym p t om a t ic
im p rove m e n t is u n com m on . Th e re fore, p a t ie n t s ca n be follow e d clin ica lly ove r
t im e, a n d if t h e p a t ie n t ’s p a in p rogre s s e s d e s p it e n on s u rgica l t h e ra p y, re fe rra l
for la m in e ct om y s h ou ld be con s id e re d . Su rge ry re s u lt s in be t t e r p a in re lie f for
s eve ra l ye a r s . How eve r, in co h o r t s t u d ie s , 30% o f p a t ie n t s h a d s eve re p a in
4 ye a rs a ft e r s u rge ry a n d 10% re q u ire d re op e ra t ion (1).
Ch ron ic low ba ck p a in is ch a lle n gin g for bot h t h e p a t ie n t a n d clin icia n . In
s t u d ie s , p re d ict o r s o f p e r s is t e n t b a ck p a in a n d w o r s e o u t co m e s a t 1 ye a r
in clu d e d t h e p re s e n ce of n on orga n ic s ign s , m a la d a p t ive p a in cop in g be h aviors ,
h igh ba s e lin e fu n ct ion a l im p a irm e n t , p s ych ia t ric com orbid it ie s , a n d low ge n -
e ra l h e a lt h s t a t u s . Dep re s s ion , job d is s a t is fa ct ion or d is a bilit y com p e n s a t ion ,
a n d t h os e in volve d in lit iga t ion a re a ls o m ore like ly t o h a ve p rolon ge d ba ck
p a in a n d p e rs is t e n t u n e xp la in e d s ym p t om s . Ba s e lin e p a in a n d t h e p re s e n ce of
ra d icu la r s ym p t om s w e re n ot p re d ict ive of p e rs is t e n t p a in (6).
Co nclusio ns
Low ba ck p a in is com m on a n d w ill a ffe ct t h e m a jorit y of a d u lt p a t ie n t s in t h e ir
life t im e. De s p it e w id e va ria t ion s in t h e clin ica l eva lu a t ion a n d m a n a ge m e n t of
low ba ck p a in , ove ra ll ou t com e s for m os t p a t ie n t s a re good , a n d eve n w it h a
h e rn ia t e d d is c, clin ica l im p rove m e n t is a ch ieve d w it h in 6 w e e ks . Mo s t b a ck
28 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
ICD9 (Co n t in u e d )
729.0 Rhe umatism, rhe umatic (acu t e NEC)
724.9 b ack
756.12 Spo ndylo listhe sis (co n g e n it al) (lu m b o sacral)
738.4 acq u ire d
738.4 d e g e n e rat ive
738.4 t rau m at ic
756.11 Spo ndylo lysis (co n g e n it al)
738.4 acq u ire d
756.11 lu m b o sacral re g io n
721.90 Spo ndylo sis
721.3 lu m b ar, lu m b o sacral
721.42 w it h m ye lo p at h y
Sprain, strain (jo in t ) (lig am e n t ) (m u scle )
846.9 lo w b ack
846.0 lu m b o sacral
724.6 ch ro n ic o r o ld
s
e
Ste no sis (cicat ricial)
m
724.00 sp in al
o
r
d
724.02 lu m b ar, lu m b o sacral
n
y
724.09 sp e ci e d re g io n NEC
S
724.01 t h o racic, t h o raco lu m b ar
n
i
a
P
l
a
n
o
i
Re fe re nce s
g
e
R
1. Deyo RA, We in s t e in JN . Low ba ck p a in . N Engl J Med 2001 ;344 (5 ):363 –370 .
2
2. Ch ou R, Qa s e e m A, Sn ow V, e t a l. Dia gn os is a n d t re a t m e n t of low ba ck p a in : a jo in t clin ica l p ra ct ice
N
gu id e lin e from t h e Am e r ica n Colle ge o f Ph ys icia n s a n d t h e Am e r ica n Pa in So cie t y. A nn Intern Med
O
I
2007 ;147 :478 –491 .
T
C
3. Ka t z JN , Ha rris MB. Lu m ba r s p in a l s t e n os is . N Engl J Med 2008 ;358 (8 ):818 –825 .
E
4. Ma rkm a n JD, Ga u d KG. Lu m ba r s p in a l s t e n os is in old e r a d u lt s : cu rre n t u n d e rs t a n d in g a n d fu t u re d ire c-
S
t ion s . Clin Geriatr Med 2008 ;24 :369 –388 .
5. Ebe ll MH . Dia gn os in g lu m ba r s p in a l s t e n os is . A m Fam Physician 2009 ;80 (10 ):1145 –1147 .
6. Ch o u R, Sh e k e lle P. W ill t h is p a t ie n t d eve lop p e rs is t e n t d is a blin g low b a ck p a in ? JA MA 2010 ;303 (13 ):
1295 –1302 .
CHAPTER
4 Shoulder Pa in
Dennis W . Boulw are
A 26-ye ar-o ld m an p re se n t s
Clinica l Pre se nta tio n
Sh ou ld e r p a in is on e of t h e m os t com -
S
w it h a 10-d ay h ist o ry o f rig h t
E
m on com p la in t s s e e n in a p rim a ry ca re
C
sh o u ld e r an d u p p e r arm p ain ,
T
s e t t in g e s p e cia lly w it h e ld e rly p a t ie n t s .
I
O
w o rse w it h lif t in g h is arm o ve r Most ca u ses of sh ou ld er p a in a re d u e to
N
soft tiss u e p eria rticu la r p roblem s s u ch a s
2
h is h e ad an d in t e rf e rin g w it h
R
rota tor cu ff im p in gem en t or in ju ry, bu rs i-
e
sle e p as h e can n o t n d a
g
tis , a n d /or a n a d h esive ca p su litis (frozen
i
o
p o sit io n o f co m f o rt . He h as s h ou ld e r) a s op p os e d t o gle n oh u m e ra l
n
a
t rie d re st an d ace t am in o p h e n a r t h r it is . Th e clin ica l co n t e x t of t h e
l
P
a
w it h o u t re lie f . No t rau m a o r sh ou ld er p a in often p rovid es in sigh t in to
i
n
t h e s o u rce o f t h e p r o b le m s u ch a s a
S
p re cip it at in g e ve n t is re co lle ct -
y
h is t ory of a s ys t e m ic in a m m a t ory or
n
e d , b u t h e h ad re ce n t ly co m p le t e d re -p ain t in g h is b e d ro o m
d
d egen era tive con d ition , rep etitive u se, or
r
o
o ve r t h e w e e k e n d , 2 w e e k s ag o .
m
recen t in ju ry. Th is ch a p ter a d d resses th e
e
clin ica l s e t t in g of n on t ra u m a t ic is ola t e d
s
s h ou ld e r p a in , a n d for a d is cu s s ion of
sh ou ld er p a in d u e to system ic or gen era lized d isea ses su ch a s rh eu m a t oid a rth ri-
t is , p olym ya lgia rh e u m a t ica , or os t e oa rt h rit is , t h e re a d e r s h ou ld re fe r t o t h os e
sp eci c ch a p ters.
Mo s t ca u s e s of s h ou ld e r p a in ca n b e a t t ribu t e d t o s oft -t is s u e s t ru ct u re s
s u r ro u n d in g t h e gle n o h u m e ra l jo in t , a s o p p o s e d t o t h o s e o rigin a t in g fro m
gle n oh u m e ra l a rt h rit is . An u n d e rs t a n d in g of t h e a n a t om y a n d biom e ch a n ics of
t h e s h ou ld e r, cou p le d w it h a focu s e d p h ys ica l e xa m in a t ion t o loca lize t h e a n a -
t om ic s ou rce of p a in , t yp ica lly p rovid e s t h e clin icia n w it h a n a ccu ra t e d ia gn o-
s is (Fig. 4.1 ). Prop e r a n d e ffe ct ive m a n a ge m e n t ca n be im p le m e n t e d on ly a ft e r
t h e s ou rce of t h e p a in is id e n t i e d a ccu ra t e ly.
Th e s h ou ld e r is t h e m os t e xible a n d m obile join t in t h e bod y. Th is m obilit y
is a ch ieve d by h avin g a bon y ba ll-a n d -s ocke t join t w it h a la rge ba ll a n d a re la -
t ive ly s m a ll s ocke t . Th is re la t ive ly u n s t a ble a rra n ge m e n t is m a d e s e cu re by t h e
s u rrou n d in g e xt ra -a rt icu la r s t ru ct u re s in clu d in g t h e va riou s liga m e n t s , la bru m ,
ro t a t o r cu ff, b icip it a l t e n d o n , d e lt o id m u s cle s , a n d s o o n . Typ ica lly, s h o u ld e r
p a in is d u e t o d ys fu n ct ion or d is ru p t ion of t h e s u p p ort in g s oft -t is s u e s t ru c-
t u re s , a s o p p o s e d t o gle n o h u m e ra l a r t h r it is . Th e m o s t co m m o n ly in vo lve d
s t ru ct u re s ca u s in g s h ou ld e r p a in a re t h e rot a t or cu ff, t h e s u ba crom ia l bu rs a ,
t h e bicip it a l t e n d on , a n d t h e s yn ovia l ca p s u le.
Th e rs t s t e p in eva lu a t in g t h e p a t ie n t is t o co n rm t h a t t h ey a re d e s cr ib -
in g a s h o u ld e r jo in t p a in o r a jo in t -re la t e d p ro ble m a s t h ey o ft e n re fe r t o p a in
in t h e t ra p e z iu s m u s cle a s “s h o u ld e r p a in .” Pa in fro m t h e s h o u ld e r jo in t o r it s
re la t e d p e r ia r t icu la r s t r u ct u re s is fe lt in t h e a re a ove r t h e d e lt o id m u s cle o r
30
Ch a p te r 4 Sh ou ld e r Pa in 31
Coracoclavicular Coracoclavicular
ligament (conoid) ligament (trapezoid)
Clavicle
Coracoacromial
ligament Acromioclavicular
ligament
Acromion
Subdeltoid bursa
Subscapular Coracohumeral
bursa ligament
Glenohumeral
ligament
Synovial sheath
around biceps
tendon
s
e
m
o
r
d
n
y
Figure 4 .1 The shoulder joint illustra ting the rela tionship of the glenohumera l joint, the supra spina tus tendon
S
of the rota tor cuff, a nd the long hea d of the biceps tendon. The a rea between the humera l hea d a nd a cromion
n
i
process is occupied by the suba cromia l bursa . From Hendrickson T. Ma ssa ge for Orthopedic Conditions .
a
P
Ba ltimore: Lippincott Willia ms & Wilkins; 2002.
l
a
n
o
i
g
t h e u p p e r bra ch iu m . Pa in d e s cr ib e d in t h e t ra p e z iu s m u s cle is like ly d u e t o
e
R
t ra p e z iu s m u s cle s t ra in o r re fe r re d from t h e ce rvica l s p in e . If t h e p a t ie n t con -
2
N
r m s t h a t t h e p a in is lo ca liz e d t o t h e d e lt o id a re a a n d / or t h e u p p e r b ra ch iu m ,
O
t h e n p ro ce e d w it h a n eva lu a t io n o f t h e s h o u ld e r jo in t a n d it s p e r ia r t icu la r
I
T
C
s t r u ct u re s .
E
S
His t orica l q u a lit ie s rega rd in g s eve rit y or q u a lit y of p a in a re lim it e d in id e n -
t ifyin g t h e ca u s e of p a in , w h e re a s p re cip it a t in g a n d a llevia t in g fa ct ors , re ce n t
re p e t it ive n on rou t in e a ct ivit ie s (h ou s e p a in t in g, w a llp a p e r h a n gin g, e t c.), a n d /
or in ju rie s ca n p rovid e s om e in s igh t . Sh ou ld e r p a in p re cip it a t e d by u s e is t h e
m os t com m on p re s e n t in g com p la in t a n d ce rt a in u s e s of t h e a ffe ct e d a rm ca n
be h e lp fu l. Th e rot a t or cu ff is t yp ica lly a ffe ct e d in t h e e xt e rn a l rot a t ors , e s p e -
cia lly t h e s u p ra s p in a t u s . Pa in fe lt w it h fo rw a rd e x io n , a b d u ct io n , o r a ct ive
CLINICAL POINTS e xt e rn a l rot a t ion of t h e s h ou ld e r t yp ica lly s u gge s t s in volve m e n t of t h e rot a t or
• Sh o u ld e r p a in is o ft e n d u e cu ff. Pa in on a bd u ct ion , bu t n ot on e xt e rn a l rot a t ion or forw a rd e xion of t h e
t o a so ft t issu e ca u se su ch s h ou ld e r s u gge s t s t h e s u ba crom ia l bu rs a a s t h e ca u s e of p a in . Noct u rn a l p a in
a s t e n d o n it is o r b u rsit is, d u rin g s le ep a n d t h e in a bilit y t o n d a re s t fu l re cu m be n t p os it ion in be d a re
ra t h e r t h a n a rt h rit is. a ls o com m on com p la in t s of a rot a t or cu ff p roble m or t h e s u ba crom ia l bu rs a .
• Th e p h ysica l e xa m in a t io n
o f t h e sh o u ld e r is e sse n t ia l
in id e n t ifyin g t h e ca u se . Exa mina tio n
• The pain frequently radiates Th e p h ys ica l e x a m in a t io n o f t h e s h o u ld e r is cr it ica l in id e n t ifyin g t h e ca u s e
in t o t h e b ra ch iu m .
a n d m a n a gin g s h o u ld e r p a in . A s ys t e m a t ic r o u t in e e x a m in a t io n o f t h e
• Exp lo rin g re ce n t o ve ru se o r s h o u ld e r w ill h e lp t h e c lin ic ia n id e n t ify t h e c a u s e o f t h e s h o u ld e r p a in
t ra u m a m a y h e lp id e n t ify q u ick ly a n d e ffe ct ive ly. Th e e x a m in a t io n w ill fo cu s o n t h e ra n ge o f p a s s ive
t h e ca u se .
m o t io n in ro t a t io n , a b d u ct io n , a n d fo r w a rd e x io n a s w e ll a s p r ovo ca t ive
• Wh e n e xa m in a t io n o f t h e m a n e u ve r s t o a t t e m p t t o re p ro d u ce t h e p a in by a ct ive m o t io n , p a lp a t io n , o r
sh o u ld e r is fru it le ss in re s is t a n ce . Te n d e r n e s s p re s e n t o n a ct ive m o t io n t h a t is a b s e n t o n t h e s a m e
id ent ifying a cause, con sid er
m o t io n p a s s ive ly u s u a lly s u gge s t s a t e n d in it is a s t h e p a in is e licit e d w h e n
re ferred pa in fro m a ce rvical
ra d icu lo p a t h y. t e n s io n is p la ce d o n t h e t e n d o n . Typ ica lly, t h e p a t ie n t w ill b e gu a rd in g t h e
p a in fu l s h o u ld e r vo lu n t a r ily o r in vo lu n t a r ily a n d t h e e x a m in a t io n w ill b e
32 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
S
E
C
T
I
O
Figure 4 .2 Mea suring pa ssive rota tion. From Berg D, Worza la K. Atla s of Figure 4 .3 Mea suring pa ssive glenohumera l
N
Adult Physica l Dia gnosis . Phila delphia : Lippincott Willia ms & Wilkins; 2006. a bduction a nd forwa rd exion. From Berg D,
2
Worza la K. Atla s of Adult Physical Diagnosis .
R
Philadelphia: Lippincott Williams & Wilkins; 2006.
e
g
i
o
n
a
in s igh t fu l o n ly if t h e p a t ie n t is re la x e d a n d co o p e ra t ive . Th e p r u d e n t clin i-
l
P
cia n w ill e x a m in e t h e n o n -t e n d e r s h o u ld e r r s t t o p re p a r e t h e p a t ie n t fo r
a
i
n
e x a m in a t io n o f t h e p a in fu l s h o u ld e r.
S
St a r t t h e e x a m in a t io n w it h t h e p a t ie n t s it t in g on t h e e xa m in a t ion t a ble
y
n
in fro n t o f yo u . Pa s s ive ly e x t h e e lb ow t o 90 d e gre e s w it h t h e p a t ie n t ’s e lb ow
d
r
o
t o t h e ir s id e a n d ge n t ly u s e t h e fo re a r m t o ro t a t e t h e s h o u ld e r join t in t e r n a lly,
m
a s it t yp ica lly w ill n o t p re cip it a t e t e n d e r n e s s a n d w ill a id in ga in in g t h e
e
s
p a t ie n t ’s co n d e n ce , a n d t h e n t e s t fo r e x t e r n a l ro t a t io n (Fig. 4.2 ). Pa s s ive
in t e r n a l ro t a t io n t o 90 d e gre e s a n d p a s s ive e x t e r n a l ro t a t io n t o 90 d e gre e s a re
n o r m a l, a n d is t yp ica lly p a in le s s b u t d im in is h e s s ligh t ly w it h a ge . In t e r n a l
ro t a t io n is ra re ly t e n d e r o r lim it e d , b u t d e cre a s e d p a s s ive e x t e r n a l ro t a t io n
w ill s u gge s t s t r u ct u ra l b a r rie rs t o fu ll p a s s ive m ot ion in clu d in g b on y a n d s oft
t is s u e s t r u ct u re s . Os t e o p h yt e s from d e ge n e ra t ive join t d is e a s e o r a co n t ra ct e d
jo in t ca p s u le fr o m a d h e s ive ca p s u lit is , o r a fro z e n s h o u ld e r, a r e co m m o n
ca u s e s a n d w ill re q u ire im a gin g s t u d ie s t o d iffe re n t ia t e . No n -t e n d e r d e cre a s e d
p a s s ive ro t a t io n m a y in d ica t e t h e la t e r s t a ge s o f a d h e s ive ca p s u lit is o r s t a ble
d e ge n e ra t ive jo in t d is e a s e . Te n d e rn e s s on p a s s ive e xt e rn a l ro t a t io n o n ly m a y
in d ica t e a n a ct ive a d h e s ive ca p s u lit is o r a ct ive o s t e o a r t h r it is , w h e re a s t e n -
d e rn e s s o n p a s s ive in t e r n a l a n d e x t e r n a l rot a t ion s ca n s u gge s t a ct ive s yn ovi-
t is from in fe ct io u s o r in a m m a t o ry ca u s e s .
Ne xt , p os it ion you rs e lf a t t h e p a t ie n t ’s s id e a n d s t a bilize t h e s ca p u la w it h
you r h a n d clos e r t o t h e p a t ie n t ’s ba ck by p la cin g you r n ge rs on t h e h orizon t a l
s ca p u la r s p in e a n d you r t h u m b a lon g t h e s ca p u la ’s la t e ra l bord e r in h ibit in g it s
a bilit y t o s lid e la t e ra lly ove r t h e ribs . Us e you r forw a rd h a n d t o gra s p t h e e lbow
a n d w it h t h e p a t ie n t re la xe d , p a s s ive ly a bd u ct t h e s h ou ld e r t o m e a s u re gle n o-
h u m e ra l a bd u ct ion (Fig. 4.3 ). Norm a l gle n oh u m e ra l a bd u ct ion is 90 d egre e s , bu t
a ga in d im in is h e s w it h a gin g. Un le s s t h e p a t ie n t is co m p le t e ly re la xe d , t h e
t e ch n iq u e m a y n e e d t o b e d o n e s eve ra l t im e s t o a s s e s s a ccu ra t e ly t h e t r u e
ra n ge of m ot ion . Aft e r m e a s u rin g gle n oh u m e ra l a bd u ct ion , re le a s e t h e s ca p u la
a n d m e a s u re fu ll a bd u ct ion w h ich s h ou ld a p p roa ch 180 d egre e s . Th e n m e a s u re
forw a rd e xion by p a s s ive ly e xin g t h e s h ou ld e r a n t e riorly t o m e a s u re e xion ,
w h ich s h ou ld be 180 d egre e s . Th e s u p ra s p in a t u s t e n d on re s id e s in t h e s p a ce
Ch a p te r 4 Sh ou ld e r Pa in 33
s
cu ff is in vo lve d . Th e s e m a n e u ve r s w ill n o t in d ica t e if t h e re is a t e a r o f t h e
e
m
ro t a t o r cu ff, ro t a t o r cu ff t e n d in it is , o r ca lci c t e n d in it is o f t h e s u p ra s p in a t u s
o
r
t e n d o n , w h ich a re a ll co m m o n ca u s e s o f s h ou ld e r p a in .
d
n
Bicip it a l t e n d in it is is a le s s com m on ca u s e of s h ou ld er p a in t h a n p roble m s
y
S
w it h t h e rot a t or cu ff or s u ba crom ia l bu rs it is , a n d s h ou ld be s u s p e ct ed if t h e p re-
n
i
ce d in g exa m in a t ion fa ils t o e licit a n y t e n d ern e s s . Bicip it a l t e n d in it is m os t com -
a
P
m on ly occu rs a s t h e t e n d on t rave rs e s t h e h u m e ra l h e a d t h rou gh t h e bicip it a l
l
a
n
groove on t h e a n t e rior s u rfa ce of t h e h u m e ra l h e a d . Bicip it a l t en d in it is a t t h is
o
i
level ca n be d et e ct e d by t h e p re s e n ce of t e n d ern e s s on d ire ct p a lp a t ion of t h e
g
e
R
t e n d on w it h in t h e bicip it a l groove of t h e h u m e ra l h e a d a n d /or t h rou gh Ye r-
2
ga s on ’s m a n e u ve r, a p rovoca t ive t es t . Pla ce you r t h u m b w it h m od e ra t e p res s u re
N
on th e a n t e rior s u rfa ce of t h e s h ou ld e r a n d p a s s ively rot a t e t h e s h ou ld e r u s in g
O
I
T
t h e fore a rm a s a leve r w it h t h e p a t ie n t h old in g t h e e lbow a t 90 d egre e s . You r
C
E
t h u m b w ill s e n s e t h e bicip it a l groove a s it d ip s in t o it a n d t h e p a t ie n t w ill fe e l
S
t e n d e rn e s s a s you r t h u m b rid es ove r t h e t e n d on w it h in t h e bicip it a l groove. Con -
rm a t ion ca n be a ch ieve d t h rou gh Yerga s on ’s m a n e u ve r, w h ich t e s t s t h e t e n d on
by a ct ive is om e t ric loa d in g. Have t h e p a t ien t p la ce h is or h er fu lly exe d e lbow
a t t h e s id e w it h t h e w ris t fu lly s u p in a t e d . Gra s p t h e p a t ien t ’s h a n d a n d a s k t h e
p a t ien t t o res is t you r a t t e m p t t o s im u lt a n e ou s ly ext e n d t h e e lbow a n d p ron a t e
t h e w ris t . Th is m a n eu ve r a ct ive ly loa d s t h e bicep s t e n d on a n d s h ou ld e licit t e n -
PATIENT ASSESSMENT d e rn e s s a t t h e s h ou ld e r w h e n a n a ct ive bicip it a l t e n d in it is is p res en t .
Occa s ion a lly, s h ou ld e r p a in is n ot d u e t o d ys fu n ct ion or d is ru p t ion of t h e
• Alle via t in g a n d s h ou ld e r join t or it s s u rrou n d in g s u p p ort ive s oft -t is s u e s t ru ct u re s . If t h e p re -
e xa ce rb a t in g fa ct o rs ca n
b e h e lp fu l, e sp e cia lly ce d in g e xa m in a t ion fa ils t o rep rod u ce t h e p a t ie n t ’s com p la in t a n d id e n t ify t h e
re ce n t o ve rh e a d u se s ou rce of t h e p a in w it h in t h e s h ou ld e r a re a , t h e n a con s id e ra t ion of re fe rre d
o f a rm . s h ou ld e r p a in is m e rit e d . Pa in from a ce rvica l ra d icu lop a t h y oft e n ra d ia t e s t o
• Te n d e rn e ss o n a ct ive t h e s h ou ld e r a re a . Ke e p in g t h e s h ou ld e r in a n e u t ra l n on -t e n d e r p os it ion w h ile
iso m e t ric lo a d in g b u t n o t t e s t in g t h e ce rvica l s p in e for p a s s ive h yp e re xt e n s ion com bin e d w it h p a s s ive
p a ssive ra n g e o f m o t io n la t e ra l b e n d in g a n d / o r ro t a t io n m a y p re cip it a t e a n d re p ro d u ce t h e p a t ie n t ’s
su g g e st s t e n d in it is. ch ie f com p la in t of s h ou ld e r p a in . Le s s com m on ly, vis ce ra l p a t h ology from t h e
• Te n d e rn e ss o n p a ssive p a n cre a s or ga llbla d d e r w ill re fe r p a in t o t h e s h ou ld e r.
ra n g e o f m o t io n b u t n o t
a ct ive iso m e t ric lo a d in g
su g g e st s a ct ive a d h e sive
ca p su lit is o r a ct ive Studie s
o st e o a rt h rit is.
Th e la bora t ory is of n o h e lp in eva lu a t in g t h e p a t ie n t w it h s h ou ld e r p a in ; t h e
• Reserve imaging studies for p h ys ica l e xa m in a t ion is m ore e n ligh t e n in g.
recurrent or recalcitrant
In a cu t e s h ou ld e r p a in , im a gin g is ra re ly h e lp fu l a n d s h ou ld be a void e d
sh o u ld e r p a in .
u n le s s a fra ct u re is a con s id e ra t ion .
34 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
s
e
m
1. In fe rior os t e op h yt e of a d ege n e ra t ive a crom iocla vicu la r join t . Th e os t e op h yt e
o
r
w ill e n croa ch in t o t h e a crom ioh u m e ra l s p a ce a n d re s u lt in a bon y im p in ge -
d
n
m e n t of t h e rot a t or cu ff. Th is n d in g m ay in d ica t e t h e n e e d for a s u rgica l
y
S
con s u lt a t ion .
n
i
2. Ca lci c t e n d in it is . Ca lci ca t ion of t h e rot a t or cu ff is a con s e q u e n ce of t h e
a
P
ch ron icit y of t h e in a m m a t ion a n d n ot a ca u s e of t h e t e n d in it is . It in d ica t e s
l
a
a m ore ch ron ic con d it ion a n d t h e n e e d for con t in u e d t h e ra py. Eve n t u a lly t h e
n
o
i
ca lci ca t ion m a y re s olve a s w ill t h e con d it ion .
g
e
3. Scleros is a n d cys t ic d ege n e ra t ion of t h e h u m era l gre a t e r t u be ros it y. Th is im -
R
2
p lie s a ch ron ic a n d s eve re im p in ge m e n t of t h e h u m e ra l h ea d a ga in s t t h e a c-
N
rom ion w it h con cu rre n t im p in gem e n t of t h e rot a t or cu ff w it h con s eq u e n t ia l
O
I
join t in s t a bilit y. Th is n d in g im p lie s t h e n e e d for a s u rgica l con s u lt a t ion .
T
C
4. Na rrow in g or oblit e ra t ion of t h e a crom ioh u m e ra l s p a ce. Th is n d in g ca n
E
S
on ly occu r w it h a t t rit ion or a com p le t e t e a r of t h e rot a t or cu ff, in d ica t in g
in s t a bilit y of t h e join t . If s e e n on p la in ra d iogra p h y, a s u rgica l con s u lt a t ion
m a y be re q u ire d .
ICD9
727.3 Bursitis NEC
726.10 sh o u ld e r
726.90 Capsulitis (jo in t )
726.0 ad h e sive (sh o u ld e r)
De g e ne ratio n, de g e ne rative
718.01 sh o u ld e r
De rang e me nt
718.30 re cu rre n t
718.31 sh o u ld e r re g io n
718.91 sh o u ld e r re g io n
Diso rde r
727.9 b u rsa
726.10 sh o u ld e r re g io n
733.90 cart ilag e NEC
718.01 sh o u ld e r re g io n
716.60 Mo no arthritis
716.61 sh o u ld e r (re g io n )
(Co n t in u e d )
36 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
ICD9 (Co n t in u e d )
715.91 Oste o arthro sis/ Oste o arthritis sho ulde r (d e g e n e rat ive )
(h yp e rt ro p h ic)
780.96 Pain(s)
719.40 jo in t
719.41 sh o u ld e r (re g io n )
726.90 Pe riarthritis (jo in t )
726.2 sh o u ld e r
726.90 –Te ndinitis, te ndo nitis
727.82 calci c
726.11 sh o u ld e r
Additio na l Re a ding
1. Hu s n i EM , Don oh u e JP. Pa in fu l s h ou ld e r a n d re e x s ym p a t h e t ic d ys t ro p h y s yn d rom e . In Koo p m a n W J,
S
More la n d LW, e d s ; A rthritis and A llied Conditions , 15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s & W ilkin s ;
E
C
2005 :2133 –2151 .
T
2. Bou lw a re DW. Th e p a in fu l s h ou ld e r . In Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of
I
O
Rheum atology . Ph ila d e lp h ia : Lip p in cot t Willia m s & Wilkin s ;2003 :43 –47 .
N
3. Wood w a rd TW , Be s t TM . Th e p a in fu l s h ou ld e r: p a rt 1. Clin ica l eva lu a t ion . A m Fam Physician 2000 ;61 :3079 –
2
3088 .
R
4. Woo d w a rd TW, Be s t TM . Th e p a in fu l s h ou ld e r : p a rt 2. Acu t e a n d ch ron ic d is ord e rs . A m Fam Physician
e
g
2000 ;61 :3291 –3300 .
i
o
n
a
l
P
a
i
n
S
y
n
d
r
o
m
e
s
CHAPTER
5 Pa inful Feet
Dennis W. Boulw are and Gustav o R. Heudebert
s
Foot p a in a n d los s of fu n ct ion m a y be
m ark e t in g e xe cu t ive
e
m
ca u s e d by a n u m be r of p roblem s a n d ca n
co m p lain s o f p ain f u l
o
be t h e m a n ife s t a t ion of a la rge n u m be r
r
d
f e e t t h at are in t e rf e r-
n
of d e n e d clin ica l e n t it ie s . Foot p a in is a
y
S
in g w it h h e r ab ilit y s ym p t om , n ot a d ia gn os is , a n d a p re cis e
n
i
d ia gn o s is s h o u ld b e m a d e t o e n s u re
a
t o w o rk . He r w o rk
P
p rop e r t re a t m e n t , w h ich is s p e ci c for
l
in vo lve s w e arin g d re ss sh o e s ap p ro p riat e f o r h e r p o sit io n an d
a
t h a t p a rt icu la r p roble m . If t h e p h ys icia n
n
o
o f t e n lo n g p e rio d s o f st an d in g w h ile m ak in g p re se n t at io n s. p e rce ive s t h e p roble m s im p ly a s “foot
i
g
e
p a in ,” a s u cce s s fu l ou t com e is u n like ly
R
He r b u sin e ss f o o t w e ar is t yp ically e le vat e d h e e ls an d h e r
a n d eve n t h o u gh fo o t p ro ble m s a re
2
e xam in at io n re ve als a p e s cavu s t yp e o f f o o t w it h n u m e ro u s
N
ext re m e ly com m on , t h e foot is la rge ly a n
O
h ard co rn s o n h e r t o e s.
I
ign ored a re a .
T
C
Fo r p ra ct ica l p u r p o s e s , t h e fo o t is
E
S
d ivid e d a n a t o m ica lly a s t h e fo re fo o t ,
t h e m id foot , a n d t h e h in d foot . Th e fore foot com p ris e s t h e t oe s , t h e ir re s p e ct ive
m e t a t a rs a l bon e s , a n d s u rrou n d in g s oft t is s u e s . Th e h in d foot is d e n e d a s t h e
e ra co m p ris in g t h e ca lca n e o u s a n d t h e t a lu s w it h t h e ir co r re s p o n d in g s u r-
rou n d in g s oft t is s u e s . Fin a lly, t h e m id foot is t h e a re a occu p ie d by t h e cu boid ,
n avicu la r, a n d t h re e cu n e iform bon e s (la t e r, in t e rm e d ia t e, a n d m e d ia l) a n d t h e
corre s p on d in g s u rrou n d in g s oft t is s u e. Mos t of t h e n on t ra u m a t ic d is ord e rs of
t h e foot w ill occu r in t h e fore foot a n d h in d foot a re a ; fu rt h e rm ore, a n d for t h e
p u rp os e s of cla rit y, w e w ill cla s s ify t h e s e d is ord e rs n os ologica lly a s re la t e d t o
m e ch a n ica l or n e u rologica l e t iologie s .
37
38 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Figure 5.1 Pes pla nus deformity with loss of the Figure 5.2 Severe pes ca vus seen in spa stic neurologi-
longitudina l arch of the foot. From Berg D, ca l disorders.
Worza la K. Atla s of Adult Physical Dia gnosis .
Phila delphia , PA: Lippincott Willia ms & Wilkins;
2006.
Pe s Planus
S
E
Pe s p la n u s , or a t fe e t , is oft e n a s ym p t om a t ic bu t ca n ca u s e fa t igu e of t h e foot
C
T
m u s cle s a n d a ch in g w it h in t ole ra n ce t o p rolon ge d w a lkin g or s t a n d in g (Fig. 5.1 ).
I
O
Th e m os t com m on t yp e is t h e exible a t foot a lt h ou gh ot h e r ca u s e s of a t fe e t
N
2
a re t a rs a l coa lit ion , con ge n it a l ve rt ica l t a lu s , a n d ru p t u re of t h e t ibia lis p os t e rior
R
t e n d on , w h ich ca u s e s t h e t yp ica l u n ila t e ra l, a cq u ire d a t foot . In p e s p la n u s ,
e
g
t h e re is los s of t h e lon git u d in a l a rch on t h e m e d ia l a s p e ct of t h e foot , t h e ca l-
i
o
n
ca n e u s is eve rt e d (va lgu s ), a n d on a m bu la t ion ou t -t oe in g ca n be s e e n ; t h e s e
a
l
ch a n ge s a re m ore a p p a re n t on w e igh t be a rin g. Th is con d it ion is la rge ly in h e r-
P
a
it e d a n d is s e e n w it h ge n e ra lize d h yp e rm obilit y.
i
n
S
y
Pe s Cavus
n
d
An u n u s u a lly h igh m e d ia l lon git u d in a l a rch ch a ra ct e rize s p e s cavu s , or cla w
r
o
foot , a n d in s eve re ca s e s ca u s e s a h igh lon git u d in a l a rch re s u lt in g in s h ort e n -
m
e
in g of t h e foot (Fig. 5.2 ). W it h t h e a bn orm a lly h igh lon git u d in a l a rch , t h e re is
s
re la t ive s h ort e n in g of t h e e xt e n s or liga m e n t s ca u s in g d ors i e xion of t h e m e t a -
t a rs op h a la n ge a l (MTP) join t s a n d p la n t a r e xion of t h e p roxim a l in t e rp h a la n -
ge a l a n d d is t a l in t e rp h a la n ge a l join t s givin g t h e cla w in g a p p e a ra n ce of t h e
t oe s . Th e p la n t a r fa s cia m a y be con t ra ct e d a n d t h e ca lca n e u s is u s u a lly in a
va ru s (in ve rt e d ) p os it ion . In ge n e ra l, t h e t e n d e n cy t o p e s cavu s is in h e rit e d bu t
ca n be a clu e t o a n u n d e rlyin g n e u rologic d is ord e r, s u ch a s m ye lom e n in goce le,
Ch a rco t –Ma r ie –Too t h d is e a s e , o r Frie d re ich a t a xia . Alt h ou gh p e s ca vu s ca n
ca u s e foot fa t igu e, p a in , a n d t e n d e rn e s s ove r t h e m e t a t a rs a l h e a d s w it h ca llu s
form a t ion , it ca n be a s ym p t om a t ic. Ca llu s e s ca n be p re s e n t ove r t h e d ors u m of
t h e t oe s from in cre a s e d frict ion t o foot w e a r.
Hallux Valg us
In h a llu x va lgu s , d evia t ion of t h e la rge t oe la t e ra l t o t h e m id lin e a n d d evia t ion
of t h e rs t m e t a t a rs a l m e d ia lly occu r. A bu n ion (a d ve n t it iou s bu rs a ) of t h e h e a d
of t h e rs t MTP join t m ay be p re s e n t , oft e n ca u s in g p a in , t e n d e rn e s s , a n d sw e ll-
in g. Ha llu x va lgu s is m ore com m on in w om e n a n d m ay re s u lt from a ge n e t ic
t e n d e n cy, p oorly t t e d foot w e a r, or s e con d a ry t o ch ron ic a rt h rit id e s s u ch a s
rh e u m a t oid a rt h rit is , ch ron ic gou t , or os t e oa rt h rit is .
Bunio ne tte
A bu n ion e t t e, or t a ilor's bu n ion , is a p rom in e n ce of t h e ft h m e t a t a rs a l h e a d
re s u lt in g from t h e ove rlyin g bu rs a a n d a loca lize d ca llu s . Pre s s u re from s h oe s
ca n ca u s e p a in , a n d t e n d e rn e s s m a y be p re s e n t ove r t h e sw olle n bu rs a .
Hamme r To e
In h a m m e r t oe s , t h e p roxim a l in t e rp h a la n ge a l join t is e xe d a n d t h e t ip of t h e
t oe p oin t s d ow n w a rd . Th e s e con d t oe is m os t com m on ly in volve d a n d ca llu s e s
m a y fo rm a t t h e t ip o f t h e t o e a n d ove r t h e d o r s u m o f t h e in t e rp h a la n ge a l
join t s , re s u lt in g from frict ion a ga in s t t h e s h oe. Ha m m e r t oe m a y be con ge n it a l,
a cq u ire d s e con d a ry t o h a llu x va lgu s or im p rop e r foot w e a r. W h e n h a m m e r t oe s
a re a s s ocia t e d w it h h yp e re xt e n s ion of t h e MTP join t s , t h e d e form it y is kn ow n
a s “cocke d -u p t oe s .” Th is m ay be s e e n in rh e u m a t oid a rt h rit is .
Me tatarsalg ia
s
Pa in a ris in g from t h e m e t a t a rs a l h e a d s , kn ow n a s m e t a t a rs a lgia , is a s ym p t om
e
m
re s u lt in g from a va rie t y of con d it ion s . Pa in on s t a n d in g a n d t e n d e rn e s s on p a l-
o
r
p a t ion of t h e m e t a t a rs a l h e a d s a re p re s e n t . Ca llu s e s ove r t h e m e t a t a rs a l h e a d s
d
n
a re u s u a lly s e e n . Th e ca u s e s of m e t a t a rs a lgia a re m a n y, in clu d in g foot s t ra in ,
y
S
u s e of h igh -h e e l s h oe s , a n eve rt e d foot , t ra u m a , s e s a m oid it is , h a llu x va lgu s ,
n
i
ch ron ic a rt h rit is , foot s u rge ry, or a foot w it h a p e s ca vu s d e form it y.
a
P
l
a
n
Me tatarsal Stre ss Fracture
o
i
Pa in , sw e llin g, t e n d e rn e s s , a n d occa s ion a l e ryt h e m a d eve lop ove r t h e m e t a t a r-
g
e
R
s a l a re a , u s u a lly w it h ou t a n y cle a r h is t ory of t ra u m a . Th e n e ck of t h e s e con d
2
m e t a t a rs a l bon e is m os t fre q u e n t ly in volve d , bu t a ll m e t a t a rs a ls ca n be s it e s of
N
fra ct u re (Fig. 5.3 ). W h ile ove ru s e s u ch a s joggin g a re com m on ca u s e s , s t re s s
O
I
T
fra ct u re s ca n be s e e n in rh e u m a t oid a rt h rit is or ge n e ra lize d os t e op oros is or t h e
C
E
e ld e rly w it h ou t a p re cip it a t in g id e n t i a ble eve n t or a ct ivit y. Th e key t o d ia gn o-
S
s is of s t re s s fra ct u re s of t h e foot is t o h a ve a h igh in d e x of s u s p icion . Th e d if-
cu lt y in m a k in g t h e d ia gn o s is is t h a t in it ia l ra d iogra p h s u s u a lly s h ow n o
a bn orm a lit ie s re q u irin g a rep e a t ra d iogra p h s eve ra l w e e ks la t e r t o d e m on s t ra t e
h e a lin g w it h ca llu s form a t ion . Bon e s ca n s ca n be h e lp fu l t o e s t a blis h a n e a rly
d ia gn os is a s t h ey s h ow a n in cre a s e in u p t a ke ove r t h e fra ct u re s it e.
Se samo id Injurie s
Le s ion s of t h e s e s a m oid bon e s of t h e big t oe m ay e xh ibit loca l p a in a n d t e n d e r-
n e s s u n d e r e it h e r t h e m e d ia l or la t e ra l s e s a m oid . Th e p a in m ay h ave a gra d u a l
on s e t or begin a bru p t ly follow in g a cu t e t ra u m a a n d is e xa ce rba t e d by d ors i e x-
ion of t h e big t oe or u p on w e igh t be a rin g. Re cogn ize d ca u s e s of s e s a m oid p a in ,
w h ich h a s loos e ly be e n ca lle d s e s a m oid it is , a re rep e t it ive s t ra in from a ct ivit ie s
s u ch a s d a n cin g or lon g-d is t a n ce ru n n in g, s t re s s fra ct u re, t ra u m a t ic fra ct u re,
bip a rt it e s e s a m oid , a n d os t e och on d rit is .
Achille s Te ndinitis
Ach ille s t e n d in it is u s u a lly res u lt s from t ra u m a , a t h le t ic overa ct ivit y, or im p rop -
erly t t in g s h oe s w it h a s t iff h e e l cou n t e r, bu t it ca n a ls o a ris e from in a m m a t ory
con d it ion s s u ch a s a n kylos in g s p on d ylit is , Re it e r s yn d rom e, gou t , rh e u m a t oid
40 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
S
E
C
T
I
O
N
2
R
e
g
i
o
n
a
l
A B
P
a
i
n
S
Figure 5.3 Meta ta rsa l stress fra cture 2 weeks (A) a fter injury a nd 6 weeks (B) la ter demonstra ting ea rly periostea l rea ction a t 2 weeks a nd ca llus forma -
y
n
tion a t 6 weeks. With permission from Da ffner RH. Clinica l Ra diology: The Essentia ls , 3rd ed. Phila delphia , PA: Lippincott Willia ms & Wilkins; 2007.
d
r
o
m
e
s
a rt h rit is , a n d ca lciu m pyrop h os p h a t e d ep os it ion d is e a s e. Pa in , sw ellin g, a n d t e n -
d e rn e s s occu r over t h e Ach ille s t e n d on a t it s a t t a ch m e n t a n d in t h e a re a p roxi-
m a l t o t h e a t t a ch m e n t . Crep it u s on m ot ion a n d p a in on d ors i e xion m ay be
p re s e n t .
Plantar Fasciitis
Pla n t a r fa s ciit is occu rs p rim a rily be t w e e n 40 a n d 60 ye a rs of a ge bu t ca n b e
s e e n in a ll a ge s . A gra d u a l on s e t of p a in in t h e p la n t a r a re a of t h e h e e l u s u a lly
occu rs bu t m a y occu r follow in g t ra u m a or from ove ru s e a ft e r a ct ivit ie s s u ch a s
t a kin g p a rt in a t h le t ics , w a lkin g for a p rolon ge d t im e, w e a rin g im p rop e rly t -
t in g s h oe s , or s t rikin g t h e h e e l w it h s om e force. Th e p a in is ch a ra ct e ris t ica lly
s
m o s t s eve re in t h e m o rn in g u p o n a ris in g e s p e cia lly w it h t h e rs t few s t e p s
e
m
from be d . Aft e r a n in it ia l im p rove m e n t , t h e p a in m a y ge t w ors e la t e r in t h e d ay
o
r
e s p e cia lly a ft e r p rolon ge d s t a n d in g or w a lkin g, or a ft e r p rolon ge d p e riod s of
d
n
in a ct ivit y a ga in . Pa lp a t ion t yp ica lly reve a ls t e n d e rn e s s a n t e rom e d ia lly on t h e
y
S
m e d ia l ca lca n e a l t u be rcle a t t h e origin of t h e p la n t a r fa s cia . Mos t p a t ie n t s w it h
n
i
h e e l p a in h ave ca lca n e a l s p u rs , bu t t h e s p u r it s e lf is n ot like ly t h e ca u s e of p a in .
a
P
l
a
n
Po ste rio r Tibial Te ndinitis and Rupture
o
i
Pa in , sw e llin g, a n d loca lize d t e n d e rn e s s ju s t p os t e rior t o t h e m e d ia l m a lle olu s
g
e
R
occu r in p os t e rior t ibia l t e n d in it is . Ext e n s ion a n d e xion m ay be n orm a l, bu t
2
p a in is p re s e n t on a ct ive in ve rs ion a ga in s t re s is t a n ce or p a s s ive eve rs ion . Th e
N
d is com fort is u s u a lly w ors e a ft e r a t h le t ic eve n t s .
O
I
T
Ru p t u re of t h e p os t e rior t ibia lis t e n d on , w h ich is n ot com m on ly re cogn ize d ,
C
E
is a ca u s e of a p rogre s s ive a t foot . It m ay be ca u s e d by t ra u m a , ch ron ic t e n d on
S
d ege n e ra t ion , or rh e u m a t oid a rt h rit is . An in s id iou s on s e t of p a in , sw e llin g, a n d
t e n d e rn e s s occu r s a lo n g t h e co u rs e of t h e t e n d on ju s t d is t a l t o t h e m e d ia l
m a lle olu s . Th e u n ila t e ra l d e form it y of h in d foot va lgu s a n d fore foot a bd u ct ion
is a n im p ort a n t n d in g. Th e fore foot a bd u ct ion ca n be s e e n be s t from be h in d ;
m ore t oe s a re s e e n from t h is p os it ion t h a n w ou ld be s e e n n orm a lly. Th e re s u lt
of t h e s in gle h e e l ris e t e s t is p os it ive w h e n t h e p a t ie n t is u n a ble t o ris e on t o t h e
ba ll of t h e a ffe ct e d foot w h ile t h e con t ra la t e ra l foot is off t h e oor. Com p u t e d
t om ogra p h y (CT) a n d MRI a re h e lp fu l in t h e d ia gn os is of t e n d on ru p t u re.
NEUROLOGICAL PROBLEMS
Th e foot is a fre q u e n t s it e of n e u rologic s ym p t om s , s om e of w h ich a re com m on
a n d ot h e rs of w h ich a re ra re. Th e u s u a l s ym p t om is n u m bn e s s of s om e p ort ion
of t h e foot , bu t t h is com p la in t is oft e n ign ore d a s be in g n on s p e ci c. Th e s ym p -
t om s of n u m bn e s s , t in glin g, p a re s t h e s ia s , bu rn in g p a in , or p in s a n d n e e d le
s e n s a t ion s h ou ld rs t p oin t t o a p os s ible n e u rologic le s ion . Th e m os t com m on
ca u s e of n u m bn e s s of t h e fe e t is p e rip h e ra l n e u rop a t h y, a lt h ou gh a n u m be r of
42 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Mo rto n Ne uro ma
Mid d le -a ge d w o m e n a re m o s t fre q u e n t ly a ffe ct e d by Mo r t o n n e u ro m a , a n
e n t ra p m e n t n e u rop a t h y of t h e in t e rd igit a l n e rve occu rrin g m os t oft e n be t w e e n
t h e t h ird a n d fou rt h t oe s . Pa re s t h e s ia s a n d a bu rn in g, a ch in g t yp e of p a in a re
u s u a lly e xp e rie n ce d in t h e fou rt h t oe. Th e s ym p t om s a re m a d e w ors e by w a lk-
in g on h a rd s u rfa ce s or w e a rin g t igh t s h oe s or h igh -h e e l s h oe s . Te n d e r n e s s
m ay be e licit e d by p a lp a t ion be t w e e n t h e t h ird a n d fou rt h m e t a t a rs a l h e a d s .
Occa s ion a lly, a n e u rom a is s e e n be t w e e n t h e s e con d a n d t h ird t oe s . Com p re s -
s ion of t h e in t e rd igit a l n e rve by t h e t ra n s ve rs e m e t a t a rs a l liga m e n t a n d p os -
s ibly by a n in t e rm e t a t a rs op h a la n ge a l bu rs a or s yn ovia l cys t m ay be re s p on s ible
for t h e e n t ra p m e n t .
s
a n d a Tin e l s ign m ay be p re s e n t . Tra u m a , s ca r t is s u e, a n d ga n glia h a ve be e n
e
m
re p ort e d a s ca u s e s of e n t ra p m e n t .
o
r
d
n
y
S
Exa mina tio n
n
i
a
P
A p rop e r p h ys ica l e xa m in a t ion of t h e foot le a d s t o t h e a n a t om ic loca liza t ion of
l
a
t h e s ou rce of t h e p a in s ym p t om s , h e lp s t o id e n t ify t h e s t a t ic a n d m e ch a n ica l
n
o
a bn orm a lit ie s of t h e foot , a n d a id s in d e t e ct in g a n u n d e rlyin g d is e a s e. Look a t
i
g
t h e s h oe s for e xce s s ive w e a r on t h e h e e ls a n d s ole s . Ext re m e la t e ra l h e e l w e a r
e
R
ca n s ign ify h in d fo o t (ca lca n e a l) va ru s . An e x a m in a t io n o f ga it is va lu a ble in
2
d ia gn os in g a n d t re a t in g m a n y foo t p ro ble m s . Th e p a t ie n t w a lks ba re foot e d
N
O
w it h t h e fe e t a n d a n kle s e xp os e d , a n d t h e h in d foot , m id foot , a n d fore foot a re
I
T
C
view e d s ep a ra t e ly.
E
S
Ob s e r ve t h e fo o t fo r s w e llin g, d e fo r m it y, a n d e ryt h e m a o r o t h e r s k in
ch a n ge s . Pa lp a t ion t o d e t e ct t e n d e rn e s s is im p ort a n t for d ia gn os is . Pa lp a t e t h e
s u bt a la r join t in t h e n e u t ra l p os it ion for t e n d e rn e s s a n d a lign m e n t . Look for
fore foo t va ru s or fo re fo ot va lgu s . Exa m in e t h e m id t a rs a l a re a for t e n d e rn e s s
a n d m obilit y. Exa m in e for ra n ge of m ot ion a n d t e n d e rn e s s or sw e llin g of t h e
MTP join t s . Ch e ck for h a m m e r t oe s , cocke d -u p t oe s , a n d t e n d e rn e s s or sw e llin g
o f t o e s . Obs e r ve t h e t oe n a ils for a bn o rm a lit ie s . Ch e ck t h e ca lca n e u s on t h e
NOT TO BE MISSED p la n t a r s u rfa ce for t e n d e rn e s s . Exa m in e t h e Ach ille s t e n d on , re t ro ca lca n e a l
bu rs a , p os t e rior t ibia l t e n d on , a n d p e ron e a l t e n d on for sw e llin g, t e n d e rn e s s ,
• Me t a t a rsa l st re ss fra ct u re s s u blu xa t ion , or ru p t u re.
Id e n t ify ca llu s e s t o reve a l a re a s of e xce s s ive s t re s s e s on t h e foot . De s cribe
• Ru p t u re o f t h e Ach ille s
t e n d o n o r p o st e rio r t ib ia l t h e loca t ion of ca llu s e s . Id e n t ify corn s , w h ich a re h yp e rke ra t ot ic le s ion s s e c-
tendon on d a ry t o p re s s u re. Ha rd corn s occu r ove r bon y p rom in e n ce s a n d t yp ica lly a re
fou n d on t h e la t e ra l a s p e ct of t h e ft h t oe. Soft corn s occu r be t w e e n t h e t oe s .
Studie s
Th e s t a n d a rd p la in ra d iogra p h view s in clu d e s t a n d in g a n t e rop os t e rior, s t a n d -
in g la t e ra l, a n d obliq u e (p ron a t e d ), d ep ict in g t h e m e d ia l a s p e ct of t h e foot . It is
im p ort a n t t o obt a in t h e a n t e rop os t e rior a n d la t e ra l ra d iogra p h s in t h e s t a n d in g
p os it ion t o d e m on s t ra t e t h e a n a t om ic re la t ion s h ip s of t h e foot in t h e ir fu n c-
t ion a l p os it ion . In t h e la t e ra l view, t h e x-ra y be a m p a s s e s from la t e ra l t o m e d ia l.
Ot h e r s p e cia l view s a re t h e la t e ra l obliq u e (s u p in a t e d ) t o vis u a lize a n a cce s s ory
n a vicu la r bon e ; s e s a m oid view, w h ich is a n a xia l, obliq u e p os it ion (t ilt e d la t e ra l
of s e s a m oid s ); a n d a xia l view of t h e h e e l (Ha rris ) for ca lca n e a l fra ct u re s .
44 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Tre a tme nt
ORTHOSES
Ort h ot ics is t h e e ld of corre ct in g foot d e form it ie s by m e a n s of e xt e rn a l s u p -
S
p ort , a n d d evice s u s e d for t h is t a s k a re kn ow n a s ort h os e s . Th e s e ort h os e s a re
E
C
u s e d t o re lieve a n d /or cu s h ion a n a re a of p re s s u re, s u p p ort a n a re a of colla p s e,
T
I
O
or con ve rt a biom e ch a n ica lly a bn orm a l foot in t o a biom e ch a n ica lly fu n ct ion a l
N
foot d u rin g t h e s t a n ce p h a s e of ga it . In s h ort , t h e s e m e ch a n ica l d evice s h e lp
2
re s t ore los t fu n ct ion or h e lp m a in t a in op t im a l fu n ct ion by a lt e rin g biom e ch a n -
R
e
ics . Ort h os e s m ay p rovid e p a in re lie f a n d com p e n s a t e for m u s cle a n d liga m e n t
g
i
o
w e a kn e s s by d e cre a s in g force s p a s s in g t h rou gh p a in fu l w e igh t -be a rin g a re a s ,
n
a
s t a bilizin g or im m obilizin g s u blu xin g join t s , a n d rep os it ion in g t oe s .
l
P
Th e ra n ge of t h e s e ort h ot ic d evice s va rie s from s im p le in e xp e n s ive p a d s
a
i
n
ava ila ble in d ru gst ores t o com p lex, exp en sive, cu st om -m a d e orth oses . Th e im p or-
S
ta n ce a n d va lu e of foot orth os es in th e t rea tm en t of foot d isord ers is ofte n u n d er
y
n
recogn ize d . Th e p h ysicia n sh ou ld est a blis h a rela t ion sh ip w ith a p ed ort h ot ist (a n
d
r
o
ort h ot is t w h o is t ra in ed in foot d evices ), a n ort h ot ist , or a t ra in ed th era p ist w h o
m
ca n fa brica te orth os es th a t a re s p eci c for t h e p roblem .
e
s
Foot ort h os e s ca n be d ivid e d in t o t h re e t yp e s : d evice s t h a t re lieve p re s s u re
on va riou s p a rt s of t h e foot ; t h os e t h a t cu s h ion t h e foot a n d d e cre a s e im p a ct ;
a n d t h os e t h a t a re cu s t om m a d e t o corre ct a bn orm a l biom e ch a n ics a n d re s t ore
be t t e r fu n ct ion of t h e foot . Ort h os e s t h a t re lieve p re s s u re on s p e ci c a re a s of
t h e foo t a re ge n e ra lly foa m o r fe lt w it h a n a d h e s ive ba ckin g. Th e s e ca n be
s h a p e d s p e ci ca lly for p re s s u re a re a s s u ch a s u n d e r t h e rs t , s e con d , or ft h
m e t a t a rs a l h e a d s . Th e p a d is p la ce d ju s t p roxim a l t o t h e a re a of p re s s u re.
Th e s e con d t yp e of ort h os is , w h ich re d u ce s im p a ct a n d cu s h ion s t h e foot ,
is con s t ru ct e d of m a t e ria l com p os e d of m icroce llu la r ru bbe r. Th e s e a re t ra n s -
fe ra ble t o d iffe re n t s h oe s a n d a re u s e d in m ild ca s e s . Ad d it ion a l m a t e ria ls u s e d
in ort h os e s t h a t re d u ce im p a ct a n d cu s h ion t h e foot a re clos e d -ce ll t h e rm o-
p la s t ic, p olye t h yle n e foa m d evice s , a n d vis coe la s t ic m a t e ria l. Th e s e m a t e ria ls
ca n be m old e d t o t h e con t ou r of t h e foot .
Th e t h ird t yp e of ort h os is is t h e bio m e ch a n ica l cu s t o m -fa brica t e d t yp e ,
w h ich a t t e m p t s t o re s t ore t h e s u bt a la r join t t o a n e u t ra l p os it ion . Th e s e m ay be
rigid , s e m i e xible, or s oft , d ep e n d in g u p on t h e n e e d . Th e t h e rm op la s t ic m a t e ri-
a ls a re t h e s e m i e xible t yp e s . Th e rigid t yp e is u s u a lly com p os e d of a n a crylic,
rigid p olyu re t h a n e foa m , or p olyp rop yle n e. As p a rt of t h is t yp e of ort h os is , a
“p os t ,” w h ich is a w e d ge, ca n be in corp ora t e d t o s u p p ort t h e foot a n d corre ct
t h e a bn orm a lit y. If fore foot va ru s is p re s e n t , t h e n a m e d ia l p os t is u s e d ; a n d if
fore foot va lgu s is p re s e n t , t h e n a la t e ra l p os t is d evis e d . Likew is e, a m e d ia l p os t
is u s e d t o corre ct p ron a t ion (eve rs ion ) of t h e h in d foot , w h e re a s a la t e ra l p os t is
u s e d t o co r re ct h in d fo o t s u p in a t io n (in ve r s io n ). Typ ica lly, a cu s t o m -m a d e
ort h os is m a y in corp ora t e s eve ra l fe a t u re s t o a d d re s s t h e foot p roble m s , a n d if
n e e d e d , a ll t h re e t yp e s of foot ort h os e s ca n be com bin e d in t o on e ort h os is . A
Ch a p te r 5 Pa in fu l Fe e t 45
SHOE MODIFICATION
s
It is im p ort a n t t o h ave a ge n e ra l u n d e rs t a n d in g of s h oe con s t ru ct ion a n d ava il-
e
m
a ble s h oe m od i ca t ion s t o h e lp t re a t foot p roble m . As a s t a rt , on e ca n s im p ly
o
r
e xa m in e s h oe bot t om s for w e a r a n d t e a r t o d e t e rm in e t h e a bn orm a l force s
d
n
in volve d . A va rie t y of m od i ca t ion s ca n be m a d e. Ext ra -d e p t h s h oe s w it h a
y
S
la rge t oe box s h ou ld be u s e d t o a ccom m od a t e xe d d e form it ie s s u ch a s cla w e d
n
i
t oe s a n d t o p rovid e room for foot a n d a n kle –foot ort h os e s . Ot h e rw is e, corn s
a
P
m a y d eve lop w h e re t h e p rox im a l in t e rp h a la n ge a l join t s o f t h e t o e s or o t h e r
l
a
n
p a rt s of t h e foot ru b on t h e s u p e rior p a rt of t h e s h oe. For p a t ie n t s w it h t oe
o
i
d e fo r m it ie s , s h o e clo s u re s ca n b e m o d i e d . Tra d it io n a l s h o e la ce s ca n b e
g
e
R
ch a n ge d t o Ve lcro clos u re s . Ela s t ic la ce s ca n rep la ce regu la r la ce s , e ffe ct ive ly
2
t u rn in g t h e s h oe in t o a loa fe r t yp e. Sh oe s w it h p rop e r clos u re s a re ge n e ra lly
N
p re fe rre d ove r loa fe rs , h ow eve r, a s loa fe rs m a in t a in t h e ir p la ce on t h e foot by
O
I
T
t e n s ion .
C
E
A Th om a s h e e l, w h ich is a m e d ia l e xt e n s ion of t h e h e e l, m ay be a d d e d t o
S
s u p p o rt t h e lo n git u d in a l a rch . Re p la cin g t h e regu la r s h o e h e e l w it h a “s o lid
a n kle cu s h ion h e e l” m ay be h e lp fu l for h e e l p a in or a fu s e d a n kle, a s t h is h e e l
ca n s im u la t e a n kle p la n t a r e xion w h ile w a lkin g. A rocke r bot t om s ole m a y be
h e lp fu l for a fu s e d a n kle, h a llu x rigid u s , or ot h e r t oe d e form it ie s by s u bs t it u t -
in g for t h e p u s h -off a n d h e e l-s t rike p h a s e of w a lkin g.
Ligh t e r s h oe s a re e a s ie r t o w e a r bu t h ave le s s s t a bilit y a n d d u ra bilit y. He a v-
ie r s h oe s m a y h a ve gre a t e r s t a bilit y a n d d u ra bilit y bu t a re m o re d if cu lt t o
ca rry. Ult im a t e ly, t h e s h oe m u s t be com fort a ble, h a ve a good t , a n d be a e s -
t h e t ica lly a p p e a lin g. Ot h e r w is e , it w ill n ot b e u s e d . On e ca n a lw a ys a d vis e
p a t ie n t s t o w e a r t h e ir s p e cia l s h oe s a t h om e a n d on t h e w a y t o w ork, a n d t o
ch a n ge w h e n t h ey ge t t h e re.
In a le g le n gt h d is cre p a n cy, a lift ca n be a t t a ch e d t o t h e o u t s id e o f t h e
w h ole s h oe of t h e s h ort leg a n d n ot ju s t t o t h e s ole or h e e l. Th e s h oe ra is e
s h ou ld be on e h a lf t o t h re e fou rt h s of t h e leg le n gt h d is cre p a n cy. Th e d iffe re n ce
s h o u ld p ro b a bly b e 1 cm t o co n s id e r co rre ct in g. How eve r, if t h e leg le n gt h
d is cre p a n cy is n o t a re ce n t eve n t , a n d e s p e cia lly if it is a s ym p t om a t ic, it is
p rob a bly be s t le ft u n t re a t e d , s in ce ch a n gin g w a lkin g biom e ch a n ics a ft e r ye a rs
of com p e n s a t ion m ay re s u lt in n ew s ym p t om s .
BRACES
A p a t e lla r t e n d on –be a rin g ort h os is is h e lp fu l for t h e p roble m of p a in a n d lim i-
t a t ion in a m bu la t ion d u e t o d e s t ru ct ive ch a n ge s of t h e a n kle or s u bt a la r join t
s u bs e q u e n t t o rh e u m a t oid a rt h rit is or ot h e r in a m m a t ory a rt h rit is . Th is p a t e l-
la r t e n d on –be a rin g bra ce, w h ich p rovid e s w e igh t be a rin g on t h e p a t e lla r t e n d on
46 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
MODALITIES
Th e m os t com m on ly u s e d m od a lit ie s a re h e a t a n d cold . Me t h od s of s u p e r cia l
h e a t in g for t h e fe e t in clu d e h ot p a cks , h e a t in g p a d s , h yd rocolla t or p a cks , h ot
w a t e r bot t le s , h e a t e d w h irlp ools , a n d in fra re d la m p s . Hyd rot h e ra p y in a w h irl-
p ool ca n p rovid e s u p e r cia l h e a t t o t h e w h ole foot . At h om e, h ot ba t h s a n d foot
s oa ks , e s p e cia lly in t h e m orn in g, ca n be u s e d for re lie f. Ult ra s ou n d m a y be u s e d
t o h e a t t e n d on s a n d d e ep e r s t ru ct u re s .
Coolin g of t is s u e s ca n be obt a in e d w it h coola n t s p rays , ice p a cks , ba s in s of
ice w a t e r, a n d froze n food p a cka ge s . Coolin g a ls o ca u s e s va s ocon s t rict ion , w it h
a re d u ct io n o f blo o d ow a n d a d e cre a s e in m e t a b o lic a ct ivit y in t h e re gio n
S
t re a t e d . In ge n e ra l, p a t ie n t s s e e m t o p re fe r h e a t ; h ow eve r, bot h h e a t a n d cold
E
C
m a y be u s e d a lt e rn a t ive ly a s a con t ra s t ba t h .
T
I
O
N
2
THERAPEUTIC EXERCISES
R
e
g
Th e ra p e u t ic e xe rcis e m ay be broa d ly cla s s i e d in t o t h re e grou p s : (a ) ra n ge of
i
o
m ot ion or s t re t ch in g, (b) s t re n gt h e n in g (re s is t ive ), a n d (c) a e robic (e n d u ra n ce ).
n
a
In m a n y ca s e s , a s im p le h om e e xe rcis e p rogra m is a d e q u a t e a n d m ay be t a u gh t
l
P
t o t h e p a t ie n t by t h e p h ys icia n . Ot h e r ca s e s re q u ire t h e p re s crip t ion of a m ore
a
i
n
form a l p h ys ica l t h e ra py p rogra m . An e xe rcis e p re s crip t ion s h ou ld in clu d e t h e
S
y
e xe rcis e fre q u e n cy, in t e n s it y, t yp e, a n d d u ra t ion .
n
d
Ra n ge -o f-m ot ion e x e rcis e s a re im p o rt a n t d u rin g t h e a ct ive p h a s e of a n
r
o
in a m m a t ory a rt h rit is t o m a in t a in m obilit y of t h e a n kle, s u bt a la r, t a rs a l, a n d
m
e
MTP join t s . An kle e xe rcis e s in clu d e foot circle s , a ct ive d ors i e xion , a n d p la n t a r
s
e xion . W rit in g t h e a lp h a be t w it h t h e t oe s a n d clot h t u gs w it h t h e t o e s a n d
foot p rovid e ra n ge of m ot ion t o t h e join t s of t h e foot . Aft e r t h e a cu t e p h a s e h a s
re s olve d , s t re n gt h e n in g e xe rcis e s a ga in s t a re s is t a n ce ca n be u s e d . Th e a n kle
m a y be s t re t ch e d w it h ru bbe r t u bin g. Pa t ie n t s ca n be a s ke d t o p u s h t h e ir fe e t
a ga in s t a bo a rd a t t a ch e d t o t h e be d . Bicycle rid in g, sw im m in g, a n d a row in g
m a ch in e a re n on –w e igh t -be a rin g e xe rcis e s t h a t ca n h e lp m a in t a in ca rd iova s -
cu la r con d it ion in g.
STEROID INJECTIONS
Loca l s t e ro id in je ct io n s ca n be h e lp fu l in ce r t a in e n t ra p m e n t n e u ro p a t h ie s
(Mort on n e u rom a , s u p e r cia l p e ron e a l n e rve, s u ra l n e rve, a n d a n t e rior t a rs a l
t u n n e l s yn d rom e s ) a n d loca l in a m m a t ory con d it ion s s u ch a s a re t roca lca n e a l
bu rs it is , p os t e rior t ibia l t e n d on it is , or p la n t a r fa s ciit is . St e roid in je ct ion s of a n
WHEN TO REFER
Ach ille s t e n d on it is a re t o b e a vo id e d , a s t h ey a re lin k e d w it h ru p t u re of t h e
• Te n d o n ru p t u re s sh o u ld b e t e n d on .
re fe rre d t o a n o rt h o p e d ic
su rg e o n .
• Cu st o m o rt h o se s a re Clinica l Co urse
re q u ire d .
Th rou gh ju d iciou s u s e of n on s t e roid a l a n t i-in a m m a t ory d ru gs , re s t , ort h os e s
• Wh e n a n in a m m a t o ry w h e n in d ica t e d , a n d loca l s t e roid in je ct ion s w h e n in d ica t e d , t h e s e con d it ion s
a rt h rit is is id e n t i e d
ca n be m a n a ge d e ffe ct ive ly. In ca s e s in volvin g t e n d on ru p t u re or bon y d e form -
re q u irin g d ise a se m o d ify-
in g a n t irh e u m a t ic d ru g s. it y t h a t co n t rib u t e s t o t h e p a in fu l co n d it io n , t h e n a s u rgica l re fe rra l is in d i-
ca t e d .
Ch a p te r 5 Pa in fu l Fe e t 47
ICD9
727.3 Bursitis NEC
726.79 an k le
726.79 f o o t
924.9 Co ntusio n (sk in su rf ace in t act )
924.21 an k le
924.20 f o o t (w it h an k le ) (e xclu d in g t o e (s))
De rang e me nt
718.97 an k le (in t e rn al)
718.90 jo in t (in t e rn al)
718.97 an k le
718.97 f o o t
718.30 re cu rre n t
718.37 an k le
718.37 f o o t
Diso rde r
733.90 cart ilag e NEC
s
718.07 an k le
e
m
718.07 f o o t
o
r
716.60 Mo no arthritis
d
n
716.67 an k le
y
S
716.67 f o o t (an d an k le )
n
i
a
715.9 Oste o arthro sis/ Oste o arthritis (d e g e n e rat ive ) (h yp e rt ro p h ic)
P
715.97 an k le an d f o o t
l
a
n
780.96 Pain(s)
o
i
719.40 jo in t
g
e
R
719.47 an k le
2
719.47 f o o t
N
848.9 Sprain, strain (jo in t ) (lig am e n t ) (m u scle ) (t e n d o n )
O
I
T
845.00 an k le
C
E
845.00 an d f o o t
S
845.10 f o o t
782.3 Sw e lling
719.07 an k le
729.81 f o o t
Additio na l Re a ding
1. Biu n d o JJ, Ru s h PJ. Pa in fu l fe e t . In : Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of Rheu-
m atology . Ph ila d e lp h ia , PA: Lip p in cot t Willia m s a n d Wilkin s ; 2003 :48 –61 .
2. Es p in os a N , Brod s ky JW, Ma ce ira E. Me t a t a rs a lgia . J A m A cad Orthop Surg 2010 ;18 :474 –485 .
3. Ba rt on CJ, Mu n t e a n u SE, Me n z HB, e t a l . Th e e f ca cy of foot ort h os e s in t h e t re a t m e n t of in d ivid u a ls w it h
p a t e llofe m ora l p a in s yn d rom e : a s ys t e m a t ic review . Sports Med 2010 ;40 :377 –395 .
4. Sim p s on MR, How a rd TM . Te n d in op a t h ie s of t h e foot a n d a n kle . A m Fam Physician 2009 ;80 :1107 –1114 .
5. Th om a s JL, Ch ris t e n s e n JC, Kra vit z SR, e t a l. Am e rica n College of Foot a n d An kle Su rge on s h e e l p a in com -
m it t e e. Th e d ia gn os is a n d t re a t m e n t of h e e l p a in : a clin ica l p ra ct ice gu id e lin e -revis ion 2010 . J Foot A nkle
Surg 2010 ;49 :S1 –S19 .
CHAPTER
6 Mecha nica l Disorders
of the Knee
Dennis W . Boulw are
Intro ductio n
A 25-ye ar-o ld m an p re se n t s
Me ch a n ic a l d is o r d e r s o f t h e k n e e
S
w it h a 3-d ay h ist o ry o f rig h t
E
in clu d e clin ica l co n d it io n s ca u s e d by
C
T
k n e e af t e r p layin g so cce r w it h m a lfu n ct ion , t ra u m a , or d ege n e ra t ion of
I
O
f rie n d s in t h e p ast w e e k e n d .
N
a s p e ci c in t ra -a r t icu la r a n d / o r e xt ra -
2
Despite rest and acetam inophen, a rt icu la r com p on e n t of t h e kn e e in t e r-
R
fe r in g w it h n o r m a l k n e e fu n ct io n . An
e
h e is st ill in p ain , u n ab le t o
g
in t e rn a l d e ra n ge m e n t of t h e kn e e com -
i
o
st raig h t e n h is k n e e co m p le t e ly
n
m on ly re fe rs t o a d is ord e r of t h e in t ra -
a
l
an d h is k n e e o ccasio n ally a rt icu la r com p on e n t s , m ore com m on ly
P
a
b u ck lin g . t h e a rt icu la r ca rt ila ge , m e n is cu s b ro-
i
n
ca rt ila ge, colla t e ra l liga m e n t s , or cru ci-
S
y
n
a t e liga m e n t s (Fig. 6.1 ). Dis o rd e r s o f
d
r
e xt ra -a rt icu la r com p on e n t s of t h e kn e e
o
m
join t in clu d e p a t e llofe m ora l m a la lign m e n t a n d in s u f cie n cy of t h e q u a d ricep s
e
s
or h a m s t rin g m u s cle grou p s , a n d a re con s id e re d a s m e ch a n ica l d is ord e rs t oo.
Sign i ca n t m e ch a n ica l d is ord e rs of t h e kn e e ca u s in g in s t a bilit y, if con t in -
u e d u n a ba t e d , eve n t u a lly le a d t o os t e oa rt h rit is . Exp e rim e n t a l a n im a l m od e ls of
os t e oa rt h rit is t yp ica lly in volve in it ia t in g a n in t e rn a l d e ra n ge m e n t of t h e join t ,
follow e d by con t in u e d u s e of t h e lim b. Th e m os t com m on m od e ls of e xp e ri-
m e n t a l os t e o a rt h rit is in clu d e p a rt ia l m e d ia l m e n is ce ct om y o r t ra n s e ct io n of
t h e a n t e rior cru cia t e liga m e n t . In ju rie s of t h e m e d ia l m e n is cu s a n d a n t e rior
cru cia t e liga m e n t a re com m on a n d a s ou r p op u la t ion a ge s a n d be com e s m ore
e n ga ge d in re cre a t ion a l a n d s p ort s -re la t e d a ct ivit ie s , m e ch a n ica l d is ord e rs of
t h e kn e e w ill be com e m ore p reva le n t a n d , if n ot re cogn ize d e a rly, w ill re s u lt in
CLINICAL POINTS a n in cre a s e d p reva le n ce of os t e oa rt h rit is of t h e kn e e.
• Me ch a n ica l d iso rd e rs ca n
le a d t o kn e e in st a b ilit y a n d
p re m a t u re o st e o a rt h rit is. Clinica l Pre se nta tio n
• Th e p h ysica l e xa m in a t io n Mos t kn e e p a in re s u lt s from d is ru p t ion of on e of t h e m a n y com p on e n t s t h a t
o f t h e kn e e is e sse n t ia l in
com p ris e a fu n ct ion a l kn e e join t . Th e s e com p on e n t s in clu d e t h e a rt icu la r h ya -
id e n t ifyin g t h e ca u se .
lin e ca rt ila ge, t h e s u p p ort in g m e n is ca l broca rt ila ge, a n d t h e va riou s liga m e n t s .
• Bu cklin g o f a p a in fu l kn e e An u n d e rs t a n d in g of t h e a n a t om y a n d biom e ch a n ics of t h e kn e e cou p le d w it h
is co m m o n a n d n o t a lw a ys
a fo cu s e d p h ys ica l e xa m in a t io n of va riou s com p on e n t s of t h e kn e e u s u a lly
a sso cia t e d w it h a t o rn
m e n iscu s. id e n t ify t h e ca u s e of p a in . Th is ch a p t e r focu s e s on d e ra n ge m e n t s of t h e m e n is ci,
liga m e n t s , a n d p a t e llofe m ora l a lign m e n t a s a ca u s e of kn e e p a in s in ce t h ey a re
• Ch ro n ic m e n isca l t e a rs a re
t h e m os t com m on m e ch a n ica l d is ord e rs of t h e kn e e.
co m m o n ly a sso cia t e d w it h
o st e o a rt h rit is. In ge n e ra l, p a t ie n t s com p la in of kn e e p a in p rim a rily w it h u s e a n d fu rt h e r
h is t ory is of lim it e d va lu e in id e n t ifyin g t h e m e ch a n ica l d is ord e r ot h e r t h a n t h e
48
Ch a p te r 6 Me ch a n ica l Dis ord e rs of t h e Kn e e 49
a cu it y o f t h e p a in a n d a n id e n t i a ble p re cip it a t in g
eve n t . Bu cklin g of t h e kn e e w it h w e igh t -be a r in g is
a s s o cia t e d w it h a ll t yp e s o f in t e r n a l d e ra n ge m e n t s
a n d m ore com m on ly occu r s a s a re e xive m u s cu la r
re la x a t io n t o t h e s u d d e n o n s e t o f p a in , ca u s in g t h e
Lateral Post. cruciate kn e e t o “give w a y.” Tru e lockin g of t h e kn e e, t h ou gh ,
collateral
ligament
ligament s h o u ld fo cu s t h e clin icia n o n a t or n a n d d is p la ce d
Medial collateral m e n is cu s ge t t in g e n t ra p p e d w it h in t h e join t .
Ant. cruciate
ligament
ligament Acu t e in ju rie s w it h id e n t i a ble p recip it a t in g eve n t s
Medial meniscus s u ch a s t ra u m a or in ju ry com m on ly in volve m en is cu s
Lateral or liga m e n t d a m a ge w it h im m e d ia t e p a in , a n d con t in -
meniscus
u e d p a in w it h w e igh t -be a rin g or u s e of t h e lim b a n d
oft en lim it e d ra n ge of m ot ion s econ d a ry t o t h e p a in . If
t h e a cu t e in ju ry re s u lt e d in a d is p la ce m e n t of t h e t orn
m e n is cu s , p a t ien t s oft en com p la in of a p a in fu l “ca t ch -
in g” or “p op p in g” s en s a t ion in t h e kn e e. La rge s u d d e n
e ffu s ion s s u gge s t a h e m a rt h ros is t h a t is m ore com -
Figure 6.1 Ana tomica l components of the knee tha t ca n ca use a m on ly s e en w it h t orn liga m e n t s a s op p os ed t o a t orn
s
mecha nica l disorder of the knee. From Koopma n WJ, Morela nd LW, eds. m en is cu s . Liga m e n t s a re va s cu la rize d s t ru ct u re s , a n d
e
m
Arthritis a nd Allied Conditions: A Textbook of Rheuma tology, 15th ed.
d a m a ge t o t h e liga m en t u s u a lly re s u lt s in a h e m a rt h ro-
o
Phila delphia : Lippincott Willia ms & Wilkins; 2005.
r
s is . Effu s ion s t h a t occu r la t e r ca n be s e e n in e it h e r liga -
d
n
m e n t or m e n is cu s d a m a ge. An exa m in a t ion of t h e join t
y
S
w ill h e lp id e n t ify t h e s ou rce of d a m a ge.
n
i
Th e a bs e n ce of a n id e n t i a ble p re cip it a t in g eve n t s u gge s t s a d ege n e ra t ive
a
P
p roce s s t h a t eve n t u a lly re a ch e d a t ip p in g p oin t ca u s in g clin ica l s ym p t om s . Pa r-
l
a
n
t icu la rly w it h a ch ron ic t e a r of t h e m e n is cu s , t h e re is u s u a lly le s s p a in t h a n a n
o
i
a cu t e t e a r, a n d t h e re is fre q u e n t ly a la ck o f a n y re co gn iz a ble p re cip it a t in g
g
e
R
eve n t . Ch ron ic m e n is ca l t e a rs a re t yp ica lly a s s ocia t e d w it h os t e oa rt h rit is , a n d
2
a p re cip it a t in g ca u s e m ay be a s s im p le a s a s q u a t t in g a n d t w is t in g m a n e u ve r
N
or a s im p le m is s t e p . Ch ron ic p a in w it h u s e of t h e kn e e a n d ep is od ic e ffu s ion s
O
I
T
of t h e kn e e oft e n p re ce d e t h e p a t ie n t ’s eve n t u a l vis it t o s e e t h e p h ys icia n . Wit h
C
E
ch ro n ic d e ra n ge m e n t s , lim it a t io n in ra n ge o f m o t io n is le s s o f a p ro m in e n t
S
fe a t u re t h a n w it h a cu t e a n d d is p la ce d t e a rs .
Com p la in ts of p a in w ith u se a re com m on in a ll m ech a n ica l d isord ers of th e
kn ee, bu t p a in felt in th e a n terior of th e kn ee or w ith d escen d in g sta irs or in clin ed
s u rfa ce s a s op p os e d t o a s ce n d in g s t a irs or d e s ce n d in g s u rfa ce s a re com m on
com p la in ts of p a tellofem ora l com p a rtm en t p roblem s . Pa tien ts w ith p a tellofem o-
ra l p a in often com p la in of p a in a fter p rolon ged p eriod s of im m obility w ith th e
kn ee in exed p osition s su ch a s sittin g a t a d esk or rid in g in a n a u tom obile; w h en
resu m in g a ctivity a ga in , th e con d ition w ill often ca u se p a in for a brief p eriod of
PATIENT ASSESSMENT tim e, su ch a s th e rst few step s a fter resu m in g a s ta n d in g p osition .
Pa in fe lt in t h e p op lit ea l a rea is t yp ica lly d u e t o e ffu s ion s d is t en d in g t h e join t
1. Wo rse p a in w it h ca p s u le or d u e t o a n e ffu s ion ca u s in g a p op lit e a l cys t t o ll, ca u s in g p a in from
d e sce n d in g st a irs o r d is t e n t ion of t h e cys t . Pop lit e a l p a in d oe s n ot oft e n id e n t ify t h e s ou rce of t h e
d e clin in g su rfa ce s m e ch a n ica l d is ord e r ca u sin g t h e in crea s ed s yn ovia l u id t o a ccu m u la t e a s m u ch
su g g e st s p a t e llo fe m o ra l
a s re e ct d is t e n t ion of t h e p op lit e a l cys t or join t ca p s u le. Pop lit e a l cys t s a re com -
d ise a se .
m on in m a n y in d ivid u a ls a n d com m u n ica t e w it h t h e join t s p a ce, bu t t yp ica lly
2. Te st in g fo r in st a b ilit y is a re n ot u id - lle d excep t w h en t h e p re s s u re in t h e s yn ovia l s p a ce in cre a s e s a n d
crit ica l in lig a m e n t o u s
s yn ovia l u id is p u m p ed from t h e join t in t o t h e p op lit e a l cys t . Th e com m u n ica -
le sio n s.
t ion be t w ee n t h e cys t a n d join t s p a ce d oe s n ot a lw ays a llow t h e u id t o ret u rn
3. Disp la ce d m e n isca l t o t h e join t s p a ce, bu t w ill even t u a lly be re a bs orbed w h en t h e join t s p a ce p res -
fra g m e n t s ca n b e co m e
s u re re t u rn s t o n orm a l a n d n o fu rt h e r u id is p u m p e d in t h e p op lit ea l cys t .
e n t ra p p e d a n d lo ck t h e
kn e e .
4. Re se rve im a g in g st u d ie s Physica l Finding s
fo r re cu rre n t o r re ca lci-
t ra n t kn e e p a in . Th e p h ys ica l e xa m in a t ion is t h e m os t h e lp fu l in t h e clin ica l eva lu a t ion of t h e
p a t ie n t a s va riou s m a n e u ve rs a llow t h e clin icia n t o t e s t e a ch com p on e n t of
50 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
s
A com p let e t e a r w ill d evia t e s ign i ca n t ly a n d m ay n ot h ave s ign i ca n t a s s oci-
e
m
a t ed t e n d e rn e s s . Sin ce t h e m e d ia l colla t e ra l liga m e n t is rm ly a t t a ch e d t o t h e
o
r
m ed ia l m e n is cu s , a n d d is ru p t ion of on e s t ru ct u re oft e n lea d s t o in ju rie s t o t h e
d
n
ot h er s t ru ct u re in t h e m e d ia l com p a rt m e n t , a t orn m e d ia l colla t e ra l liga m e n t
y
S
freq u e n t ly h a s a n a s s ocia t e d t orn m ed ia l m e n is cu s in volved . Con ve rs e ly, va ru s
n
i
force a p p lie d t o t h e d is t a l leg s t ill h e ld in t h is p os it ion ca n be u s e d t o d e t e ct
a
P
s im ila r s ign s in t h e la t e ra l com p a rt m e n t , im p lica t in g a la t e ra l colla t e ra l liga m e n t
l
a
n
in ju ry a n d ca n be follow e d by p a lp a t ion a lon g t h e la t era l join t lin e for t e n d e r-
o
i
n e s s. Mos t colla t e ra l liga m e n t a bn orm a lit ie s ca n be q u a n t i e d by t h e d egre e of
g
e
R
d is p la cem e n t . A gra d e I la xit y w ou ld rep res e n t u p t o 5 m m of a d d it ion a l m ot ion ;
2
gra d e II, 6 t o 10 m m ; gra d e III, 11 t o 15 m m ; a n d gra d e IV, 15 m m of a d d it ion a l
N
d is p la cem e n t . Ca u t ion s h ou ld be exe rcis e d in in t e rp re t in g t h is m a n eu ve r be ca u s e
O
I
T
“rela t ive” la xit y of t h e colla t e ra l liga m e n t s is oft e n s e en in kn e e s w it h los s of fu ll
C
E
a rt icu la r ca rt ila ge t h ickn e s s d u e t o ch ron ic os t e oa rt h rit is .
S
A t orn a n t e rior cru cia t e liga m e n t is be s t t e s t e d by t h e a n t e rior d raw e r s ign
or La ch m a n t e s t . Th is m a n e u ve r is p e rform e d w it h t h e p a t ie n t s e a t e d com fort -
a bly or s u p in e. Th e kn e e is p a s s ive ly e xe d t o 25 d egre e s a n d t h e foot xe d in
p la ce w it h on e h a n d a n d a n t e rior force p la ce d on t h e t ibia re la t ive t o t h e fe m -
ora l con d yle s d ra w in g t h e t ibia l p la t e a u t ow a rd t h e clin icia n . Norm a lly t h e re is
n o m ore t h a n 5 m m of d is p la ce m e n t a n d a n t e rior d is p la ce m e n t of t h e t ibia l
p la t e a u re la t ive t o t h e fe m ora l con d yle 5 m m in d ica t e s a t orn or la x a n t e rior
cru cia t e liga m e n t . Te n d e rn e s s e licit e d by t h is m a n e u ve r in t h e a bs e n ce of d is -
p la ce m e n t s u gge s t s a n in com p le t e t e a r of t h e a n t e rior cru cia t e liga m e n t . Th e
p os t e rior cru cia t e liga m e n t is be s t t e s t e d by t h e p os t e rior d raw e r s ign , w h ich is
p e rform e d w it h t h e kn e e in 90 d egre e s of e xion . Fixin g t h e p a t ie n t ’s foot w it h
on e h a n d a n d d is p la cin g t h e t ibia l p la t e a u p os t e riorly, re la t ive t o t h e fe m ora l
con d yle s s h ou ld re s u lt in n o m ore t h a n 5 m m of d is p la ce m e n t . Pos t e rior cru ci-
a t e liga m e n t p roble m s a re m u ch le s s com m on ly s e e n t h a n a n t e rior cru cia t e
liga m e n t is s u e s . Aga in , ca u t ion s h ou ld be e xe rcis e d in in t e rp re t in g t h e s e t e s t s
in p a t ie n t s w it h ch ron ic os t e oa rt h rit is a n d re la t ive la xit y of t h e liga m e n t s d u e
t o a rt icu la r ca rt ila gin ou s los s .
If t h e e xa m in a t ion h a s n ot d e t e rm in e d a ca u s e for t h e p a in t h u s fa r, t h e
clin icia n s h ou ld con s id e r p a t e llofe m ora l in volve m e n t . In p a t e llofe m ora l m a la -
lign m e n t , t h e e n d re s u lt is a d a m a ge d p a t e lla r a rt icu la r s u rfa ce ca u s in g p a in
w it h u s e. Join t e ffu s ion s a re n ot com m on ly s e e n in p a t e llofe m ora l d is e a s e, bu t
a ll e ffu s ion s corre la t e w it h t h e d egre e of in a m m a t ion a n d h is t op a t h ology of
t h e a rt icu la r ca rt ila ge a n d s eve re le s ion s of t h e p a t e lla r a rt icu la r ca rt ila ge ca n
ca u s e a n e ffu s io n . In p a t e llo fe m o ra l d is e a s e, t h e p a s s ive ra n ge o f m o t io n is
p re s e rve d , bu t m ot ion of t h e kn e e in e xion a n d e xt e n s ion fre q u e n t ly ca u s e s
52 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
TREATMENT
In p rim a ry ca re t h e in it ia l t re a t m e n t con s id e ra t ion is t o d e t e rm in e t h e n e e d for
s u rgica l t re a t m e n t , p a rt icu la rly in ca s e s of liga m e n t ou s a n d m e n is ca l le s ion s .
In ge n e ra l t h e gre a t e r t h e s eve rit y gra d e t h e m ore like ly s u rgica l in t e rve n t ion
w ill be re q u ire d . Th is gu id e lin e is p a rt icu la rly t ru e for in d ivid u a ls w h o w is h t o
re s u m e a n a ct ive life s t yle, a s in t e rn a l d e ra n ge m e n t follow e d by a ct ive u s e is
t h e e xp e rim e n t a l m od e l for in d u cin g os t e oa rt h rit is . Le s ion s of t h e cru cia t e a n d
colla t e ra l liga m e n t s w it h m ore t h a n a gra d e II le s ion (ove r 10 m m of m ot ion )
a re a t gre a t e r ris k of fu t u re p re m a t u re os t e oa rt h rit is a n d s h ou ld be re fe rre d t o
ort h op e d ic s u rge ry for con s id e ra t ion of re p a ir. For m e n is ca l in ju rie s t h a t h ave
lockin g of t h e kn e e from a d is p la ce d fra gm e n t , re fe rra l t o ort h op e d ic s u rge ry is
re com m e n d e d . Me n is ca l t e a rs t h a t a re n ot d is p la ce d or d o n ot re s u lt in e n t ra p -
m e n t ca n be t re a t e d con s e rva t ive ly.
For a ll ot h e r in ju rie s a n d le s ion s t re a t e d by t h e p rim a ry ca re clin icia n , con -
s e r va t ive ge n e ra l m a n a ge m e n t s h o u ld s t a rt w it h re s t , ice, co m p re s s io n , a n d
Ch a p te r 6 Me ch a n ica l Dis ord e rs of t h e Kn e e 53
s
Su p e rvis e d re h a b ilit a t io n is a n im p or t a n t m o d a lit y of t re a t m e n t fo r a ll
e
m
k n e e in ju r ie s , bu t p a rt icu la r ly w it h cru cia t e liga m e n t ou s in ju rie s w h e re t h e
o
r
goa l of s t re n gt h e n in g t h e h a m s t rin g m u s cle re la t ive t o t h e q u a d ricep s d ep e n d s
d
n
o n t h e t yp e of liga m e n t o u s in ju ry. Aft e r a n t e rio r cr u cia t e liga m e n t in ju rie s ,
y
S
p h ys ica l t h e ra p y s h ou ld be d ire ct e d t ow a rd a ch ievin g h a m s t rin g a n d q u a d ri-
n
i
ce p s m u s cle s of re la t ive ly e q u a l s t re n gt h . Th is is u n like t h e n orm a l s it u a t ion
a
P
w h e re t h e q u a d rice p s m u s cle is rou gh ly 50% s t ron ge r t h a n t h e h a m s t rin g. In
l
a
n
p os t e rior cru cia t e liga m e n t in ju rie s , t h e q u a d ricep s m u s cle s a re s t re n gt h e n e d
o
i
m a xim a lly t o e n s u re kn e e s t a bilit y. Ea ch p a t ie n t m u s t h ave a p h ys ica l s t re n gt h -
g
e
R
e n in g regim e n s p e ci ca lly t a ilore d t o t h e in ju ry. In ca s e s of p a t e llofe m ora l d is -
2
e a s e from p a t e lla r m a la lign m e n t , s u p e rvis e d p h ys ica l t h e ra py is in d ica t e d t o
N
s t re t ch t h e la t e ra l re t in a cu lu m , h a m s t rin g, a n d iliot ibia l ba n d in con ce rt w it h
O
I
T
WHEN TO REFER s t re n gt h e n in g e x e rcis e s o f t h e q u a d r ice p s m u s cle s , p a r t icu la r ly t h e va s t u s
C
E
m e d ia lis . Qu a d rice p s -s t re n gt h e n in g e xe rcis e s u t ilizin g t h e la s t 30 d egre e s o f
S
1. Lig a m e n t o u s t e a rs w it h e xt e n s ion t o s t re n gt h e n t h e va s t u s m e d ia lis m u s cle a re p ivot a l in p a t e lla r la x-
h ig h g ra d e in st a b ilit y it y t o e n h a n ce t h e ve ct or force of t h e q u a d ricep s m u s cle s in ke ep in g t h e p a t e lla
re q u ire re fe rra l t o a n w it h in t h e in t e rcon d yla r groove a n d lim it in g la t e ra l m ot io n a n d d evia t ion .
o rt h o p e d ic su rg e o n .
He a vily loa d e d is ot on ic e xe rcis e s w it h fu ll ra n ge of m ot ion (i.e., fu ll s q u a t s w it h
2. Disp la ce d m e n isca l w e igh t s ) s h ou ld be avoid e d in p a t e llofe m ora l d is e a s e.
fra g m e n t s t h a t ca u se Art h roce n t e s is a n d a s p ira t ion of s yn ovia l u id for la rge e ffu s ion s ca n h e lp
e n t ra p m e n t re q u ire
re fe rra l t o a n o rt h o p e d ic d e co m p re s s a la rge t e n s e e ffu s io n a n d p rovid e im m e d ia t e re lie f. In s t illin g
su rg e o n . in t ra -a rt icu la r cort icos t e roid s ca n re lieve p a in in ca s e s a s s ocia t e d w it h os t e -
oa rt h rit is w it h p a t e llofe m ora l d is e a s e or s m a ll m e n is ca l t e a rs .
Clinica l Co urse
In ca s e s of m ild d e ra n ge m e n t w it h ou t in s t a bilit y of t h e kn e e or a d is p la ce d
m e n is ca l fra gm e n t , t h e ou t com e is good w it h a re t u rn t o fu ll a ct ivit y in w e e ks .
In p a t ie n t s w it h a s t ro n g fa m ily h is t o ry o f o s t e o a r t h r it is a n d / o r o b e s it y, a
d e ra n ge m e n t of t h e kn e e w it h in s t a bilit y m ay le a d t o a n in cre a s e d like lih ood
of os t e oa rt h rit is . Th e ris k of p re m a t u re os t e oa rt h rit is va rie s d ire ct ly w it h t h e
s eve rit y of t h e kn e e in s t a bilit y a n d s eve re le s ion s s h ou ld be re fe rre d t o ort h o-
p e d ic s u rge ry for con s id e ra t ion of s t a biliza t ion re p a ir. Pa t ie n t s w it h a n in cre a s e d
ris k from fa m ily h is t ory of os t e oa rt h rit is , obe s it y, a n d /or in s t a bilit y s h ou ld be
a d vis e d s t ron gly t o con t in u e p h ys ica l con d it ion in g of t h e kn e e a s p re s cribe d by
p h ys ica l t h e ra p y a n d t o los e w e igh t w h e n a p p rop ria t e t o id e a l bod y w e igh t a s
m u ch a s p os s ible.
In re cu r re n t kn e e p a in o r p a in fa ilin g t o im p rove a ft e r s eve ra l w e e ks of
con s e rva t ive t h e ra py, re fe rra l t o ort h op e d ic s u rge ry m a y be w a rra n t e d .
54 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
ICD9
Bake r’s
727.51 cyst (k n e e )
727.3 Bursitis NEC
726.60 k n e e
726.61 p e s an se rin u s
726.65 p re p at e llar
924.9 Co ntusio n (sk in su rf ace in t act )
924.11 k n e e
924.5 le g
924.10 lo w e r (w it h k n e e )
Cyst (m u cu s) (re t e n t io n ) (se ro u s) (sim p le )
727.51 Bak e r’s (k n e e )
De g e ne ratio n, de g e ne rative
718.0 art icu lar cart ilag e NEC
717.5 k n e e
717.7 p at e lla
S
De rang e me nt
E
C
718.0 cart ilag e (art icu lar) NEC •
T
I
O
717.9 k n e e
N
718.36 re cu rre n t
2
718.90 jo in t (in t e rn al)
R
e
717.9 k n e e
g
i
o
718.30 re cu rre n t
n
a
718.36 k n e e
l
P
717.9 k n e e (cart ilag e ) (in t e rn al)
a
i
n
Diso rde r
S
733.90 cart ilag e NEC
y
n
d
717.9 k n e e
r
o
715.96 Oste o arthro sis/ Oste o arthritis (d e g e n e rat ive ) (h yp e rt ro p h ic) k n e e
m
780.96 Pain(s)
e
s
719.46 k n e e
848.9 Sprain, strain (jo in t ) (lig am e n t ) (m u scle ) (t e n d o n )
844.9 k n e e
844.9 an d le g
717.5 o ld
726.90 Te ndinitis, te ndo nitis
726.61 p e s an se rin u s
Additio na l Re a ding
1. Hu s n i EM , Don oh u e JP. Pa in fu l s h o u ld e r a n d re e x s ym p a t h e t ic d ys t rop h y s yn d rom e . In Koo p m a n W J,
More la n d LW, e d s . A rthritis and A llied Conditions , 15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s ;
2005 ; 2133 –2151 .
2. Bou lw a re DW. Th e p a in fu l s h ou ld e r . In Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of
Rheum atology . Ph ila d e lp h ia : Lip p in co t t Willia m s & Wilkin s ; 2003 ; 43 –47 .
3. Wood w a rd TW, Be s t TM . Th e p a in fu l s h ou ld e r : p a r t 1. Clin ica l eva lu a t io n . A m Fam Physician 2000 ;61 :
3079 –3088 .
4. Woo d w a rd TW, Be s t TM . Th e p a in fu l s h ou ld e r : p a rt 2. Acu t e a n d ch ron ic d is ord e rs . A m Fam Physician
2000 ;61 :3291 –3300 .
CHAPTER
7 Hip Pa in
Carol Croft
s
e
a n d p e lvis is co m p le x , e n co m p a s s in g
m
p ro g re sse d in se ve rit y f o r t h e
o
t h e h ip a n d t h e s a croilia c (SI) join t s , d if-
r
d
last m o n t h . Th e p ain e sp e cially fe re n t grou p s of m u s cle s , t e n d on s a n d
n
y
b o t h e rs h im at n ig h t m ak in g b u r s a e , a n d t h e va r io u s va s cu la r a n d
S
n
n e u ra l s t r u ct u re s t h a t cro s s t h e h ip
i
it d if cu lt t o lie o n h is sid e ,
a
P
join t . Re fe rre d p a in ca n a ris e from t h e
w h ich is h is p re f e rre d sle e p in g
l
ilio p s oa s re gion , lu m b os a cra l s p in e , or
a
n
p o sit io n . On e xam in at io n , h e
o
re t rop e rit o n e a l s p a ce. Th u s , t h e d iffe r-
i
g
h as a n o rm al g ait w it h f u ll e n t ia l d ia gn o s is is b ro a d a n d in clu d e s
e
R
n o n t e n d e r, p assive m o t io n in t ra -a rt icu la r p a t h ology, e xt ra -a rt icu la r
2
p a t h ology, a n d m im icke r s . Th e h is t ory
N
in clu d in g ro t at io n . M o d e rat e t e n d e rn e ss is d e t e ct e d o n
O
a n d e xa m in a t ion a re crit ica l t o n a rrow
I
T
p alp at io n o f t h e le f t g re at e r t ro ch an t e r.
C
t h e broa d d iffe re n t ia l d ia gn os is .
E
S
Clinica l Pre se nta tio n
Pa tien ts freq u en tly d escribe p a in in th e groin , u p p er th igh , or bu ttock a s “h ip ” p a in .
Pa in in th e groin or m ed ia l th igh region is m ore often d u e to h ip p a th ology a n d
CLINICAL POINTS a rises from irrita tion of th e join t ca p su le, syn ovia l lin in g, or bot h . Lu m bosa cra l
• Co rre ct d ia g n o sis d e p e n d s sp in e p a th ology ca n ca u se referred p a in to th e bu ttocks , la tera l th igh , or groin .
o n u n d e rst a n d in g t h e h ip La tera l th igh p a in is often a ttribu ted to troch a n teric bu rsitis or a d d u ctor ten d in itis.
a n a t o m y. Eva lu a t ion of t h e p a t ie n t s h ou ld begin w it h con s id e ra t ion of a ge, leve l a n d
• Ca re fu l h ist o ry a n d t yp e of a ct ivit y, p a s t in ju rie s , p a s t s u rge rie s , a n d com orbid it ie s . Poin t e d q u e s -
e xa m in a t io n . t io n in g a b o u t ch ild h o o d h ip p r o b le m s , s u ch a s h ip d ys p la s ia , s lip p e d
• Co g n iza n ce o f p a st h ip ca p it a l fe m ora l e p ip h ys is (SCFE), a n d Legg-Ca lve -Pe rt h e s d is e a s e is im p ort a n t
p a t h o lo g y in clu d in g d e ve l- t o d e t e rm in e t h e like lih ood of e a rly d ege n e ra t ive a rt h ros is . Dire ct e d q u e s t ion -
o p m e n t a l h ip d ysp la sia a n d in g s h ou ld a d d re s s a n y lim it a t ion s of p a t ie n t fu n ct ion in clu d in g im p a irm e n t in
ch ild h o o d d ia g n o se s. a ct ivit ie s of d a ily livin g, s u ch a s d on n in g s ocks , ge t t in g in a n d ou t of t h e ca r,
• Magnetic resonance imaging joggin g, w a lkin g, a n d clim bin g s t a irs . Sym p t om s t h a t re fe r t o t h e s p in e, low e r
is b e co m in g t h e st a n d a rd a bd om e n , a n d n e u rop a t h ic p a in s h ou ld be q u e s t ion e d . Com orbid it ie s ca n be a n
fo r e va lu a t io n o f so ft t issu e im p ort a n t clu e t o t h e like lih ood of ava s cu la r n e cros is (AVN) in clu d in g clot t in g
a n d ca rt ila g e st ru ct u re s d is ord e rs , h yp e rlip id e m ia , u s e of a lcoh ol a n d t oba cco, a n d p reviou s t re a t m e n t
a ro u n d t h e h ip jo in t .
w it h cort icos t e roid s . Th e s ocia l h is t ory in clu d in g t yp e of w ork a n d re cre a t ion a l
• Ea rly d ia g n o sis o f st ru ct u ra l e xe rcis e a n d e xp os u re t o a lt it u d e ca n a ls o p rovid e gu id a n ce a s t o t h e p re t e s t
h ip d ise a se m a y p re ve n t p roba bilit y of s e riou s h ip p a t h ology.
d e ve lo p m e n t o f se ve re
o st e o a rt h rit is a n d t h e n e e d Hip p a in in ch ild re n is o ft e n a cu t e a n d a re s u lt o f o n e o f t h e t h re e co m -
fo r t o t a l h ip re p la ce m e n t . m o n d is o rd e r s o f t h e h ip jo in t : a cu t e t ra n s ie n t s yn ovit is , Le gg-Ca lve -Pe r t h e s ’
d is e a s e , a n d SCFE (1 ). Th e t yp ica l p re s e n t a t io n o f h ip p a in in ch ild r e n is
55
56 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Figure 7.1 Legg-Calve-Perthes disease of left hip. Epiphysis is narrowed and radiodense. A subchondral fracture is
also visible. (With permission from Fleisher GR, Ludwig S, Baskin MN. Atlas of Pediatric Emergency Medicine .
Philadelphia, PA: Lippincott Williams & Wilkins; 2004.)
S
E
C
T
I
re fe r re d p a in t o t h e a n t e r io r t h igh a n d k n e e jo in t w it h lim p in g a n d re fu s in g
O
N
t o w a lk . Tra n s ie n t s yn ovit is is a s e lf-lim it e d , in a m m a t o ry co n d it io n w it h
2
e ffu s io n o f t h e h ip jo in t . In a b o u t h a lf t h e ca s e s , a h is t o ry o f p re ce d in g u p p e r
R
e
re s p ira t o r y in fe ct io n o r m ild t ra u m a ca n b e e licit e d . Pe r t h e s ’ d is e a s e is a
g
i
re s u lt o f is ch e m ic n e cro s is o f t h e fe m o ra l h e a d t h a t le a d s t o co lla p s e o f t h e
o
n
e p ip h ys is fo llow e d by re m o d e lin g. Boys a re m ore o ft e n a ffe ct e d a n d t h e a ge
a
l
P
ra n ge fo r o n s e t is b e t w e e n a ge s 2 a n d 13 ye a r s . Me d ica l t re a t m e n t s in clu d e
a
i
a n t i-in a m m a t o ry d r u gs , p h ys ica l t h e ra p y (PT), a n d b ra cin g t o a ch ieve o p t i-
n
S
m a l p o s it io n in g o f t h e fe m o ra l h e a d in t h e a ce t a bu la r cu p . Su rge ry fo r p rox i-
y
n
m a l fe m o ra l o s t e o t o m y is s o m e t im e s p e r fo r m e d . Ab o u t h a lf o f u n t re a t e d
d
r
p a t ie n t s w ill go o n t o d eve lo p e a r ly o n s e t o s t e o a r t h r it is (OA) o f t h e h ip . SCFE
o
m
is a d is e a s e of a d ole s ce n ce a n d is a ls o m ore com m on in boys . It is fe lt t o re s u lt
e
s
from s oft e n in g of t h e e p ip h ys e a l ca rt ila ge a t a d o le s ce n ce a n d is m ore com m on
in ch ild re n w it h e n d o crin o p a t h ie s , s u ch a s h yp ogo n a d is m , h yp o p it u it a r is m ,
a n d h yp o t h yro id is m . Su rgica l t re a t m e n t is w a r ra n t e d e a r ly a s o n ly a cu t e
s lip p e d e p ip h ys is ca n b e re d u ce d , a n d it is u s u a lly p e r fo r m e d b ila t e ra lly
be ca u s e of h igh ris k of re cu rre n ce on t h e u n a ffe ct e d s id e. Con ge n it a l d ys p la s ia
of t h e h ip join t is com m on a n d oft e n d e t e ct e d w it h rou t in e n ew born s cre e n in g.
W h e n d ia gn os is is d e laye d , lim p in g a n d w e a kn e s s of t h e s u rrou n d in g m u s cle s
a re t h e t yp ica l clin ica l s ign s . X-ra ys a re u s u a lly d ia gn os t ic, a n d re fe rra l t o a n
ort h op e d ic s u rge on for a ge a p p rop ria t e t re a t m e n t s is a p p rop ria t e (Fig. 7.1 ).
Hip p a in in a d ole scen t s a n d you n g a th let es m ay rep re s e n t avu ls ion fra ct u re s
a t t h e s it e of t h e bon y in s ert ion of t h e t e n d on s of t h e re ct u s fe m oris , iliop s oa s ,
s a rt oriu s , or ot h e r region a l m u s cu la t u re. Tre a t m e n t is u s u a lly re s t a n d n on s t e r-
oid a l a n t i-in a m m a t ory m e d ica t ion s (Fig. 7.2 ).
Hip Pa in in Adults
Acu t e h ip p a in loca t e d in t h e groin re gion in t h e s e t t in g of a cu t e t ra u m a in
a d u lt s is m os t oft e n d u e t o fra ct u re of t h e fe m o ra l h e a d or a ce t a bu lu m . Ot h e r
co m m o n ca u s e s in clu d e s t re s s fra ct u re s , AVN, m u s cu la r s t ra in o f t h e a d d u ct o r
o r ilio p s o a s m u s cle s a n d t e n d o n s , a n d iliop e ct in e a l b u rs it is . La bra l t e a r s , fe m -
o roa ce t a b u la r im p in ge m e n t , a n d OA ca n a ll be s ign s o f re s id u a l s e q u e la e o f
d eve lop m e n t a l d is ord e rs o f t h e h ip join t . In a m m a t ory a r t h rop a t h ie s , s u ch a s
r h e u m a t o id a r t h r it is , ca lciu m p yro p h o s p h a t e d ih yd ra t e d e p o s it io n d is e a s e ,
a n d s e p t ic a rt h rit is s h o u ld be e n t e rt a in e d in t h e corre ct clin ica l circu m s t a n ce s .
Ch a p te r 7 Hip Pa in 57
Right Hip
(Anterior)
Iliac crest
Articular surface
Tendons (cut)
Iliofem oral l. Su perior pu bic ram u s Gluteus medius
Piriformis
Greater Pubic Obturator internus
trochanter sym p hysis Obturator externus
Iliopsoas major
Obtu rator
foram en
s
e
Inferior p ubic ram u s
m
o
r
Fem u r Ischiu m
d
n
Lesser trochanter
y
S
n
i
a
P
l
a
n
Figure 7.2 Anterior right hip liga ments. (Asset provided by Ana tomica l Cha rt Co.)
o
i
g
e
R
2
Th e ort h op e d ic lit e ra t u re h a s lon g a t t rib u t e d m u ch of t h e OA in t h e h ip
N
join t t o a n a t om ica l d e form it ie s . Os t e oa rt h rit is of t h e h ip is oft e n s e con d a ry t o
O
I
T
con ge n it a l or d eve lop m e n t a l a bn orm a lit ie s s u ch a s d eve lop m e n t a l d ys p la s ia of
C
E
t h e h ip , Pe rt h e ’s d is e a s e a n d SCFE. Prim a ry os t e oa rt h rit is w a s p re s u m e d t o be
S
id iop a t h ic (d u e t o d eve lop m e n t a l a bn orm a lit ie s of t h e a rt icu la r ca rt ila ge ), bu t
m o re re ce n t in form a t io n s u gge s t t h e m e ch a n is m in t h e s e ca s e s is fe m o ro a -
ce t a b u la r im p in ge m e n t ra t h e r t h a n e xce s s ive co n t a ct s t re s s (2 ). Ace t a b u la r
d ys p la s ia is a s h a llow n e s s of t h e a ce t a bu lu m t h a t le a d s t o u n e q u a l d is t ribu t ion
of s t re s s on t h e a ce t a bu la r ca rt ila ge, la bra l t e a rs , a n d OA. It is oft e n a com p o-
n e n t o f d eve lo p m e n t a l d ys p la s ia o f t h e h ip , w h ich p re d o m in a n t ly a ffe ct s
w om e n . Ot h e r a n a t om ica l a bn orm a lit ie s of t h e a ce t a bu lu m s u ch a s p rot ru s ion
re s u lt in ove rcove ra ge a n d re s u lt a n t im p in ge m e n t be t w e e n t h e a ce t a bu la r rim
a n d t h e fe m o ra l h e a d –n e ck ju n ct io n . Ace t a b u la r p ro t ru s io n m a y b e s e e n in
Ma rfa n s yn d rom e a n d rh e u m a t oid a rt h rit is , bu t m os t ca s e s a re id iop a t h ic.
An a t om ic va ria t ion s in t h e fe m u r ca n a ls o le a d t o s ign i ca n t a bn orm a lit ie s
in h ip join t m e ch a n ics . Th e m os t com m on ly re cogn ize d fe m ora l a bn orm a lit y is
ca lle d “a p is t ol grip d e form it y” a n d is fe lt t o be a m a jor ca u s e of OA of t h e h ip
in m e n . Th e d e form it y re s e m ble s m ild SCFE a n d m ay be a d eve lop m e n t a l va ri-
a n t t h a t is re la t e d . Te a r s o f t h e a ce t a b u la r la b r u m h a ve b e e n d e s cr ib e d in
p a t ie n t s w it h d eve lop m e n t a l h ip d ys p la s ia , Pe rt h e s ’ d is e a s e, p reviou s SCFE,
p revio u s t ra u m a , a n d in a s s o cia t io n w it h fe m o ro a ce t a b u la r im p in ge m e n t .
Pa t ie n t s w ill ge n e ra lly re p o r t gra d u a l o n s e t o f s ym p t o m s b u t o cca s io n a lly
re la t e t h e o n s e t o f p a in t o t ra u m a o f s o m e k in d . Th e p a in is ge n e ra lly b o t h
d u ll a n d s h a rp groin p a in a n d occa s ion a lly is a ls o p re s e n t in t h e bu t t ock a n d
w ors e n e d w it h a ct ivit y or p rolon ge d s it t in g (3 ).
In t ra -a rt icu la r loos e bod ie s re s u lt from va riou s ca u s e s in clu d in g OA, AVN,
p igm e n t e d villon od u la r s yn ovit is , os t eoch on d rit is d is s eca n s , a n d p rior t ra u m a t o
t h e h ip, s u ch a s d is loca t ion w it h re d u ct ion . Me ch a n ica l s ym p t om s like clickin g,
lockin g, ca t ch in g, or givin g w ay a re com m on a lon g w it h groin p a in a n d s t iffn e s s .
58 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Bursae
Iliop ectineal bu rsae
Deep trochanteric bu rsae
Trochanteric bu rsae
Figure 7.3 Hip bursa e. (Asset provided by Ana tomica l Cha rt Co.)
Ch a p te r 7 Hip Pa in 59
s
e
p a t h ology.
m
Th e Mu lt ice n t e r Art h ros copy of t h e Hip Ou t com e s Re s e a rch Ne t w ork grou p
o
r
d
id e n t i e d com m on p ra ct ice a m on g s p e cia lis t s in t h e e xa m in a t ion of t h e h ip
n
y
(re fe re n ce 25, Ma r t in a r t icle ) (6 ). Be gin n in g w it h t h e s t a n d in g p o s it io n t h e
S
n
e xa m in e r s h ou ld a s s e s s t h e h e igh t o f t h e s h o u ld e rs a n d ilia c cre s t s on e a ch
i
a
s id e, obs e rve s p in a l a lign m e n t in clu d in g e xion t o d e t e ct s colios is , a n d p e r-
P
l
form s in gle leg s t a n ce t e s t in g. We a kn e s s on t h e a ffe ct e d s id e w ill re s u lt in a
a
n
d rop in t h e con t ra la t e ra l bu t t ock w h e n s t a n d in g on t h e p a in fu l leg. Ga it a bn or-
o
i
g
m a lit ie s oft e n h e lp t o d e t e ct p a t h ology ow in g t o t h e t ra n s fe r of d yn a m ic a n d
e
R
s t a t ic loa d s t o t h e liga m e n t s a n d os s e ou s s t ru ct u re s (Figs . 7.4 a n d 7.5 ).
2
N
O
I
T
C
E
S
Normal hip Weak hip
abductors abductors
Figure 7.4 Trendelenburg sign. (With permission Figure 7.5 Wea k hip a bductors. (With permission
from Bickley LS, Szilagyi P. Ba tes’ Guide to Physica l from Bickley LS, Szila gyi P. Ba tes’ Guide to Physica l
Exa mina tion a nd History Ta king , 8th ed. Examination and History Taking, 8th ed. Philadelphia,
Phila delphia , PA: Lippincott Willia ms & Wilkins.) PA: Lippincott Willia ms & Wilkins, 2003.)
60 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Figure 7.6 Technique for FABER ma neuver. Figure 7.7 Technique for Ober’s ma neuver use- Figure 7.8 Technique for grea ter trocha nteric
(With permission from Berg D, Worza la K. Atla s ful to a ssess for tightness in the iliotibia l ba nd. bursa a ssessment: pa ssive hip forwa rd exion
of Adult Physical Diagnosis . Phila delphia, PA: (With permission from Berg D, Worza la K. Atla s a nd interna l rota tion. (With permission from
Lippincott Willia ms & Wilkins; 2006.) of Adult Physical Diagnosis . Philadelphia, PA: Berg D, Worza la K. Atla s of Adult Physica l
Lippincott Willia ms & Wilkins; 2006.) Diagnosis . Phila delphia , PA: Lippincott Willia ms
& Wilkins; 2006.)
Gluteal
muscles
s
e
m
o
r
d
n
y
Intertrochanteric
S
line
n
i
a
P
l
a
Inferior ramus
n
Ischial tuberosity
o
Lesser of pubis
i
g
trochanter
e
R
2
N
O
I
T
Shaft
C
E
of femur
S
Figure 7.9 Anteroposterior radiogra ph of the hip joint. (With permission from Snell RS. Clinical Anatomy, 7th ed.
Phila delphia , PA: Lippincott Willia ms & Wilkins; 2003.)
Subchondral Subchondral
cysts sclerosis
Nonuniform
joint space
Osteophyte
S
E
C
T
I
O
Buttressing
N
Lateral and
2
A B
superior migration
R
e
g
Figure 7.10 Degenerative joint disease: HIP. A. Diagram. B. Radiograph. Note the following fea tures: non-
i
o
uniform loss of joint spa ce (1), subchondra l sclerosis (2), subchondra l bone cysts (3), osteophytes (4 ), cortica l
n
a
buttressing (5), a nd thickened weight-bea ring tra becula e (6 ). (With permission from Yochum TR, Rowe LJ. Yochum
l
and Rowe’s Essentials of Skeletal Ra diology, 3rd ed. Phila delphia , PA: Lippincott Willia ms & Wilkins; 2004.)
P
a
i
n
Dyn a m ic s on ogra p h y of t h e bu rs a e a rou n d t h e h ip m ay be h e lp fu l, t h ou gh
S
y
MRI is m ore s e n s it ive for d e t e ct in g in a m e d bu rs a e a n d m u s cu la r t e a rs .
n
d
MRI is p a rt icu la rly e ffe ct ive a t d e t e ct in g AVN a n d is t h e gold s t a n d a rd s in ce
r
o
m
s ign i ca n t join t d e s t ru ct ion ca n occu r p rior t o evid e n ce of ra d iogra p h ic a bn or-
e
m a lit ie s on p la in ra d iogra p h s . Likew is e, MRI ca n d e t e ct s oft t is s u e a bn orm a li-
s
t ie s , s u ch a s p igm e n t e d villon od u la r s yn ovit is (Figs . 7.11 t o 7.13 ) (8 ).
Me d ica l a n d s u rgica l t re a t m e n t o p t ion s fo r OA in t h e la s t d e ca d e ca n be
o ffe re d t o p a t ie n t s b e fo re a d va n ce d jo in t in vo lve m e n t re q u ir in g t o t a l jo in t
Figure 7.11 A: Tra nsverse t1-weighted ima ge of a pa tient (supine) with hip pa in on long-term steroid thera py for
lupus erythema tosus shows nonspeci c ma rrow edema (a rrow) in the left femora l hea d (f). The loca tion a nd
clinica l context of this nding a re suggestive of a va scula r necrosis, but the ima ging a ppea ra nce is otherwise
nonspeci c. a , a ceta bulum; b , bla dder. (From Koopma n WJ, Morela nd LW. Arthritis a nd Allied Conditions: A
Textbook of Rheuma tology, 15th ed. Phila delphia , PA: Lippincott Willia ms & Wilkins; 2005.)
Ch a p te r 7 Hip Pa in 63
s
seen (a rrowhea d ). (With permission from Yochum TR, Rowe LJ. Yochum a nd h igh e r d ia gn os t ic p e rform a n ce t h a n MRI for d e t e ct -
e
m
Rowe’s Essentia ls of Skeleta l Ra diology, 3rd ed. Phila delphia , PA: Lippincott in g la bra l t e a rs bu t h a s low e r d ia gn os t ic p e rform -
o
r
Willia ms & Wilkins; 2004.) a n ce fo r eva lu a t io n of t h e a rt icu la r ca r t ila ge . MRI
d
n
t e ch n o logy is co n t in u in g t o evo lve , a n d a d va n ce s
y
S
t h a t p rovid e h igh e r s p a t ia l re s olu t ion a n d im p rove d t is s u e con t ra s t w ill h e lp
n
i
id e n t ify t h os e p a t ie n t s for w h om e a rly in t e rve n t ion w it h a rt h ros cop y w ill be
a
P
be n e cia l.
l
a
n
o
i
g
e
R
2
N
O
I
T
C
E
S
Figure 7.13 Inguinal mass: history of right hip pain. A: Soft tissue window
computed tomogra phic (CT), a xia l pelvis. Note the cystic, low a ttenua tion
ma ss immedia tely a nterior to the right femora l hea d (a rrow). B: Proton
density–weighted ma gnetic resona nce ima ging (MRI), a xia l pelvis. The a rea
of decrea sed a ttenua tion on the CT study displa ys a homogeneous low
signa l intensity on MRI (a rrow). C: T2-weighted MRI, a xia l pelvis. Observe
the homogeneous hyperintense signa l intensity in this loca lized uid collec-
tion (a rrow). These ndings a re consistent with iliopsoa s bursitis. Comment:
This patient’s history includes an inguinal hernia and the recent onset of right
hip pain. At physical examination, a slightly pulsatile soft tissue mass was noted
on deep palpation. (With permission from Yochum TR, Rowe LJ. Yochum and
Rowe’s Essentials of Skeletal Radiology, 3rd ed. Philadelphia: Lippincott Williams
& Wilkins; 2004.)
64 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
Re fe re nce s
1. Za ch e r J, Gu rs ch e A. ‘Hip ’ p a in . Best Pract and Res Clin Rheum 2003 ;17 :71 –85 .
2. Ga n z R, Le u n ig M , Le u n i-Ga n z K, Ha r ris W H . Th e e t iology o f o s t e oa rt h rit is of t h e h ip : a n in t egra t e d
m e ch a n ica l con ce p t . Clin Orthop Relat Res. 2008 Fe b ;466 (2 ):264 –72 .
3. Tibor LM , Se kiya JK. Diffe re n t ia l d ia gn os is of p a in a rou n d t h e h ip join t . A rthroscopy 2008 ;24 :1407 –1421 .
4. St ra u s s E, Nh o S, Ke lly B. Greater Trochanteric Pain Syndrom e. Sprots Med A rthrosc Rev. 2010 ;18:11.
5. Sch a p ira D, Na h ir M , Sch a rf Y. Troch a n t e ric bu rs it is : a com m on clin ica l p roble m . A rch Phys Med Rehabil.
1986 ;67 :815 –7 .
6. Ma rt in HD, Sh e a rs SA, Pa lm e r IJ. Eva lu a t ion of t h e h ip . Sports Med A rthrosc Rev 2010 ;18 :63 –75 .
7. You n g-Jo K, Bix by S, Ma m is h TC. Im a gin g s t r u ct u ra l a b n o rm a lit ie s in t h e h ip join t : in s t a b ilit y a n d
im p in ge m e n t a s a ca u s e of os t e o a rt h rit is . Sem in Musculoskelet Rad 2008 ;12 :334 –345 .
8. Kijow s ki R. Clin ica l ca rt ila ge im a gin g of t h e kn e e a n d h ip join t s . A m J Rad 2010 ;195 : 618 –628 .
9. Hu n t e r DJ Ph a rm a cologic t h e ra py for os t e oa rt h rit is –t h e e ra of d is e a s e m od i ca t ion . Nature Rev Rheum .
2010 ;7 (1 ):13 –22 .
10. Cu s h JJ, Lip s ky PE. Ap p roa ch t o a rt icu la r a n d m u s cu lo s ke le t a l d is ord e r s . In : Fa u ci AS, Bra u n w a ld E,
Ka s p e r DL, e t a l. Harris on ’s Prin ciples an d Pract ice of In t ern al M edicin e, 17t h e d : h t t p :/ / w w w.
a cce s s m e d icin e.com /con t e n t .a s p x?a ID = 2869993.
s
e
m
o
r
d
n
y
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CHAPTER
8 Sports-Related Conditions
a nd Injuries
Lisa L. W illett
A 52 ye ar o ld m ale w it h t yp e
Injurie s o f the
2 d iab e t e s m e llit u s b e g an an
Ro ta to r Cuff
S
E
CLINICAL PRESENTATION
C
e xe rcise p ro g ram t o im p ro ve
T
I
O
h is d iab e t ic co n t ro l. He h as Rota tor cu ff ten d in itis is com m on in
N
a th letes w h o p a rticip a te in rep etitive
2
b e e n p layin g t e n n is t h re e
overh ea d a ctivities, s u ch a s soft ba ll,
R
e
t im e s a w e e k f o r t h e p ast ba s eba ll, te n n is , or golf. Th e rot a tor
g
i
o
m o n t h . He p re se n t s t o h is cu ff is com p rised of fou r m u scles, th e
n
a
p h ysician co m p lain in g o f s u p ra s p in a t u s , in fra s p in a t u s , t e re s
l
P
m in or, a n d su bsca p u la ris, w h ose ten -
a
rig h t sh o u ld e r p ain . Th e
i
d on s a tta ch to th e p roxim a l h u m eru s
n
p ain is w o rse in ce rt ain
S
(Fig. 8.1 ). Im p in gem en t of th e ten d on s
y
n
p o sit io n s. be t w e e n t h e h e a d of t h e h u m e ru s
d
r
o
Sp o rt in g act ivit ie s are an a n d th e a crom ion ca n lea d to in a m -
m
m a tion a n d su bseq u en t tea rs of on e
e
im p o rt an t co m p o n e n t o f a h e alt h y lif e st yle . Pat ie n t s o f all ag e s
s
or m ore of th e ten d on s. Th e su p ra sp -
are e n co u rag e d b y p h ysician s t o e xe rcise f o r h e alt h b e n e t s. in a tu s is th e m ost freq u en tly in volved .
Ho w e ve r, sp o rt s act ivit ie s can le ad t o in ju rie s. A s o u r ad u lt Sym p tom s in clu d e “a ch e-like” sh ou l-
p o p u lat io n ag e s an d a larg e r p ro p o rt io n o f t h e p o p u lat io n d er p a in , often w orse a t n igh t, exa cer-
ba ted by a bd u ction or exion of th e
e m b race s h e alt h ie r lif e st yle , sp o rt s-re lat e d co n d it io n s an d in ju rie s
a rm a s w ell a s a ctivities th a t in volve
are p re d ict e d t o in cre ase . ove rh e a d m ove m e n t of t h e a rm . If
Th e re are m an y t yp e s o f sp o rt s-re lat e d in ju rie s, ran g in g f ro m t h e t e a r is com p le t e, p a t ie n t s m ay
ch ro n ic o ve ru se t o t rau m at ic in ju rie s. Lo w e r e xt re m it y o ve ru se n ote w ea kn ess a n d d ecrea s ed ra n ge
of m otion (2 ).
in ju rie s o ccu r f ro m jo g g in g , w alk in g , ju m p in g , o r cyclin g .
Exam p le s o f ch ro n ic o ve ru se in ju rie s in clu d e p at e llo f e m o ral p ain
syn d ro m e an d A ch ille s t e n d in it is. Of t h e o ve ru se in ju rie s o f t h e EXAMINATION
Th e p h ys ica l e xa m fin d in gs va ry
u p p e r e xt re m it y, b o t h ro t at o r cu ff t e n d in it is an d lat e ral e p i-
d ep en d in g on w h ich of th e fou r ten -
co n d ylit is are t h e m o st co m m o n . In ju rie s re lat e d t o t rau m a can d on s a re in volved , a n d th e d egree of
re su lt f ro m h ig h -im p act sp o rt in g act ivit ie s, an d in clu d e lig am e n t in ju ry. If th ere is on ly in a m m a tion ,
t e ars (su ch as an an t e rio r cru ciat e lig am e n t t e ar), lig am e n t th e p a tien t w ill exp erien ce p a in ; p a r-
t ia l or fu ll-t h ickn e s s t e a rs re s u lt s in
sp rain s (lat e ral an k le sp rain ), f ract u re s, jo in t d islo cat io n s, o r h e ad
w e a kn e s s a n d d e cre a s e d ra n ge of
in ju rie s. Th e e p id e m io lo g y o f sp o rt in g in ju rie s is lim it e d . In st u d - m otion . Alth ou gh over 20 m a n eu vers
ie s (1), lo w e r e xt re m it y in ju rie s are m o re co m m o n t h an u p p e r h ave be e n d e s cribe d t o t e s t rot a t or
e xt re m it y, w it h t h e m o st co m m o n sit e s b e in g t h e k n e e an d an k le . cu ff t e a rs , t h e 3 m a n e u ve rs m os t
u s e fu l for p re d ict in g a rot a t or cu ff
66
Ch a p te r 8 Sp orts-Rela ted Con d ition s a n d In ju rie s 67
Supraspinatus
Acromion
Suprascapular
notch
Coracoid process
Supraspinatus
Humerus
Spine of
scapula
Subscapularis
A Infraspinatus
Teres minor
s
Teres major
e
m
(cut)
B
o
r
d
Figure 8.1 Rota tor cuff muscles. A, a nterior; B, posterior. The supra spina tus (A a nd B), infra spina tus (B), teres minor (B), a nd subsca pula ris (A) ca nva s
n
y
the perimeter of the glenohumera l joint ca psule. (From Moore KL, Agur AMR. Essentia l Clinica l Ana tomy, 2nd ed. Ba ltimore: Lippincott Willia ms & Wilkins,
S
2002. Figure 7.12, p. 425.)
n
i
a
P
l
a
n
tea r a re: su p ra sp in a tu s w ea kn ess , w ea kn ess in ext ern a l rota -
o
i
tion , a n d a p ositive im p in gem en t sign (3,4). Th e test to elicit
g
e
R
s u p ra s p in a t u s w e a kn e s s (“e m p t y ca n s ign ”) in volve s h avin g
2
th e p a tien t a bd u ct h is a rm to 90 d egrees, w ith 30 d egrees for-
N
w a rd a d d u ct ion . Wit h t h e p a t ie n t ’s t h u m b p oin t in g d ow n
O
I
T
tow a rd th e oor, th e exa m in er p u sh es d ow n on th e a rm a t th e
C
E
d is t a l h u m e ru s a s t h e p a t ie n t re s is t s . To e licit w e a kn e s s in
S
extern a l rot a tion , a n d in g con sis ten t w ith in fra sp in a tu s com -
p rom is e, th e p a tien t h old s h is a rm s a ga in st h is tors o, exes
h is elbow s a t 90 d egrees w ith th e th u m bs tu rn ed u p a n d t h e
a rm rota ted in tern a lly 20 d egrees. Th e p a tien t is th en a sked to
extern a lly rota te th e a rm a ga in st th e exa m in er’s resista n ce. A
p os it ive im p in ge m e n t s ign (Fig. 8.2 ) is e licit e d w it h t h e a rm
d ow n , ext e rn a lly rot a t e d a n d t h e n p a s s ive ly e leva t e d t o a n
overh ea d p osition . Th e p a tien t w ill exp erien ce p a in w ith in ter-
n a l rot a t ion of t h e a rm . An ot h e r m a n e u ve r, t h e p a in fu l a rc
s ign (Fig. 8.3 ) ca n be h elp fu l t o exclu d e a rot a t or cu ff te a r; a
p ositive is in terp reted w h en p a in is elicited w ith a ctive ra n ge
of m otion betw een 60 a n d 100 d egrees of a bd u ction a n d it h a s
a h igh sen sitivity (97.5%) for rota tor cu ff t ea r. Th erefore, if th is
sign is absen t, th e p a t ien t is u n likely to h ave a tea r.
STUDIES
If t h e e x a m a n d h is t o ry a re co n s is t e n t w it h ro t a t o r cu ff
t e n d in it is , fu rt h e r s t u d ie s a re n ot n e ce s s a ry. How eve r, if t h e
p a in p e r s is t s , p la in ra d io gra p h s a re in d ica t e d . Su p e r io r
Figure 8.2 Impingement sign. Impingement of the grea ter m igra t ion of t h e h u m e ra l h e a d ca n be s e e n if a la rge rot a t or
tuberosity on the cora coa cromia l liga ment occurs when the cu ff t e a r is p re s e n t . Ma gn e t ic re s on a n ce im a gin g (MRI) is t h e
shoulder is forwa rd exed to 90 degrees a nd interna lly rota ted,
reproducing the pa tient’s pa in. From Kova l KJ, MD a nd
p re fe rre d t e s t for d ia gn os in g rot a t or cu ff d is ord e rs , a lt h ou gh
Zuckerma n JD, MD. Atla s of Orthopa edic Surgery: A Multimeida l u lt ra s on ogra p h y is e m e rgin g a s a cos t -e ffe ct ive a lt e rn a t ive
Reference. Phila delphia : Lippincott Willia ms & Wilkins, 2004. w it h s im ila r s e n s it ivit y a n d s p e ci cit y.
68 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
S
E
C
T
I
O
N
2
R
e
Figure 8.3 Pa inful a rc sign. From Moore KL, PhD, FRSM, FIAC & Da lley AF II, PhD. Clinica l Oriented Ana tomy (4th
g
i
ed.). Ba ltimore: Lippincott Willia ms & Wilkins, 1999.
o
n
a
l
P
a
i
n
TREATMENT
S
y
Mu lt ip le t h e ra p ie s a re a va ila ble t o t re a t ro t a t o r cu ff in ju r ie s . Non o p e ra t ive
n
d
t h e ra p y con s is t s of 6 w e e ks t o 3 m on t h s of n on s t e ro id a l a n t i-in a m m a t ory
r
o
m
a ge n t s (NSAIDS), in t ra -a rt icu la r s t e roid in je ct ion s , p a s s ive a n d a ct ive e xe rcis e s
e
w it h p h ys ica l t h e ra p y, p lu s h e a t , cold , or u lt ra s on ogra p h y t h e ra p y. Pa t ie n t s w h o
s
fa il n on op e ra t ive t re a t m e n t ca n be re fe rre d t o ort h op e d ics for s u rgica l rep a ir
w it h op e n , m in i-op e n , or a rt h ros cop ic t e ch n iq u e s . In a s ys t e m a t ic review of 137
s t u d ie s of n on op e ra t ive a n d op e ra t ive t re a t m e n t s (5 ), evid e n ce w a s n ot con clu -
s ive t o re com m e n d on e t h e ra py ove r a n ot h e r. Old e r a ge, in cre a s e d s ize of t h e
t e a r, a n d gre a t e r p re op e ra t ive s ym p t om s w e re a s s ocia t e d w it h re cu rre n t t e a rs .
Du ra t ion of s ym p t om s w a s n ot a s s ocia t e d w it h p oore r ou t com e s .
CLINICAL POINTS
• Ove ru se in ju rie s a re CLINICAL COURSE
co m m o n w h e n p a t ie n t s Rega rd le s s of t h e t re a t m e n t a p p roa ch , t h e m a jorit y of p a t ie n t s w it h rot a t or cu ff
b e g in e xe rcise p ro g ra m s. in ju rie s im p rove.
• Lo w e r e xt re m it y in ju rie s
a re m o re co m m o n t h a n
u p p e r e xt re m it y, w it h t h e Pa te llo fe mo ra l Pa in Syndro me
m o st co m m o n sit e s b e in g
t h e kn e e a n d a n kle . CLINICAL PRESENTATION
• Th e m o st co m m o n ca u se o f Pa t e llofe m ora l p a in s yn d rom e (PFPS) is on e of t h e m os t com m on s p ort s in ju -
kn e e p a in a m o n g st p a t ie n t s rie s , a n d t h e m os t com m on ca u s e of kn e e p a in (1 ). It is s e e n in s p ort s in volvin g
e xe rcisin g is p a t e llo fe m o ra l ru n n in g, ju m p in g, q u ick s t op s , a n d t u rn in g. Th e ca u s e of p a t e llofe m ora l p a in is
p a in syn d ro m e . d u e t o m a la lign m e n t of t h e p a t e lla a s it t ra cks in t h e t roch le a r groove of t h e
• Co n se rva t ive m a n a g e m e n t fe m u r. Sym p t om s o f PFPS in clu d e u n ila t e ra l or bila t e ra l a n t e rior kn e e p a in ,
w it h re st , ice , p h ysica l d e s cribe d a s a d u ll a ch e in t h e p e ri- or re t ro-p a t e lla r region of t h e kn e e. It is
t h e ra p y, a n d n o n st e ro id a l in it ia t e d by t h e s p ort in g a ct ivit y, bu t ca n p rogre s s t o be com e con s t a n t . Pa in is
a n t i-in a m m a t o ry a g e n t s is
e ffe ct ive rst lin e t h e ra p y. e xa ce rba t e d by s q u a t t in g, w a lkin g u p or d ow n s t a irs , a n d p rolon ge d s it t in g. It
is a ls o kn ow n a s ch on d rom a la cia p a t e lla e or p a t e llofe m ora l join t s yn d rom e (2 ).
Ch a p te r 8 Sp orts-Rela ted Con dition s a n d In ju rie s 69
PHYSICAL EXAMINATION
Seve ra l e xa m m a n e u ve rs h ave be e n d e s cribe d , bu t evid e n ce t o s u p p ort t h e ir
d ia gn os t ic u t ilit y is lim it e d . Th e p h ys ica l e xa m is oft e n n orm a l in p a t ie n t s w it h
PFPS, a n d t h e d ia gn os is is m a d e from t h e p a t ie n t ’s clin ica l h is t ory, a n d e xclu d -
in g o t h e r ca u s e s o f kn e e p a in . On e m a y n d a t ro p h y o f t h e va s t u s m e d ia lis
m u s cle, t igh t h a m s t rin gs , a n d p a t e lla r in s t a bilit y. To a s s e s s for t h e p re s e n ce of
p a t e lla r in s t a bilit y, t h e p a t ie n t ’s kn e e is e xe d t o 20 d egre e s . Ma n u a l p re s s u re
is a p p lie d b o t h m e d ia lly a n d la t e ra lly t o t h e p a t e lla r. Dis p la ce m e n t o f t h e
p a t e lla m ore t h a n 75% of it s w id t h s u gge s t s a n in cre a s e d ris k for s u blu xa t ion .
STUDIES
Fu rt h e r d ia gn os t ic t e s t in g is n ot w a rra n t e d on ce a clin ica l d ia gn os is of PFPS is
m a d e, a n d w h e n t ra u m a , e ffu s ion , or ot h e r con ce rn in g s ym p t om s a re a bs e n t .
Pla in ra d iogra p h s m ay d e m on s t ra t e evid e n ce of p a t e llofe m ora l m a la lign m e n t .
La t e ra l view s ca n d e m o n s t ra t e p a t e lla a lt a (a h igh -r id in g p a t e lla , w h ich
in cre a s e s ris k for s u blu xa t ion ), p a t e lla r t ilt , a n d t roch le a r d e p t h . An in fra p a t e l-
la r, or “s u n ris e view,” d e m on s t ra t e s p a t e llofe m ora l a rt icu la t ion a n d m a y be a
fu rt h e r clu e of m a la lign m e n t .
s
e
m
o
TREATMENT
r
d
n
Tre a t m e n t of PFPS is p rim a rily con s e rva t ive a n d in clu d e s NSAIDs , re s t , a n d ice.
y
S
Ph ys ica l t h e ra py is im p ort a n t t o p rovid e d yn a m ic s t a biliza t ion of t h e p a t e lla .
n
i
Th is in clu d e s e xe rcis e s t o s t re n gt h e n t h e va s t u s m e d ia lis m u s cle, a n d t h e ra p y
a
P
t o s t re t ch t h e iliot ibia l ba n d a n d h a m s t rin g m u s cle s . Pa t e lla r t a p in g a n d s t a bi-
l
a
n
liza t ion bra ce s w it h a h ole for p a t e lla r t ra ckin g a re re com m e n d e d . Pu blis h e d
o
i
d a t a a ls o s u p p ort a cu p u n ct u re a n d u lt ra s ou n d t h e ra py.
g
e
R
2
CLINICAL COURSE
N
O
It ca n t a ke s eve ra l m on t h s t o a ch ieve s ym p t om a t ic re lie f. If t h e re is n o im p rove -
I
T
m e n t a ft e r 9 m on t h s of con s e rva t ive t h e ra p y, s u rgica l re a lign m e n t of t h e p a t e l-
C
E
lofe m ora l join t ca n be con s id e re d .
S
Ilio tibia l Ba nd Syndro me
CLINICAL MANIFESTATIONS
Th e iliot ibia l ba n d con s t it u t e s con n e ct ive t is s u e t h a t con n e ct s t h e iliu m t o t h e
bu la . Tra u m a d u e t o ove ru s e, m os t com m on ly s e e n in lon g d is t a n ce ru n n e rs ,
ca n m a n ife s t it s e lf a s a d u ll a ch e u n d e rn e a t h t h e la t e ra l a s p e ct of t h e kn e e a s
t h e ba n d t rave rs e s n e xt t o t h e la t e ra l fe m ora l con d yle on it s w ay t o in s e rt on t h e
bu la . On occa s ion s t h e p a in ra d ia t e s u p t h e t h igh follow in g t h e cou rs e of t h e
ba n d u p t o it s in s e rt ion in t h e iliu m . W h ile t h is s yn d rom e is a lm os t e xclu s ive ly
s e e n on ru n n e rs , s p e ci c ris k fa ct ors in clu d e ru n n in g lon ge r d is t a n ce s t h a n t h e
p a t ie n t is a ccu s t om e d t o ru n , ru n n in g on u n eve n s u rfa ce s , or h avin g u n eve n
con t a ct w it h t h e s u rfa ce a s it h a p p e n s w h e n w e a rin g w orn s h oe s .
EXAMINATION
W h ile clin ica l s ym p t om s a re h igh ly ch a ra ct e ris t ic of t h is s yn d rom e, e s p e cia lly
in t h e righ t s u bs e t of p a t ie n t s , t h e re is on e m a n e u ve r t h a t ca n h e lp con rm t h e
d ia gn o s is . Pla cin g t h e p a t ie n t o n t h e la t e ra l d e cu b it u s p o s it io n , w it h t h e
a ffe ct e d lim b u p w a rd , t h e e x a m in e r m ove s t h e a ffe ct e d lim b fo r w a rd a n d
d ow n w a rd in a n a t t e m p t t o re p rod u ce t h e s ym p t om s in t h e a ffe ct e d a re a ; on
occa s ion s p a in is n ot re p rod u ce d bu t t igh t n e s s ca n be fe lt a lon g t h e iliot ibia l
ba n d . For com p a ris on t h e m a n e u ve r is rep e a t e d by t e s t in g t h e op p os it e ilia l-
ba n d w it h t h e p a t ie n t n ow in t h e la t e ra l d e cu bit u s p os it ion w it h t h e a ffe ct e d
s id e d ow n w a rd .
70 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
TREATMENT
Ma n a ge m e n t for t h is co n d it io n is m o s t ly s u p p or t ive , in clu d in g re s t . Us e o f
NSAIDS is in d ica t e d for re lie f of p a in . Th e u s e of loca l cort icos t e roid s in je ct ion
s h ou ld be lim it e d t o p a t ie n t s n ot re s p on d in g t o m ore con s e rva t ive m e a s u re s ;
p a t ie n t s s h ou ld re s t ra in from ru n n in g a t le a s t for 2 t o 3 w e e ks a ft e r t h e in je c-
t ion . Ru n n in g on eve n s u r fa ce s a n d w e a rin g a p p rop ria t e ru n n in g s h oe s ca n
a ls o h e lp a llevia t e t h is p roble m .
CLINICAL COURSE
Mos t p a t ie n t s im p rove d d ra m a t ica lly w it h re s t a n d t h e u s e of NSAIDS. Occa -
s ion a l p a t ie n t s re q u ire t h e u s e of loca l cort icos t e roid s in je ct ion s . Ra re ly s u rgi-
ca l re le a s e of t h e ba n d m igh t p rove cu ra t ive for p a t ie n t s .
PHYSICAL EXAMINATION
Th e p h ys ica l e xa m n d in gs va ry w it h t h e e xt e n t of in ju ry. Pa in on p a lp a t ion is
com m on , w it h sw e llin g a n d lim it e d ra n ge of m ot ion w it h foot d ors i e xion . A
t e n d e r n od u le on t h e t e n d on t h a t m ove s w it h a n kle e xion ca n be p a lp a t e d .
If t h e p a t ie n t h a s a n Ach ille s ru p t u re, a p a lp a ble ga p m ay be n ot e d
a t t h e ru p t u re s it e, follow e d by sw e llin g, e d e m a , a n d bru is in g. Th e
Th om p s on (Fig. 8. 4 ) t e s t re lia bly p re d ict s a co m p le t e ru p t u re . Th e
p a t ie n t is p la ce d p ron e on t h e e xa m in a t ion t a ble, w it h t h e a n kle s
s u s p e n d e d off t h e t a ble ; t h e e xa m in e r t h e n s q u e e ze s t h e p os t e rior
ca lf t o e licit a n orm a l p la n t a r e xion re s p on s e. If t h e re is a bs e n ce of
p la n t a r e x io n , co n s id e re d a p o s it ive Th o m p s o n t e s t , t h e n t h e
p a t ie n t like ly h a s a t e n d on ru p t u re a n d im a gin g s h ou ld be p u rs u e d .
Ult ra s o u n d a n d MRI a re b o t h u s e fu l fo r t h e d ia gn o s is o f a n d t o
d e t e rm in e t h e e xt e n t of t h e Ach ille s t e n d on in ju ry. If a t e a r is s u s -
p e ct e d clin ica lly, a n MRI is t h e t e s t of ch oice.
Figure 8.4 The Thompson Test demonstra tes a rup-
ture of the Achilles tendon. Ada pted from Browner B, TREATMENT
Jupiter J, Levine A. S ke le ta l Tra u m a : Fra ctu re s ,
Dis lo ca tio n s , a n d Lig a m e n to u s In ju rie s , 2nd ed. Tre a t m e n t o f Ach ille s t e n d in it is is co n s e r va t ive , a n d in clu d e s
Phila delphia : WB Sa unders, 1997. NSAIDs , re s t , a n d ice. Ph ys ica l t h e ra py e xe rcis e s h ave be e n s h ow n
Ch a p te r 8 Sp orts-Rela ted Con dition s a n d In ju rie s 71
CLINICAL COURSE
Mos t p a t ie n t s w it h Ach ille s t e n d on it is re cove r fu lly w it h co n s e rva t ive t re a t -
m e n t ; r is k o f re cu rre n ce is u n for t u n a t e ly co m m o n o n ce ove ru s e a ct ivit y is
re in it ia t e d . Ap p rop ria t e ort h ot ics d evice s , gra d u a l re e n ga ge m e n t w it h a ct ivi-
t ie s , a n d a p p rop ria t e w a rm in g u p m a n e u ve rs a re of h e lp . Pa t ie n t s w it h a ru p -
t u re d Ach ille s t e n d on m a n a ge d in a n on s u rgica l fa s h ion h ave p oor p rogn os is
w it h h igh ra t e of re -ru p t u re a n d lon g t e rm fu n ct ion a l m orbid it y.
Ankle Spra in
s
CLINICAL PRESENTATION
e
m
o
An k le in ju r ie s a re a m o n g t h e m o s t co m m o n o f a ll m u s cu lo s k e le t a l in ju r ie s .
r
d
Th e m o s t co m m o n m e ch a n is m o f in ju ry re s u lt s fro m a la t e ra l a n k le in ve r-
n
y
S
s io n w h e re t h e a n k le jo in t is in p la n t a r e x io n , ca u s in g t h e a n k le t o “ro ll” (7 )
n
Sp o r t in g a ct ivit ie s s u ch a s b a s k e t b a ll, s o cce r, a n d ice s k a t in g a re h igh r is k
i
a
P
a ct ivit ie s fo r a n k le in ju ry, a s is a h is t o ry o f a p r io r a n k le s p ra in . Th e la t e ra l
l
a
co lla t e ra l a n k le liga m e n t s a re m o s t e a s ily in ju re d , a n d in clu d e t h e a n t e r io r
n
o
a n d p o s t e r io r t a lo b u la r liga m e n t s (ATFL a n d PTFL) a n d t h e ca lca n e o b u la r
i
g
liga m e n t (CFL) (Fig. 8. 5 ). High a n k le s p r a in s , o r s yn d e s m o t ic s p ra in s , a r e
e
R
ca u s e d by d o r s i e x io n a n d eve r s io n o f t h e a n k le w it h in t e r n a l ro t a t io n o f t h e
2
N
t ib ia , w it h in ju ry t o t h e p o s t e r io r a n d a n t e r io r t ib io b u la r liga m e n t s . An k le
O
I
T
C
E
Right foot — Lateral view
S
Fibula
Tibia
Talus
Cuboid bone
Figure 8.5 Ankle liga ments, right foot, la tera l view. Asset provided by Ana tomica l Cha rt Co.
72 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
s p ra in s a r e cla s s i e d a s Gra d e 1 t h r o u gh 3 d e p e n d in g o n t h e s e ve r it y o f
in ju ry (p re s e n ce o f a t e a r, fu n ct io n a l s t a t u s , p a in a n d s w e llin g, e cch ym o s is ,
a n d w e igh t -b e a r in g a b ilit y).
PHYSICAL EXAMINATION
On p h ys ica l e xa m in a t ion , t h e a n kle s h ou ld be in s p e ct e d for sw e llin g, e cch ym o-
s is , a n d t h e loca t ion a n d d egre e of p a in on p a lp a t ion . Ma n e u ve rs , s u ch a s t h e
a n t e rior d raw e r t e s t a n d t h e t a la r t ilt t e s t eva lu a t e for join t s t a bilit y (Fig. 8.6 ).
Th e a n t e rior d raw e r t e s t eva lu a t e s for a n ATFL t e a r. Th e e xa m in e r s t a bilize s t h e
a ffe ct e d low e r leg w it h on e h a n d w h ile cu p p in g t h e h e e l w it h t h e ot h e r h a n d .
An t e rior force is a p p lie d t o t h e h e e l in a n a t t e m p t t o m ove t h e t a lu s a n t e riorly.
Th e a m ou n t of d is p la ce m e n t is t h e n com p a re d t o t h e u n a ffe ct e d a n kle. Th e
t a la r t ilt t e s t eva lu a t e s a ca lca n e o bu la r liga m e n t t e a r. In s t e a d of a n t e rior force,
a n in ve rs ion s t re s s is a p p lie d t o t h e t a lu s . Pa t ie n t s w it h a n kle in ju rie s s h ou ld
a ls o be eva lu a t e d w it h t h e Ot t a w a An kle Ru le s (8 ). Th e s e clin ica l p re d ict ion
ru le s h a ve a lm os t 100% s e n s it ivit y for a n kle fra ct u re a n d if n ega t ive, e ffe ct ive ly
ru le s ou t a fra ct u re. If p os it ive, ra d iogra p h ic im a gin g s h ou ld be obt a in e d .
S
E
C
T
TREATMENT
I
O
N
Tre a t m e n t of la t e ra l a n kle s p ra in s is con t rove rs ia l a n d lim it e d by la ck of clin i-
2
ca l t ria ls (9 ). Acu t e ly, p a t ie n t s s h ou ld a p p ly re s t , ice, com p re s s ion , a n d e leva -
R
e
t io n , a n d p ro t e ct t h e a n kle fro m fu rt h e r in ju ry for 72 h ou r s . Th e evid e n ce
g
i
o
n
a
l
P
a
i
n
S
y
n
d
r
o
m
e
s
PATIENT ASSESSMENT
• Exa m m a n e u ve rs ca n
d e t e rm in e w h e t h e r a
lig a m e n t t e a r is p re se n t .
• So m e h ig h ly se n sit ive
m a n e u ve rs (Ot t o w a ru le s)
a re e ffe ct ive a t d e cre a sin g
t h e like lih o o d o f a sig n i -
ca n t t e a r o r fra ct u re .
• Im a g in g is in d ica t e d w h e n
a lig a m e n t o r t e n d o n t e a r
is su sp e ct e d .
• Ult ra so u n d a n d MRI ca n
d e t e rm in e t h e d e g re e o f
t e n d o n in ju ry. Figure 8.6 Eva lua tion of a nkle joint sta bility. The a nterior dra wer test
(to p ) a nd the ta la r tilt test (b o tto m ).
Ch a p te r 8 Sp orts-Rela ted Con d ition s a n d In ju rie s 73
s
e
m
733.16 b u la
o
733.14 h ip
r
d
n
733.11 h u m e ru s
y
S
733.12 rad iu s (d ist al)
n
i
733.19 sp e ci e d sit e NEC
a
P
733.16 t ib ia
l
a
733.12 u ln a
n
o
733.12 w rist
i
g
e
780.96 Pain(s)
R
719.40 jo in t
2
N
719.46 k n e e
O
726.1 Ro tato r cuff syndro me o f sho ulde r and allie d diso rde rs
I
T
C
840.4 Ro tato r cuff (capsule )
E
S
726.32 Late ral e pico ndylitis
717.83 Old disruptio n o f ante rio r cruciate lig ame nt
Sprain, strain (jo in t ) (lig am e n t ) (m u scle )
848.9 (t e n d o n )
845.00 an k le
845.00 an d f o o t
841.9 e lb o w
845.10 f o o t
842.10 h an d
843.9 h ip
843.9 an d t h ig h
WHEN TO REFER 844.9 k n e e
844.9 an d le g
• Ph ysica l t h e ra p y re fe rra l
is im p o rt a n t fo r t re a t in g 717.5 o ld
ro t a t o r cu ff in ju rie s, p a t e l- 844.9 le g
lo fe m o ra l p a in syn d ro m e , 844.9 an d k n e e
a n d Ach ille s t e n d in it is. 846.9 lo w b ack
• Pa t ie n t s w h o fa il n o n o p - 846.0 lu m b o sacral
e ra t ive p h ysica l t h e ra p y 724.6 ch ro n ic o r o ld
a ft e r 6 t o 9 m o n t h s m a y
b e n e t fro m o rt h o p e d ic
in t e rve n t io n .
• Un st a b le jo in t s sh o u ld b e Re fe re nce s
re fe rre d fo r o rt h o p e d ic 1. Mu rray IR, Mu rra y SA, Ma cKe n zie K, Co le m a n S. How evid e n ce ba s e d is t h e m a n a ge m e n t of t w o com m on
e va lu a t io n . s p ort s in ju rie s in a s p ort s in ju ry clin ic? Br J Sports Med 2005 ;39 :912 –916 .
2. Ba rry NN , McGu ire JL. Ove ru s e s yn d rom e s in a d u lt a t h le t e s . Rheum Dis Clin North A m 1996 ;22 (3 ):515 –530 .
74 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
3. Ebe ll MH. Dia gn os in g rot a t o r cu ff t e a rs . A m Fam Physician 2005 ;71 (8 ):1587 –1588 .
4. Bu rba n k KM , St eve n s o n JH , Cza rn e cki GR, e t a l. Ch ron ic s h ou ld e r p a in : Pa rt I. Evaluation and Diagnosis, A m
Fam Physician 2008 ;77 (4 ):493 –497 .
5. Se id a JC, Le Bla n c C, Sch ou t e n JR, e t a l. Sys t e m a t ic Review : Non op e ra t ive a n d op e ra t ive t re a t m e n t s for
ro t a t or cu ff t e a rs . A nn Intern Med 2010 ;153 (4 ):246 –255 .
6. Ma gn u s s e n RA, Du n n W R, Th om s on AB. Non op e ra t ive t re a t m e n t of m id p ort ion Ach ille s t e n d in op a t h y: A
s ys t e m a t ic review. Clin J Sport Med 2009 ;19 :54 –64 .
7. Ivin s D. Acu t e a n kle s p ra in : An u p d a t e. A m Fam Physician 2006 ;74 :1714 –1726 .
8. Mich a e l JA, St ie ll IG. An kle In ju rie s . In Tin t in a lli JE, Ke le n GD, St a p czyn s ki JS, e d s . Em ergency Medicine: A
Com prehensiv e Study Guide, 6t h e d , McGraw Hill , 2004 .
9. Ke rkh offs GMMJ, Row e BH , As s e n d e lft W JJ, e t a l. Im m obilis a t ion a n d fu n ct ion a l t re a t m e n t for a cu t e la t e ra l
a n kle liga m e n t in ju rie s in a d u lt s . Cochrane Database of System atic Rev iew s 2002 ;(3 ):CD003762 .
S
E
C
T
I
O
N
2
R
e
g
i
o
n
a
l
P
a
i
n
S
y
n
d
r
o
m
e
s
SECTION
3
Chapter 11 Sys te m ic Lu pu s
Eryth e m atos u s
Michelle A . Petri
75
76 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Chapter 18 Pre gn an cy an d
Rh e u m atic Dis e as e s
Michael Lockshin
CHAPTER
9 Rheuma toid Arthritis,
Including Sjögren’s
Syndrome
Zachary M . Pruhs, Jam es R. O’Dell, and Ted R. Mikuls
s
e
s
Intro ductio n
a
e
A 45-ye ar-o ld w o m an
s
i
D
p re se n t s w it h 4 m o n t h s o f Rh e u m a t oid a rt h rit is (RA) is a s ys -
c
i
t e m ic in a m m a t ory d is e a s e w it h
t
a
w o rse n in g p ain an d st iff -
m
it s p r im a ry m a n ife s t a t io n in t h e
u
n e ss in h e r n g e r jo in t s, s yn oviu m . Th e h a llm a rk of t h e d is -
e
h
R
w rist s, an d b alls o f t h e e a s e is a ch ron ic, s ym m e t ric p ol-
c
f e e t b ilat e rally. He r sym p - ya rt h rit is (s yn ovit is ) t h a t t yp ica lly
i
c
a ffe ct s t h e h a n d s , w ris t s , a n d fe e t
e
t o m s are w o rse in t h e
p
S
in it ia lly a n d la t e r m ay in volve a n y
m o rn in g , im p ro ve w it h
3
s yn ovia l join t . Alt h ou gh RA p rim a -
N
act ivit y, an d are asso ciat - rily in volve s t h e s yn oviu m , fe a t u re s
O
I
T
e d w it h o ccasio n al of s ys t e m ic d is e a s e a re p re s e n t in
C
E
a lm o s t a ll p a t ie n t s a n d ra n ge in
w arm t h an d sw e llin g
S
s eve rit y from fa t igu e t o s eve re m u l-
o f t h e h an d s. Han d rad io g rap h s sh o w p e riart icu lar e ro sio n s an d t is ys t e m va s cu lit is . In re ce n t ye a rs ,
o st e o p e n ia (Fig . 9.1 ). s ign ifica n t a d va n ce s in t h e ra p y
h ave occu rre d , h ow eve r, RA con t in -
u e s t o re s u lt in s u bs t a n t ia l m orbid -
it y for m os t p a t ie n t s . RA p a t ie n t s h ave a h igh e r m or-
t a lit y ra t e t h a n t h e ge n e ra l p op u la t ion t h a t is p rim a rily
re la t e d t o in cre a s e d ca rd iova s cu la r d is e a s e bu rd e n .
Epide mio lo g y
RA a ffe ct s a ll ra cia l grou p s w orldw id e a n d w h ile it is
s e e n m ore com m on ly in s om e p op u la t ion s , t h e p reva -
le n ce in m os t coh ort s is e s t im a t e d t o be 0.5% t o 1%. In
t h e d eve lo p e d w o r ld t h e re a p p e a r s t o b e a t re n d
t ow a rd d e cre a s in g RA in cid e n ce a n d p reva le n ce s in ce
t h e 1960s . Ove ra ll, RA is t w o t o t h re e t im e s m ore p rev-
a le n t in w o m e n t h a n in m e n . A s t u d y in Min n e s o t a
re p o r t e d a n in cid e n ce o f 50/100,000 p e r s o n -ye a r s in
m e n a n d 98/100,000 p e rs o n -ye a rs in w o m e n (1 ). Th e
p re p o n d e ra n ce o f w o m e n w it h n ew o n s e t RA w a s
Figure 9.1 Ra diogra ph of ha nds a nd wrists in a pa tient with rheuma toid m os t s t rikin g in t h e you n ge r a ge grou p s , bu t n e a r ly
a rthritis; ndings demonstra te peria rticula r osteopenia a nd erosions. e q u a l for p a t ie n t s 75 ye a rs of a ge. Th e in cid e n ce of
77
78 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Table 9.1 Ext ra-art icular Manifest at ions of Rheumat oid Art hrit is
SYSTEM MANIFESTATIONS
Mu co cu t a n e o u s Su b cu t a n e o u s n o d u le s, p yo d e rm a g a n g re n o su m ,
Sjö g re n ’s syn d ro m e
Ca rd io p u lm o n a ry Ple u rit is, p u lm o n a ry b ro sis, in t e rst it ia l lu n g
d ise a se , b ro n ch ie ct a sis, co ro n a ry a rt e ry d ise a se /
a t h e ro scle ro sis, p e rica rd it is (ca n b e co n st rict ive )
Va scu la r Va scu lit is
Re n a l Glo m e ru lo n e p h rit is (ra re )
Op h t h a lm o lo g ic Re t in a l va scu lit is, scle rit is, e p iscle rit is
He m a t o lo g ic An e m ia o f ch ro n ic d ise a se , t h ro m b o cyt o sis, Fe lt y’s
syn d ro m e (t ria d o f le u co p e n ia , sp le n o m e g a ly, a n d
RA), la rg e g ra n u la r lym p h o cyt e (LGL) syn d ro m e
Ne u ro lo g ic Ne u ro p a t h y
s
Mu scu lo ske le t a l Ost e o p o ro sis
e
s
a
e
s
i
D
c
i
t
a
m
Th e d ia gn os is of RA s h ou ld be con s id e re d in a n y p a t ie n t w it h in a m m a -
u
e
t o ry a r t h r it is , e s p e cia lly if t h e h a n d s a n d fe e t a re in vo lve d . Th e p a t ie n t ’s
h
R
re s p on s e t o t h e q u e s t ion , “W h a t is t h e w ors t t im e of d ay for you r join t s ?” is
c
oft e n t e llin g. Pa t ie n t s w it h in a m m a t ory a rt h rit is s u ch a s RA u s u a lly re p ort
i
c
e
s ign i ca n t m o rn in g s t iffn e s s (o ft e n la s t in g 1 h o u r), w h e re a s p a t ie n t s w it h
p
S
os t e oa rt h rit is (OA) a n d ot h e r m e ch a n ica l s yn d rom e s a re u s u a lly w ors e la t e r in
3
t h e d a y a ft e r a ct ivit y. In a d d it ion , s ign i ca n t fa t igu e m a y be p re s e n t eve n in
N
O
e a rly RA.
I
T
C
E
S
EXTRA- ARTICULAR MANIFESTATIONS OF RA
Ext ra -a rt icu la r m a n ife s t a t ion s of RA (ExRA) ra n ge in s eve rit y from n od u la r s kin
le s ion s t o s ys t e m ic va s cu lit is (Ta ble 9.1 ). In a la rge coh ort s t u d y ove r a 30-ye a r
t im e s p a n , m ore t h a n 40% of RA p a t ie n t s h a d e xt ra -a rt icu la r in volve m e n t w it h
n e a rly 13% of t h os e ca t egorize d a s s eve re (3 ). Th e m os t fre q u e n t m a n ife s t a t ion s
of ExRA w e re s u bcu t a n e ou s n od u le s fou n d in 34% of p a t ie n t s . Th e m os t fre -
PATIENT ASSESSMENT
q u e n t s eve re m a n ife s t a t ion of ExRA w a s p e rica rd it is (5%). Pre d ict ors of s eve re
• Bila t e ra l p o lya rt icu la r ExRA in clu d e s m okin g a t t im e of d ia gn os is , a n t i-CCP a n d RF p os it ivit y. Im p or-
in a m m a t o ry a rt h rit is t a n t ly, p a t ie n t s w it h ExRA h ave s ign i ca n t ly in cre a s e d m orbid it y a n d p a t ie n t s
o ft e n co n n e d t o t h e w it h s eve re ExRA h ave a m a rke d ly in cre a s e d m ort a lit y.
h a n d s a n d fe e t m a y b e
ch a ra ct e rist ic e a rly in t h e
d ise a se co u rse .
SJÖGREN’S SYNDROME
• In a m m a t o ry m a rke rs
Sjögre n ’s s yn d rom e is w e ll re cogn ize d a s a n e xt ra -a rt icu la r m a n ife s t a t ion of
(ESR a n d CRP) m a y b e
n o rm a l a t t h e t im e o f RA. Sjögre n ’s is a con n e ct ive t is s u e d is e a s e a ffe ct in g t h e e xocrin e gla n d s ch a r-
p re se n t a t io n in o n e t h ird a ct e rize d by d ry eye s a n d m ou t h t h a t is fre q u e n t ly a s s ocia t e d w it h ot h e r con -
t o h a lf o f t h e p a t ie n t s. n e ct ive t is s u e d is e a s e s in clu d in g RA (4 ). Sjögre n ’s s yn d rom e is oft e n cla s s i e d
• Rh e u m a t o id fa ct o r (RF) by w h e t h e r it is p rim a ry (occu rrin g in is ola t ion ) or s e con d a ry (occu rrin g con -
is p o sit ive in ∼70% o f com it a n t ly w it h a n ot h e r rh e u m a t ic con d it ion ) w it h s ign s a n d s ym p t om s t h a t
p a t ie n t s b u t is n o t sp e ci c; ca n be m im icke d in s e le ct vira l in fe ct ion s (e.g., He p a t it is C, HIV), lym p h op rolif-
a n t i-CCP a n t ib o d y h a s a e ra t ive m a lign a n cy, a n d s a rcoid os is . Th e re la t ion s h ip be t w e e n RA a n d Sjögre n ’s
sim ila r se n sit ivit y t o RF b u t
w a s r s t n o t e d in 1933 by He n rik Sjö gre n h im s e lf. Pa t ie n t s s u ffe r in g fro m
is h ig h ly sp e ci c ( 95% )
fo r RA. Sjögre n ’s w ill oft e n p re s e n t w it h p a rot id a n d la crim a l gla n d sw e llin g in a d d i-
t ion t o t h e ir s ym p t om a t ic com p la in t s .
80 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
S
E
C
T
I
O
N
3
S
p
Figure 9.2 Osteoa rthritis versus rheuma toid a rthritis joint involvement (da rker circles represent a ffected joints).
e
c
From O’Dell JR. Rheuma toid a rthritis: the clinica l picture. In: Koopma n WJ, ed. Arthritis a nd Allied Conditions: A
i
c
Textbook of Rheuma tology, 14th ed. Phila delphia : Lippincott Willia ms & Wilkins, 2001:1153–1186, with permis-
R
sion.
h
e
u
m
a
Dia gn o s is m a y be a id e d by t h e Sch irm e r’s (a s s e s s in g for ocu la r d ryn e s s )
t
i
c
a n d Ros e Be n ga l t e s t s a s w e ll a s s a liva ry gla n d or lip biop s y; p os it ive s e rologie s
D
for ANA, a n t i-SSA/SSB, a n d RF a re ch a ra ct e ris t ic of Sjögre n ’s s yn d rom e. Sjö-
i
s
e
gre n ’s m a y e xh ibit e xt ra gla n d u la r in volve m e n t in clu d in g vis ce ra l (h e a rt , lu n gs ,
a
s
e
kid n ey, ga s t roin t e s t in a l t ra ct , ce n t ra l/p e rip h e ra l n e rvou s s ys t e m ) a n d n on -vis -
s
ce ra l (s k in , m u s cle s , join t s ) m a n ife s t a t io n s . Cla s s i ca t io n of t h e d is e a s e is
gu id e d by t h e revis e d ru le s for cla s s i ca t ion from t h e Am e rica n –Eu rop e a n Con -
s e n s u s Grou p (Ta ble 9.2 ).
Table 9.2 Revised Int ernat ional Classi cat ion Crit eria for
Sjögren’s
s
e
m u co sa ) fo ca l lym p h o cyt ic sia lo a d e n it is, e va lu a t e d b y a n e xp e rt h ist o p a t h o lo -
s
a
g ist , w it h a fo cu s sco re o f 1 o r m o re , d e n e d a s a n u m b e r o f lym p h o cyt ic fo ci
e
s
(w h ich a re a d ja ce n t t o n o rm a l-a p p e a rin g m u co u s a cin i a n d co n t a in m o re
i
D
t h a n 50 lym p h o cyt e s) p e r 4 m m 2 o f g la n d u la r t issu e
c
i
t
a
5. Sa liva ry g la n d in vo lve m e n t : o b je ct ive e vid e n ce o f sa liva ry g la n d in vo lve m e n t
m
d e n e d b y a p o sit ive re su lt fo r a t le a st o n e o f t h e fo llo w in g d ia g n o st ic t e st s:
u
e
Un st im u la t e d w h o le sa liva ry o w ( 1.5 m L in 15 m in u t e s)
h
R
Pa ro tid sia lo gra ph y sho win g the p re se n ce o f d iffu se sia le ct asia s (p u nct at e,
c
ca vita ry, or d e st ru ctive pa tt e rn), with out e vid e n ce of ob st ructio n in th e
i
c
m a jo r d u cts
e
p
Sa liva ry scin t ig ra p h y sh o w in g d e la ye d u p t a ke , re d u ce d co n ce n t ra t io n , o r
S
d e la ye d e xcre t io n o f t ra ce r
3
N
6. Au t o a n t ib o d ie s: p re se n ce in t h e se ru m o f o n e o r b o t h o f t h e fo llo w in g
O
a u t o a n t ib o d ie s:
I
T
C
An t ib o d ie s t o Ro (Sjö g re n ’s syn d ro m e A) a n t ig e n s
E
S
An t ib o d ie s t o La (Sjö g re n ’s syn d ro m e B) a n t ig e n s
Re vise d ru le s fo r cla ssi ca t io n
Fo r p rim a ry Sjö g re n ’s syn d ro m e :
In p a t ie n t s w it h o u t a n y p o t e n t ia lly a sso cia t e d d ise a se , p rim a ry Sjö g re n ’s
syn d ro m e m a y b e d e n e d a s fo llo w s:
Th e p re se n ce o f a n y fo u r o f t h e six it e m s is in d ica t ive o f p rim a ry Sjö g re n ’s
syn d ro m e , a s lo n g a s e it h e r h ist o p a t h o lo g y o r se ro lo g y is p o sit ive
Th e p re se n ce o f a n y t h re e o f t h e fo u r o b je ct ive crit e ria it e m s (i.e ., it e m s 3, 4, 5,
a n d 6)
Fo r se co n d a ry Sjö g re n ’s syn d ro m e :
In p a t ie n t s w it h a p o t e n t ia lly a sso cia t e d d ise a se (e .g ., a n o t h e r w e ll-d e n e d
connective tissue disease), the presence of item 1 or item 2 plus any two from among
items 3, 4, and 5 may be considered as indicative of secondary Sjögren’s syndrome
Exclu sio n crit e ria :
Pa st h e a d a n d n e ck ra d ia t io n t re a t m e n t
He p a t it is C in fe ct io n
AIDS
Pre e xist in g lym p h o m a
Sa rco id o sis
Gra ft ve rsu s h o st d ise a se
Use o f a n t ich o lin e rg ic d ru g s (sin ce a t im e sh o rt e r t h a n fo u rfo ld t h e h a lf-life
o f t h e d ru g )
METACARPOPHALANGEAL JOINTS
Tw o t yp ica l d e fo r m it ie s m a y o ccu r a t t h e m e t a ca r-
p op h a la n ge a l (MCP) join t s —vola r or p a lm a r s u blu xa -
t io n o f t h e n ge r s re la t ive t o t h e m e t a ca rp a l bo n e s
a n d u ln a r d evia t ion (Fig. 9.5 ). Mos t ca s e s of u ln a r d evi-
a t ion a re a ccom p a n ie d by ra d ia l d evia t ion of t h e w ris t ,
rou gh ly p rop ort ion a l t o t h e d egre e of u ln a r d evia t ion
of t h e n ge rs . Alt h ou gh RA is t h e m os t com m on ca u s e
of u ln a r d evia t ion , ot h e r a rt h rit id e s , a s w e ll a s ce rt a in
n e u rologic d e cie n cie s , m ay re s u lt in u ln a r d evia t ion
a s w e ll.
WRISTS
Figure 9.5 Ulna r devia tion a nd subluxa tion of digits with boutonniere Th e w ris t is t h e s it e of m u lt ip le p ot e n t ia l p roble m s in
deformity of second digit. p a t ie n t s w it h RA. Th e com bin a t ion of u ln a r d rift of t h e
Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 83
ELBOW
Elbow in volve m e n t is oft e n d e t e ct e d by p a lp a ble s yn o-
via l p ro life ra t io n a t t h e ra d io h u m e ra l jo in t a n d is
s
e
com m on ly a ccom p a n ie d by a e xion d e form it y. If s yn -
s
a
ovit is o r e ffu s io n is p re s e n t in t h e e lb ow, co m p le t e
e
s
i
e xt e n s ion w ill n ot occu r; t h e re fore , com p le t e e xt e n -
D
s ion is a n e x ce lle n t s ign t h a t s ign i ca n t s yn ovit is or
c
i
t
a
e ffu s io n is a b s e n t . Ole cra n o n b u rs a l in vo lve m e n t is
m
com m on , a s a re rh e u m a t oid n od u le s in t h e bu rs a a n d
u
e
Figure 9.6 Ra diogra ph showing wrist destruction a nd subluxa tion in a a lon g t h e e xt e n s or s u rfa ce of t h e u ln a (Fig. 9.8 ). Uln a r
h
R
pa tient with RA. Willia m J. Koopma n, La rry W. Morela nd, Arthritis a nd
n e rve e n t ra p m e n t a n d corre s p on d in g n e u rop a t h y ca n
c
Allied Conditions: A Textbook of Rheumatology, 15th ed. Philadelphia:
i
occu r w it h s ign i ca n t e lbow in volve m e n t .
c
Lippincott Willia ms & Wilkins, 2005.
e
p
S
3
SHOULDERS
N
O
Sh ou ld e rs a re com m on ly in volve d , w it h n oct u rn a l p a in be in g p a rt icu la rly t rou -
I
T
blin g, a s it is oft e n d if cu lt for p a t ie n t s w it h s h ou ld e r p roble m s t o n d a com -
C
E
fort a ble p os it ion for s le ep. Sw e llin g occu rs in it ia lly a n t e riorly bu t m ay be d if -
S
cu lt t o d e t e ct a n d is p re s e n t on e xa m in a t ion in a m in orit y of p a t ie n t s a t a n y
p oin t in t im e.
CERVICAL SPINE
Ne ck p a in on m ot ion a n d occip it a l h e a d a ch e a re com -
m o n m a n ife s t a t io n s o f ce r vica l s p in e in vo lve m e n t
a n d occu r in a p rop ort ion of p a t ie n t s w it h lon g-s t a n d -
in g d is e a s e . Th e a t la n t o a x ia l (C1–C2) jo in t is a s yn -
oviu m -lin e d join t a n d is s u s cep t ible t o t h e s a m e p ro-
life ra t ive s yn ovit is a n d s u bs e q u e n t in s t a bilit y t h a t a re
s e e n in t h e p e rip h e ra l join t s . Th e p os s ibilit y of s ign i -
ca n t C1–C2 in s t a bilit y s h o u ld b e co n s id e re d b e fo re a
Figure 9.10 Pa tient with RA a nd a la rge right knee effusion. From
Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions: A
p a t ie n t w it h RA u n d e rgo e s s u rgica l p ro ce d u re s t o
Textbook of Rheuma tology, 15th ed. Phila delphia : Lippincott Willia ms & a void com p ro m is e t o t h e ce r vica l cord or bra in s t e m
Wilkins, 2005. d u rin g in t u ba t ion or a s t h e p a t ie n t is t ra n s fe rre d w h ile
Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 85
s
e
a n t ibod y is s e e n a lm os t exclu s ive ly in RA. Oft e n re la t ive ly u n re m a rka ble e a rly in
s
• Pa t ie n t s w it h RA sh o u ld
a
t h e d is e a s e cou rs e, ra d iogra p h s of in volve d join t s m ay s h ow s oft t is s u e sw e llin g,
e
b e e va lu a t e d fo r ce rvica l
s
i
D
sp in e in vo lve m e n t p e ria rt icu la r os t e op e n ia , a n d p e ria rt icu la r e ros ion s w it h d is e a s e p rogre s s ion .
c
e sp e cia lly a s p a rt o f a n y Acu t e p h a s e re a ct a n t s (e ryt h rocyt e s e d im e n t a t ion ra t e a n d C-re a ct ive p rot e in )
i
t
a
p re o p e ra t ive a sse ssm e n t . a re e leva t e d in 50% of p a t ie n t s a t p re s e n t a t ion a n d m ay be va lu a ble in a s s e s s -
m
u
• Alt h o u g h u n co m m o n , in g re s p on s e t o t h e ra py. Ot h e r la bora t ory a bn orm a lit ie s m ay in clu d e a n e m ia of
e
h
crico a ryt e n o id jo in t ch ron ic d is e a s e a n d re a ct ive t h rom bocyt os is . Alt h ou gh n ot u n ive rs a lly e m p loye d ,
R
in vo lve m e n t m a y le a d t o
c
MRI a n d u lt ra s ou n d m ay be s e n s it ive in d e t e ct in g e a rly ch a n ge s in RA.
a irw a y o b st ru ct io n .
i
c
e
• RA is ch a ra ct e rize d b y a
p
Dia g no sis o f Rhe uma to id Arthritis
S
h ig h e r risk fo r m a lig n a n cy
3
in clu d in g lym p h o m a (n o n -
N
Ho d g kin ) a n d lu n g ca n ce r. Th e im p ort a n ce of m a kin g a n a ccu ra t e d ia gn os is of RA a s e a rly a s p os s ible ca n -
O
I
T
n ot be ove re m p h a s ize d . All m od e rn t re a t m e n t p a ra d igm s s t re s s e a rly a ggre s s ive
C
E
d is e a s e -m od ifyin g a n t irh e u m a t ic d ru g (DMARD) t h e ra py. It is crit ica l t o e n s u re
S
t h a t e ffe ct ive t re a t m e n t s a re begu n w h e n t h ey h ave t h e m a xim u m ch a n ce of
m a kin g t h e bigge s t d iffe re n ce s , w h ile a t t h e s a m e t im e p rot e ct in g p a t ie n t s w h o
d o n ot h ave RA from t h e p ot e n t ia l t oxicit ie s of u n n e ce s s a ry t h e ra p ie s .
Table 9.4 The 1987 Revised Crit eria for t he Classi cat ion of
Rheumat oid Art hrit is
CRITERION DEFINITION
1. Mo rn in g st iffn e ss Mo rn in g st iffn e ss in a n d a ro u n d t h e jo in t s la st in g
a t le a st 1 h o u r b e fo re m a xim a l im p ro ve m e n t
2. Art h rit is o f t h re e o r At le a st t h re e jo in t a re a s sim u lt a n e o u sly h a ve h a d
m o re jo in t a re a s so ft t issu e sw e llin g o r u id (n o t b o n y o ve rg ro w t h
a lo n e ) o b se rve d b y a p h ysicia n . Th e 14 p o ssib le
a re a s a re rig h t o r le ft PIP, MCP, w rist , e lb o w,
kn e e , a n kle , a n d MTP jo in t s
3. Art h rit is o f h a n d jo in t s At le a st o n e a re a sw o lle n (a s d e n e d a b o ve ) in a
w rist , MCP, o r PIP jo in t
4. Sym m e t ric a rt h rit is Sim u lt a n e o u s in vo lve m e n t o f t h e sa m e jo in t a re a s
(a s d e n e d in 2) o n b o t h sid e s o f t h e b o d y (b ila t -
e ra l in vo lve m e n t o f PIPs, MCPs, o r MTPs is a cce p t -
a b le w it h o u t a b so lu t e sym m e t ry)
s
e
5. Rh e u m a t o id n o d u le s Su b cu t a n e o u s n o d u le s, o ve r b o n y p ro m in e n ce s,
s
a
o r e xt e n so r su rfa ce s o r in ju xt a -a rt icu la r re g io n s,
e
o b se rve d b y a p h ysicia n
s
i
D
6. Se ru m rh e u m a t o id fa ct o r De m o n st ra t io n o f a b n o rm a l a m o u n t s o f se ru m
c
i
t
rh e u m a t o id fa ct o r b y a n y m e t h o d fo r w h ich t h e
a
m
re su lt h a s b e e n p o sit ive in 5% o f n o rm a l co n t ro l
u
su b je ct s
e
h
R
7. Ra d io g ra p h ic ch a n g e s Ra d io g ra p h ic ch a n g e s t yp ica l o f rh e u m a t o id
c
a rt h rit is o n p o st e ro a n t e rio r h a n d a n d w rist
i
c
ra d io g ra p h s, w h ich m u st in clu d e e ro sio n s o r
e
p
u n e q u ivo ca l b o n y d e ca lci ca t io n lo ca lize d in o r
S
m o st m a rke d a d ja ce n t t o t h e in vo lve d jo in t s
3
(o st e o a rt h rit is ch a n g e s a lo n e d o n o t q u a lify)
N
O
I
T
Fo r cla ssi ca t io n p u rp o se s, a p a t ie n t sh a ll b e sa id t o h a ve rh e u m a t o id a rt h rit is if h e /sh e h a s sa t is e d a t
C
E
le a st 4 o f t h e se 7 crit e ria . Crit e ria 1 t h ro u g h 4 m u st h a ve b e e n p re se n t fo r a t le a st 6 w e e ks. Pa t ie n t s w it h
S
t w o clin ica l d ia g n o se s a re n o t e xclu d e d . De sig n a t io n a s cla ssic, d e n it e , o r p ro b a b le rh e u m a t o id a rt h rit is
is n o t t o b e m a d e .
Ad a p t e d fro m Arn e t t e t a l. Th e Am e rica n Rh e u m a t ism Asso cia t io n 1987 Re vise d Crit e ria fo r t h e
Cla ssi ca t io n o f Rh e u m a t o id Art h rit is. A rt h rit is Rh e u m 1988 ;31 (3 ):315 –324 .
CRYSTALLINE ARTHROPATHIES
Pa t ie n t s w it h gou t d eve lop u ric a cid crys t a l d e p os it ion in t h e join t s a n d m ay
p re s e n t w it h s ym p t om s s im ila r t o RA. Cla s s ica lly, gou t p re s e n t s w it h p od a gra
(in a m m a t ion a n d p a in in t h e gre a t t oe ) or p a u cia rt icu la r join t sw e llin g w it h
e xq u is it e p a in . In con t ra s t t o RA, t h e re is a m a le p re p on d e ra n ce a n d t yp ica lly
m a le p a t ie n t s d eve lop s ym p t om s in t h e t h ird a n d fou rt h d e ca d e s of life (w it h
w om e n d eve lop in g in it ia l a re s m u ch la t e r, w e ll a ft e r m e n op a u s e ). High s e ru m
u ric a cid is s u gge s t ive bu t n ot d ia gn os t ic of gou t , h ow eve r, u ric a cid leve ls m a y
be n orm a l or eve n low d u rin g a cu t e gou t a t t a cks . De n it ive d ia gn os is is m a d e
t h ro u gh a s p ira t ion o f in t ra ce llu la r n ega t ive ly bire fr in ge n t u ric a cid crys t a ls
from t h e s yn ovia l u id , e xa m in e d u n d e r p ola rize d m icros cop y. In s e le ct ca s e s
ch ron ic gou t ca n p re s e n t in a “p s e u d o-rh e u m a t oid ” fa s h ion . Th u s , gou t s h ou ld
88 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
SLE
Pa t ie n t s w it h SLE m ay p re s e n t w it h p olya rt icu la r a rt h rit is a n d a rt h ra lgia s s im -
ila r t o RA w it h a s im ila r jo in t d is t rib u t io n . How eve r, p a t ie n t s w it h SLE fre -
S
E
q u e n t ly h a ve ot h e r d is e a s e m a n ife s t a t ion s in clu d in g s kin a n d in t e rn a l orga n
C
T
in volve m e n t . Th e p re s e n ce of p h ot os e n s it ive s kin ra s h , s e ros it is , re n a l d is e a s e,
I
O
or h e m a t ologic a bn orm a lit y (e.g., cyt op e n ia s ) in a p a t ie n t w it h in a m m a t ory
N
a rt h rit is is s u gge s t ive of SLE. Ad d it ion a lly, 95% of p a t ie n t s w it h SLE w ill h a ve
3
S
a p o s it ive a n t in u cle a r a n t ibod y (ANA) t it e r a s op p os e d t o 30% t o 40% of RA
p
e
p a t ie n t s . Th e p re s e n ce of a n t i-d ou ble s t ra n d e d DNA or a n t i-Sm it h a n t ibod y is
c
i
h igh ly s p e ci c t o SLE.
c
R
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e
u
SPONDYLOARTHROPATHIES
m
a
Th e s p o n d ylo a rt h ro p a t h ie s (re a ct ive a rt h rit is , p s o ria t ic a rt h rit is , a n d in a m -
t
i
c
m a t ory bow e l d is e a s e ) m ay a p p e a r s im ila r t o RA a t p re s e n t a t ion . Th e s p on d y-
D
i
s
loa rt h rop a t h ie s oft e n p re s e n t w it h in a m m a t ion fou n d a t e n t h e s is or s it e of
e
a
t e n d on in s e rt ion s (Ach ille s t e n d on in s e rt ion , p la n t a r fa s cia , s h a ft s of n ge rs or
s
e
t oe s ) kn ow n a s e n t h e s it is . As ym m e t ric oligoa rt h rit is (few e r t h a n fou r join t s ),
s
u s u a lly of t h e w e igh t -be a rin g join t s , is m ore com m on in t h e s e d is ord e rs t h a n
in RA. Th e p re s e n ce of con ju n ct ivit is /irit is , u re t h rit is , a n d m u cocu t a n e ou s or
in t e s t in a l m a n ife s t a t ion s in t h e s p on d yloa rt h rop a t h ie s a ls o d iffe re n t ia t e t h e s e
con d it ion s from RA. In a d d it ion , in a m m a t ory s ym p t om s of t h e a xia l s ke le t on
s t ron gly s u gge s t t h e d ia gn os is of on e of t h e s p on d yloa rt h rop a t h ie s , re cogn iz-
in g t h a t RA ca n a ffe ct t h e ce rvica l s p in e.
PALINDROMIC RHEUMATISM
Pa lin d rom ic rh e u m a t is m is a re m it t in g, re cu rrin g, n on d e s t ru ct ive, in a m m a -
t ory a rt h rit is w it h re cu rre n ce s ove r a t le a s t 6 m on t h s . At t a cks ra re ly la s t m ore
t h a n 1 w e e k a n d ge n e ra lly in volve on ly a few join t s , w it h t h e join t s u lt im a t e ly
in volve d be in g s im ila r t o t h os e in volve d in t yp ica l RA. Th e d is e a s e eve n t u a lly
evolve s in t o t yp ica l RA ove r t im e in on e q u a rt e r t o h a lf of t h e p a t ie n t s . Wom e n
w it h RF a n d /or a n t i-CCP a n t ibod y w it h e a rly h a n d in volve m e n t a re m ore like ly
t o d eve lop RA t h a n p a t ie n t s w it h ou t t h e s e fe a t u re s .
POLYMYALGIA RHEUMATICA
Polym ya lgia rh e u m a t ica (PMR) ge n e ra lly p re s e n t s w it h a n a bru p t t o s u ba cu t e
on s e t of p a in a n d s t iffn e s s in t h e s h ou ld e r a n d h ip gird le s of p a t ie n t s 50 ye a rs
of a ge. Feve r, w e igh t los s , a n d le t h a rgy ca n occu r a n d m ay be s eve re. Re s t rict ion
of s h ou ld e r m ove m e n t s e con d a ry t o p a in a n d s oft -t is s u e con t ra ct u re is com -
m o n . Th e s t iffn e s s a n d re s t rict e d m o b ilit y a re e x q u is it e ly s e n s it ive t o t re a t -
m e n t w it h m od e s t d os e p re d n is on e, w it h m a rke d clin ica l re s p on s e s t yp ica lly
obs e rve d w it h d os e s a s low a s 10 t o 15 m g/d a y. Pe rs is t e n t s m a ll join t s yn ovit is
of t h e h a n d s a n d fe e t d is t in gu is h e s RA from PMR, a lt h ou gh m orn in g s t iffn e s s
m ay ot h e rw is e be id e n t ica l. RA of a cu t e on s e t w it h PMR s ym p t om s in t h e e ld -
s
e
e rly oft e n h a s a n e xce lle n t p rogn os is .
s
a
e
s
i
D
VIRAL ARTHRITIS
c
i
t
Po lya r t h rit is m a y b e t h e p re s e n t in g fe a t u re o f vira l in fe ct io n s . Clu e s le a d in g
a
m
t o t h e e t iologic a ge n t m a y be evid e n t in t h e h is t o ry a n d e x a m in a t io n . In co n -
u
e
t ra s t t o RA, vira l a s s o cia t e d a r t h r it is is m o re o ft e n s e lf-lim it e d . Feve r a n d
h
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cu t a n e o u s m a n ife s t a t io n s m a y s u gge s t a n in fe ct io u s p ro ce s s . Vira l in fe ct io n s
c
t h a t ca n clos e ly m im ic RA in clu d e ru be lla , p a rvovir u s B19, a n d vira l h e p a t it is
i
c
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(p a r t icu la r ly h e p a t it is C w h ich ca n le a d t o ch ro n ic a rt h ra lgia s a n d low -t it e r
p
S
p os it ive RF).
3
N
O
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Tre a tme nt
T
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S
GOALS
Th e s t a t u s of t h e in d ivid u a l p a t ie n t a t a n y p oin t in t im e s h ou ld a lw a ys be
a s s e s s e d re la t ive t o t re a t m e n t goa ls . Sp e ci c t re a t m e n t goa ls a re w e ll a ccep t e d
a n d e a s y t o u n d e rs t a n d in s u ch con d it ion s a s h yp e rt e n s ion , h yp e rlip id e m ia , or
d ia be t e s . In RA, goa ls a re m ore d if cu lt t o q u a n t ify bu t n o le s s im p ort a n t . Wit h
im p rovin g t h e ra p ie s , re m is s ion is be com in g a m ore re a lis t ic, a lt h ou gh s t ill e lu -
s ive, goa l. No on e s in gle m e a s u re a d e q u a t e ly d e s cribe s t h e s t a t u s of a p a t ie n t
w it h RA. Ra t h e r, com bin a t ion s of a bn orm a lit ie s d e t e ct e d by la bora t ory t e s t in g,
p h ys ica l e x a m in a t io n , ra d iologic e xa m in a t ion , a n d a s s e s s m e n t of p a in a n d
fu n ct ion a l s t a t u s a re u s e d .
Th e Am e rica n College of Rh e u m a t ology (ACR) h a s re com m e n d e d a core s e t
o f com p o s it e cr it e r ia (Ta ble 9.5 ) fo r t h e o n go in g eva lu a t io n o f t h e ra p ie s in
p a t ie n t s w it h RA. Th e com p on e n t s of t h is core s e t a re e xce lle n t p a ra m e t e rs t o
follow in in d ivid u a l p a t ie n t s in clin ica l p ra ct ice, a s w e ll a s in clin ica l re s e a rch
s it u a t ion s . Fre q u e n t ly u s e d com p os it e m e a s u re s of d is e a s e a ct ivit y in clu d e t h e
Dis e a s e Act ivit y Score (DAS), t h e Rou t in e As s e s s m e n t of Pa t ie n t In d e x Da t a 3
(RAPID-3), a n d t h e Clin ica l Dis e a s e Act ivit y In d e x (CDAI). Th e la t t e r m e a s u re s
ca n be ca lcu la t e d in “re a l-t im e ” w it h s u gge s t e d t h re s h old s d e n e d corre s p on d -
in g t o low d is e a s e a ct ivit y a n d re m is s ion .
Me dica tio ns
Th e re a re fou r m a in cla s s e s of m e d ica t ion s u s e d in t h e t re a t m e n t of RA: n on -
s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs ), cort icos t e roid s , s yn t h e t ic DMARDs ,
90 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
SYNTHETIC DMARDs
Give n t h e lo n g-t e r m go a l o f s u p p r e s s io n o f in a m m a t io n in RA, s yn t h e t ic
DMARDs h a ve b e co m e a co r n e r s t o n e o f t h e ra p y. Me t h o t r e x a t e in p a r t icu la r
h a s d e m o n s t ra t e d u t ilit y in p re ve n t in g d is e a s e p r o gre s s io n a s w e ll a s re d u c-
in g m o r t a lit y in RA p a t ie n t s (7 ). W it h a n e s t a blis h e d t ra ck re co rd , a cce p t a ble
r is k o f t o x icit y, a n d low co s t , m e t h o t re x a t e n ow co n s t it u t e s r s t -lin e t h e r-
a p y fo r RA in t h e a b s e n ce o f co n t ra in d ica t io n s t o it s u s e . Ot h e r s yn t h e t ic
DMARDs in c lu d e le u n o m id e , s u lfa s a la z in e , m in o cy c lin e , a z a t h io p r in e ,
cyclo s p o r in e , a n d h yd r o x ych lo r o q u in e . In 2008 t h e ACR is s u e d re co m m e n -
d a t io n s fo r t h e u s e o f s yn t h e t ic DMARDs in RA p a t ie n t s w h o h a d n o t p re vi-
o u s ly r e c e ive d DMARDs b a s e d o n d is e a s e d u r a t io n a n d a c t iv it y ( 8 ). Ea ch
m e d ic a t io n h a s u n iq u e s id e e ffe c t p r o le s a n d m o n it o r in g r e q u ir e m e n t s
(Ta ble 9.6 ). Syn t h e t ic DMARDs a re fre q u e n t ly u s e d in co m b in a t io n a s w e ll a s
co n co m it a n t ly w it h t h e b io lo gic DMARDs t o a ch ieve o p t im a l co n t ro l o f RA
d is e a s e a ct ivit y.
T a b l e 9 . 6 G u i d e l i n e s f o r M o n i t o r i n g t h e T r e a t m e n t o f R h e u m a t o i d A r t h r i t i s
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t r a t e g i e s f o r R h e u m a t o i d A r t h r i t i s . N E n g l J M e d 2 0 0 4 ; 3 5 0 :
( 2 ) :5 9 1 – 6 0 2 .
91
92 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
BIOLOGIC DMARDs
Biologic DMARDs rep re s e n t a re la t ive ly n ew cla s s of a ge n t s d e s ign e d t o in h ibit
t h e in a m m a t ory p roce s s by s e le ct ive ly t a rge t in g cyt okin e s a n d ot h e r ce llu la r
liga n d s . Th e re a re cu rre n t ly n in e biologic DMARDs a p p rove d in t h e t re a t m e n t
of RA. Sim ila r t o s yn t h e t ic DMARDs , t h e ACR h a s is s u e d re com m e n d a t ion s for
t h e u s e of biologic DMARDs in clu d in g e t a n e rcep t , in ixim a b, a d a lim u m a b, a n a -
kin ra , a ba t a cep t , a n d rit u xim a b (8 ). Biologic a ge n t s a re t yp ica lly e m p loye d a s
s e con d -lin e t h e ra py a n d a re oft e n u s e d in con ju n ct ion w it h a s yn t h e t ic DMARD,
p a rt icu la rly m e t h ot re xa t e. Us e of m u lt ip le biologics con cu rre n t ly is n ot re com -
m e n d e d d u e t o h igh e r ra t e s o f a d ve rs e eve n t s , p a rt icu la rly s e rio u s in fe ct io n
a n d la ck of a d d it ive e ffe ct . In cre a s e d ris k of s e riou s in fe ct ion s is a con ce rn w it h
t h e u s e of biologic DMARDs , a n d s cre e n in g for la t e n t t u be rcu los is p rior t o in i-
t ia t ion of t re a t m e n t is re com m e n d e d . Th e biologic DMARDs s h ou ld be a d m in -
is t e re d u n d e r t h e d ire ct ion of a rh e u m a t ologis t .
ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )•
cryst als (se e also Go u t )
275.49 [712.1] d icalciu m p h o sp h at e •
275.49 [712.2] p yro p h o sp h at e •
275.49 [712.8] sp e ci e d NEC•
079.99 [711.5] d u e t o o r asso ciat e d w it h viral d ise ase NEC•
274.00 g o u t y
274.01 acu t e
s
e
s
714.30 ju ve n ile rh e u m at o id (ch ro n ic) (p o lyart icu lar)
a
e
714.31 acu t e
s
i
D
714.33 m o n o art icu lar
c
i
714.32 p au ciart icu lar
t
a
m
714.4 p o st rh e u m at ic, ch ro n ic (Jacco u d ’s)
u
696.0 p so riat ic
e
h
R
714.0 rh e u m at ic
c
acu t e o r su b acu t e – se e Fe ve r, rh e u m at ic
i
c
714.0 ch ro n ic
e
p
720.9 sp in e
S
3
714.0 rh e u m at o id (n o d u lar)
N
714.1 w it h sp le n o ad e n o m e g aly an d le u k o p e n ia
O
I
714.2 visce ral o r syst e m ic in vo lve m e n t
T
C
714.30 ju ve n ile (ch ro n ic) (p o lyart icu lar)
E
S
714.31 acu t e
714.33 m o n o art icu lar
714.32 p au ciart icu lar
716.9 Arthro pathy
136.1 [711.2]Be h çe t ’s •
714.4 p o st rh e u m at ic, ch ro n ic (Jacco u d ’s)
729.0 Fibro sitis (p e riart icu lar) (rh e u m at o id )
274.9 Go ut , g o u t y
274.00 art h rit is
274.01 acu t e
274.00 art h ro p at h y
274.01 acu t e
274.02 ch ro n ic (w it h o u t m e n t io n o f t o p h u s (t o p h i))
274.03 w it h t o p h u s (t o p h i)
274.03 t o p h i
274.81 e ar
274.82 sp e ci e d sit e NEC
710.0 Lupus
695.4 e ryt h e m at o su s (d isco id ) (lo cal)
710.0 d isse m in at e d
710.0 syst e m ic
719.3 Palindro mic, arthritis •
725 Po lymyalg ia
725 rh e u m at ica
94 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Re fe re nce s
1. Ga brie l SE, Crow s on CS , O’Fa llon W M . Th e ep id e m iology of rh e u m a t oid a rt h rit is in Roch e s t e r, Min n e -
s ot a , 1955–1985 . A rthritis Rheum . 1999 ;42 (3 ):415 –420 .
2. Wa lit t B, Pe t t in ge r M , We in s t e in A, e t a l. Effe ct s of p os t m e n op a u s a l h orm on e t h e ra p y on rh e u m a t oid
a rt h rit is : t h e w om e n ’s h e a lt h in it ia t ive ra n d om ize d con t rolle d t ria ls . A rthritis Rheum . 2008 ;59 (3 ):302 –310 .
3. Tu re s s o n C, O’Fa llon W M , Crow s on CS, e t a l . Ext ra -a r t icu la r d is e a s e m a n ife s t a t ion s in r h e u m a t o id
a rt h rit is : in cid e n ce t re n d s a n d ris k fa ct o rs ove r 46 ye a rs . A nn Rheum Dis . 2003 ;62 (8 ):722 –727 .
4. Th e a n d e r E, Ja cobs s on LT. Re la t ion s h ip of Sjogre n ’s s yn d rom e t o ot h e r con n e ct ive t is s u e a n d a u t oim -
m u n e d is ord e rs . Rheum Dis Clin North A m . 2008 ;34 (4 ):935 –47, viii–ix . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/
q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe d &d o p t =Cit a t ion &lis t _u id s =18984413.
5. O’De ll JR. Th e ra p e u t ic s t ra t egie s for rh e u m a t oid a rt h rit is . N Engl J Med . 2004 ;350 (25 ):2591 –2602 . h t t p ://
w w w.n cbi.n lm .n ih .gov/e n t rez/q u e ry.fcgi?cm d =Re t rieve&d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s=15201416.
6. Wolfe F, Ca p la n L, Mich a u d K. Tre a t m e n t for rh e u m a t oid a rt h r it is a n d t h e ris k o f h os p it a liza t io n fo r
p n e u m on ia : a s s ocia t io n s w it h p re d n is on e, d is e a s e -m o d ifyin g a n t ir h e u m a t ic d r u gs , a n d a n t i-t u m o r
n e cros is fa ct o r t h e ra p y. A rthritis Rheum . 2006 ;54 (2 ):628 –634 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.
fcgi?cm d =Re t rieve &d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s =16447241.
7. Ch oi HK, He rn a n MA, Se ege r JD, e t a l . Me t h ot re xa t e a n d m ort a lit y in p a t ie n t s w it h rh e u m a t oid a rt h rit is :
a p ros p e ct ive s t u d y. Lancet . 2002 ;359 (9313 ):1173 –1177 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.fcgi?c
m d =Re t rieve &d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s =11955534.
8. Sa a g KG, Te n g GG, Pa t ka r NM , e t a l. Am e rica n College of Rh e u m a t ology 2008 re com m e n d a t ion s for t h e
u s e of n on biologic a n d biologic d is e a s e -m od ifyin g a n t irh e u m a t ic d ru gs in rh e u m a t oid a rt h rit is . A rthri-
tis Rheum . 2008 ;59 (6 ):762 –784 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe
d &d op t =Cit a t ion &lis t _u id s =18512708.
S
E
9. Sokka T. Lon g-t e rm ou t com e s of rh e u m a t oid a rt h rit is . Curr Opin Rheum atol. 2009 ;21 (3 ):284 –290 . h t t p ://
C
w w w.n cbi.n lm .n ih .gov/en t rez/q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s =19342954.
T
I
10. Pin cu s T, Sokka T, Ka u t ia in e n H . Pa t ie n t s s e e n for s t a n d a rd rh e u m a t oid a rt h rit is ca re h ave s ign i ca n t ly
O
N
be t t e r a rt icu la r, ra d iogra p h ic, la bo ra t ory, a n d fu n ct ion a l s t a t u s in 2000 t h a n in 1985 . A rthritis Rheum .
2005 ;52 (4 ):1009 –1019 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe d &d o p t
3
=Cit a t ion &lis t _u id s =15818706.
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CHAPTER
10 The Seronega tive
Spondyloa rthropa thies
Dennis W . Boulw are
A 22-ye ar-o ld m an
Clinica l
Pre se nta tio n
s
p re se n t s w it h a
e
s
a
3-m o n t h h ist o ry o f For m a n y ye a rs t h e s e ron ega t ive
e
s
s p o n d y lo a r t h r o p a t h ie s w e r e
i
D
lo w b ack st iff n e ss
co n fu s e d u n d e r s t a n d a bly w it h
c
i
t
w h e n h e rst arise s r h e u m a t o id a r t h r it is d u e t o
a
m
in t h e m o rn in g . co m m o n fe a t u re s o f s ign i ca n t
u
e
m o r n in g ge l a n d in a m m a t o ry
h
He n d s t h at ch an g -
R
p e r ip h e ra l a r t h r it is . Th is le d t o
c
in g h is e xe rcise
co n fu s io n in t e r m in o lo gy w it h
i
c
h ab it s an d g o in g
e
n a m e s s u ch a s r h e u m a t o id
p
S
t o t h e g ym e arly in s p o n d y lit is , r h e u m a t o id va r i-
3
a n t s , a n d s o o n . W it h b e t t e r
N
t h e m o rn in g h e lp s
O
u n d e rs t a n d in g of t h e h is t ocom -
I
re d u ce t h e d u rat io n
T
p a t ibilit y ge n e s , t h ou gh , t h ey a re
C
E
o f st iff n e ss. His f at h e r an d p at e rn al g ran d f at h e r h ave e xp e rie n ce d kn ow n n ow t o be a clin ica lly a n d
S
a lif e t im e o f b ack p ro b le m s w it h xe d st o o p e d p o st u re s an d h e is e t io lo gica lly d is t in ct clu s t e r o f
co n ce rn e d h e w ill h ave a sim ilar o u t co m e . d is e a s e s w it h s h a re d co m m o n
fe a t u re s a n d clin ica l ch a ra ct e ris -
t ics t h a t d is t in gu is h t h e m fro m
e a ch ot h e r. Th is ch a p t e r d is cu s s e s t h e fou r m a in t yp e s of s e ron ega t ive s p on d y-
loa rt h rop a t h ie s : a n kylos in g s p on d ylit is , re a ct ive a rt h rit is or Re it e r’s d is e a s e,
p s or ia t ic a rt h r it is , a n d e n t e ro p a t h ic a r t h rit is a s s o cia t e d w it h in a m m a t o ry
bow e l d is e a s e (IBD). As a grou p , t h ey a re rh e u m a t oid fa ct or n ega t ive, h e n ce t h e
n a m e s e ro n ega t ive, a n d h a ve ra d iogra p h ic a n d / or clin ica l s a cro iliit is , t yp ica l
ve rt e bra l a bn orm a lit ie s , in a m m a t ory p e rip h e ra l a rt h rit is , e n t h e s op a t h y, u ve a l
t ra ct in volve m e n t , fa m ilia l clu s t e rin g, a n d t h e fre q u e n t p re s e n ce of h u m a n le u -
kocyt e a n t ige n B27 (HLA-B27).
All of t h e s e con d it ion s a re a form of a n in a m m a t ory a rt h rit is a n d s ign i -
ca n t m orn in g ge l p h e n om e n on is e xp e ct e d d u rin g t im e s of a ct ive in a m m a -
t io n . St iffn e s s re q u ir in g ove r a n h ou r t o re s o lve a ft e r p ro lo n ge d p e r io d s of
in a ct ivit y, s u ch a s im m e d ia t e ly a ft e r a w a ke n in g in t h e m orn in g, is a com m on
fe a t u re a n d t h e d u ra t io n re q u ire d fo r re s o lu t io n o ft e n co r re la t e s w it h t h e
s eve rit y of t h e con d it ion . Morn in g ge l or m orn in g s t iffn e s s is a com m on fe a -
t u re w it h a ll in a m m a t o ry a rt h r it id e s a n d like ly le d t o t h e e a rly con fu s ion
w it h rh e u m a t o id a rt h rit is . Sim ila rly, a ct ivit y h e lp s t o im p rove t h e s e n s a t io n of
s t iffn e s s a n d p a t ie n t s w it h a n y in a m m a t o ry a rt h r it is w ill re p o rt im p rove -
m e n t w it h a ct ivit y a s o p p o s e d t o w o r s e n in g w it h a ct ivit y, a s is co m m o n in
m e ch a n ica l d is o rd e r s a n d o s t e o a r t h r it is . Th e p a t t e r n o f p e r ip h e ra l jo in t
95
96 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Re a ctive Arthritis
Alt h ou gh com m on ly a s s ocia t e d w it h Re it e r’s s yn d rom e a n d t h e cla s s ic t ria d of
a rt h rit is , u re t h rit is , a n d u ve it is , re a ct ive a rt h rit is in clu d e s m a n y m ore e xt ra -
a r t icu la r m a n ife s t a t io n s t h a n t h e cla s s ic t r ia d , e s p e cia lly in vo lvin g t h e
s kin a n d t h e m u cos a l m e m bra n e s . Th e a rt h rit is is u s u a lly a n a cu t e, a d d it ive,
a n d a s ym m e t ric on e w it h e n t h e s it is a n d /or a xia l a rt h rit is com m on ly s e e n a n d
co m b in e d w it h k e ra t o d e r m a ble n o r rh a gicu m , d ia rrh e a , ce rvicit is , u re t h rit is ,
co n ju n ct ivit is , p a in le s s o ra l u lce r s , a n d / o r circin a t e b a la n it is . Id e n t ifyin g a
p rior re ce n t in fe ct iou s eve n t is n ot a lw a ys p o s s ible , bu t re a ct ive a rt h rit is is
kn ow n t o occu r a ft e r d ys e n t e ric t yp e illn e s s or ge n it ou rin a ry in fe ct ion s . Typ i-
ca lly, re a ct ive a rt h rit is fo llow s t h e in fe ct io n w it h in 1 t o 4 w e e k s , w it h feve r
be in g com m on a n d a rt h rit is be in g t h e la s t clin ica l fe a t u re t o p re s e n t . Re a ct ive
a rt h r it is is t h e m os t com m o n m u s cu los ke le t a l con d it ion s e e n in a ct ive HIV
in fe ct ion a n d HIV s h ou ld be con s id e re d in a n y n ew d ia gn os is of re a ct ive a rt h ri-
t is , or w ors e n in g re a ct ive a rt h rit is . Fin a lly, re a ct ive a rt h rit is is re p ort e d t o occu r
a ft e r t re a t m e n t of in fe ct ion s or im m u n iza t ion .
s
e
s
Pso ria tic Arthritis
a
e
s
i
D
Ps oria s is is a ch ron ic a u t oim m u n e s kin con d it ion t h a t h a s a h igh e r p reva le n ce
c
i
of a coe xis t in g ch ron ic in a m m a t ory a rt h rit is t h a n is s e e n in t h e ge n e ra l p op u -
t
a
m
la t ion . Th e s kin d is e a s e u s u a lly p re d a t e s t h e on s e t of a rt h rit is , a lt h ou gh t h e
u
con ve rs e re la t ion s h ip is s e e n a n d t h e con cu rre n t on s e t of p s oria s is a n d a rt h ri-
e
h
R
t is is t h e le a s t com m on m od e of p re s e n t a t ion . Th e p a t t e rn of join t in volve m e n t
c
is va ria ble bu t t yp ica lly follow s ve d iffe re n t p a t t e rn s : s ym m e t ric p olya rt h rit is ,
i
c
d is t a l in t e rp h a la n ge a l join t in volve m e n t , oligoa rt h rit is , a rt h rit is m u t ila n s , a n d
e
p
a xia l in volve m e n t .
S
3
N
O
Ente ro pa thic Arthritis Asso cia te d w ith
I
T
C
Infla mma to ry Bo w e l Dise a se
E
S
Th e in clu s ion o f IBD in t h is grou p o f d is e a s e s e m p h a s ize s t h e re la t ion s h ip
be t w e e n gu t in a m m a t ion a n d join t in a m m a t ion . Ot h e r ga s t roin t e s t in a l con -
d it ion s , s u ch a s ce lia c d is e a s e, a n d in t e s t in a l byp a s s s u rge ry a re occa s ion a lly
a ccom p a n ie d by join t in a m m a t ion , bu t t h e s e a re n ot con s id e re d a s s p on d y-
loa rt h rop a t h ie s . Croh n ’s d is e a s e a n d u lce ra t ive colit is a re d is cu s s e d t oge t h e r
s in ce t h e m u s cu los ke le t a l a n d ga s t roin t e s t in a l fe a t u re s ca n n ot be e a s ily d if-
fe re n t ia t e d . Mu s cu los ke le t a l is s u e s a re t h e m os t com m on e xt ra in t e s t in a l m a n -
ife s t a t ion s of IBD a n d a p p e a r in 2% t o 20% of p a t ie n t s w it h e it h e r u lce ra t ive
co lit is o r Cro h n ’s d is e a s e, w it h p e rip h e ra l a r t h rit is s e e n m o re fre q u e n t ly in
p a t ie n t s w it h colon ic in volve m e n t a n d m ore e xt e n s ive bow e l d is e a s e. Th e fre -
q u e n cy of p e rip h e ra l a rt h rit is in IBD ra n ge s u p t o 20% of p a t ie n t s , w it h a h igh e r
p reva le n ce in Croh n ’s d is e a s e. In bot h Croh n ’s d is e a s e a n d u lce ra t ive colit is ,
t h e a rt h r it is ge n e ra lly is p a u cia rt icu la r, a s ym m e t ric, fre q u e n t ly t ra n s ie n t or
m igra t o ry, a n d t yp ica lly n o n d e s t r u ct ive w it h co m m o n re cu r re n ce s . In fre -
q u e n t ly, t h e p e rip h e ra l a rt h rit is be com e s ch ron ic a n d d e s t ru ct ive. En t h e s op a -
t h ie s ca n ca u s e s a u s a ge d igit d e form it ie s , Ach ille s t e n d in it is , a n d p la n t a r fa s -
ciit is . Axia l in volve m e n t in volvin g t h e s a croilia c join t s or s p in e occu rs in bot h
d is e a s e s w it h p reva le n ce ra t e s of 10% t o 20% for s a croiliit is a n d 7% t o 12% for
s p on d ylit is re p ort e d , a lt h ou gh t h e a ct u a l gu re s a re p roba bly h igh e r be ca u s e of
t h e e xis t e n ce of s u bclin ica l a xia l in volve m e n t .
In m os t ca s e s of Croh n ’s d is e a s e, in t e s t in a l s ym p t om s a n t e d a t e or coin cid e
w it h t h e jo in t m a n ife s t a t io n s , w it h t h e a r t icu la r s ym p t o m s p re ce d in g t h e
in t e s t in a l s ym p t om s by ye a rs . In u lce ra t ive colit is , t h e re is a m ore d is t in ct t e m -
p ora l re la t ion s h ip be t w e e n a t t a cks of a rt h rit is a n d a re s of bow e l d is e a s e.
98 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Figure 10 .1 Exa miner a ttempting to pa lpa te directly the sa croilia c joints, Figure 10 .2 Testing for sa croiliitis by a nterior loa ding of pelvis, with weight
which lie inferior to the posterior superior ilia c spines. The sa cra l dimples on the a nterior superior ilia c spines of the pelvis.
ma rk the posterior superior ilia c spine, which is the superior end of the
sa croilia c joint.
Ch a p te r 10 Th e Se ron ega t ive Sp on d yloa rt h rop a t h ie s 99
s
e
Sp in a l in vo lve m e n t t yp ica lly s t a r t s in t h e lu m b a r
s
a
re gio n a n d a s ce n d s u p t h e s p in e . Lo s s o f lu m b a r e x -
e
s
i
io n is a n e a r ly eve n t a n d ca n b e d e t e ct e d by u s e o f
D
c
t h e m o d i e d Sch ö b e r ’s t e s t (Fig. 10.6A, B). W it h t h e
i
t
a
p a t ie n t s t a n d in g e re ct , t h e clin icia n w ill p la ce o n e
m
m a r k b e t w e e n t h e p o s t e r io r s u p e r io r ilia c s p in e s a n d
u
e
u s e a t a p e m e a s u re , p la cin g t h e 0 e n d 10 cm a b ove
h
R
t h e o r igin a l m a r k . Th e clin icia n w ill h o ld t h e 0 e n d o f
c
i
t h e t a p e m e a s u r e in p la ce a n d a s k t h e p a t ie n t t o
c
e
b e n d fo r w a rd a t t e m p t in g t o t o u ch t h e ir t o e s a n d fu lly
p
S
e x in g t h e lu m b a r s p in e . Th e clin icia n w ill m e a s u re
3
t h e d is t a n ce o f d is p la ce m e n t w h e n t h e lu m b a r s p in e
N
O
is fu lly e x e d fro m t h e 0 e n d o f t h e t a p e m e a s u re t o
I
T
C
t h e o r igin a l m a r k b e t w e e n t h e p o s t e r io r s u p e r io r
E
S
ilia c s p in e s . A n o r m a l lu m b a r s p in e w ill in cre a s e t h e
d is t a n ce fro m 10 t o a t le a s t 15 cm . Ex a m in a t io n o f
t h e t h o ra cic a n d ce r vica l s p in e s h o u ld a ls o b e p e r-
fo r m e d w it h p a r t icu la r e m p h a s is fo r lim it e d m o t io n
Figure 10 .4 Testing for sa croiliitis using Ga enslen’s ma neuver pla cing
leg in hypertension a nd loa ding the pelvis by torque. in ch e s t e x cu r s io n by m e a s u r in g ch e s t circu m fe re n ce
b e t w e e n fu ll in s p ira t io n a n d e x p ira t io n . Fle x io n co n -
t ra ct u r e s o f t h e ce r vica l s p in e ca n b e d e t e ct e d by
m e a s u r in g t h e ce r vica l e ch e o r d is t a n ce fro m t h e
o ccip u t t o t h e w a ll w h e n t h e p a t ie n t s t a n d s w it h
t h e ir b a ck t o t h e w a ll w it h t h e ir h e e ls , k n e e s , b u t -
t o ck , a n d s h o u ld e r s p re s s e d a ga in s t t h e w a ll. A n o r-
m a l ce r vica l e ch e is 0 cm .
An e x a m in a t io n fo r e x t ra -a r t icu la r m a n ife s t a -
t ion s , p a rt icu la rly of t h e s kin a n d m u cou s m e m bra n e s
is e s s e n t ia l. Th e p e rip h e ra l a n d a xia l a rt icu la r in volve -
m e n t w ill n ot d iffe re n t ia t e be t w e e n t h e s e ron ega t ive
s p o n d y lo a r t h r o p a t h ie s a n d o n ly t h e p r e s e n ce o r
a b s e n ce o f t h e e x t ra -a r t icu la r fe a t u re s w ill h e lp in
id e n t ifyin g t h e corre ct d ia gn os is .
Studie s
Th e la b o ra t o r y is o f lit t le h e lp in e va lu a t in g t h e
Figure 10 .5 Testing for sa croiliitis using Pa trick’s test a nd loa ding the p a t ie n t w it h a s u s p e ct e d s e r o n e ga t ive s p o n d ylo a r-
pelvis by torque. t h ro p a t h y e x ce p t t o con r m t h e p re s e n ce o f s ys t e m ic
100 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
S
E
C
T
I
O
N
A B
3
S
p
e
Figure 10 .6 A. Sta rt of the modi ed Schöber’s test mea suring 10 cm a bove the midline between the sa cra l dimples or posterior superior
c
i
ilia c spine with the pa tient erect. B. End of the modi ed Schöber’s test mea suring the a dditiona l dista nce a bove the midline between the
c
sa cra l dimples or posterior superior ilia c spine with the pa tient ma xima lly exed a ttempting to touch their toes.
R
h
e
u
m
a
in a m m a t io n t h ro u gh a n a b n o r m a l C-re a ct ive p ro t e in o r e ryt h ro cyt e s e d i-
t
i
c
m e n t a t io n ra t e . Th e u s e o f HLA-B27 is d e b a t a ble a s it is n o t a lw a ys fo u n d in
D
t h e s e ro n e ga t ive s p o n d ylo a r t h rop a t h ie s a n d ca n b e fou n d in ce r t a in p o p u la -
i
s
e
t io n s w it h o u t a n in a m m a t o ry a r t h r o p a t h y. Sin ce low b a ck p a in is a ve ry
a
s
e
co m m o n a ilm e n t , t h e p re s e n ce o f HLA-B27 ca n re s u lt in e r ro n e o u s d ia gn o s e s
s
o f a s e ron e ga t ive s p on d ylo a r t h ro p a t h y.
Im a gin g s t u d ie s ca n be h e lp fu l in s eve ra l of t h e s e ron ega t ive s p on d yloa r-
t h rop a t h ie s . In s u s p e ct e d s a croiliit is , p la in x-ra y w ill id e n t ify s a cro iliit is or
s p o n d ylit is w it h m o re p re cis io n t h a n p h ys ica l e x a m in a t io n . In a n kylo s in g
s p o n d ylit is , t h e s a cro ilia c in vo lve m e n t is bila t e ra l a n d s t a rt s e a rly w it h e ro -
s ion s a lon g t h e s a croilia c join t , follow e d la t e r by s cle ros is a n d eve n t u a l fu s ion .
In p s oria t ic a rt h rit is , re a ct ive a rt h rit is , a n d e n t e rop a t h ic a rt h rit is , t h e s a croilia c
in volve m e n t ca n be u n ila t e ra l a n d in volve m ore e xu be ra n t s cle ros is t h a n s e e n
NOT TO BE MISSED in a n kylos in g s p on d ylit is . W h e n t h e re is s p in a l in volve m e n t , s yn d e s m op h yt e s
w ill be s e e n a n d t e n d t o be m ore e xu be ra n t a n d p rolife ra t ive in p s oria t ic a rt h ri-
• Pso ria sis t is a n d re a ct ive a rt h rit is a s op p os e d t o a n kylos in g s p on d ylit is . Ea rly s yn d e s m o-
• En t h e sit is p h yt e s com m on ly occu r in t h e t h o ra colu m ba r a re a a n d a re be s t view e d o n
• Ke ra t o d e rm a la t e ra l view s a s ca lci ca t ion of t h e a n n u lu s bros is or a n t e rior lon git u d in a l
b le n o rrh a g icu m liga m e n t s h ow s rs t on t h is view.
Ra d iogra p h ic a p p e a ra n ce of p e rip h e ra l join t s is s im ila r t o t h a t of rh e u m a -
• Circin a t e b a la n it is
t oid a rt h rit is e xcep t in t h e ca s e of p s oria t ic a rt h rit is , w h ich ca u s e s a n e ros ive
• Uve it is o r a n t e rio r irit is p a t t e rn t h a t cre a t e s a p e n cil-in -cu p a p p e a ra n ce of t h e join t . In t h e s e ca s e s , t h e
• Mu co u s m e m b ra n e p roxim a l com p on e n t of t h e join t is w h it t le d t o a p oin t a n d t h e d is t a l con ve x
in vo lve m e n t w it h o ra l s u rfa ce broa d e n s t o t a ke on t h e a p p e a ra n ce of a cu p .
u lce rs, re ct a l u lce rs, a n d
so o n
• In a m m a t o ry b o w e l Tre a tme nt
d ise a se , b o t h u lce ra t ive
co lit is a n d Cro h n ’s d ise a se Th e m a jor a im s of m a n a ge m e n t in clu d e p a t ie n t e d u ca t ion rega rd in g t h e n a tu ra l
h is t ory of t h e con d it ion , rea s on a ble rea s su ra n ce of t h e p a t ien t’s exp ecta t ion s , t h e
Ch a p te r 10 Th e Se ron ega t ive Sp on d yloa rt h rop a t h ie s 101
Clinica l Co urse
Th e clin ica l cou rs e for t h e s e ron ega t ive s p on d yloa rt h rop a t h ie s va rie s con s id e r-
s
e
a bly for e a ch con d it ion a n d w it h in e a ch con d it ion . In a n kylos in g s p on d ylit is ,
s
a
s a croiliit is is s e e n in virt u a lly a ll ca s e s , bu t p e rip h e ra l a rt h rit is is le s s com m on .
e
s
i
An kylos in g s p on d ylit is is m ore com m on in you n g m e n w h o h a ve t yp ica l low
D
c
ba ck p a in a n d s t iffn e s s , bu t w h e n it occu rs in w om e n a n d ch ild re n , t h ey ca n
i
t
a
h a ve a n a t yp ica l p re s e n t a t ion w it h m ore p e rip h e ra l a rt h rit is , e n t h e s it is , a n d
m
ce rvica l in volve m e n t . Th e p rogn os is in a n kylos in g s p on d ylit is is good in m os t
u
e
p a t ie n t s w h e re on ly 10% be com e s ign i ca n t ly d is a ble d a n d 90% a re a ble t o
h
R
p u rs u e fu ll-t im e e m p loym e n t . A p re d ict a ble p a t t e rn of d is e a s e u s u a lly e m e rge s
c
i
a ft e r t h e rs t 10 ye a rs w it h d e s t ru ct ive h ip in volve m e n t be in g a n in d ica t or of a
c
e
p oor fu n ct ion a l ou t com e.
p
S
In re a ct ive a rt h rit is , t h e p rogn os is a n d cou rs e of in d ivid u a l p a t ie n t s w it h
3
N
Re it e r s yn d ro m e a re va r ie d a n d u n p re d ict a ble , re ga rd le s s o f w h e t h e r t h ey
O
p re s e n t w it h t h e cla s s ic t ria d , ACR cr it e r ia , o r in com p le t e Re it e r s yn d ro m e .
I
T
C
Mo s t p a t ie n t s d e m on s t ra t e a n in it ia l e p is o d e o f a cu t e a rt h rit is w it h a m e a n
E
S
d u ra t io n of 2 t o 3 m on t h s , bu t w h ich m a y la s t u p t o a ye a r. Som e p a t ie n t s
d eve lop re cu rre n t a t t a cks w it h d is e a s e -fre e in t e rva ls . A m in orit y of p a t ie n t s
d e m on s t ra t e s a ch ron ic cou rs e of p e rip h e ra l a rt h rit is a n d t h ey h a ve a gre a t e r
p ot e n t ia l for p rogre s s ive s p on d ylit is . Pre d ict in g w h ich p a t ie n t s w ill d eve lop
re cu rre n t a t t a cks or ch ron ic re a ct ive a rt h rit is is d if cu lt a n d in e xa ct . Fa ct ors
t h a t m ay p re d ict a p oore r or m ore ch ron ic ou t com e in clu d e h ip a rt h rit is , ESR
30 m m /h ou r, p oor re s p on s e t o NSAIDs , lu m ba r s p in e in volve m e n t , s a u s a ge
d igit s , a n d /o r a n on s e t b e fore 16 ye a r s of a ge . Ye t d e s p it e t h e p ot e n t ia l fo r
ch ron ic d is e a s e, s t u d ie s h ave s h ow n t h a t p a t ie n t s w it h re a ct ive a rt h rit is t yp i-
ca lly m a in t a in a h igh e r leve l of con t in u e d e m p loym e n t t h a n in d ivid u a ls w it h
o t h e r in a m m a t o ry a r t h r it id e s . Seve re d is a b ilit y is u n co m m o n a n d is fre -
q u e n t ly s e co n d a ry t o a ggre s s ive , d e s t r u ct ive low e r-e x t re m it y in vo lve m e n t ,
a ggre s s ive a xia l in volve m e n t , or blin d n e s s .
In p s o r ia t ic a r t h r it is , t h e re ca n b e s eve ra l p a t t e r n s o f jo in t in vo lve m e n t ,
w it h t h e p o lya r t ic u la r p a t t e r n r e s e m b lin g r h e u m a t o id a r t h r it is , t h e m o s t
WHEN TO REFER co m m o n fo r m . Th e p o lya r t icu la r p a t t e r n r e s p o n d s w e ll t o d is e a s e m o d ifyin g
a n t i- r h e u m a t ic d r u gs a n d c lin ic a lly h a s a go o d o u t c o m e a llo w in g fu ll
• Wh e n in d o u b t o f t h e
e xa ct d ia g n o sis. fu n ct io n in g a n d co n t in u e d e m p loym e n t . Mo r e a ggr e s s ive d is e a s e re s p o n d s
w e ll t o m o r e a ggr e s s ive d is e a s e m o d ifyin g a n t i- r h e u m a t ic d r u gs s u ch a s
• Wh e n t h e p e rip h e ra l
m e t h o t r e x a t e a n d t h e TNF in h ib it o r s t h a t a r e u s e d fo r t re a t in g p s o r ia s is a s
a rt h rit is is d e fo rm in g ,
e ro sive , a n d /o r d e st ru ct ive . w e ll.
In bot h p s oria t ic a rt h rit is a n d e n t e rop a t h ic a rt h rit is a s s ocia t e d w it h IBD,
• Wh e n d ise a se m o d ifyin g
a ggre s s ive t re a t m e n t o f t h e p s o ria s is a n d IBD is h igh ly re co m m e n d e d , a s in
a n t i-rh e u m a t ic d ru g s a re
needed. s o m e ca s e s t h e s eve r it y o f t h e a rt h rit is p a ra lle ls t h e s eve rit y o f t h e s k in o r
bow e l d is e a s e.
102 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
569.9 [713.1] d u e t o o r asso ciat e d w it h g ast ro in t e st in al co n d it io n NEC
099.3 [711.1] Re it e r’s d ise ase /Re act ive art h rit is
696.0 p so riat ic
720.9 Spo ndylitis
720.0 an k ylo sin g (ch ro n ic)
Additio na l Re a ding
1. Davis JC. An kylos in g s p on dylit is . In Koop m a n W J, More la n d LW, e d s . A rthritis and A llied Conditions . 15t h e d .
Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2005 ;1319 –1334 .
2. Kh a n MA, Siep e r J. Re a ct ive a rt h rit is . In Ko op m a n W J, More la n d LW, e d s . A rthritis and A llied Conditions .
15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2005 ;1335 –1356 .
3. Be n n e t t RM . Ps oria t ic a rt h rit is . In Koop m a n W J, More la n d LW, e d s . A rthritis and A llied Conditions . 15t h e d .
Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2005 ;1357 –1374 .
4. Mie la n t s H , Ba e t e n D, De Keys e r F, Veys EM . En t e ro p a t h ic a rt h rit is . In Koop m a n W J, More la n d LW, e d s .
S
A rthritis and A llied Conditions . 15t h e d . Ph ila d e lp h ia : Lip p in cot t W illia m s a n d Wilkin s , 2005 ;1375 –1400 .
E
C
5. Bou lw a re DW, Arn e t t FC, Cu s h JJ, Lip s ky PE, Be n n e t t RM , Mie la n t s H , De Keys e r F, Veys EM . Th e s e ron ega -
T
t ive s p on d yloa rt h rop a t h ie s . In Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of Rheum a-
I
O
tology . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2003 ;127 –163 .
N
3
S
p
e
c
i
c
R
h
e
u
m
a
t
i
c
D
i
s
e
a
s
e
s
CHAPTER
11 Systemic Lupus
Erythema tosus
Michelle A . Petri
s
p re se n t s t o h e r p rim ary care d o c-
e
s
Sy s t e m ic lu p u s e r y t h e m a t o s u s
a
t o r w it h co m p lain t s o f 9 m o n t h s
e
s
(SLE) is a m u lt is ys t e m a u t oim m u n e
i
D
o f f at ig u e , p ain in m u scle s in clu d - d is e a s e . It o ccu r s p re d o m in a n t ly
c
i
t
in g t h e n e ck an d sh o u ld e r are a, in w om e n , bu t 10% of p a t ie n t s a re
a
m
an d re d ch e e k s af t e r su n e xp o - m e n . Th e o n s e t is p re d o m in a n t ly
u
e
in t h e 20s a n d 30s , bu t it ca n p re s e n t
h
su re , last in g f o r an h o u r o r so .
R
in o ld e r p a t ie n t s (it is ra re b e fo re
c
On t h e p h ysical e xam in at io n , p u be rt y). It is bot h m ore com m on
i
c
t h e ch e e k s h ave several pustules.
e
a n d m o r e s e ve r e in Afr ic a n –
p
S
Laboratory d at a are o rd e re d Am erica n s a n d Hisp a n ic–Am erica n s
3
t h a n in Ca u ca sia n s . It is e st im a ted
N
an d sh o w a p o sit ive A NA 1:80
O
th a t a bou t 300,000 Am erica n s h ave
I
(h o m o g e n e o u s p at t e rn ), n o rm al
T
SLE.
C
E
co m p le t e b lo o d co u n t , n o rm al
S
ch e m ist rie s, an d n o rm al u rin alysis. Do e s sh e h ave syst e m ic lu p u s PATHOGENESIS
e ryt h e m at o su s? Lu p u s a u t oa n t ib od ie s a re p re s e n t
for 5 t o 7 ye a rs be fore t h e clin ica l
on s e t of SLE occu rs . Th e re is a p olyge n ic ge n e t ic p r e d is p o s it io n , w it h a s
m a n y a s 100 ge n e s , m a n y a ffe ct in g in a m m a t ory p a t h w ays , s u ch a s HLA DR
a n d DQ a lle le s , in t e rfe ron , in t e rle u kin -6, a n d t h e glu cocort icoid re ce p t or p a t h -
w ay. Fe m a le h orm on e s a re a n ot h e r fa ct or in p a t h oge n e s is . Me n w it h SLE t e n d
t o be h yp oa n d roge n ic. Abn orm a l re s p on s e s t o com m on viru s e s , s u ch a s Ep s t e in
Ba rr viru s , m a y p la y a n in cit in g role (1 ). En viron m e n t a l p re cip it a n t s in clu d e
u lt raviole t ligh t , t rim e t h op rim /s u lfa , in fe ct ion s , s ilica , a n d m e rcu ry.
ORGAN MANIFESTATIONS
Be ca u s e SLE is a m u lt is ys t e m d is e a s e, m u lt ip le p re s e n t a t ion s a re p os s ible. Th e
m o s t co m m o n o rga n s in vo lve d a t p re s e n t a t io n a re cu t a n e o u s a n d m u s cu -
los ke le t a l.
Cuta ne o us Lupus
In SLE, t h e re ca n be a cu t e, s u ba cu t e, a n d ch ron ic s u bt yp e s of cu t a n e ou s lu p u s .
Acu t e cu t a n e ou s lu p u s is a p h ot os e n s it ive m a cu lop a p u la r in a m m a t ory ra s h .
Cla s s ica lly it is ca lle d a “m a la r ra s h ” if on t h e brid ge of t h e n os e a n d ch e e ks ,
bu t it ca n a ls o be on t h e “V” a re a of t h e ch e s t or on t h e fore a rm s . It is u s u a lly
103
104 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
ra is e d a n d la s t s fo r d a ys t o m o n t h s . It m u s t b e d iffe re n t ia t e d fro m u s h e s /
CLINICAL POINTS blu s h e s , a cn e ros a ce a (w it h p u s t u le s ), s e borrh e a , s ola r u rt ica ria (w it h p ru rit u s ),
• SLE is b o t h m o re co m m o n a n d p olym orp h ou s ligh t e ru p t ion . In t h e ca s e p re s e n t a t ion , t h e re w e re p u s t u le s
a n d m o re se ve re in a n d a h is t ory of t ra n s ie n t ra s h : bot h w ou ld a rgu e a ga in s t lu p u s .
Africa n –Am e rica n s a n d Su ba cu t e cu t a n e ou s lu p u s e ryt h e m a t os u s (SCLE) ca n occu r in a n a n n u la r
Hisp a n ic–Am e rica n s t h a n form (t h a t m a y be m is t a ke n for a fu n ga l ra s h or Lym e d is e a s e ) or a p s oria form
in Ca u ca sia n s.
ra s h . SCLE ca n occu r w it h ou t SLE, a n d in m a n y ca s e s is ca u s e d or a ggrava t e d
• Mo st re d ch e e ks a re n o t by co m m o n ly u s e d m e d ica t io n s , in clu d in g h yd ro ch lo ro t h ia z id e , t e rb in a n e ,
t h e lu p u s m a la r ra sh . A s t a t in s , ca lciu m -ch a n n e l blo cke rs , ACE-in h ibit o rs , in t e rfe ron a lp h a a n d b e t a ,
lu p u s ra sh sh o u ld b e ra ise d
a n d sh o u ld p e rsist fo r d a ys
a n d TNF in h ibit ors (2 ).
t o w e e ks. Th e p re cip it a t in g Th e m os t com m on ch ron ic cu t a n e ou s lu p u s is d is coid lu p u s . It ca n occu r
u lt ra vio le t e xp o su re m a y w it h ou t SLE. On ly a bou t 5% of p a t ie n t s w it h d is coid lu p u s p rogre s s t o SLE. Dis -
h a ve b e e n d a ys b e fo re coid lu p u s is a s ca rrin g ra s h , u s u a lly on t h e s ca lp , e a rs , fa ce, a n d a rm s . It ca n
(ra t h e r t h a n im m e d ia t e ). be d is gu rin g, le a d in g t o s ca rrin g a lop e cia , a n d h yp o- a n d h yp e rp igm e n t a t ion .
SLE ca n a ls o ca u s e cu t a n e ou s va s cu lit is , p re s e n t in g a s p a lp a ble p u rp u ra or
(Co ntin u e d )
d igit a l ga n gre n e, bu t t h is is ra re.
S
MUSCULOSKELETAL LUPUS
E
C
T
Th e m a jorit y of SLE p a t ie n t s w ill h ave in a m m a t ory a rt h ra lgia s , m e a n in g join t
I
O
p a in w it h m orn in g s t iffn e s s , in t h e d is t ribu t ion of t h e s m a ll join t s of t h e h a n d s
N
(PIPs a n d MCPs ) a n d w ris t s , a n d , le s s com m on ly, la rge join t s . Th e re ca n be t ru e
3
S
s yn ovit is of t h e s e join t s . Eros ion s a re u n u s u a l. In s t e a d , SLE p a t ie n t s ca n d eve lop
p
e
Ja ccou d ’s a rt h rop a t h y, w it h re d u cible join t d e form a t ion d u e t o t e n d on a n d liga -
c
i
m e n t la xit y. Myos it is ca n occu r in SLE, bu t it is ra re. W h e n a p a t ie n t w it h SLE
c
R
h a s m u s cle p a in , t h e u s u a l ca u s e is brom ya lgia .
h
e
u
m
a
LUPUS NEPHRITIS
t
i
c
Lu p u s n ep h rit is p re s e n t s a s p rot e in u ria , h e m a t u ria , a n d s om e t im e s re d blood
D
i
s
ce ll ca s t s . It is s u bd ivid e d in t o m e s a n gia l, m e s a n gia l p rolife ra t ive, foca l, d iffu s e
e
a
p rolife ra t ive, m e m bra n ou s , a n d e n d -s t a ge s cle ros is . A re n a l biop s y is n e ce s s a ry
s
e
t o d e t e rm in e t h e In t e rn a t ion a l Socie t y of Nep h rology (ISN) cla s s , w h ich le a d s
s
t o im p or t a n t in form a t io n on p rogn o s is a n d t re a t m e n t . Diffu s e p rolife ra t ive
glom e ru lon ep h rit is (Cla s s IV) is t h e m os t like ly cla s s t o le a d t o re n a l fa ilu re.
HEMATOLOGIC LUPUS
CLINICAL POINTS (Con tin ue d )
SLE ca n a ffe ct a ll ce ll lin e s . Th e m os t com m on n d in g is le u kop e n ia a n d lym -
• SCLE m a y b e ca u se d o r
p h op e n ia . Pre d n is on e ca n ca u s e or w ors e n lym p h op e n ia . Us u a lly cyt op e n ia s
w o rse n e d b y co m m o n ly
u se d d ru g s. fro m lu p u s a re m ild a n d d o n ot re q u ire t re a t m e n t . Au t oim m u n e h e m olyt ic
a n e m ia is u s u a lly Coom bs p os it ive. Th e m os t fre q u e n t a n e m ia s fou n d in SLE
• Mu scle p a in in a n SLE
p a t ie n t s , h ow eve r, a re iron -d e cie n cy a n e m ia a n d t h e a n e m ia of ch ron ic d is -
p a t ie n t is u su a lly b ro m y-
a lg ia (n o t m yo sit is). e a s e (a ls o ca lle d t h e a n e m ia of ch ron ic in a m m a t ion ). Th rom bocyt op e n ia ca n
occu r d u e t o SLE, a s w e ll a s d u e t o a n t ip h os p h olip id a n t ibod ie s .
• Th e m o st fre q u e n t a n e m ia s
in SLE a re iro n -d e cie n cy
a n d t h e a n e m ia o f ch ro n ic
d ise a se /in a m m a t io n . SEROSITIS
SLE ca n ca u s e p le u ris y, p le u ra l e ffu s ion s , p e rica rd it is , p e rica rd ia l e ffu s ion , a n d
ra re ly, a s cit e s .
NEUROLOGIC LUPUS
SLE ca n le a d t o p s ych os is , s e izu re s , s t roke, com a , e n ce p h a lop a t h y, cra n ia l n e u -
rop a t h y, p e rip h e ra l n e u rop a t h y, m ye lit is , a n d m on on e u rit is m u lt ip le x (3 ). Th e
m os t com m on n e u rologic com p la in t , t h ou gh , is cogn it ive im p a irm e n t , t h a t ca n
occu r in 80% p a t ie n t s , 10 ye a rs a ft e r d ia gn os is (4 ).
Ch a p te r 11 Sys t e m ic Lu p u s Eryt h e m a t os u s 105
CONSTITUTIONAL
Act ive SLE ca n le a d t o feve r, w e igh t los s , lym p h a d e n op a t h y, a n d s p le n om ega ly.
Alt h ou gh fa t igu e ca n be p a rt of a n a cu t e SLE a re, m os t ch ron ic fa t igu e in SLE
is n ot a s s ocia t e d w it h a ct ive lu p u s , bu t ra t h e r w it h brom ya lgia , d e con d it ion -
in g, d e p re s s ion , h yp ot h yroid is m , a n e m ia , a n d ot h e r com orbid it y.
s
e
m ore like ly d u e t o d is coid lu p u s (ca u s in g s ca rrin g a lop e cia ) or a lop e cia a re a t a .
s
a
SLE p a t ie n t s ca n h a ve live d o re t icu la r is , a vio la ce o u s m o t t lin g o f t h e
e
s
i
e xt re m it ie s . Th is ca n a ls o occu r from a n t ip h os p h olip id a n t ibod ie s .
D
c
i
t
a
m
HEAD
u
e
SLE p a t ie n t s w it h s e con d a ry Sjögre n ’s m a y h ave p a rot id e n la rge m e n t or eye or
h
R
m ou t h d ryn e s s .
c
i
c
e
p
S
NECK
3
SLE ca n ca u s e ce rvica l lym p h a d e n op a t h y, u s u a lly s m a ll in s ize. Th yroid e n la rge -
N
O
m e n t ca n occu r from a u t oim m u n e t h yroid d is e a s e.
I
T
C
E
S
CHEST
SLE ca n ca u s e re s t rict ive lu n g d is e a s e. Th is ca n le a d t o ba s ila r cra ckle s . Lu p u s
p le u ris y m a y ca u s e a p le u ra l ru b or p le u ra l e ffu s ion .
HEART
Pe rica rd it is ca n ca u s e a p e rica rd ia l ru b or d is t a n t h e a rt s ou n d s , if t h e re is la rge
p e rica rd ia l e ffu s io n . Pu lm on a ry h yp e r t e n s io n ca n ca u s e a n a cce n t u a t e d P2.
Act ive lu p u s ca u s e s t a ch yca rd ia . He a rt m u rm u rs a re ve ry com m on in SLE.
ABDOMEN
Ab d o m in a l s e ro s it is ca n ca u s e a s cit e s . Bu d d -Ch ia r i (fro m a n t ip h o s p h o lip id
a n t ibod ie s ) a ls o ca u s e s a s cit e s . SLE ca n ca u s e h ep a t os p le n om ega ly.
EXTREMITIES
Pe d a l e d e m a ca n be a s ign of lu p u s n e p h rit is or p u lm on a ry h yp e rt e n s ion . Ray-
n a u d ’s p h e n om e n on is com m on in SLE.
MUSCULOSKELETAL
Lu p u s ca n ca u s e t e n d e rn e s s or t ru e sw e llin g of t h e PIPs , MCPs , w ris t s , kn e e s ,
a n d a n kle s (bu t n ot t h e DIP join t s ). Te n d e rn e s s in m u s cle s is u s u a lly brom y-
a lgia , n ot lu p u s m yos it is . A p roxim a l m yop a t h y ca n occu r from cort icos t e roid s .
106 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Ma la r ra sh He m a t o lo g ic d iso rd e r
Disco id ra sh Im m u n o lo g ic d iso rd e r:
Ph o t o se n sit ivit y An t i-d sDNA
Ora l u lce rs An t i-Sm
Art h rit is Lu p u s a n t ico a g u la n t
Se ro sit is An t ica rd io lip in
Re n a l d iso rd e r Fa lse –p o sit ive t e st fo r syp h ilis
Ne u ro lo g ic d iso rd e r An t in u cle a r a n t ib o d y
NEUROLOGIC
SLE ca n ca u s e cra n ia l a n d p e rip h e ra l n e u rop a t h y, a n d lon git u d in a l m ye lit is .
An t ip h os p h olip id a n t ibod ie s ca n ca u s e s t roke.
S
E
C
Studie s
T
I
O
N
LABORATORY ASSESSMENT
3
S
Th e la b o ra t o ry a s s e s s m e n t t o d ia gn o s e SLE in clu d e s t h e t e s t s n e ce s s a ry t o
p
e
a s s e s s orga n in volve m e n t (com p le t e blood cou n t w it h d iffe re n t ia l, s e ru m cre -
c
i
a t in in e, u rin a lys is , u rin e p rot e in /cre a t in in e ra t io) bu t a ls o a ba t t e ry of s e rologic
c
R
t e s t s o f lu p u s a u t oa n t ib od ie s , in clu d in g ANA, a n t i-d s DNA, a n t i-Ro, a n t i-La ,
h
e
a n t i-Sm it h , a n t i-RNP, d ire ct Coom bs , a n t ip h os p h olip id a n t ibod ie s (lu p u s a n t i-
u
m
coa gu la n t a n d a n t ica rd iolip in ), C3, a n d C4.
a
t
i
c
Diag no sis o f SLE
D
i
s
Th e d ia gn os is of lu p u s is s t ill a n a rt . Th e re a re cla s s i ca t ion crit e ria for SLE,
e
a
w h ich ca n be h e lp fu l. Th e ACR Cla s s i ca t ion Crit e ria re q u ire s t h e p re s e n ce of
s
e
fou r of t h e e leve n crit e ria t o cla s s ify a p a t ie n t a s h a vin g SLE. Alt h ou gh n ot p e r-
s
fe ct , t h ey d o e m p h a s ize t h e m u lt is ys t e m n a t u re of t h e d is e a s e. ANA is n ot s u f-
cie n t t o d ia gn o s e lu p u s – m o s t p e o p le w it h a p o s it ive ANA a re n o rm a l. A
p a t ie n t w it h ANA a n d m u s cle p a in , for e xa m p le, like ly h a s brom ya lgia (n ot
lu p u s ) – a s in t h e ca s e p re s e n t a t ion (Ta ble 11.1 ).
Clinica l Co urse
SLE is a b ou t e q u a lly d ivid e d in t o t h e “ a re p a t t e rn ”, in w h ich p a t ie n t s h a ve
e xa ce rba t ion s follow e d by im p rove m e n t , a n d “ch ron ic a ct ivit y”, in w h ich t h e re
is a lw ays s om e a ct ivit y. Re m is s ion , n ot re q u irin g p re d n is on e or im m u n os u p -
PATIENT ASSESSMENT p re s s ive t re a t m e n t , is ve ry ra re.
Su rviva l in SLE h a s im p rove d s in ce t h e 1950s , bu t p la t e a u e d in t h e 1980s .
• A t ru e p h o t o se n sit ive
ra sh sh o u ld b e ra ise d a n d Ea rly in SLE, t h e m a jor ca u s e s of d e a t h a re a ct ive d is e a s e a n d in fe ct ion , w h e re a s ,
sh o u ld la st fo r d a ys t o la t e r in SLE, t h e m a jor ca u s e of d e a t h is ca rd iova s cu la r d is e a s e (5 ).
w e e ks a ft e r su n e xp o su re .
• Fib ro m ya lg ia is m u ch
m o re co m m o n t h a n lu p u s. Tre a tme nt
Are b ro m ya lg ia t e n d e r
p o in t s p re se n t ? Is t h e re GENERAL MEASURES
p ro lo n g e d m o rn in g SLE p a t ie n t s s h ou ld p ra ct ice s u n p rot e ct ion a n d u s e s u n s cre e n a s u lt raviole t
st iffn e ss in t h e sm a ll ligh t in cre a s e s SLE a re s . Be ca u s e of t h e h igh ris k of ca rd iova s cu la r d is e a s e, a
jo in t s o f t h e h a n d s a n d
low fa t , low ch ole s t e rol d ie t is re com m e n d e d .
w rist s t o su g g e st in a m -
m a t o ry p o lya rt h ra lg ia ? SLE in cre a s e s t h e ris k of in fe ct ion . Va ccin a t ion s fo r in u e n za ye a rly a n d
p n e u m o co ccu s eve ry 5 ye a r s a re re co m m e n d e d . On ly in a ct iva t e d va ccin e s
Ch a p te r 11 Sys t e m ic Lu p u s Eryt h e m a t os u s 107
HYDROXYCHLOROQUINE
Hyd roxych loroq u in e s h ou ld be p re s cribe d t o a ll SLE p a t ie n t s . Th e d os e is 400
m g (200 m g t w ice d a ily) in a n a ve ra ge p e rs on , bu t t h e d os e s h ou ld n ot e xce e d
6.5 m g/kg, a n d s h ou ld be re d u ce d in re n a l in s u f cie n cy or re n a l fa ilu re. Hyd rox-
ych loroq u in e h e lp s cu t a n e ou s lu p u s a n d lu p u s a rt h rit is . It p reve n t s 50% of SLE
a re s (6 ), h e lp s t o p reve n t re n a l a n d n e u rologic lu p u s , im p rove s s u rviva l, a n d
s
e
im p rove s h yp e r lip id e m ia . Th e r is k o f re t in o p a t h y is o n e o u t o f 5,000 a ft e r
s
a
5 ye a rs of u s e.
e
s
i
D
c
NSAIDs
i
t
a
m
u
NSAIDs a re h e lp fu l for lu p u s a rt h rit is a n d s e ros it is . How eve r, t h ey s h ou ld n ot
e
h
be u s e d in p a t ie n t s w it h lu p u s n e p h rit is . Lon g-t e rm u s e m a y in cre a s e t h e ris k
R
c
of ca rd iova s cu la r d is e a s e. Ibu p rofe n m ay block t h e t h e ra p e u t ic e ffe ct of a s p irin .
i
c
e
p
S
PREDNISONE/ CORTICOSTEROIDS
3
N
Pre d n is on e le a d s t o 80% of p e rm a n e n t orga n d a m a ge a ft e r t h e d ia gn os is of SLE
O
(7 ). It s u s e s h ou ld be m in im ize d . A ch ron ic n e e d for p re d n is on e s h ou ld le a d t o
I
T
C
a re fe rra l t o a rh e u m a t ologis t , w h o ca n con s id e r t h e a d d it ion of s t e roid -s p a rin g
E
S
regim e n s . Mild /m od e ra t e lu p u s a re s m a y be t re a t e d w it h a “bu rs t ” of s t e roid s
(m e d rol d os e p a ck or on e t im e in t ra m u s cu la r t ria m cin olon e 100 m g) in s t e a d of
ch ron ic ora l s t e roid s . Seve re a re s m a y re q u ire “p u ls e ” t h e ra py w it h in t rave -
n ou s m e t h ylp re d n is olon e 1000 m g for 3 d ays , follow e d by ora l p re d n is on e. Th e
ris k of os t e on e cros is goe s u p d ra m a t ica lly w it h d os e s of ora l p re d n is on e of 20
m g or h igh e r.
IMMUNOSUPPRESSIVE DRUGS
Me tho tre xate
Me t h ot re xa t e is h e lp fu l for lu p u s a rt h rit is a n d cu t a n e ou s lu p u s . Dos e s a re u s u -
a lly be t w e e n 7.5 a n d 25 m g w e e kly, w it h d a ily fo lic a cid . Mon it or in g of t h e
com p le t e blood cou n t a n d live r fu n ct ion t e s t s is n e ce s s a ry. It ca n n ot be u s e d in
p regn a n cy.
Le uno mide
Le u n om id e is u s e d for lu p u s a rt h rit is a n d h a s s h ow n be n e t for lu p u s n e p h ri-
t is a s w e ll. Dos e s va ry from 10 t o 20 m g d a ily. Mon it orin g of t h e com p le t e blood
cou n t a n d live r fu n ct ion t e s t s is n e ce s s a ry. Mild h a ir los s ca n occu r. It ca n n ot
be u s e d in p regn a n cy.
Azathio prine
Aza t h iop rin e is a n im m u n os u p p re s s ive d ru g w it h broa d a p p lica bilit y in SLE.
Do s e s o f 1 m g t o 2 m g/ k g a re u s u a lly u s e d . Th io p u r in e m e t h ylt ra n s fe ra s e
(TPMT) t e s t in g is re com m e n d e d t o id e n t ify p a t ie n t s a t gre a t e r ris k of t oxicit y
108 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
WHEN TO REFER
ANTIPHOSPHOLIPID ANTIBODIES
• To co n rm d ia g n o sis Abou t 50% of SLE p a t ie n t s m ay h ave a n a n t ip h os p h olip id a n t ibod y (lu p u s a n t i-
• Be fo re in st it u t in g coa gu la n t , a n t ica rd iolip in , or a n t i-be t a 2 glycop rot e in I). Th e s e a n t ibod ie s ca u s e
co rt ico st e ro id s h yp e rco a gu la b ilit y a n d in cre a s e p re gn a n cy lo s s . Pro p h yla ct ic t h e ra p y w it h
a s p irin (81 m g) a n d h yd rox ych lo ro q u in e is re com m e n d e d . Us e of e s t roge n ,
• If t h e p a t ie n t re q u ire s
m o re t h a n 7.5 m g o f SERMs , a n d t h a lid om id e s h ou ld be a void e d , a s t h ey in cre a s e t h e ris k of t h rom -
p re d n iso n e b os is . If a n SLE p a t ie n t w it h a n t ip h o s p h o lip id a n t ibo d ie s h a s a t h rom b ot ic
eve n t , t h e n a n t icoa gu la t ion (w it h a t a rge t INR of 2 t o 3) is re com m e n d e d life -
• To e va lu a t e p ro t e in u ria
lon g (14 ).
• Fo r a ra sh n o t re sp o n sive
t o h yd ro xych lo ro q u in e
• Fo r CNS sym p t o m a t o lo g y SJÖGREN’S SYNDROME
• Fo r d ysp n e a Te n p e rce n t of SLE p a t ie n t s w ill d eve lop Sjögre n ’s s yn d rom e. On ly a bou t h a lf of
p a t ie n t s w it h s e con d a ry Sjögre n ’s w ill h ave Sjögre n ’s a u t oa n t ibod ie s (a n t i-Ro
Ch a p te r 11 Sys t e m ic Lu p u s Eryt h e m a t os u s 109
ICD9
s
710.0 Lupus
e
s
695.4 d isco id (lo cal)
a
e
695.4 e ryt h e m at o d e s (d isco id ) (lo cal)
s
i
D
695.4 e ryt h e m at o su s (d isco id ) (lo cal)
c
i
710.0 d isse m in at e d
t
a
m
710.0 syst e m ic
u
710.0 [583.81] n e p h rit is
e
h
R
710.0 [580.81] acu t e
c
710.0 [582.81] ch ro n ic
i
c
583.9 Ne phritis, ne phritic (alb u m in u ric) (az o t e m ic) (co n g e n it al) (d e g e n -
e
p
e rat ive ) (d iff u se ) (d isse m in at e d ) (e p it h e lial) (f am ilial) (f o cal) (g ran u lo -
S
3
m at o u s) (h e m o rrh ag ic) (in f an t ile ) (n o n su p p u rat ive , e xcre t o ry) (u re m ic)
N
710.0 [583.81] lu p u s
O
I
T
710.0 [580.81] acu t e
C
E
710.0 [582.81] ch ro n ic
S
714.4 p o st rh e u m at ic, ch ro n ic (Jacco u d ’s)
Re fe re nce s
1. Ha rley JB, Ja m e s JA. Ep s t e in -Ba rr viru s in fe ct ion m ay be a n e n viron m e n t a l ris k fa ct or for s ys t e m ic lu p u s
e ryt h e m a t os u s in ch ild re n a n d t e e n a ge rs [le t t e r]. A rthritis Rheum 1999 ;42 (8 ):1782 –1783 .
2. Ca lle n JP. Dru g-in d u ce d s u ba cu t e cu t a n e ou s lu p u s e ryt h e m a t os u s . Lupus 19 (9 ):1107 –1011 .
3. Ha n ly JG, Urow it z MB, Su L, , e t a l. Pros p e ct ive a n a lys is of n e u rop s ych ia t ric eve n t s in a n in t e rn a t ion a l
d is e a s e in cep t ion coh ort of SLE p a t ie n t s . A nn Rheum Dis 2010;69(3):529–535 .
4. Brey RL, Hollid ay SL, Sa kla d AR, e t a l. Ne u rop s ych ia t ric s yn d rom e s in SLE: Preva le n ce u s in g s t a n d a rd ize d
d e n it ion s in t h e Sa n An t on io St u d y of Ne u rop s ych ia t ric Dis e a s e Coh ort . Neurology 2002 ;58 :1214 –1220 .
5. Urow it z MB, Gla d m a n DD, Abu -Sh a kra M , e t a l . Mor t a lit y s t u d ie s in s ys t e m ic lu p u s e ryt h e m a t os u s .
Re s u lt s from a s in gle ce n t e r. III. Im p rove d s u rviva l ove r 24 ye a rs . J Rheum atol 1997;24 (6 ):1061 –1065 .
6. Ca n a d ia n Hyd roxych loro q u in e St u d y Grou p . A ra n d om ize d s t u d y of t h e e ffe ct of w it h d raw in g h yd roxy-
ch loroq u in e s u lfa t e in s ys t e m ic lu p u s e ryt h e m a t os u s . N Engl J Med. 1991 ;324 :150 –154 .
7. Gla d m a n DD, Urow it z MB, Ra h m a n P, e t a l . Accru a l of orga n d a m a ge ove r t im e in p a t ie n t s w it h s ys t e m ic
lu p u s e ryt h e m a t os u s . J Rheum atol 2003;30 (9 ):1955 –1959 .
8. Gin zle r EM , Dooley MA, Ara n ow C, e t a l. Mycop h e n ola t e m ofe t il or in t rave n ou s cyclop h os p h a m id e fo r
lu p u s n ep h rit is . N Engl J Med 2005;353 (21 ):2219 –2228 .
9. Con t re ra s G, Pa rd o V, Le cle rcq B, e t a l. Se q u e n t ia l t h e ra p ie s for p rolife ra t ive lu p u s n ep h rit is . N Engl J Med
2004;350 (10 ):971 –980 .
10. Ap p e l GB, Con t re ra s G, Dooley MA, e t a l. Mycop h e n ola t e m ofe t il ve rs u s cyclop h os p h a m id e for in d u ct ion
t re a t m e n t of lu p u s n ep h rit is . J A m Soc Nephrol 2009 ;20 (5 ):1103 –1112 .
11. Pe t ri M , Bro d s ky RA, Jon e s RJ, Gla d s t on e D, Filliu s M , Ma gd e r LS . High d os e Cyclop h os p h a m id e ve rs u s
Mon t h ly In t ra ve n ou s Cyclop h o s p h a m id e fo r Sys t e m ic Lu p u s Eryt h e m a t os u s : A p ros p e ct ive Ra n d -
om ize d Tria l . A rthritis Rheum 2010 ;62 :1487 –1493 .
110 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
12. Bu r t RK, Tra yn or A, St a t ku t e L, e t a l. Non m ye loa bla t ive h e m a t op oie t ic s t e m ce ll t ra n s p la n t a t ion for
s ys t e m ic lu p u s e ryt h e m a t os u s . J A m er Med A ssoc 2006 ;295 :527 –535 .
13. Nava rra SV, Gu zm á n RM , Ga lla ch e r AE, e t a l. Ef ca cy a n d s a fe t y of be lim u m a b in p a t ie n t s w it h a ct ive
s y s t e m ic lu p u s e r y t h e m a t o s u s : a ra n d o m is e d , p la ce b o -co n t r o lle d , p h a s e 3 t r ia l . Lancet 2011 ;
377 (9767):721–731 .
14. Crow t h e r MA, Gin s be rg JS, Ju lia n J, e t a l. A co m p a ris on of t w o in t e n s it ie s of w a rfa rin for t h e p reve n t ion
of re cu rre n t t h rom bos is in p a t ie n t s w it h t h e a n t ip h os p h olip id a n t ibod y s yn d rom e . N Engl J Med 2003 ;
349 (12 ):1133 –1138 .
15. Pe t ri M , La ka t t a C, Ma gd e r L, e t a l . Effe ct of p re d n is on e a n d h yd roxych loroq u in e on coron a ry a rt e ry
d is e a s e ris k fa ct ors in s ys t e m ic lu p u s e ryt h e m a t os u s : a lon git u d in a l d a t a a n a lys is . A m J Med 1994 ;96 :
254 –259 .
S
E
C
T
I
O
N
3
S
p
e
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i
c
R
h
e
u
m
a
t
i
c
D
i
s
e
a
s
e
s
CHAPTER
12 Ra yna ud’s Phenomenon
a nd Systemic Sclerosis
Laura B. Hughes and Barri Fessler
A 42-ye ar-o ld m an
Ra yna ud’s
Phe no me no n
s
p re se n t s co m p lain in g
e
s
INTRODUCTION
a
o f sw o lle n h an d s.
e
s
i
Rayn a u d ’s p h en om en on (RP) is a n
D
His n g e rs t u rn b lu e
c
exa ggera t ed va s osp a s tic resp on s e
i
t
an d w h it e , an d are
a
t o cold tem p era tu re or em ot ion a l
m
asso ciat e d w it h p ain s tress . First d e scribed by Ma u rice
u
e
h
w h e n e xp o se d t o Rayn a u d in 1862 it is ch a ra ct e r-
R
ized by in term it ten t a cra l ble a ch -
c
co ld t e m p e rat u re s.
i
in g, fo llow e d by cya n o s is a n d
c
He n o t e s h e art b u rn
e
e ryt h rod erm a . Th e t yp ica l t ricolor
p
S
an d t h e se n sat io n s e q u e n ce is d rive n by va s ocon -
3
N
o f f o o d st ick in g s trict ion of d igita l a rteries (w h ite
O
p h a s e ), d e cre a s e d blood ow in
I
in h is e so p h ag u s.
T
C
ca p illa r ie s a n d ve n u le s (b lu e
E
Exam in at io n re ve als d iff u se ly e d e m at o u s h an d s w it h sk in t h ick e n in g
S
p h a s e ), fo llow e d by r e a ct ive
aff e ct in g t h e n g e rs. Nail-f o ld m icro sco p y sh o w s d ilat e d lo o p s w it h h yp e re m ia (re d p h a s e ). Po p u la -
are as o f d ro p o u t (Fig . 12.1). t ion -ba s e d s u rveys e s t im a t e t h e
p r e va le n ce o f RP in w o m e n
be t w e e n 6% a n d 20% a n d m e n
betw een 3% a n d 12.5% (1 ).
111
112 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
STUDIES
Ra yn a u d ’s p h e n om e n on is a clin ica l d ia gn os is . If s e con d a ry ca u s e s a re s u s -
p e ct e d , a n eva lu a t ion t o a s s e s for a t h e ros cle rot ic d is e a s e is in d ica t e d a s w e ll
a s for a n u n d e rlyin g con n e ct ive t is s u e d is ord e r, in clu d in g s e rologie s for SLE,
Sjögre n ’s s yn d rom e, a n d a n a u t oim m u n e m yos it is .
TREATMENT
Tre a t m e n t ch oice s for RP d e p e n d on t h e s eve rit y of t h e con d it ion a n d t h e p re s -
e n ce of a n u n d e rlyin g d is e a s e . Th e goa ls of t h e ra p y a re t o im p rove q u a lit y of
life a n d p reve n t t is s u e in ju ry. In p a t ie n t s w it h p rim a ry RP, a con s e rva t ive , n on -
p h a r m a co lo gic a p p ro a ch is m o s t im p o r t a n t , a lt h o u gh m e d ica t io n s m a y b e
n e ce s s a ry. Ge n e ra l e d u ca t io n rega rd in g t h e d is e a s e it s e lf a s w e ll a s t h e u s e o f
n o n p h a rm a co logic life s t yle m o d i ca t io n s is re co m m e n d e d . Avo id in g u n n e c-
e s s a ry cold e xp os u re or s u d d e n t e m p e ra t u re ch a n ge s s u ch a s m ovin g from a
h o t e n viro n m e n t t o a n a ir-co n d it io n e d ro o m is e s s e n t ia l. Pa t ie n t s s h o u ld
u n d e rs t a n d t h a t t h e e n t ire bod y a n d n ot ju s t t h e d igit s s h ou ld be ke p t w a rm .
St ra t e gie s s u ch a s w e a r in g t h e r m a l u n d e r w e a r, h a t s , s ca r ve s , a n d in s u la t e d
foot w e a r h e lp ke e p t h e bod y w a rm . Th e d igit s s h ou ld be p rot e ct e d from cold
w it h glove s a n d / or h a n d w a rm e rs . Pa t ie n t s s h ou ld a void m e d ica t ion s t h a t p ro-
m o t e va s o con s t rict ion , s u ch a s d e con ge s t a n t s , a m p h e t a m in e s , be t a -blocke rs ,
a n d ca ffe in e. Sim ila rly, s m okin g ce s s a t ion is a ls o re com m e n d e d be ca u s e n ico-
t in e is va s ocon s t rict ive. Ph ys ica l m a n e u ve rs t h a t p rom ot e va s od ila t ion in t h e
d igit s ca n a ls o be t a u gh t t o le s s e n t h e s eve rit y of a n a t t a ck, in clu d in g rot a t in g
Ch a p te r 12 Rayn a u d ’s Ph e n om e n on a n d Sys t e m ic Scle ros is 113
t h e a rm s in a w in d m ill p a t t e rn a n d p la cin g t h e h a n d s in w a rm w a t e r or in a
w a r m b o d y fo ld (s u ch a s t h e a x illa ). If t h e s e m e a s u re s fa il t o im p rove t h e
q u a n t it y a n d /or s eve rit y of a t t a cks , t h e re a re a n u m be r of p h a rm a cologic t h e r-
a p ie s t h a t ca n be in it ia t e d . Ca lciu m ch a n n e l blocke rs a re t h e m os t w id e ly u s e d
cla s s o f d ru gs fo r t h e t re a t m e n t o f RP. Am o n g t h e d iffe re n t cla s s e s of ca lciu m
ch a n n e l blo ck e rs , t h e d ih yd rop yrid in e gro u p h a s b e e n t h e m os t e ffe ct ive, w it h
d os e s of n ife d ip in e ra n gin g from 30 t o 180 m g d a ily or a m lod ip in e from 5 t o
20 m g d a ily. Th e lon g-a ct in g or s low -re le a s e p rep a ra t ion s a re ge n e ra lly p re fe rre d
a s t h ey a re be t t e r t ole ra t e d a n d a ch ieve a m ore s u s t a in e d re s p on s e. If a p a t ie n t
h a s a s u b o p t im a l re s p o n s e t o m a x im u m -d o s e ca lciu m ch a n n e l blo cke rs , t h e
a d d it io n o f a d ire ct va s o d ila t or —s u ch a s t op ica l n it roglyce r in —ca n be u s e d .
In d ire ct va s od ila t ors h a ve a ls o be e n eva lu a t e d , in clu d in g a n giot e n s in con ve rt -
in g e n zym e (ACE) in h ibit ors (e.g., e n a la p ril, ca p t op ril), a n giot e n s in II re ce p t or
a n t a go n is t s (e .g., lo s a r t a n ), a n d s e le ct ive s e rot on in re u p t a ke in h ibit or s (e .g.,
u ox e t in e ). Mo re re ce n t ly, p h o s p h o d ie s t e ra s e t yp e 5 in h ibit o rs (e.g., s ild e n a l,
t a d a la l, va rd e n a l) h a ve be e n u s e d for p a t ie n t s w it h s eve re RP w it h d igit a l
is ch e m ia . Bo s e n t a n , a n e n d o t h e lin 1 re ce p t o r a n t a go n is t , h a s d e m o n s t ra t e d
s u cce s s in t re a t in g d igit a l u lce rs in p a t ie n t s w it h s cle ro d e rm a a n d s e co n d a ry
s
e
RP. Pra zos in , a s ym p a t h olyt ic a ge n t , a n d p e n t oxyp h illin e, a p h os p h o d ie s t e ra s e
s
a
in h ib it o r, h a ve a ls o b e e n re p o r t e d t o im p rove RP s ym p t o m s . Digit a l o r t h o ra cic
e
s
i
s ym p a t h e ct o m y o r in t ra ve n o u s p ro s t a gla n d in in fu s io n s (e .g., ilo p ro s t , e p o -
D
c
p ros t e n o l) ca n be u t iliz e d in p a t ie n t s w it h RP w h o a re re fra ct o ry t o ora l m e d i-
i
t
a
ca l t h e ra p y, t yp ica lly in t h e a cu t e s e t t in g w h e re t h e re is cr it ica l d igit a l is ch e m ia .
m
Low -d o s e a s p ir in h a s a ls o b e e n r e c o m m e n d e d in p a t ie n t s w it h d igit a l
u
e
is ch e m ia .
h
R
c
i
c
CLINICAL COURSE
e
p
S
Pa t ie n t s w it h p rim a ry RP a re u n like ly t o d eve lop p rogre s s ion of t h e ir d is e a s e or
3
d a m a ge d igit a l is ch e m ia . Ed u ca t ion a bou t t h e n a t u re of RP a n d in s t ru ct ion in
N
O
n on p h a rm a cologic m e a s u re s ca n o ft e n re d u ce t h e fre q u e n cy a n d s eve rit y o f
I
T
a t t a cks a n d im p rove q u a lit y of life. Pa t ie n t s w it h s e con d a ry RP, e s p e cia lly t h os e
C
E
w it h SSc, a re m ore like ly t o d eve lop d igit a l u lce rs a n d t is s u e is ch e m ia . Re fe rra l
S
t o a rh e u m a t ologis t is re com m e n d e d for p a t ie n t s w it h s e con d a ry RP or d if cu lt -
t o-t re a t p rim a ry RP.
s
e
t ory of a n t e ce d e n t h igh -d os e cort icos t e roid u s a ge. Th e m a n ife s t a t ion s in clu d e
s
a
m a lign a n t h yp e rt e n s ion p re s e n t in 90% of p a t ie n t s , a lon g w it h a ris in g cre a t i-
e
s
i
n in e a n d m icroa n giop a t h ic h e m olyt ic a n e m ia a n d t h rom bocyt op e n ia . Norm o-
D
c
t e n s ive SRC occu rs in 10% of p a t ie n t s .
i
t
a
Mu s cu lo s ke le t a l in vo lve m e n t in clu d e s a r t h ra lgia s , n o n e ro s ive a r t h r it is ,
m
join t con t ra ct u re s be ca u s e of re s t rict ion of m ot ion from s kin t h icke n in g, t e n -
u
e
d on frict ion ru bs , m yop a t h y, a n d com p re s s ion n e u rop a t h ie s . Bon e re s orp t ion of
h
R
t h e d igit a l t u ft s (ca lle d a cro-os t e olys is ) d eve lop s be ca u s e of ch ron ic va s cu la r
c
i
in s u f cie n cy a n d is ch e m ia . Ca rp a l t u n n e l s yn d rom e or u ln a r n e u rop a t h y m a y
c
e
be s e e n be ca u s e of com p re s s ion from cu t a n e ou s bros is .
p
S
3
N
O
STUDIES
I
T
C
Th e re a re s eve ra l a u t oa n t ibod ie s t h a t ca n be obs e rve d in p a t ie n t s w it h SSc;
E
S
h ow eve r, 40% t o 50% of p a t ie n t s d o not h ave on e of t h e s e a n t ibod ie s . Th e re fore
if a n a n t ibod y is p re s e n t , it is h e lp fu l in e s t a blis h in g t h e d ia gn os is a n d p re d ict -
in g t h e p rogn os is , bu t it is n ot e s s e n t ia l for t h e d ia gn os is . Th e ce n t rom e re p a t -
t e rn on ANA t e s t in g (a ls o ca lle d a n t ice n t rom e re a n t ibod ie s ) is a s s ocia t e d w it h
lim it e d SSc, PAH, a n d s eve re RP w it h is ch e m ia . Th e n u cle ola r p a t t e rn on ANA
t e s t in g is a ls o a s s ocia t e d w it h SSc. An t i-DNA t op ois om e ra s e 1 (a ls o kn ow n a s
a n t i-ScL70) a n t ibod ie s a re a s s ocia t e d w it h d iffu s e SSc a n d p u lm on a ry bros is .
An t ibod ie s t o RNA p olym e ra s e III a re a s s ocia t e d w it h a n in cre a s e d ris k of SRC
a n d d e cre a s e d in cid e n ce of lu n g d is e a s e (6 ,10 ).
In co n t ra s t t o m a n y ot h e r a u t o im m u n e d is e a s e s , a cu t e -p h a s e re a ct a n t s
(e .g., e ryt h rocyt e s e d im e n t a t ion ra t e , C-re a ct ive p rot e in ) a re n o t e leva t e d in
SSc. If t h ey a re e leva t e d , a s e a rch for a con com it a n t con d it ion —s u ch a s in fe c-
t ion , m a lign a n cy, or a n ot h e r in a m m a t ory d is e a s e —is w a rra n t e d . An e m ia of
ch ron ic d is e a s e is fre q u e n t ly s e e n in SSc; if iron -d e cie n cy a n e m ia is n ot e d , GI
eva lu a t ion for blood los s is in d ica t e d .
Th e d ia gn os is of SSc is e s t a blis h e d on t h e ba s is of a com bin a t ion of ch a r-
a ct e ris t ic s ym p t om s , p h ys ica l n d in gs , s p e ci c s e rologie s , a n d s om e t im e s s kin
biop s ie s . Th e p u blis h e d cla s s i ca t ion crit e ria (u s e d for e n rollin g p a t ie n t s in t o
clin ica l t ria ls in t h e p a s t ) con s is t of a m a jor crit e rion (p roxim a l s cle rod e rm a )
a n d t w o or m ore m in or crit e ria (s cle rod a ct yly, d igit a l p it t in g s ca rs or los s of
s u bs t a n ce from t h e n ge r p a d , a n d biba s ila r p u lm on a ry bros is ). Th e s e crit e ria
a re in a d e q u a t e be ca u s e t h ey om it t h e m a jorit y of p a t ie n t s w it h lim it e d SSc a n d
d o n o t in co rp o ra t e SSc-a s s ocia t e d a n t ibo d ie s ; t h e re fo re , t h ey a re cu r re n t ly
be in g revis e d (7 ). Cu t a n e ou s bros is is n ot s p e ci c t o SSc; t h e re a re s eve ra l ot h e r
bros in g d is ord e rs t h a t h a ve be e n d e s cribe d , in clu d in g n ep h roge n ic bros in g
116 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
CLINICAL COURSE
Scre e n in g fo r re s t r ict ive lu n g d is e a s e a n d p u lm o n a ry va s cu la r d is e a s e in
p a t ie n t s w it h SSc—con s is t in g of p u lm on a ry fu n ct ion t e s t s a n d a n e ch oca rd io-
gra m (w it h s p e cia l a t t e n t ion t o t h e righ t s id e of t h e h e a rt a n d p u lm on a ry a rt e ry
p re s s u re )—s h ou ld be p e rform e d a t d ia gn os is for ba s e lin e m e a s u re m e n t a n d a t
le a s t a n n u a lly t h e re a ft e r, m ore fre q u e n t ly (eve ry 3–6 m on t h s ) if t h e p a t ie n t h a s
ra p id ly p rogre s s ive s k in d is e a s e o r is s ym p t o m a t ic. If t h e PFTs s u gge s t a n
u n d e rlyin g re s t rict ive lu n g d is e a s e, a h igh -re s olu t ion CT of t h e lu n gs s h ou ld be
Ch a p te r 12 Rayn a u d ’s Ph e n om e n on a n d Sys t e m ic Scle ros is 117
s
e
Raynaud’s
s
a
443.0 d ise ase o r syn d ro m e (p aro xysm al d ig it al cyan o sis)
e
s
Scle ro sis, scle ro tic
i
D
710.1 syst e m ic (p ro g re ssive )
c
i
t
a
Scle ro de rma, scle ro de rmia (acro scle ro t ic)
m
(d iff u se ) (g e n e raliz e d ) (p ro g re ssive )
u
e
710.1 (p u lm o n ary)
h
R
701.0 circu m scrib e d
c
701.0 lin e ar
i
c
e
701.0 lo caliz e d (lin e ar)
p
S
778.1 n e w b o rn
3
N
O
I
T
C
E
Re fe re nce s
S
1. Fra e n k e l L. Ra yn a u d ’s p h e n o m e n o n : Ep id e m io logy a n d r is k fa ct o r s . Cu rr Rheum atol Rep 2002 ;4 (2 ):
123 –128 .
2. Rich t e r JG, Sa n d e r O, Sch n e id e r M , e t a l . Dia gn os t ic a lgorit h m for Rayn a u d ’s p h e n om e n on a n d va s cu la r
s kin le s ion s in s ys t e m ic lu p u s e ryt h e m a t os u s . Lupus 2010 ;19 (9 ):1087 –1095 .
3. Ba ks t R, Me rola JF, Fra n ks AGJ, e t a l. Rayn a u d ’s p h e n om e n on : Pa t h oge n e s is a n d m a n a ge m e n t . J A m A cad
Derm atol 2008 ;59 (4 ):633 –653 .
4. Le Roy EC, Me d s ge r TA, Jr . Ra yn a u d ’s p h e n om e n o n : A p rop o s a l fo r cla s s i ca t io n . Clin Ex p Rheum atol
1992 ;10 (5 ):485 –488 .
5. Block JA, Se q u e ira W. Rayn a u d ’s p h e n om e n on . Lancet 2001 ;357 (9273 ):2042 –2048 .
6. Pe re ra A, Fe rt ig N , Lu ca s M , Me d s ge r TA, Jr . Clin ica l s u bs e t s , s kin t h ickn e s s p rogre s s ion ra t e a n d s e ru m
a n t ibo d y leve ls in s ys t e m ic s cle ro s is p a t ie n t s w it h a n t i-t o p o is o m e ra s e I a n t ib od y. A rthritis Rheu m
2007 ;56 :2740 –2746 .
7. Hu d s on M , Frit zle r MJ, Ba ron M ; Ca n a d ia n Scle rod e rm a Re s e a rch Grou p . Sys t e m ic s cle ros is ; e s t a blis h in g
d ia gn os t ic crit e ria . Medicine (Baltim ore) 2010 ;89 (3 ):159 –165.
8. Kh a n n a D, De n t on CP. Evid e n ce -ba s e d m a n a ge m e n t of ra p id ly p rogre s s ive s ys t e m ic s cle ros is . Best Pract
Res Clin Rheum atol 2010 ;24 (3 ):387 –400 .
9. Tyn d a ll AJ, Ba n n e rt B, Von k M , e t a l. Ca u s e s a n d ris k fa ct ors for d e a t h in s ys t e m ic s cle ros is : A s t u d y from
t h e EULAR Scle rod e rm a Tria ls a n d Re s e a rch (EUSTAR) d a t a ba s e . A nn Rheum Dis 2010 ;69 (10 ):1809 –1815.
10. Glid d on AE, Dore CJ, Du n p h y J, e t a l . An t in u cle a r a n t ibod ie s a n d clin ica l a s s ocia t ion s in a Brit is h Coh ort
w it h lim it e d cu t a n e ou s s ys t e m ic s cle ros is . J Rheum atol, 2011 :38 (4 ):702 –705 .
CHAPTER
13 In ammatory
Myopathies: Polymyositis,
Derma tomyositis, a nd
Rela ted Conditions
Irene Z . W hitt and Frederick W . Miller
S
E
C
T
I
O
N
3
Clinica l Pre se nta tio n
S
p
A p re vio u sly h e alt h y
e
c
In a m m a t o ry m yop a t h ie s a re d is -
54-ye ar-old librarian com es
i
c
e a s e s ch a ra ct e r iz e d by a cq u ire d
R
t o t h e clin ic co m p lain in g m u s cle in a m m a t io n . Th is t e r m
h
e
o f “t ire d an d so re arm s e n co m p a s s e s a la rge n u m b e r o f
u
m
an d le g s” f o r t h e p re vio u s d is ord e rs t h a t in clu d e vira l, fu n ga l,
a
t
i
a n d p a ra s it ic in fe ct ion s of m u s cle,
c
7 w e e k s. Th is cam e o n
D
t oxic m yop a t h ie s , a n d ot h e r ca u s e s
i
s
g rad u ally af t e r a cru ise
e
o f m u s c le d a m a g e . W h e n t h e
a
t o t h e Carib b e an , w h ile
s
a p p r o p r ia t e c lin ic a l, la b o r a t o r y,
e
s
p layin g g o lf in t h e su n a n d p a t h o logic s t u d ie s e lim in a t e
k n ow n ca u s e s o f m u s cle in a m -
all d ay, b u t sh e h as co n -
m a t io n , a d ia gn o s is o f id io p a t h ic
t in u e d t o g e t w e ak e r, t o t h e p o in t t h at sh e n e e d s h e lp g e t t in g in a m m a t o ry m yo p a t h y (IIM) ca n
in an d o u t o f h e r b at h t u b an d h as d if cu lt y re ach in g h ig h sh e lve s be m a d e (1 ). Id iop a t h ic in a m m a -
at w o rk . De sp it e avo id in g t h e su n sin ce t h e cru ise e n d e d , sh e h as t ory m yop a t h y is ve ry ra re, w it h a n
in cid e n ce o f a p p ro x im a t e ly 9 t o
a f ain t , p e rsist e n t “su n b u rn ” o n h e r h an d s an d k n e e s. Sh e is
12 ca s e s / m illio n / ye a r. It t yp ica lly
f at ig u e d an d h as d if cu lt y w it h b re at h in g w h ile g o in g u p st airs. m a n ife s t s e it h e r in you n g ch ild re n
Sh e h as n o t ice d m o re h e art b u rn t h an u su al, an d so m e t im e s so lid or in a d u lt s in t h e ft h d e ca d e of
f o o d “co m e s b ack u p .” Sh e d e n ie s t ak in g an y illicit d ru g s, h as h ad life , t h o u gh it ca n p re s e n t a t a n y
a ge. Wom e n a re m ore a ffe ct e d t h a n
n o m e d icat io n ch an g e s re ce n t ly, an d d rin k s w in e o n ly o ccasio n ally.
m e n (2 ).
Lo o k in g at h e r ch art , yo u n o t e t h at sh e h as h ad a n o rm al t h yro id - Th e t h re e m o s t co m m o n
st im u lat in g h o rm o n e an d e le ct ro lyt e p an e l in t h e p ast 1 ye ar, fo r m s o f IIM a r e p o ly m yo s it is
b u t sh e d id n o t g e t t h e m am m o g ram , Pap an ico lao u sm e ar, o r (PM) a n d in clu s io n b o d y m yo s it is
(IBM), w h e r e in fla m m a t io n is
co lo n o sco p y yo u h ad re co m m e n d e d .
fo u n d in m u lt ip le m u s c le s , a n d
d e r m a t o m yo s it is (DM), in w h ich
in a m m a t o ry ch a n ge s o ccu r in t h e s k in a s w e ll a s m u s cle s . In PM a n d DM,
in a m m a t io n is a ls o fr e q u e n t ly s ys t e m ic, a n d o ccu r s in o t h e r o rga n s s u ch
a s t h e jo in t s , lu n gs , h e a r t , o r ga s t r o in t e s t in a l (GI) t ra ct . Th is in a m m a t io n
m a n ife s t s a s d ire ct o rga n in lt ra t io n by m o n o n u cle a r ce lls , fr e q u e n t im m u n e
a b n o r m a lit ie s , a n d t h e p r o d u ct io n o f a u t o a n t ib o d ie s . Th is , in a d d it io n t o a
118
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 119
d e m o n s t ra t e d r e s p o n s e t o t h e ra p ie s t h a t d e cr e a s e in a m m a t io n , h a s le d t o
CLINICAL POINTS t h e cla s s i ca t io n o f IIM a s a u t o im m u n e d is e a s e s . Ye t , t h e IIM t h e m s e lve s
• Id io p a t h ic in a m m a t o ry a r e a h e t e r o ge n e o u s gr o u p o f r a r e s yn d r o m e s t h a t d iffe r c o n s id e r a b ly in
m yo p a t h y is a d ia g n o sis t h e ir clin ica l p re s e n t a t io n s , p a t h o lo gic n d in gs , d is e a s e co u r s e s , a n d p ro g-
o f e xclu sio n , a n d t h e n o s e s (3 ).
d iffe re n t ia l d ia g n o sis Mos t p a t ie n t s w it h DM p re s e n t w it h ch a ra ct e ris t ic ra s h e s ove r t h e kn u ckle s
ca n b e ch a lle n g in g .
(Got t ron ’s p a p u le s ; s e e Fig. 13.1A) or a rou n d t h e eye s (h e liot rop e ra s h ; Fig. 13.1B)
• Sym m e t ric p ro xim a l m u scle a n d p rogre s s ive, s ym m e t ric p roxim a l m u s cle w e a kn e s s , m ore p ron ou n ce d in
w e a kn e ss p re d o m in a t e s; a t h e le gs t h a n t h e a r m s , evo lvin g ove r w e e k s t o m o n t h s . Pa t ie n t s w it h PM
g o o d fu n ct io n a l a sse ssm e n t
o f t h e p a t ie n t is re q u ire d
p re s e n t w it h t h e w e a kn e s s , bu t n ot t h e ra s h . Th ey u s u a lly h a ve h ip m u s cle
in o rd e r t o d ist in g u ish t ru e w e a kn e s s , a n d n ot ice in cre a s in g d if cu lt y ge t t in g u p from a ch a ir or clim bin g
w e a kn e ss fro m p a in t h a t s t a irs . Th e s h ou ld e r m u s cle s oft e n be com e s ym p t om a t ic la t e r, re s u lt in g in d if-
lim it s fu n ct io n . cu lt y com bin g t h e h a ir or re a ch in g obje ct s on h igh s h e lve s . Im p ort a n t ly, on ly
• Ra sh e s in DM ca n b e on e q u a rt e r of p a t ie n t s w it h DM or PM h ave s ign i ca n t m u s cle p a in or t e n d e r-
su b t le , a n d m o st a re n o t n e s s . In t h e a bs e n ce of obje ct ive w e a kn e s s , h ip or s h ou ld e r gird le p a in a s t h e
p a t h o g n o m o n ic. on ly p re s e n t in g com p la in t s u gge s t s a n a lt e rn a t ive d ia gn os is , s u ch a s p olym y-
• Pa t ie n t s m a y h a ve clin ica l a lgia rh e u m a t ica .
w e a kn e ss b e fo re o r in t h e Ot h e r s ke le t a l m u s cle s ca n be a ffe ct e d , a n d 20% of p a t ie n t s h a ve d ys p h a gia
s
e
a b se n ce o f e le va t e d m u scle (w it h n a s a l regu rgit a t ion of liq u id s s ign ifyin g gre a t e r s eve rit y), w h ile a s m a lle r
s
a
e n zym e s; a m u scle b io p sy s u bs e t e xp e rie n ce s re s p ira t ory in s u f cie n cy from re s p ira t ory m u s cle w e a kn e s s .
e
is re q u ire d in m o st ca se s
s
i
Su bt le s ign s of e xt ra m u s cu la r in a m m a t ion m a y a ls o be p re s e n t if ca re fu lly
D
fo r d e n it ive d ia g n o sis,
c
e sp e cia lly in p a t ie n t s w it h - s ou gh t . Pa t ie n t s m ay h ave p rofou n d fa t igu e, p e rs is t e n t u n e xp la in e d low -gra d e
i
t
a
o u t t h e p a t h o g n o m o n ic feve rs , s ym m e t ric s m a ll-join t a rt h ra lgia s or a rt h rit is , a bd om in a l p a in , d ys p n e a
m
ra sh o f DM. on e xe rt ion from in t e rs t it ia l lu n g d is e a s e, or p a lp it a t ion s (from ca rd ia c con d u c-
u
e
t io n a bn o r m a lit ie s ) a n d h e a r t fa ilu re re la t e d t o d ire ct in a m m a t io n o f t h e
h
• Ca n ce r h a s b e e n a sso cia t e d
R
w it h IIM, e sp e cia lly DM; ca rd ia c m u s cle.
c
i
a g e -a p p ro p ria t e ca n ce r
c
e
scre e n in g sh o u ld b e
p
S
p e rfo rm e d . Wo m e n w it h
DIFFERENTIAL DIAGNOSIS
3
IIM sh o u ld b e e va lu a t e d
N
fo r o va ria n ca n ce r. Th e IIM a re s ys t e m ic con n e ct ive t is s u e d is e a s e s , a n d m a n y o t h e r o rga n s ys -
O
I
T
t e m s ca n b e in vo lve d , re s u lt in g in a w id e ra n ge o f p o s s ible p re s e n t a t ion s a n d
C
E
s ym p t o m s t h a t ca n m im ic m a n y o t h e r d is o rd e r s . Th u s , t h e d iffe re n t ia l d ia g-
S
n o s is o f IIM in clu d e s t h e m a n y d is o rd e rs a s s o cia t e d w it h m u s cle com p la in t s
a n d is co n s id e ra bly ch a lle n gin g, n o t o n ly b e ca u s e o f t h e p le t h o ra o f co n d i-
t io n s t o b e co n s id e re d , b u t a ls o b e ca u s e IIM a re s o ra re t h a t few clin icia n s a re
NOT TO BE MISSED t h o ro u gh ly fa m ilia r w it h t h e s e d is e a s e s . On e be gin s w it h cle a rly d e n in g t h e
p a t ie n t ’s p r im a ry p ro ble m s . Sin ce p a t ie n t s m a y u s e “w e a k n e s s ” a n d “p a in ”
A Diffe re ntial Diag no sis o f in t e rch a n ge a bly, q u e s t io n s s h o u ld fo cu s o n (1 ) d is t in gu is h in g m ya lgia s fro m
Muscle We akne ss o r Pain t r u e w e a k n e s s , w h ich is o ft e n p a in le s s , by fo cu s in g o n t h e p a t ie n t s ’ fu n c-
Nonin ammatory t io n a l a b ilit ie s (w h a t t h ey ca n a n d ca n n o t d o in t h e ir d a ily ro u t in e ) (2 ); t h e
Myopathies lo ca t io n o f w e a k n e s s (p rox im a l m u s cle s in PM a n d DM vs . d is t a l m u s cle s in
• En d o crin e (h yp o - a n d IBM a n d o t h e r d is o rd e r s ; s ym m e t r ic w e a k n e s s in PM a n d DM vs . a s ym m e t r ic
h yp e rt h yro id ism , m u s cle in vo lve m e n t in IBM a n d o t h e r d is o rd e r s ) (3 ); t h e t im e fra m e a n d
a cro m e g a ly, d ia b e t e s, t e m p o o f s ym p t o m p rogre s s io n a n d w h e t h e r a t ro p h y is p re s e n t , s ign ifyin g a
Cu sh in g ’s syn d ro m e , ch ro n ic co u r s e m o s t co n s is t e n t w it h d ys t ro p h ie s (4 ); a n d a n y a s s o cia t e d n o n -
Ad d iso n ’s d ise a se , h yp o -
a n d h yp e rp a ra t h yro id ism , m u s cu la r s ym p t o m s s u ch a s fa t igu e , low -gra d e feve r s , ra s h e s , b re a t h in g o r
hypocalcemia, hypokalemia) sw a llow in g d if cu lt ie s , a rt h r it is o r a r t h ra lgia s , w h ich s u gge s t a s ys t e m ic d is -
e a s e , s u ch a s IIM.
• To xic (e t h a n o l,
co rt ico st e ro id s, co ca in e , Ne x t , o n e n e e d s t o co n s id e r p o s s ible ca u s e s . Ha s t h e in d ivid u a l b e e n
st a t in s, b ra t e s) exp osed to a n y m yotoxin s , licit or illicit d ru gs, bota n ica l or ot h er over-th e-cou n ter
p r e p a ra t io n s t h a t co u ld r e s u lt in m yo p a t h y, o r a m e t a b o lic a b n o r m a lit y
• Me t a b o lic (a cid m a lt a se
d e cie n cy, ca rn it in e s u ch a s h yp o ka le m ia ? Ha s t h e p a t ie n t h a d a n y re ce n t u n u s u a l e xp os u re, in fe c-
d e cie n cy, u re m ia ) t io n , or t ra ve l? Are t h e re a n y s ym p t o m s o r n d in gs t h a t s u gge s t t h yro id or
p a ra t h yroid d is e a s e, d ia be t e s , or a n u n d e rlyin g m a lign a n cy? Is t h e re a fa m ily
• Co n g e n it a l
h is t o ry o f a s im ila r d is o rd e r t h a t w o u ld s u gge s t a d ys t ro p h y o r in h e r it e d
• Mit o ch o n d ria l m yo p a t h y?
(Co n t in u e d )
120 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
A B
S
E
C
T
I
O
N
3
S
p
e
c
i
c
R
h
e
u
C D
m
a
t
i
c
D
i
s
e
a
s
e
s
E F
Figure 13.1 Skin cha nges seen in derma tomyositis. A: Gottron’s pa pules a re sca ly pa pules overlying the extensor surfa ces of the ha nds (over the meta -
ca rpopha la ngea l a nd proxima l interpha la ngea l joints in this ca se), elbows, knees, or ma lleoli. This pa tient a lso ha s scleroda ctyly a nd a rthritis of the
meta ca rpopha la ngea l a nd proxima l interpha la ngea l joints. B: The heliotrope ra sh is a purplish discolora tion a round the eyes, especia lly on the upper
lids. C: Linea r extensor erythema overlies the extensor surfa ce of the ha nds beyond the usua l loca tion of Gottron’s pa pules or sign. D: Periungua l va s-
culitic cha nges a nd cuticula r overgrowth. E: Photosensitive diffuse erythroderma with a ccentua ted erythema in the V of the neck (V sign) in a pa tient with
ca ncer-a ssocia ted derma tomyositis. F: Drying a nd cra cking of the skin over the la tera l a nd pa lma r surfa ces of the ngers, known a s “mecha nic’s ha nds,”
is seen frequently in pa tients with both DM a nd PM with one type of myositis-speci c a ntibodies, the a utoa ntibodies to a minoa cyl-tRNA syntheta ses (the
a ntisyntheta se syndrome). With permission from Miller W. Frederick in a mma tory myopa thies: Polymyositis, derma tomyositis, a nd rela ted conditions.
In: Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions: A Textbook of Rheuma tology. 15th ed. Ba ltimore: Lippincott Willia ms & Wilkins;
2005:6–7.
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 121
DIAGNOSTIC CRITERIA
NOT TO BE MISSED (Co n t in u e d )
Crit e ria t o d e n e t h e IIM s yn d rom e s a n d d is t in gu is h t h e m from ot h e r m yop a -
Muscular Dystro phie s t h ie s w e re p rop os e d m ore t h a n 30 ye a rs a go (4 ) a n d re m a in u s e fu l t od ay. Sin ce
• Myo t o n ia t h e s e a re d ia gn os e s of e xclu s ion , on e m u s t rs t d o a n eva lu a t ion d ire ct e d by t h e
h is t ory a n d p h ys ica l e xa m in a t ion n d in gs t o e xclu d e t h e m a n y ot h e r ca u s e s of
• Ne u rop a t hie s [am yo t ro ph ic
m yop a t h y. On ce t h is h a s be e n a ccom p lis h e d , a d ia gn os is of IIM ca n be m a d e
la t e ra l scle ro sis (ALS),
Guilla in –Ba rre syn drom e , u s in g t h e n d in gs of a cu t e or s u ba cu t e s ym m e t ric p roxim a l m u s cle w e a kn e s s ,
d ia b e t ic p le xop a th y] s ign i ca n t e leva t ion of m u s cle e n zym e s , ch a ra ct e ris t ic EMG a bn orm a lit ie s , a n d
m u s cle biop s y n d in gs or ra s h e s con s is t e n t w it h IIM (Ta ble 13.1 ). In u n cle a r
• Ne u ro m u scu la r ju n ct io n
d iso rd e rs (Ea t o n –La m b e rt ca s e s , a d d it ion a l clu e s t h a t ca n a s s is t in m a kin g t h e d ia gn os is of IIM in clu d e
syn d ro m e a n d m ya st h e n ia t h e p re s e n ce of a n t in u cle a r a n t ibod ie s (ANA) or m yos it is a u t oa n t ibod ie s (5 ), a
g ra vis) fa m ily h is t ory of a u t oim m u n e d is e a s e, d e t e ct ion of in a m m a t ory ch a n ge s in
• Ove ru se syn d ro m e s m u s cle s by m a gn e t ic re s on a n ce im a gin g (MRI) (6 ), or a clin ica l re s p o n s e t o
im m u n os u p p re s s ive t h e ra p y (Ta ble 13.2 ).
• Pa ra n e o p la st ic
In clu s ion b o d y m yo s it is is t h e m o s t co m m on IIM o ccu rr in g in p a t ie n t s
(carcinomatous neuropathy,
ca ch e xia , m yo n e cro sis) old e r t h a n 50 ye a rs . Pa t ie n t s w it h IBM u s u a lly fu l ll t h e IIM crit e ria , bu t in con -
t ra s t , h a ve m ore s low ly p rogre s s ive w e a k n e s s o f t h e q u a d r ice p s a n d d is t a l
• Rh a b d o m yo lysis
m u s cle s of t h e a rm s , in a s om ew h a t a s ym m e t ric fa s h ion ; low e r e leva t ion s of
s
e
s
• Te n d o n it is–fa sciit is s e ru m CK leve ls ; a n d ch a ra ct e ris t ic a m ylo id d e p o s it s a n d rim m e d va cu o le s
a
e
w it h in m yocyt e s s e e n on ligh t m icros cop y. Som e in a m m a t ory ch a n ge s m ay
s
In ammato ry Myo pathie s
i
D
be p re s e n t , bu t a m yloid d ep os it ion p re d om in a t e s . Alt h ou gh s om e p a t ie n t s m a y
c
In fe ct io u s
i
in it ia lly im p rove w it h im m u n o s u p p re s s ive t re a t m e n t s , m o s t h a ve a gra d u a l
t
a
• Ba ct e ria l (St ap h ylo co ccu s,
m
a n d re le n t le s s p rogre s s ion of m u s cle w e a kn e s s .
u
St re p t o co ccu s, Clo st rid ia ,
e
Mycobacterium tuberculosis)
h
R
c
• Vira l (in u e n za ,
i
a d e n o viru s, Ep st e in –Ba rr Table 13.1 Bohan and Pet er Crit eria for t he Diagnosis of
c
e
viru s, co xsa ckie viru s, Dermat omyosit is (DM) and Polymyosit is (PM)a
p
S
h e p a t it is B a n d C, h u m a n
3
im m u n o d e cie n cy viru s
N
(HIV), human T-lymphotropic 1. Sym m e t ric w e a kn e ss, u su a lly p ro g re ssive , o f t h e p ro xim a l lim b -g ird le m u scle s
O
I
virus 1 (HTLV-1))
T
2. Ele va t io n o f se ru m le ve ls o f m u scle -a sso cia t e d e n zym e s
C
E
• Fu n g a l (Can d id a ,
S
– CK, a ld o la se , LDH, AST/SGOT, ALT/SGPT
co ccid io m yco sis)
3. EMG t ria d o f m yo p a t h y
• Pa ra sit ic (t rich in o sis,
t o xo ca ria sis, cyst ice rco sis, – Sh o rt , sm a ll, lo w -a m p lit u d e p o lyp h a sic m o t o r u n it p o t e n t ia l
t ryp a n o so m ia sis,
t o xo p la sm o sis) – Fib rilla t io n p o t e n t ia ls, e ve n a t re st
e xt e n s or w e a kn e s s ), a n d n ot e w h a t t h e p a t ie n t ca n a n d ca n n ot d o com p a re d t o
a p reviou s t im e p oin t . A s im p le a ct ivit ie s -of-d a ily-livin g q u e s t ion n a ire t h a t ca n
be e a s ily s core d is oft e n u s e fu l. Th e re m a in d e r of t h e n e u rologic e xa m in a t ion ,
in clu d in g s e n s ory t e s t in g, s h ou ld be n orm a l; n ot e t h a t m u s cle t e n d on re e xe s
a re p re s e rve d u n t il t h e w e a kn e s s is a d va n ce d . On e s h ou ld eva lu a t e t h e fu n c-
t ion of ot h e r m u s cle s a n d orga n s , in clu d in g t h e h e a rt (is t h e p u ls e irregu la r,
s u gge s t in g co n d u ct io n a bn o r m a lit ie s , o r a re t h e re s ign s o f h e a r t fa ilu re ?);
orop h a ryn x (is sw a llow in g n orm a l?); re s p ira t ory m u s cle s a n d lu n gs (n ot e t h e
p a t ie n t ’s ove ra ll re s p ira t ory e ffort in a d d it ion t o a ca re fu l lu n g e xa m in a t ion
lis t e n in g for Ve lcro cra ckle s t h a t h e ra ld in t e rs t it ia l lu n g d is e a s e or coa rs e cra ck-
le s s ign ifyin g a s p ira t ion p n e u m on ia ). An y d e t e ct e d a bn orm a lit ie s s h ou ld be
p u r s u e d w it h a p p ro p ria t e t e s t s , a s in d ica t e d , s u ch a s a n e le ct roca rd iogra m
(EKG), Ho lt e r m o n it o r in g, o r e ch o ca rd io gra m , sw a llow in g s t u d y, ch e s t x -ra y
a n d /or com p u t e d t om ogra p h ic (CT) s ca n of t h e ch e s t , a n d p u lm on a ry fu n ct ion
t e s t s w it h in s p ira t ory a n d e xp ira t ory p re s s u re s (Ta ble 13.3 ).
Ma n y o f t h e s kin le s io n s d e s cr ib e d in p a t ie n t s w it h DM a re s u b t le , a n d
be ca u s e t h ey a re oft e n m in im ize d by t h e p a t ie n t s t h e m s e lve s , t h ey m u s t be
a ct ive ly s o u gh t d u r in g t h e e x a m in a t io n . No n e o f t h e m is p a t h ogn o m o n ic,
s
e
e xce p t Got t ron ’s p a p u le s . Th e s e a re p a lp a ble le s ion s ove rlyin g t h e e xt e n s or
s
a
s u rfa ce s of t h e h a n d join t s , e lbow s , kn e e s , or m a lle oli w it h a n e ryt h e m a t ou s
e
s
i
b a s e (Fig. 13.1A ). Ot h e r ra s h e s ch a ra ct e r is t ic for DM in clu d e Got t ro n ’s s ign ,
D
c
w h ich is a s ca lin g e ryt h e m a w it h o u t p a p u le s in t h e s a m e d is t r ib u t io n a s
i
t
a
Go t t ro n ’s p a p u le s , a n d t h e h e lio t ro p e ra s h , a s u b t le , p u r p lis h d is co lo ra t io n
m
a rou n d t h e eye s (Fig. 13.1B). In t h e a b s e n ce o f a p ro m in e n t h e lio t ro p e ra s h ,
u
e
p a t ie n t s m ay h ave s u bt le p e riorbit a l e d e m a . Ot h e r com m on ra s h e s in clu d e a
h
R
s ca lin g s ca lp ra s h re s e m blin g p s o ria s is (p s e u d op s oria s is ), s om e t im e s a s s oci-
c
i
a t e d w it h p a t ch y a lo p e cia if s eve re ; lin e a r e x t e n s o r e ryt h e m a (Fig. 13.1C );
c
e
p e riu n gu a l va s cu lit ic ch a n ge s a n d cu t icu la r ove rgrow t h (Fig. 13.1D ); p h ot os e n -
p
S
s it ive e ryt h ro d e r m a ; a cce n t u a t e d e ryt h e m a in t h e V o f t h e n e ck (V s ign ;
3
Fig. 13.1E) or a rou n d t h e s h ou ld e rs (s h aw l s ign ); a n d a d ryin g a n d cra ckin g of
N
O
t h e s kin ove r t h e la t e ra l a n d p a lm a r s u rfa ce s of t h e n ge rs , kn ow n a s “m e ch a n -
I
T
C
ic’s h a n d s ” (Fig. 13.1F). In p a t ie n t s w it h ch ro n ic or s eve re s k in ra s h e s a n d in
E
S
ch ild re n , s u bcu t a n e ou s ca lciu m d ep os it s , or ca lcin os is , d eve lop ove r t im e.
Mo s t im p ort a n t ly, if IIM (a n d DM in p a rt icu la r ) is s u s p e ct e d , t h e clin ica l
eva lu a t ion is n ot com p le t e w it h ou t a t h orou gh a ge -a p p rop ria t e ca n ce r s cre e n -
in g. Mu lt ip le p op u la t ion -ba s e d s t u d ie s a n d regis t rie s h a ve fou n d a n in cre a s e d
in cid e n ce of m a lign a n cie s in p a t ie n t s w it h DM (s t a n d a rd ize d in cid e n ce ra t io
(SIR) 3.0:12.6) (7 ) a n d t o a le s s e r d egre e in p a t ie n t s w it h PM (SIR 1.9) com p a re d
t o t h e ge n e ra l p op u la t ion . Alt h ou gh t h e t yp e of m a lign a n cy va rie s a n d is oft e n
a ge s p e ci c, t h e s t ron ge s t a s s ocia t ion s w e re w it h ova ria n , lu n g, p a n cre a t ic, GI,
a n d n on -Hod gkin lym p h om a . Of s p e cia l n ot e, ova ria n ca n ce r w a s ove rre p re -
s e n t e d in s om e s e rie s a n d s h ou ld be s p e ci ca lly s cre e n e d for in w om e n w it h
IIM, e s p e cia lly DM.
Pa tho g e ne sis
W h ile t h e ca u s e s of t h e IIM a re by d e n it ion u n kn ow n , evid e n ce s u gge s t s t h a t
t h ey like ly re s u lt from on e or m ore e n viron m e n t a l s t im u li a ct in g on ge n e t ica lly
s u s ce p t ible in d ivid u a ls t o in d u ce ch ron ic im m u n e a ct iva t ion a n d s u bs e q u e n t
m yos it is . Som e e n viron m e n t a l t rigge rs a re be t t e r u n d e rs t ood t h a n ot h e rs . As
w it h t h e ca s e a t t h e begin n in g of t h is ch a p t e r, e xce s s ive e xp os u re t o u lt raviole t
ligh t h a s be e n s h ow n t o in d u ce a n d e xa ce rba t e t h e ra s h of DM. In con t ra s t , HIV
a n d HTLV-1 in fe ct ion s h ave be e n a s s ocia t e d w it h PM.
Ma n y lin e s of in d ire ct evid e n ce s u gge s t t h a t in a p p rop ria t e ce llu la r im m u n e
a ct iva t ion is re s p on s ible for t h e p a t h ologic e ffe ct s s e e n in m yos it is a n d t h a t t h e
p a t t e rn s of im m u n e a ct iva t ion a re d is t in ct be t w e e n t h e d iffe re n t IIMs , in volv-
in g d iffe re n t ce lls a n d p roce s s e s . In DM, a va s cu lop a t h y m a y be t h e p rim a ry
124 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Table 13.3 Syst emic Manifest at ions of IIM and Suggest ed Furt her Invest igat ions
Mu scu lo ske le t a l
Mu scle w e a kn e ss, p ro xim a l d ist a l, u p p e r Ot h e r cau se s: fa st in g g lu co se , Ca , Ph o s, K, TSH, GGT (if a lco h o l)
a n d lo w e r limb s, n eck, ra re ly fa cia l mu scle s
La b o ra t o ry t e st s o f m u scle e n zym e s (se e t e xt )
Ne u ro lo g ic e xa m in a t io n , EMG, m u scle b io p sy o f t h e m u scle m o st
in vo lve d ; co n sid e r MRI o f m u scle if u n cle a r sit e fo r b io p sy
Art h ra lg ia s o r a rt h rit is X-ra ys o f a ffe ct e d jo in t s
Re sp ira t o ry
Dysp n e a a t re st a n d /o r o n e xe rt io n , d ry Ch e st x-ra y
co u g h , w h e e zin g , ra le s
S
Pn e u m o n ia d u e t o a sp ira t io n o r Ch e st x-ra y, CT ch e st a s n e e d e d
E
C
im m u n o su p p re ssio n
T
In t e rst it ia l lu n g d ise a se CT ch e st w it h p ro n e p o sit io n in g ; p u lm o n a ry fu n ct io n t e st s
I
O
N
Ca rd ia c
3
Co n g e st ive h e a rt fa ilu re Ech o ca rd io g ra m
S
Arrh yt h m ia s EKG, Ho lt e r m o n it o rin g
p
e
Myo ca rd it is Rig h t ve n t ricu la r h e a rt b io p sy; ca rd ia c MRI
c
i
c
Ga st ro in t e st in a l
R
Dysa rt h ria —p o o r t o n g u e p ro p u lsio n s Fo rm a l sw a llo w in g e va lu a t io n
h
e
Dysp h a g ia —u p p e r a n d lo w e r e so p h a g e a l
u
d ysm o t ilit y
m
a
Re u x e so p h a g it is Em p iric t h e ra p y; co n sid e r EGD if p ro lo n g e d , se ve re d ysp h a g ia
t
i
c
Skin
D
i
De rm a t o m yo sit is-sp e ci c ra sh e s Clin ica l p h o t o g ra p h y (a s b a se lin e ) a n d skin b io p sy
s
e
De rm a t o m yo sit is-a sso cia t e d ra sh e s
a
s
Pa n n icu lit is
e
s
Ca lcin o sis cu t is Ca n b e se e n o n x-ra ys
Pe riu n g u a l ca p illa ry ch a n g e s Exa m in e w it h o p h t h a lm o sco p e (o n 40-d io p t e r se t t in g )
Ra yn a u d ’s p h e n o m e n o n N/A
Asso cia t io n w it h m a lig n a n cy Ag e -a p p ro p ria t e ca n ce r scre e n in g
Ova ria n ca n ce r scre e n in g in w o m e n w it h IIM
ESR, e ryt h ro cyt e se d im e n t a t io n ra t e ; CRP, c-re a ct ive p ro t e in ; ANA, a n t in u cle a r a n t ib o d y; ENA, a n t ie xt ra ct a b le n u cle a r a n t ig e n a n t ib o d y p a n e l; se e
Ta b le 13.2 fo r sp e ci cs.
Ca , se ru m ca lciu m le ve l; Ph o s, se ru m p h o sp h o ru s le ve l; K, se ru m p o t a ssiu m le ve l; TSH, t h yro id -st im u la t in g h o rm o n e ; GGT, g a m m a -g lu t a m yl
t ra n sp e p t id a se , o ft e n h e lp fu l in d ist in g u ish in g a lco h o l-re la t e d ve rsu s m yo sit is-re la t e d t ra n sa m in a se e le va t io n .
EMG, electromyography; CT, computed tomography; EKG, electrocardiogram, MRI, magnetic resonance imaging; EGD, esophagogastroduodenoscopy.
s
e
e leva t ion of s e ru m CK leve ls in IIM is d u e t o in cre a s e s in t h e MM is oe n zym e
s
a
fra ct ion , w h ich is re le a s e d from s ke le t a l m u s cle . Eleva t ion of t h e MB is oe n -
e
s
i
zym e, fou n d p rim a rily in t h e m yoca rd iu m , m a y a ls o occu r n ot on ly a s a re s u lt
D
c
o f m yo ca rd it is bu t a ls o a s a n in d ica t o r o f s ke le t a l m u s cle rege n e ra t io n a n d
i
t
a
m yo bla s t a ct iva t io n . In p a t ie n t s w it h IIM, m yobla s t a ct iva t ion a ls o re s u lt s in
m
e leva t io n o f o t h e r e n z ym e s t h a t co r re la t e w it h CK leve ls , in clu d in g la ct a t e
u
e
d e h yd roge n a s e (LDH), a ld o la s e , s e r u m glu t a m ic ox a lo a ce t ic t ra n s a m in a s e /
h
R
a s p a rt a t e a m in ot ra n s fe ra s e (SGOT/AST), a n d s e ru m glu t a m ic pyru vic t ra n s a m -
c
i
in a s e /a la n in e a m in ot ra n s fe ra s e (SGPT/ALT). Eleva t ion s of t h e la t t e r t w o h a ve
c
e
s om e t im e s le d t o u n n e ce s s a ry live r biop s ie s .
p
S
Alt h ou gh t h e s e ru m leve ls of CK a n d ot h e r m u s cle -d e rive d e n zym e s a re
3
N
ge n e ra lly u s e fu l in follow in g m yos it is a ct ivit y a n d re s p on s e s t o t h e ra p y, t h ey
O
ca n n o t s u b s t it u t e fo r a t h o ro u gh eva lu a t io n o f t h e p a t ie n t , w h ich in clu d e s
I
T
C
fu n ct ion a l a s s e s s m e n t . Firs t , t h e re is a d e la y be t w e e n t h e m a gn it u d e of t h e
E
S
e n zym e e leva t ion a n d globa l d is e a s e a ct ivit y; t h e CK leve ls t e n d t o n orm a lize 3
t o 8 w e e k s b e fore m u s cle s t re n gt h im p rove s a n d con ve rs e ly m a y r is e 5 t o
6 w e e ks a ft e r a clin ica l re la p s e is d e t e ct e d . Th e re fore, clin ica l im p rove m e n t or
w ors e n in g in t h e p a t ie n t m u s t be corre la t e d w it h CK leve ls , n ot t h e reve rs e.
Se con d , a p a t ie n t w it h IIM m a y h a ve a n orm a l CK leve l in t h e fa ce of clin ica lly
a ct ive d is e a s e , a s d e m o n s t ra t e d by m u s cle w e a k n e s s a n d a cco m p a n ie d by
in a m m a t ion on m u s cle biop s y or MRI. Th is m ay be d u e t o s u p p re s s ion of CK
by cort icos t e roid s , t h e p re s e n ce of s e ru m in h ibit ors of CK e n zym e a ct ivit y, or
e xt e n s ive m u s cle a t rop h y be ca u s e of ch ron ic d is e a s e. In a d d it ion , p a t ie n t s w it h
s ys t e m ic lu p u s e ryt h e m a t os u s , rh e u m a t oid a rt h rit is , a n d ot h e r con n e ct ive t is -
s u e d is e a s e s t e n d t o h ave a bn orm a lly low CK leve ls ; t h u s , a n orm a l CK leve l in
t h e s e p a t ie n t s m a y in d ica t e a ct ive m yos it is . In con t ra s t , ra cia l a n d ot h e r d iffe r-
e n ce s n ot t a ke n in t o a ccou n t by t h e t e s t in g la bora t ory m a y re s u lt in fa ls e ly
h igh CK leve ls . Be ca u s e CK leve ls corre la t e w it h m u s cle m a s s , Africa n Am e rica n s
h a ve s ign i ca n t ly h igh e r ba s e lin e CK leve ls t h a n Ca u ca s ia n s , a s d o m u s cu la r
a t h le t e s a n d m a ra t h on ru n n e rs .
Abn orm a lit ie s of n on s p e ci c m a rke rs of in a m m a t ion —s u ch a s le u kocyt o-
s is , e leva t e d p la t e le t cou n t s , h igh C-re a ct ive p rot e in , a n d e ryt h rocyt e s e d im e n -
t a t ion ra t e s —m a y be fou n d in p a t ie n t s w it h m yos it is . Th e s e m ay be u s e fu l in
a s s e s s in g IIM a ct ivit y, a ft e r be in g s u re t o e xclu d e ot h e r coe xis t in g p roce s s e s
s u ch a s in fe ct io n o r m a lign a n cy, w h ich ca n a ls o ca u s e t h e s e a b n o rm a lit ie s .
Tw e n t y-fo u r-h o u r u rin a ry cre a t in in e e x cre t io n , w h ich re e ct s m u s cle m a s s
a n d d a m a ge, is e leva t e d in m a n y p a t ie n t s w it h m u s cle d is e a s e s . Ad d it ion a lly,
a b n o rm a lly low s e ru m cre a t in in e leve ls m a y b e t h e re s u lt o f lo s s o f m u s cle
m a s s a n d s h ou ld a le rt on e t o t h e p re s e n ce of ch ron ic m yos it is .
126 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
IMMUNOLOGY
Im m u n ologic a bn orm a lit ie s a re s om e t im e s t h e rs t clu e t h a t a p a t ie n t h a s IIM.
Th e m os t fre q u e n t a bn orm a lit ie s a re h yp e rga m m a globu lin e m ia or t h e p re s e n ce
of a n a u t oa n t ibod y. An t in u cle a r a u t oa n t ibod ie s (ANAs ) a re t h e m os t com m on
a u t oa n t ibod ie s , bu t occu r on ly in 25% of p a t ie n t s (9 ). Th e ANA u s u a lly d is p lays
a s p e ckle d p a t t e rn , a lt h ou gh a n y ot h e r p a t t e rn ca n a ls o be p re s e n t . Ot h e r
im m u n e a bn or m a lit ie s in clu d e h yp oga m m a globu lin e m ia , m on oclon a l ga m -
m op a t h y, cryoglobu lin e m ia , a n d a va rie t y of a u t oa n t ibod ie s , s om e of w h ich a re
s t ron gly a s s ocia t e d w it h m yos it is (m yos it is a u t oa n t ibod ie s ) (Ta ble 13.2 ).
MUSCLE BIOPSY
Alt h o u gh p h ys icia n s m a y b e re lu ct a n t t o p e rfo r m a m u s cle b io p s y in w h a t
w ou ld a p p e a r t o be s t ra igh t forw a rd ca s e s of DM o r PM, a biop s y s h o u ld be
in clu d e d e a rly in t h e eva lu a t ion of m os t p a t ie n t s , give n t h e m a n y ot h e r con d i-
t ion s t h a t ca n clos e ly m im ic t h e IIM. Th e biop s y m a y reve a l a n u n e xp e ct e d
d is e a s e, s om e t im e s w it h im p o rt a n t t h e ra p e u t ic, p rogn o s t ic, or re p rod u ct ive
im p lica t io n s . It s h ou ld be obt a in e d in t h e m u s cle ju d ge d t o be t h e w e a ke s t
(u s u a lly t h e d e lt o id o r q u a d rice p s m u s cle s ), a n d o n t h e s id e o p p o s it e fro m
w h e re t h e EMG w a s p e rform e d , t o a vo id a fa ls e -p o s it ive re s u lt . No n e t h e le s s ,
t h e biop s y m ay n ot a lw a ys be d ia gn os t ic. W h e n a m u s cle ce ll d ie s for a n y re a -
s on , a s e con d a ry in a m m a t ory p roce s s m ay occu r. Th e re fore, m u s cle in a m -
m a t io n ca n b e p re s e n t in s o m e d ys t ro p h ie s , e s p e cia lly fa cio s ca p u lo h u m e ra l
a n d d ys fe rlin d ys t rop h ie s , a n d in s om e t oxic m yop a t h ie s . In a d d it ion , in a m -
m a t ion in t yp ica l m yos it is m ay be m is s e d be ca u s e of it s s p ot t y n a t u re or a s a
re s u lt of t h e ra p y. Th e yie ld ca n be im p rove d by p e rform in g a n MRI of t h e m os t
clin ica lly a ffe ct e d m u s cle s , w h ich ca n d e t e ct m u s cle in a m m a t ion a n d d a m -
a ge a n d t h u s d ire ct t h e s it e of biop s y.
W h e n it is d e t e ct e d , m u s cle in a m m a t ion in IIM con s is t s of a p re p on d e r-
a n ce of lym p h ocyt e s , w h ich a re oft e n in d ire ct con t a ct w it h a d yin g m yocyt e
(e n d o m ys ia l), a s in t h e ca s e o f cyt o t ox ic CD8 T ce lls in PM (Fig. 13.2A); o r
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 127
A B
s
e
s
a
e
s
i
D
c
i
t
a
m
u
e
h
R
c
i
c
e
p
C D
S
3
N
O
I
T
C
E
S
E F
Figure 13.2 Biopsy ndings in Myositis. A: Muscle biopsies from pa tients with polymyositis tend to show foca l endomysia l in ltra tion by mononuclea r
cells (hema toxylin a nd eosin sta in). B: Muscle biopsies from pa tients with derma tomyositis show more periva scula r a nd interstitia l in a mma tion with
perifa scicula r myo ber a trophy (modi ed trichrome sta in). C: Tra nsverse fresh-frozen section of muscle from a pa tient with inclusion body myositis dis-
pla ying purplish gra nula r ma teria l lining the multiple va cuoles in severa l myo bers a nd the presence of a ngula ted myo bers (modi ed trichrome sta in).
D: Strong a lka line phospha ta se sta ining of the interstitium is common in the IIM a nd ca n help distinguish this condition from other myopa thies, even in
the a bsence of in a mma tion. E: Trichinosis pa ra sites in a myo ber surrounded by mononuclea r in a mma tory cells in a pa tient origina lly misdia gnosed
with polymyositis (Courtesy Dr. Lori A. Love ). F: Intensely in a mma tory gra nuloma tous myositis is cha ra cterized by the presence of gra nuloma ta a nd
endomysia l in a mma tion in this pa tient with sa rcoidosis (hema toxylin a nd eosin sta in). With permission from Miller W. Frederick. In a mma tory myopa -
thies: Polymyositis, derma tomyositis, a nd rela ted conditions. In: Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions: A Textbook of
Rheuma tology. 15th ed. Ba ltimore: Lippincott Willia ms & Wilkins; 2005:6–7.
128 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
IMAGING STUDIES
Ra d iogra p h ic s t u d ies a re u s e fu l in s cre en in g for a n d a s s e s s in g ga s t roin t e s t in a l,
ca rd ia c, a n d p u lm on a ry d is e a s e, eros ive a rt h rop a t h y, or ca lci ca t ion s (Ta ble 13.3 ).
Th e re is in cre a s in g in t e re s t in u s in g MRI, a n d a re la t e d t e ch n iq u e ca lle d m a g-
n e t ic re s o n a n ce s p e ct ro s co p y, t o a s s e s s m u s cle d is e a s e b e ca u s e t h e s e t e ch -
n iq u e s a re n on in va s ive a n d ca n s a m p le la rge r vo lu m e s o f m u s cle t h a n EMG
a n d m u s cle b iop s y. St u d ie s s u gge s t t h a t a co m bin a t ion of t h e T1-w e igh t e d
im a ge a n d t h e STIR (s h ort t a u in ve rs ion rep e a t ) or ot h e r fa t -s u p p re s s e d im a ge
s h ou ld be com bin e d t o a s s e s s m u s cle d is e a s e in IIM. Mu lt ip le cros s -s e ct ion s of
t h e t h igh s a re u s u a lly u s e fu l view s , bu t t h e loca t ion t o be eva lu a t e d s h ou ld be
d ict a t e d by t h e lo ca t ion of t h e m os t s eve re t h e s ign s a n d s ym p t om s of t h e
in d ivid u a l. De s p it e t h e e xp e n s e of MRI, it m ay be a cos t -e ffe ct ive a d ju n ct for
d ia gn os in g a n d a s s e s s in g s e le ct e d p a t ie n t s by d ire ct in g t h e biop s y s it e. Of n ot e,
p a t ie n t s s h ou ld be in s t ru ct e d t o re s t for a t le a s t a n h ou r p rior t o t h e s t u d y.
WHEN TO REFER Act ive e xe rcis e ca n ca u s e m u s cle ch a n ge s t h a t re s u lt in t ra n s ie n t e leva t ion s in
• In it ia l d ia g n o sis o f IIM.
s e ru m CK leve ls a n d in a m m a t ory ch a n ge s s e e n on MRI.
• Pa t ie n t w it h IIM n o t
re sp o n d in g t o m a xim a l
d o se s o f p re d n iso n e . Tre a tme nt
• Pa t ie n t w it h IIM w it h GENERAL CONSIDERATIONS
su sp e ct e d in t e rst it ia l Fo r t h e p r im a ry ca re p h ys icia n , t h e r s t s t e p in t re a t m e n t is t o con s id e r e a r ly
lu n g d ise a se , ca rd ia c
in vo lve m e n t , o r se ve re re fe r ra l t o a s p e cia lis t fa m ilia r w it h m u s cle d is e a s e s (a r h e u m a t o lo gis t , o r
GI in vo lve m e n t . n e u ro logis t , w it h t h e a s s is t a n ce of a d e r m a t ologis t , d e p e n d in g o n t h e ca s e ).
Th e re a re m a n y re a s o n s for e a r ly re fe r ra l, in clu d in g t h e fa ct t h a t a d e la y in
• Pa t ie n t w it h ch ro n ic
IIM w it h n e w w e a kn e ss, d ia gn o s is is a s s o cia t e d w it h in cr e a s e d m o r b id it y a n d m o r t a lit y (2 ); t h a t
su sp e ct e d t o h a ve a re d . m yos it is a u t o a n t ibo d y t e s t in g a s w e ll a s s p e ci c s t a in s a n d in t e r p re t a t io n o f
m u s cle b io p s ie s fre q u e n t ly re q u ire e x p e r t is e fro m t e r t ia ry re fe r ra l ce n t e r s ;
• Pa t ie n t w it h DM w it h skin
in vo lve m e n t o n ly, n o t t h a t t h e IIM a re m u lt io rga n d is e a s e s t h a t u s u a lly n e ce s s it a t e m u lt is p e cia lt y
re sp o n d in g t o st a n d a rd eva lu a t io n a n d co o rd in a t io n o f ca re ; a n d t h a t d e d ica t e d t e r t ia ry re fe r ra l ce n t -
t h e ra p y. e r s h a ve o n go in g re s e a rch e ffo r t s t h a t a re in va lu a ble fo r p a t ie n t s w it h t h e s e
• Fo r p a t ie n t s w it h IIM ve ry ra re d is e a s e s .
w it h a n e w ly d isco ve re d Th e ra py s h ou ld be in d ivid u a lize d on t h e ba s is of p rogn os t ic fa ct ors , s eve rit y
ma ligna ncy, re fe r promptly o f d is e a s e , a n d ris k fa ct ors for a d ve rs e eve n t s a s s ocia t e d w it h t h e ra p e u t ic
t o a n o n co lo g ist , a s a ge n t s . Th e p a s t d e ca d e h a s s e e n a s h ift from t h e t ra d it ion a l a p p roa ch of s t ep p e d
t re a t m e n t o f t h e m a lig - t h e ra p y—in w h ich a s t ru ct u re d s e rie s of rs t -lin e, s e con d -lin e, a n d t h ird -lin e
n a n cy w ill u su a lly a lso
t re a t t h e IIM. a ge n t s a re p re s cribe d in ch ron ologic ord e r a s d is e a s e s eve rit y in cre a s e s —t o
m ore in d ivid u a lize d , a n d oft e n m ore a ggre s s ive, form s of t h e ra py.
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 129
REHABILITATION
Th e goa l of a ll t h e ra p y is t o op t im ize t h e fu n ct ion a l leve ls of p a t ie n t s a n d , if
p os s ible, t o re t u rn t h e m t o n orm a l. In t h is rega rd , p h ys ica l a n d occu p a t ion a l
t h e ra p y re m a in u n d e ru t ilize d m od a lit ie s . Gra d e d re h a bilit a t ion t h a t t a ke s in t o
a ccou n t t h e s t a ge a n d s eve rit y of t h e p a t ie n t ’s m yos it is is t h e be s t a p p roa ch .
s
e
Alt h ou gh be d re s t is oft e n n e ce s s a ry d u rin g p e riod s of s eve re d is e a s e, p a s s ive
s
a
ra n ge of m ot ion e xe rcis e s a n d s t re t ch in g s h ou ld be in it ia t e d e a rly, e s p e cia lly in
e
s
i
ve ry d e bilit a t e d , h os p it a lize d p a t ie n t s t o p reve n t t h e form a t ion of con t ra ct u re s .
D
As t h e d e gre e o f m yo s it is d e cre a s e s , p a t ie n t s s h o u ld in cre a s e t h e ir a ct ivit y
c
i
t
a
t h rou gh s t a ge s : a ct ive -a s s is t e d ra n ge of m ot ion , follow e d by is om e t ric, t h e n
m
is ot on ic, a n d n a lly, a e robic e xe rcis e.
u
e
h
R
c
THERAPEUTIC APPROACHES FOR MYOSITIS
i
c
e
Cort icos t e roid s re m a in t h e p rim a ry t h e ra p y for t h e IIM a n d s h ou ld be in it ia t e d
p
S
a s e a rly a s p os s ible in n e a rly a ll p a t ie n t s , w it h t h e re cogn it ion t h a t t h ey t e n d
3
N
t o re q u ire h igh d os e s for lon g p e riod s of t im e. Im p ort a n t con s id e ra t ion s in clu d e
O
a n a d e q u a t e in it ia l d os e (in m os t ca s e s a t le a s t 1 m g/kg/d a y) (1 ), con t in u a t ion
I
T
C
of p re d n is on e a t a h igh d os e u n t il or a ft e r t h e s e ru m CK be com e s n orm a l (2 ),
E
S
w h ich m a y la s t s eve ra l m on t h s , a n d a s low ra t e of p re d n is on e t a p e rin g (3 , 11 ).
Ta p e rin g p re d n is on e t oo q u ickly le a d s t o re la p s e. Th e role of p u ls e cort icos t e r-
o id s a s t re a t m e n t re m a in s u n cle a r. In d ivid u a ls w it h p o or p rogn o s t ic fa ct o rs
s h ou ld be con s id e re d for m ore a ggre s s ive t h e ra py u s in g cort icos t e roid s w it h a n
a d d e d cyt ot oxic a ge n t from t h e begin n in g of t h e ir d is e a s e.
Du rin g t h is t re a t m e n t p h a s e, bot h t h e p rim a ry ca re p h ys icia n a n d t h e s p e -
cia lis t n e e d t o a ggre s s ive ly s cre e n for, p reve n t , a n d m a n a ge com m on s id e e ffe ct s
of h igh d os e s of p re d n is on e, s u ch a s in fe ct ion s , GI u lce rs , d ia be t e s , h yp e rt e n -
s io n , h yp e rlip id e m ia , w a t e r re t e n t ion , o s t e op e n ia /os t e op oros is , a n xie t y, a n d
p s ych os is , t o n a m e a few. Ca re fu l con s id e ra t ion s h ou ld be give n t o in it ia t ion of
Pneum ocystis jirov ecii p n e u m on ia p rop h yla xis , e s p e cia lly in t h e e ld e rly or t h os e
w it h d e cre a s e d re n a l cle a ra n ce, s in ce t rim e t h op rim s u lfa m e t h oxa zole (Ba ct rim )
in t e ra ct s w it h m e t h ot re xa t e (on e of t h e cyt ot oxic a ge n t s fre q u e n t ly u s e d for
IIM), ca u s in g t oxic leve ls of m e t h ot re xa t e a n d bon e m a rrow s u p p re s s ion .
Th e t re a t m e n t of IBM re m a in s con t rove rs ia l a n d m os t p a t ie n t s w it h IBM d o
n ot re s p on d t o t h e ra p y a t t h e leve l s e e n in p a t ie n t s w it h m yos it is in t h e ot h e r
clin ica l grou p s . Pa t ie n t s w it h IBM a n d evid e n ce of a ct ive in a m m a t ion , h ow -
eve r, m ay be n e t from cort icos t e roid a n d cyt ot oxic t h e ra p y in t e rm s of s low in g
t h e ra t e of p rogre s s ion of d is e a s e. Re t ros p e ct ive review s of cort icos t e roid a n d
cyt ot oxic t h e ra py, a p ros p e ct ive op e n t ria l of in t ra ve n ou s ga m m a globu lin (IVIg),
a n d a ra n d om ize d t ria l of com bin a t ion ora l m e t h ot re xa t e p lu s a za t h iop rin e
ve rs u s h igh -d os e m e t h ot re xa t e w it h le u covorin re s cu e, a ll s u gge s t t h a t t h e ra t e
of d e t e riora t ion m ay be d e cre a s e d or s t a bilize d in t h os e p a t ie n t s .
Alt h ou gh m os t p a t ie n t s w it h DM or PM h ave a t le a s t a p a rt ia l re s p on s e t o
cort icos t e roid s , s om e d o n ot re s p on d a d e q u a t e ly, m a n y m ore exp e rie n ce d is e a s e
130 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Clinica l Co urse
Th e IIM a re s e r io u s a n d s o m e t im e s life -t h re a t e n in g d is e a s e s . Su r viva l o f
p a t ie n t s w it h m yos it is h a s be e n in cre a s in g d u rin g t h e p a s t few d e ca d e s from
50% p rior t o t h e in t rod u ct ion of cort icos t e roid t h e ra py, t o 5-ye a r s u rviva l ra t e s
of 65% in 1947 t o 1968, t o a p p roxim a t e ly 80% m ore re ce n t ly (12 ). La rge coh ort
s e rie s w it h lon g follow -u p h ave s h ow n t h a t , in ge n e ra l, a p p roxim a t e ly 20% t o
30% of p a t ie n t s w it h IIM h ave a m on op h a s ic illn e s s (a n d n o lon ge r re q u ire a n y
t h e ra p y a ft e r 2 ye a rs of t re a t m e n t ), 20% t o 30% h a ve a p olyp h a s ic illn e s s ch a r-
a ct e rize d by a re s p u n ct u a t e d w it h p e riod s of re m is s ion , w h ile t h e re s t h ave a
ch ron ic p rogre s s ive cou rs e a n d re q u ire s u s t a in e d t re a t m e n t (13 ).
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 131
Ackno w le dg me nts
We t h a n k Dr. St eve n Yt t e rbe rg for m a n y u s e fu l d is cu s s ion s a bou t m yos it is . Th is
w ork w a s s u p p ort e d by t h e in t ra m u ra l p rogra m o f t h e Na t ion a l In s t it u t e of
En viron m e n t a l He a lt h Scie n ce s , NIH.
Re fe r to Patie nt Education
s
ICD9
e
s
a
710.3 De rmato myo sitis (acu t e ) (ch ro n ic)
e
s
729.1 Myo sitis
i
D
729.1 rh e u m at ic
c
i
t
729.1 rh e u m at o id
a
m
729.1 t rau m at ic (o ld )
u
e
Po lymyo sitis (acu t e ) (ch ro n ic)
h
R
710.4 (h e m o rrh ag ic)
c
w it h in vo lve m e n t o f
i
c
e
710.4 [517.8] lu n g
p
S
710.3 sk in
3
N
O
I
T
C
E
Re fe re nce s
S
1. Plot z PH , Da la ka s M , Le ff RL, e t a l. Cu rre n t con cep t s in t h e id iop a t h ic in a m m a t ory m yop a t h ie s : p oly-
m yos it is , d e rm a t om yos it is , a n d re la t e d d is ord e rs . A nn Intern Med 1989 ;111 :143 –157 .
2. Airio A, Ka u t ia in e n H , Ha ka la M . Progn os is a n d m ort a lit y of p olym yos it is a n d d e rm a t om yos it is p a t ie n t s .
Clin Rheum atol 2006 ;25 :234 –239 .
3. Ta rgoff IN . De rm a t om yos it is a n d p olym yos it is . Curr Probl Derm atol 1991 ;3 :131 –180 .
4. Boh a n A, Pe t e r JB. Polym yo s it is a n d d e r m a t om yos it is (p a rt s 1 a n d 2). N Engl J Med 1975 ;292 :344 –347 ,
403 –407 .
5. Mille r FW . Myos it is -s p e ci c a u t oa n t ibod ie s . Tou ch s t on e s for u n d e rs t a n d in g t h e in a m m a t ory m yop a -
t h ie s . JA MA 1993 ;270 :1846 –1849 .
6. Fra s e r DD, Fra n k JA, Da la ka s M , e t a l. Ma gn e t ic re s on a n ce im a gin g in t h e id iop a t h ic in a m m a t ory
m yop a t h ie s . J Rheum atol 1991 ;18 :1693 –1700 .
7. Hill CL, Zh a n g Y, Sigu rge irs s on B, e t a l. Fre q u e n cy of s p e ci c ca n ce r t yp e s in d e rm a t om yos it is a n d p oly-
m yos it is : A p op u la t ion -ba s e d s t u d y. Lancet 2001 ;357 :96 –100 .
8. Gre e n be rg SA. Prop os e d im m u n ologic m od e ls of t h e in a m m a t ory m yop a t h ie s a n d p ot e n t ia l t h e ra p e u -
t ic im p lica t ion s . Neurology 2007 ;69 :1966 –1967 .
9. Va n cs a A, Ge rge ly L, Pon yi A, e t a l. Myo s it is -s p e ci c a n d m yo s it is -a s s ocia t e d a n t ibod ie s in ove r la p
m yos it is in com p a ris on t o p r im a ry d e rm a t op olym yos it is : Re leva n ce for clin ica l cla s s i ca t ion : re t ro-
s p e ct ive s t u d y of 169 p a t ie n t s . Joint Bone Spine 2010 ;77 :125 –130 .
10. Is e n be rg DA, Alle n E, Fa rew e ll V, e t a l., for t h e In t e rn a t ion a l Myos it is a n d Clin ica l St u d ie s Grou p (IMACS).
In t e rn a t ion a l con s e n s u s ou t com e m e a s u re s fo r p a t ie n t s w it h id iop a t h ic in a m m a t ory m yop a t h ie s .
Deve lop m e n t a n d in it ia l va lid a t ion of m yos it is a ct ivit y a n d d a m a ge in d ice s in p a t ie n t s w it h a d u lt on s e t
d is e a s e . Rheum atology 2004 ;43 :49 –54 .
11. He n gs t m a n GJD, Va n De n Ho oge n FHJ, va n En ge le n BGM . Tre a t m e n t of t h e in a m m a t ory m yop a t h ie s :
Up d a t e a n d p ra ct ica l re com m e n d a t ion s . Expert Opin Pharm acother 2009 ;10 :1183 –1190 .
12. Lu n d b e rg IE, Fo r b e s s CJ. Mo r t a lit y in id io p a t h ic in a m m a t o r y m yo p a t h ie s . Clin Ex p Rheu m atol
2008 ;26 :S109 –S114 .
13. Bron n e r IM , Va n De r Me u le n MFG, d e Vis s e r M , e t a l. Lon g-t e rm ou t com e in p olym yos it is a n d d e rm a t o-
m yos it is . A nn Rheum Dis 2006 ;65 :1456 –1461 .
CHAPTER
14 Va sculitis
Bao Quynh N. Huynh and S. Louis Bridges , Jr
A B
Figure 14 .1 Skin lesions a t presenta tion (A) a nd a fter resolution (B). By permission of Devore AE a nd Jorizzo JL.
Cha pter 39: Cuta neous sma ll vessel va sculitis. In: Va sculitis , 2nd ed. Ba ll GV a nd Bridges SLJr., eds. New York:
132 Oxford University Press, Inc.; 2008.
Ch a p te r 14 Va s cu lit is 133
Table 14.1 Classi cat ion of More Common Forms of Vasculit is,
Emphasizing t he Predominant Size of Involved Vessels
Larg e ve sse l
Gia n t ce ll (t e m p o ra l) a rt e rit is
Ta ka ya su ’s a rt e rit is
Me dium ve sse l
Po lya rt e rit is n o d o sa
He p a t it is B viru s re la t e d
Fa m ilia l Me d it e rra n e a n fe ve r
Cu t a n e o u s p o lya rt e rit is n o d o sa
Ka w a sa ki’s d ise a se
Me dium- to small ve sse l
We g e n e r’s g ra n u lo m a t o sis
Ch u rg –St ra u ss syn d ro m e
Micro sco p ic p o lya n g iit is (p o lya rt e rit is)
Va scu lit is o f co n n e ct ive t issu e d ise a se s
Be h çe t ’s syn d ro m e (m a y b e la rg e )
Small ve sse l
s
Cu t a n e o u s le u ko cyt o cla st ic a n g iit is
e
s
He n o ch –Sch ö n le in p u rp u ra
a
e
Cryo g lo b u lin e m ic va scu lit is
s
i
D
c
i
Ad a p t e d fro m Re fe re n ce (4).
t
a
m
u
e
h
R
College of Rh e u m a t ology (ACR) in 1990, w h ich p rop os e d crit e ria for t h e cla s s i -
c
i
ca t ion of s eve n d iffe re n t va s cu lit id e s (2 ). Th e s e crit e ria a re n ot m e a n t a s d ia g-
c
e
n os t ic crit e ria , a s t h ey com p a re d p a t ie n t s w it h d iffe re n t t yp e s of va s cu lit is , bu t
p
S
n ot p a t ie n t s w it h ot h e r s ys t e m ic or con n e ct ive t is s u e d is e a s e s .
3
Th e ACR cla s s i ca t io n cr it e r ia d o n o t in clu d e m icro s co p ic p o lya n giit is
N
O
(MPA) or con s id e r a n t in e u t rop h il cyt op la s m ic a n t ibod ie s (ANCA) a s d ia gn os t ic
I
T
C
crit e ria . In 1994, t h e Ch a p e l Hill Con s e n s u s Con fe re n ce (CHCC) p rod u ce d d e -
E
S
n it ion s for va s cu lit is (3 ) a n d in clu d e d MPA in it s cla s s i ca t ion crit e ria . Th ey a ls o
re cogn ize d t h a t h is t ologica l d a t a w ou ld n ot be ava ila ble for a ll p a t ie n t s , e s p e -
cia lly w h e n t h e clin ica l co n d it io n o f t h e p a t ie n t m igh t p re clu d e o b t a in in g
a p p rop ria t e biop s ie s . Fu rt h e rm ore, t h e s a m p le m igh t n ot be rep re s e n t a t ive or
t h e s a lie n t h is t ologica l fe a t u re s m ay n ot be fou n d be ca u s e of s a m p lin g e rror.
Th e cla s s i ca t ion s ch e m e in Ta ble 14.1 e m bo d ie s fe a t u re s o f bo t h ACR a n d
CHCC crit e ria , a n d is n ow w id e ly u s e d for ep id e m iologica l s t u d ie s .
La rg e - Ve sse l Va sculitis
GIANT CELL ARTERITIS
Th e re is a n in cre a s in g in cid e n ce w it h a ge, w it h ve ry few ca s e s occu rrin g in t h os e
you n ge r t h a n 50 ye a rs of a ge. Th e re is a gre a t e r in cid e n ce in w om e n , w it h a
fe m a le -t o-m a le ra t io of a rou n d 2:1 (1 ). Gia n t ce ll a rt e rit is is m ore com m on in
Ca u ca s ia n s t h a n in Africa n -Am e rica n s a n d His p a n ics . In t e re s t in gly, t h e in ci-
d e n ce of GCA va rie s w it h la t it u d e w it h in cre a s in g in cid e n ce w it h h igh e r la t it u d e.
134 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
TAKAYASU’S ARTERITIS
Th is form of va s cu lit is occu rs w orld w id e, bu t it is m ore com m on in As ia . Th e
a n n u a l in cid e n ce in m os t p op u la t ion s is 1 t o 3 p e r m illion , w it h t h e p e a k a ge
of t h e on s e t of d is e a s e in t h e t h ird d e ca d e. Th e d is e a s e is m ore com m on in
w om e n (1 ).
CLINICAL POINTS
Sma ll- Ve sse l Va sculitis
• Th e re is n o t a sp e ci c se t HENOCH–SCHONLEIN PURPURA
o f g u id e lin e s t o h e lp t h e He n och –Sch on le in p u rp u ra is m ore com m on ly s e e n in ch ild re n a n d le s s s e e n
g e n e ra l clin icia n in t h e in a d u lt s w it h a n in cid e n ce of 3 t o 10 p e r m illion (1 ).
e va lu a t io n o f a p a t ie n t
w it h su sp e ct e d va scu lit is.
• Th e cu rre n t cla ssi ca t io n CUTANEOUS SMALL- VESSEL VASCULITIS
crit e ria a re in t e n d e d m a in ly Ou r p a t ie n t w a s d ia gn os e d w it h cu t a n e ou s s m a ll-ve s s e l va s cu lit is , a ls o re fe rre d
fo r re se a rch p u rpo se s. t o a s le u kocyt ocla s t ic va s cu lit is (a h is t ologic d e s crip t ion ) a n d h yp e rs e n s it ivit y
Wh ile t h e y a re h e lp fu l fo r
va s cu lit is . Th is is m ore com m on t h a n m a n y ot h e r form s of va s cu lit is . In Nor-
fra m in g t h e d ia g n ost ic
a p p ro a ch in t h e g e n e ra l w ich from 1990 t o 1994, t h e a n n u a l in cid e n ce of biop s y-p rove n cu t a n e ou s le u -
p ra ct ice se t t in g , n o t e ve ry kocyt ocla s t ic va s cu lit is w a s 15.4 p e r m illion , w it h a h igh e r in cid e n ce in fe m a le s .
p a t ie n t w it h a g ive n d ise a se Th e Ge rm a n s t u d y rep ort e d t h a t t h e in cid e n ce of CHCC-d e n e d cu t a n e ou s le u -
w ill sa t isfy t h e se crit e ria . kocyt ocla s t ic a n giit is w a s 4 t o 9 p e r m illion be t w e e n 1998 a n d 2002.
• Th e p ra ct it io n e r o ft e n
re lie s o n t h e clin ica l h ist o ry
a n d o t h e r m o d a lit ie s, Clinica l Histo ry
s
in clu d in g la b o ra t o ry d a t a ,
e
ra d io g ra p h s, a n d h ist o p a - At p re s e n t , t h e re is n ot a s p e ci c s e t of gu id e lin e s t o h e lp t h e clin icia n in t h e
s
a
t h o lo g y in t h e d ia g n o sis eva lu a t ion of a p a t ie n t w it h s u s p e ct e d va s cu lit is . Th e cu rre n t cla s s i ca t ion cri-
e
s
i
o f va scu lit is. t e ria a re in t e n d e d m a in ly for re s e a rch p u rp os e s . W h ile t h ey a re h e lp fu l for
D
fra m in g t h e d ia gn os t ic a p p ro a ch in t h e ge n e ra l p ra ct ice s e t t in g, n o t eve ry
c
i
t
a
p a t ie n t w it h a give n d is e a s e w ill s a t is fy t h e s e crit e ria (6 ). Th u s , t h e p ra ct it ion e r
m
oft e n re lie s on t h e clin ica l h is t ory a n d ot h e r m od a lit ie s , in clu d in g la bora t ory
u
e
d a t a , ra d iogra p h s , a n d h is t op a t h ology in t h e d ia gn os is of a va s cu lit ic con d it ion .
h
R
Th e in it ia l a s s e s s m e n t in clu d e s a t h orou gh h is t ory a n d p h ys ica l e xa m in a -
c
i
t io n o f t h e p a t ie n t , w h o m a y p re s e n t o n ly w it h n o n s p e ci c co n s t it u t io n a l
c
e
s ym p t om s . Th is m a ke s t h e w orku p of s ys t e m ic va s cu lit id e s q u it e ch a lle n gin g;
p
S
h ow eve r, p a t t e rn re cogn it ion of s ign s a n d s ym p t om s t h a t h ave be e n d e m on -
3
s t ra t e d in va riou s va s cu lit ic con d it ion s ca n p rovid e t h e clin icia n a good s t a rt in g
N
O
p oin t in t h e d ia gn os t ic p roce s s (6 ).
I
T
C
A d e t a ile d h is t ory of t h e n a t u re of t h e con d it ion p rovid e s clu e s t h a t a id in
E
t h e n a l d ia gn os is of t h e u n d e rlyin g va s cu lit is . For e xa m p le, a p a t ie n t w it h
S
MPA m ay p re s e n t w it h n on s p e ci c u like s ym p t om s a n d a rt h ra lgia t h a t ca n be
p re s e n t m on t h s t o ye a rs be fore a d ia gn os is ca n be m a d e. Micros cop ic p oly-
a n giit is ca n a ls o p re s e n t a cu t e ly, w it h t h e on s e t of s ym p t om s w it h in d ays t o
w e e k s . Pa t ie n t s w it h a lve o la r h e m or r h a ge w it h p u lm o n a ry in vo lve m e n t in
ANCA-a s s o cia t e d va s cu lit is m a y re p o rt d ys p n e a , h e m o p t ys is , a n d p le u r it ic
ch e s t p a in (7 ). A h is t ory of ch ron ic s in u s it is , h e m op t ys is , a n d h e m a t u ria s u g-
PATIENT ASSESSMENT ge s t s W G, a p u lm on a ry–re n a l s yn d rom e w it h m e d iu m - t o s m a ll-ve s s e l in volve -
m e n t . Sim ila rly, a com p la in t of h e a rin g los s w a rra n t s fu rt h e r eva lu a t ion for W G
• A d e t a ile d h ist o ry a n d
a s t h e m u cos a of t h e m id d le e a r or of t h e n a s op h a ryn x m ay be in volve d in t h is
p h ysica l e xa m in a t io n is
ke y in t h e e va lu a t io n o f con d it ion (8 ). A rep ort of h e a d a ch e s , jaw cla u d ica t ion , los s of vis ion , a n d m u s cle
a p a t ie n t w it h su sp e ct e d s t iffn e s s m a y s u gge s t GCA w it h or w it h ou t p olym ya lgia rh e u m a t ica .
va scu lit is. Age a n d ot h e r ris k fa ct ors s u ch a s s m okin g h is t ory s h ou ld a ls o be kep t in
• La b o ra t o ry t e st s a re o ft e n m in d in t h e eva lu a t ion p roce s s . For e xa m p le, Kaw a s a ki’s d is e a s e is m ore com -
h e lp fu l in t h e w o rku p o f m on in ch ild re n , w h e re a s GCA is s e e n m ore fre q u e n t ly in t h e old e r p op u la t ion ,
va scu lit is. u s u a lly old e r t h a n 50 ye a rs (6 ).
• Im a g in g m o d a lit ie s in t h e
d ia g n o st ic p ro ce ss in clu d e
ch e st ra d io g ra p h s (CXR), Physica l Exa mina tio n o f the Pa tie nt
co m p u t e d t o m o g ra p h y
Ce rt a in p h ys ica l e xa m in a t ion n d in gs m ay a ls o h e lp t h e clin icia n a rrive a t a
(CT), m a g n e t ic re so n a n ce
im a g in g (MRI), a n g io g ra - d ia gn os is of va s cu lit is . Fu rt h e rm ore, t h ey p rovid e a n id e a of t h e d egre e of m u l-
p h y, a n d u lt ra so u n d . t is ys t e m in volve m e n t , s u ch a s lu n gs , kid n eys , a n d t yp e of blood ve s s e ls , t h a t is ,
a ort a . Th e p re s e n ce of bru it s m a y p oin t t ow a rd Ta ka ya s u ’s a rt e rit is , GCA, or
• Tissu e b io p sy re m a in s t h e
g o ld st a n d a rd o f d ia g n o sis. Be h çe t ’s s yn d rom e. Abd om in a l p a in in t h e s e t t in g of n ew -on s e t h igh blo od
p re s s u re a n d p e r ip h e ra l n e u ro p a t h y ra is e s t h e p o s s ib ilit y o f p o lya r t e r it is
136 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
n od os a . Th e p re s e n ce of blood p re s s u re d iffe re n ce or la ck of p u ls e in t h e a rm s
NOT TO BE MISSED s u gge s t s Ta kaya s u ’s a rt e rit is .
Ch u rg–St ra u s s s yn d rom e is a n ot h e r p u lm on a ry–re n a l s yn d rom e in w h ich a
• Ru le o u t m im icke rs o f
va scu lit is. p a t ie n t w it h a s t h m a m ay p re s e n t w it h e os in op h ilia . Cert a in vira l in fe ct ion s h ave
be e n a s s ocia t e d w it h s ys t e m ic va s cu lit id e s . For exa m p le, h ep a t it is C in fe ct ion
• Fo r visu a l sym p t o m s a n d h a s be en d e m on s t ra te d in cryoglobu lin e m ic va scu lit is , es p ecia lly w h en a ss oci-
h ig h ESR in p a t ie n t s o ld e r
t h a n 50 ye a rs, h a ve a a t ed w ith Rayn a u d ’s p h en om en on a n d p a lp a ble p u rp u ra . Moreover, h ep a t it is B
h ig h clin ica l su sp icio n fo r in fe ct ion h a s be en lin ked to p olya rte ritis n od os a . Beh cet ’s syn d rom e is ch a ra cte r-
GCA. ized by recu rren t ora l a p h t h ou s a n d gen ita l u lcers , e ryth em a n od osu m , a rth ritis,
• Re co g n ize life -t h re a t e n in g a n d u ve it is . Recu rren t ocu la r ep is od es of u veitis ca n lea d to ret in a l d a m a ge a n d
p u lm o n a ry, re n a l, blin d n es s. Th e m u cos a l u lcers in Be h ce t’s s yn d rom e a re rou n d , p a in fu l le sion s
n e u ro lo g ic, o r o cu la r w it h eryt h e m a t ou s m a rgin s a n d a re cove red w it h a yellow p s e u d om em bra n e.
m a n ife st a t io n s.
s
t ria l (9 ). Th e t re a t m e n t of va s cu lit is s h ou ld in clu d e p a t ie n t e d u ca t ion . Wit h
e
s
kn ow led ge of t h eir d is e a s e s , p a t ie n t s a re m ore like ly t o m a ke in form e d d ecis ion s
a
e
a n d com p ly w it h t re a t m e n t p la n s a n d follow -u p a s t h e m ed ica t ion s u s e d in t h e
s
i
D
t re a t m e n t of va s cu lit is a re n ot h a rm les s . Nu m e rou s on lin e re s ou rces a re ava il-
c
i
a ble t o t h e p a t ie n t ; a few a re p rovid e d h e re (s e e box t o le ft ) a s a s t a rt in g p oin t .
t
a
m
u
e
h
Clinica l Co urse
R
c
i
Th e d iffe re n t ia l d ia gn os is of va s cu lit is is broa d , in clu d in g m a n y con d it ion s t h a t
c
e
m ay m im ic t ru e va s cu lit is . In fe ct ion s , t h rom boe m bolic p h e n om e n a , a n d m a lig-
p
S
n a n cie s ca u s e in a m m a t ion a n d d a m a ge t o blood ve s s e ls , le a d in g t o clin ica l
3
N
p re s e n t a t ion s im ila rly s e e n in va s cu lit is (10 ). Th e va riou s d is e a s e s t h a t ca u s e
O
in ju ry t o blood ve s s e ls , in cit e a n in a m m a t ory p roce s s , a n d m im ic a va s cu lit ic
I
T
C
p roce s s a re p rovid e d in Ta ble 14.2 .
E
S
Fu rt h e rm ore, cu t a n e ou s m a n ife s t a t ion s a s s e e n in ou r p a t ie n t p re s e n t e d a t
t h e begin n in g of t h is ch a p t e r ca n be m is d ia gn os e d in it ia lly a s in fe ct ion s s u ch
a s ce llu lit is . Th e clin icia n s h ou ld be a r in m in d t h a t im it a t ors of va s cu lit is e xis t ,
ord e r a n y n e ce s s a ry t e s t s t o ru le ou t m im icke rs of va s cu lit is , a n d re fe r t o rh e u -
m a t ology for fu rt h e r eva lu a t ion if a d ia gn os is is s t ill in q u e s t ion .
In fectiou s orga n ism s su ch a s ba cteria , viru ses, a n d fu n gi often lea d to con d i-
tion s th a t im ita te va scu litis by eith er ca u sin g d irect va scu la r in ju ry or in d irectly
a lterin g th e va scu la r stru ctu re via im m u n e-m ed ia ted or toxic m ech a n ism s, resu lt-
in g in ch a n ges sim ila rly seen in va scu litis. For exa m p le, Salm onella h a s been im p li-
ca ted in a ortitis. Often , cen tra l n ervou s system va scu litis is secon d a ry to ba cteria l
or vira l m en in gitis or d u e to ba cteria l en d oca rd itis. Cu ta n eou s in fection s su ch a s
p a n n icu litis a n d cellu litis ca n p resen t clin ica lly, very sim ila r to tru e va scu litis.
Ma lign a n cie s ca n cre a t e a clin ica l p ict u re s im ila r t o va s cu lit is via d iffe re n t
m e ch a n is m s : (a ) in d u ct ion of im m u n e -m e d ia t e d in a m m a t ion , (b) occlu s ion of
blood ve s s e ls by e it h e r ca n ce r ce lls or cre a t ion of a h yp e rcoa gu la ble s t a t e, or
(c) in va s ion of n erves in n erva t in g blood ves s els , p rod u cin g a n eu rop a t h y m im ick-
in g tru e va scu litis. Oth er n on m a lign a n t occlu sive p rocesses su ch a s a th eroem boli
a n d a n t ip h o s p h o lip id a n t ibod y s yn d ro m e s h o u ld a ls o be con s id e re d in t h e
eva lu a t ion of s u s p e ct e d va s cu lit is (10 ).
On ce m im ickers of va scu litis h ave been ru led ou t a n d trea tm en ts h ave been
in stitu ted for tru e va scu litis, th e clin ica l cou rse of d isea se va ries from com p lete
rem ission to rela p se to refra ctorin ess to d ea th . Now a d ays, th e ra tes of rem ission
in ANCA-a ssocia ted va scu litis trea ted w ith m od ern th era py a re grea ter th a n or
eq u a l to 90%. Ou tcom e m ea su res in ANCA-a ssocia ted va scu litis in clu d e va riou s
a s se ss m en t tools su ch a s Va s cu litis Da m a ge In d ex a n d Birm in gh a m Va s cu lit is
Activity Score (BVAS), w ith th e BVAS bein g th e sta n d a rd .
138 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Re fe re nce s
1. Wa t t s R, Scot t DGI. Ep id e m iology of va s cu lit is . In : Ba ll G, Brid ge s S, Jr , e d s . Vasculitis . 2n d e d . New York :
Oxford Un ive rs it y Pre s s , In c ; 2008 :7 –22 .
2. Frie s JF, Hu n d e r GG, Blo ch DA, e t a l. Th e Am e rica n College of Rh e u m a t ology 1990 crit e ria fo r t h e cla s -
s i ca t ion of va s cu lit is . Su m m a ry. A rthritis Rheum 1990 ;33 (8 ):1135 –1136 .
3. Je n n e t t e JC, Fa lk RJ, An d ra s s y K, e t a l. Nom e n cla t u re o f s ys t e m ic va s cu lit id e s . Prop os a l of a n in t e rn a -
t ion a l con s e n s u s con fe re n ce . A rthritis Rheum 1994 ;37 (2 ):187 –192 .
4. Ba ll G, Brid ge s S, Jr . Cla s s i ca t ion of Va s cu lit is . In : Ba ll G, Brid ge s S, Jr , e d s . Vasculitis. 2n d e d . New York :
Oxford Un ive rs it y Pre s s , In c ; 2008 :3 –6 .
5. Nt a t s a ki E, Wa t t s RA, Scot t DG. Ep id e m iology of ANCA-a s s ocia t e d va s cu lit is . Rheum Dis Clin North A m
2010 ;36 (3 ):447 –461 .
6. Fe s s le r B. Ap p roa ch t o t h e d ia gn os is of va s cu lit is in a d u lt p a t ie n t s . In : Ba ll G, Brid ge s S, Jr , e d s . Vasculitis .
2n d e d . New York : Oxford Un ive rs it y Pre s s , In c ; 2008 :277 –285 .
7. Ch u n g SA, Se o P. Micros co p ic p olya n giit is . Rheum Dis Clin North A m 2010 ;36 (3 ):545 –558 .
8. Holle JU, La u d ie n M , Gros s W L. Clin ica l m a n ife s t a t ion s a n d t re a t m e n t o f Wege n e r’s gra n u lom a t o s is .
Rheum Dis Clin North A m 2010 ;36 (3 ):507 –526 .
9. St on e JH , Me rke l PA, Sp ie ra R, e t a l. Rit u xim a b ve rs u s cyclop h os p h a m id e for ANCA-a s s ocia t e d va s cu lit is .
N Engl J Med 2010 ;363 (3 ):221 –232 .
10. Ch u n g S, Sa ck K. Im it a t ors of va s cu lit is . In : Ba ll G, Brid ge s SL, Jr , e d s . Vasculitis . 2n d e d . New York : Oxford
Un ive rs it y Pre s s , In c ; 2008 :599 –621 .
s
e
s
a
e
s
i
D
c
i
t
a
m
u
e
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R
c
i
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e
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S
CHAPTER
15 Gia nt Cell Arteritis a nd
Polymya lgia Rheuma tica
A ngelo Gaffo
A 76-ye ar-o ld w h it e w o m an
Clinica l
Pre se nta tio n
S
E
p re se n t s t o h e r p rim ary care
C
T
Po lym ya lgia r h e u m a t ica (PMR)
I
p h ysician w it h a 3-m o n t h
O
a n d gia n t ce ll a rt e rit is (GCA) a re
N
h ist o ry o f p ro g re ssive
3
t w o clin ica l con d it ion s t h a t s h a re
f at ig u e , m alaise , p o o r ap p e -
S
m u lt ip le p a t h o p h ys io lo gic a n d
p
e
t it e , an d a 10-lb w e ig h t lo ss. c lin ic a l ch a r a c t e r is t ic s . Bo t h
c
i
a lm os t e xclu s ive ly a ffe ct in d ivid -
c
Sh e also re p o rt s b ilat e ral
R
u a ls o ld e r t h a n 50 ye a r s , a r e
h
sh o u ld e r an d h an d p ain . No
e
ch a ra ct e r iz e d by m u s cu lo s k e le -
u
m
visu al co m p lain t s are re p o rt - t a l p a in a n d s t iffn e s s , a n d a re
a
t
e d , an d o n e xam in at io n , sh e u s u a lly a ccom p a n ie d by p rom i-
i
c
D
is n o t ice d t o h ave m ild b ilat - n e n t co n s t it u t io n a l s ym p t o m s
i
s
s u ch a s m a la is e, w e igh t los s , a n d
e
e ral m e t acarp o p h alan g e al sw e llin g an d p ain w it h p alp at io n .
a
e leva t e d in a m m a t o ry m a rk e rs .
s
e
Lab o rat o ry n d in g s in clu d e a n o rm o ch ro m ic, n o rm o cyt ic an e m ia
s
In a d d it io n , b o t h t h e d is e a s e s
(h e m at o crit o f 28% ) an d in cre ase d in am m at o ry m ark e rs w it h an h ave a good re s p on s e t o d iffe re n t
e ryt h ro cyt e se d im e n t at io n rat e (ESR) o f 60 m m /h o u r. No e ro sio n s d o s a ge s o f glu co co r t ico id t h e r-
a p y. W h e r e a s PMR lim it s it s
are n o t e d o n h an d rad io g rap h s, an d a t e n t at ive d iag n o sis o f
in volve m e n t t o t h e m u s cu los ke l-
se ro n e g at ive rh e u m at o id art h rit is is m ad e . W h ile t h e p at ie n t w ait s e t a l s ys t e m , GCA is a p a n -a rt e ri-
f o r a rh e u m at o lo g y re f e rral sh e is p lace d o n a 10-m g d o se o f o ral t is t h a t a ffe ct s t h e a ort a a n d it s
p re d n iso n e . m a in b ra n ch e s w it h a s p e cia l,
b u t n o t e x clu s ive , p re d ile ct io n
Tw o w e e k s lat e r w h e n sh e is se e n b y a rh e u m at o lo g ist , t h e
for t h e e xt ra cra n ia l bra n ch e s of
f at ig u e , m alaise , p o o r ap p e t it e , an d art h rit is are m ild ly im p ro ve d , t h e ca ro t id a r t e ry. As a co n s e -
b u t st ill p re se n t . No visu al co m p lain t s are re p o rt e d , b u t t h e p at ie n t q u e n ce, e a rly re cogn it ion of GCA
h as d e ve lo p e d p e rsist e n t jaw d isco m f o rt an d w e ak n e ss w h ile ch e w - is e s s e n t ia l t o a vo id it s m o r e
fe a re d is ch e m ic co n s e q u e n ce s ,
in g as w e ll as h e ad ach e s, w it h scalp t e n d e rn e ss n o t e d w h ile layin g
in clu d in g irreve rs ible vis ion los s .
o n a p illo w o r w e arin g g lasse s. On p h ysical e xam in at io n t h e re is a Po ly m ya lg ia r h e u m a t ic a c a n
p alp ab le t e m p o ral art e ry (Fig . 15.1 ) an d sig n i can t scalp t e n d e rn e ss. evolve in t o GCA, w it h t h is clin i-
A d d it io n al n d in g s in clu d e co n t in u e d sh o u ld e r an d p e lvic g ird le c a l c o n t in u u m le a d in g m a n y
a u t h ors t o con s id e r PMR a form e
p ain o n p alp at io n . Lab o rat o ry n d in g s are larg e ly u n ch an g e d ,
fru s t e of GCA in w h ich ove rt va s -
w it h an ESR at 56 m m /h o u r. cu lit is h a s n ot d eve lop e d .
A t e m p o ral art e ry b io p sy is sch e d u le d in t h e n e xt d ays an d is Bot h PMR a n d GCA a p p e a r t o
sh o w n in Fig u re 15.2 . b e m o re co m m o n in w h it e s o f
n ort h e rn Eu rop e a n d e s ce n t t h a n
140
Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 141
s
e
s
a
e
s
i
D
Figure 15.1 A prominent, tender tempora l a rtery. Figure 15.2 Temporal artery biopsy in giant cell arteritis reveals a chroni-
c
i
t
Reproduced with permission from Gold DH, Weingeist cally in amed artery with marked narrowing of the lumen. Hematoxylin and
a
m
TA. Color Atla s of the Eye in Systemic Disea se . Ba ltimore: eosin stain; original magni cation 310. With permission from Tasman W,
u
Lippincott Willia ms & Wilkins; 2001. Jaeger E. The Wills Eye Hospital Atlas of Clinical Ophthalmology. 2nd ed.
e
h
Philadelphia: Lippincott Williams & Wilkins; 2001.
R
c
i
c
e
p
S
in ot h e r ra cia l grou p s . Th e in cid e n ce ra t e of GCA in w h it e s of n ort h e rn Eu ro-
3
p e a n d e s ce n t h a s be e n e s t im a t e d a t a ro u n d 20 t o 30/ 100,000. Re p ort s fro m
N
O
ot h e r grou p s in clu d in g s ou t h e rn Eu rop e a n s , Africa n Am e rica n s , As ia n s , a n d
I
T
Ara b s d e s crib e a m u ch low e r in cid e n ce ra t e a t 1 t o 11/100,000. Po lym ya lgia
C
E
rh e u m a t ica is a p p roxim a t e ly t h re e t im e s m ore com m on t h a n GCA, w h ich in
S
t u rn h a s be e n re p ort e d a s t h e m os t com m on form of va s cu lit is in t h e old e r
t h a n 50 ye a rs a ge grou p a n d t h e in cid e n ce in cre a s e s w it h a ge u n t il t h e n in t h
d e ca d e of life. Th e s e con d it ion s a re e xce e d in gly ra re in in d ivid u a ls you n ge r
t h a n 50 ye a rs . Wom e n h ave a n in cre a s e d fre q u e n cy of bot h PMR a n d GCA w h e n
com p a re d t o m e n (1.7:1 for PMR a n d 3.5:1 for GCA).
Th e ce n t ra l h is t ologic fe a t u re of GCA is t h e p re s e n ce of a n in a m m a t ory
in lt ra t e w it h p re d om in a n ce of CD4 T ce lls a n d m a crop h a ge s t h a t ca n e xt e n d
a cros s t h e w h ole e la s t ic a rt e ry ve s s e l w a ll, bu t u s u a lly con ce n t ra t e s a rou n d t h e
in t e rn a l e la s t ic la m in a (Fig. 15.2 ) (1 ). De s t ru ct ion of t h e in t e rn a l e la s t ic la m in a
is a p a t h ogn om on ic fe a t u re of GCA. Gia n t ce lls ca n be p re s e n t , bu t a re a n in con -
s is t e n t fe a t u re of t h e d is e a s e, re p ort e d in a bou t 50% o f biop s y-p rove n ca s e s .
La rge n u m be rs of gia n t ce lls in t h e biop s y s p e cim e n h ave be e n a s s ocia t e d w it h
a h igh e r ris k of is ch e m ic com p lica t ion s . Alt h ou gh brin oid n e cros is cou ld be
s e e n in ra re ca s e s , it s p re s e n ce is s o u n u s u a l t h a t it s h ou ld ra is e s u s p icion for
a lt e rn a t ive d ia gn o s e s . No ch a ra ct e r is t ic h is t op a t h ologic fe a t u re s h a ve be e n
re p ort e d for PMR, a n d t h e m a in role of biop s y is w orku p of s u s p e ct e d a ccom -
p a n yin g GCA.
Polym ya lgia rh e u m a t ica a n d gia n t ce ll a rt e rit is , ve ry like ly be in g p a rt of a
com m on p a t h op h ys iologic s yn d rom e, s h a re m a n y clin ica l ch a ra ct e ris t ics . Poly-
m ya lgia rh e u m a t ica it s e lf is con s id e re d a clin ica l m a n ife s t a t ion of GCA. Neve r-
t h e le s s , a m a jorit y of p a t ie n t s w it h PMR n eve r d eve lop ot h e r m a n ife s t a t ion s of
GCA a n d PMR is s t ill w id e ly co n s id e re d a s t a n d -a lo n e co n d it io n . Gia n t ce ll
a r t e r it is is m o s t ly re co gn iz e d by it s cra n ia l a r t e r it is a n d m u s cu lo s k e le t a l
142 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Table 15.1 Clinical Feat ures of Giant Cell Art erit is Syndromes a
POLYMYALGIA RHEUMATICA
Th e m a in clin ica l ch a ra ct e ris t ic of PMR is p a in a n d s t iffn e s s a rou n d t h e m u s -
cle s o f t h e s h ou ld e r a n d p e lvic gird le . Us u a lly t h e on s e t is s u d d e n a n d t h e
s h ou ld e r gird le is a ffe ct e d rs t . Nigh t t im e p a in is com m on , bu t in t h e m orn in gs ,
s
e
t h e s ym p t om s cou ld be s o p ron ou n ce d t h a t t h e p a t ie n t h a s m a rke d d if cu lt y
s
a
ca rin g for t h e m s e lve s a n d ca n e n d u p con n e d t o be d . Th e re is evid e n ce t h a t
e
s
i
t h e p roxim a l p a in fu l m a n ife s t a t ion s of PMR in t h e s h ou ld e r a n d p e lvic gird le
D
c
a re con s e q u e n ce of in a m m a t ion of m u lt ip le p e ria rt icu la r s h ou ld e r a n d h ip
i
t
a
bu rs a s . Pe rip h e ra l join t sw e llin g t h a t ca n p rogre s s t o in volve t h e w h ole h a n d is
m
com m on ly d e s cribe d . Tru e p e rip h e ra l a rt h rit is h e ra ld s m ore re s is t a n t d is e a s e.
u
e
Dis u s e m u s cle a t rop h y ca n d eve lop in lon g-s t a n d in g u n t re a t e d p a t ie n t s .
h
R
c
i
c
e
WASTING AND CACHEXIA
p
S
A p rom in e n t s ys t e m ic in a m m a t ory re s p on s e le a d in g t o a p re s e n t a t ion w it h
3
N
feve r, m a la is e, a n d w e igh t los s re s e m blin g a feve r of u n kn ow n origin ca n occu r.
O
It is im p ort a n t t o e m p h a s ize t h a t GCA a ccou n t s for a bou t 20% of ca s e s of feve r
I
T
C
of u n kn ow n origin in in d ivid u a ls old e r t h a n 65 ye a rs . Feve r is u s u a lly low gra d e,
E
S
bu t s p ike s of u p t o 39 C or 40 C a re n ot u n com m on . Pa ra d oxica lly, a p re s e n t a t ion
w it h t h e s e fe a t u re s a ccom p a n ie d w it h con com it a n t h igh leve ls of in a m m a t ory
m a rke rs s e e m s t o be p rot e ct ive a ga in s t t h e d eve lop m e n t of cra n ia l a rt e rit is , bu t
it is u n cle a r if t h is is be ca u s e of a n e a rlie r d ia gn os is w it h con cu rre n t e a rlie r
e xp os u re t o glu cocort icoid t h e ra p y or t h e p re d om in a n ce of in a m m a t ory fa c-
t ors t h a t m ay p rot e ct a ga in s t a rt e ria l occlu s ion .
Studie s
In bot h PMR a n d GCA, t h e clin ica l a s s e s s m e n t p rovid e s m os t of t h e e le m e n t s
n e ce s s a ry fo r t h e d ia gn o s is , w it h s om e s u p p ort p rovid e d by la bo ra t ory d a t a ,
h is t o p a t h o logy fro m a t e m p o ra l a r t e ry b io p s y, a n d ve ry u n co m m o n ly ra d io -
logic s t u d ie s .
Gia n t ce ll a rt e rit is s h ou ld be s u s p e ct e d in a n y p a t ie n t old e r t h a n 50 ye a rs
w it h s ym p t om s of PMR or t is s u e is ch e m ia in t h e h e a d , n e ck, or u p p e r t h ora x.
A h igh e ryt h rocyt e s e d im e n t a t ion ra t e (ESR) or C-re a ct ive p rot e in (CRP) t it e r a re
s u p p ort ive of t h e d ia gn os is , bu t it is ve ry im p ort a n t t o n ot e t h a t a rou n d 25% of
biop s y-p rove n ca s e s d o n ot h a ve a bn orm a l va lu e s of e it h e r a t p re s e n t a t ion .
Eleva t e d leve ls of in t e rle u kin 6 a re p rom is in g m a rke rs of d is e a s e a ct ivit y, a s
t h ey a re p a rt of t h e p a t h op h ys iologic p a t h w ay of t h e d is e a s e. How eve r, t h e ir
u s e h a s n ot be e n s t a n d a rd ize d ye t . Ot h e r com m on la bora t ory n d in gs in clu d e
m icrocyt ic a n e m ia , t h rom bocyt os is , le u kocyt os is , a bn orm a lit ie s in bioch e m ica l
live r t e s t (a lka lin e p h os p h a t a s e a n d t ra n s a m in a s e s ), a n d low leve ls of a lbu m in .
Th e role of im a gin g in t h e d ia gn os is of GCA is s t ill la rge ly u n d e t e rm in e d .
Pa t ie n t s w h o p re s e n t w it h cra n ia l a rt e rit is cou ld be con s id e re d for a Dop p le r
S
E
u lt ra s o u n d e x a m in a t io n o f t h e t e m p o ra l a r t e r ie s , w h e re a h yp o e ch oic r im
C
T
a rou n d t h e ve s s e l lu m e n (kn ow n a s t h e “h yp oe ch oic h a lo”) cou ld be a u s e fu l
I
O
n d in g in t h e p re d ict ion of ve s s e l in a m m a t ion a n d in n d in g a n a d e q u a t e s it e
N
fo r bio p s y. How eve r, t h e p ro ce d u re is h igh ly o p e ra t o r d e p e n d e n t , a n d s u bs e -
3
S
q u e n t s t u d ie s h ave n ot p rove d it s u s e fu ln e s s for d ia gn os t ic p u rp os e s . Dop p le r
p
e
u lt ra s ou n d t e ch n iq u e s cou ld be u s e fu l for t h e a s s e s s m e n t of s t e n os is in ot h e r
c
i
va s cu la r b e d s , s u ch a s t h e ve rt e b ra l o r s u b cla via n a r t e rie s . In p a t ie n t s w h o
c
R
p re s e n t w it h lim b cla u d ica t ion or s ign s of a ort ic com p rom is e (a ort ic in s u f -
h
e
cie n cy o r a n e u rys m a l d ila t a t io n ), a n a n giogra m o r a le s s in va s ive m a gn e t ic
u
m
re s on a n ce im a gin g a n giogra p h y (MRA) cou ld be con s id e re d . A s m oot h , u n iform
a
t a p e rin g in t h e a ffe ct e d p e rip h e ra l ve s s e l lu m e n is t h e ch a ra ct e ris t ic n d in g in
t
i
c
GCA. Ma gn e t ic re s o n a n ce im a gin g a n giogra p h y h a s t h e a d d it io n a l b e n e t o f
D
i
s
a llow in g t h e a s s e s s m e n t of t h e ve s s e l w a ll for t h icke n in g a n d e d e m a t h a t ca n
e
a
p re ce d e occlu s ion . Pos it ron e m is s ion t om ogra p h y w it h F18 - u orod e oxyglu cos e
s
e
ca n d e m on s t ra t e in cre a s e d u p t a ke in a ffe ct e d ve s s e ls a n d is a p rom is in g, bu t
s
s t ill n ot w id e ly a d op t e d , t e ch n iq u e for a s s e s s m e n t of d is e a s e a ct ivit y.
Th e m a in s t a y of t h e d ia gn os is of GCA is t h e h is t op a t h ologic e xa m in a t ion
of t h e t e m p ora l a rt e ry. It is im p ort a n t t o n ot e t h a t s om e p a t ie n t s d o n ot h ave
a n y t e m p ora l a rt e ry in volve m e n t , m a in ly t h e s u bs e t of p a t ie n t s w h o p re s e n t a s
a ort it is or p e rip h e ra l a rt e ria l occlu s ion , a n d m a y n ot be n e t from t h e p roce -
d u re. How eve r, t h e biop s y o f t h e t e m p ora l a rt e ry re m a in s a s a t im e -h on ore d
con rm a t ory t e s t in a gre a t m a jorit y of ca s e s a n d s h ou ld be p u rs u e d w h e n eve r
p os s ible. Ma n y m is con cep t ion s e xis t a bou t t h e t im in g a n d t e ch n ica l a s p e ct s of
t h e p roce d u re (Ta ble 15.2 ) (3, 4 ). Th e in a m m a t ory com p rom is e in d u ce d by GCA
is oft e n p a t ch y a n d cou ld be m is s e d eve n in p rop e rly p e rform e d biop s ie s . Th e
w a y t o m in im ize t h is p o s s ib ilit y is by o b t a in in g a ge n e ro u s s e gm e n t o f t h e
a rt e ry for s t u d y. At t h e ve ry le a s t 1 cm is re q u ire d , bu t s egm e n t s of 3 cm or
m ore a re p re fe rre d . Bila t e ra l s a m p le s , a lt h ou gh n ot u s u a lly fe a s ible, h ave be e n
s h ow n t o im p rove t h e d ia gn os t ic yie ld by 20% t o 40%. Mu lt ip le cu t s of t h e a rt e ry
s p e cim e n s h ou ld be p e rform e d a n d s t u d ie d . Te m p ora l a rt e ry biop s ie s a re u s e fu l
eve n 4 w e e ks in t o h igh -d o s e glu cocort ico id t h e ra p y. Th e n d in g m os t com -
m on ly a ffe ct e d by t h is t h e ra py is t h e d is a p p e a ra n ce of t h e in a m m a t ory in l-
t ra t e s from t h e ve s s e l w a ll, bu t fra gm e n t a t ion of t h e e la s t ic la m in a , e n d ot h e lia l
p rolife ra t ion , a n d eve n t h e e m p t y “n e s t s ” w h e re gia n t ce lls w e re loca t e d (in
ca s e s t h a t p re s e n t w it h gia n t ce lls ) ca n s t ill be u s e fu l a n d s u p p o rt ive o f t h e
d ia gn os is . As a con s e q u e n ce, la ck of p rom p t a cce s s t o a p h ys icia n w h o cou ld
p e rform t h e p roce d u re s h ou ld n ot be a d e t e rre n t for s t a rt in g a p p rop ria t e h igh -
d os e t h e ra p y in re a s on a bly h igh s u s p icion ca s e s . Eve n in p rop e rly p e rform e d
a n d p roce s s e d t e m p ora l a rt e ry biop s ie s , t h e re s u lt ca n be n ega t ive in u p t o 15%
Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 145
Table 15.2 Import ant Considerat ions Regarding Temporal Art ery
Biopsies for Giant Cell Art erit is
• Th e le n g t h o f t h e a rt e ry se g m e n t o b t a in e d sh o u ld b e a t le a st 1 cm , b u t le n g t h s
o f 3–4 cm a re p re fe rre d
• Bila t e ra l t e m p o ra l a rt e ry b io p sie s in cre a se t h e d ia g n o st ic yie ld b y 20% –40%
• Process and cut the entire arterial segment, as the disease has a patchy distribution
• Do n o t st rip t h e a rt e ria l sa m p le o ff it s p e ria rt e ria l co n n e ct ive t issu e . Se ve ra l
t im e s t h e d ia g n o sis ca n b e fo u n d in p e ria rt e ria l ve sse ls ra t h e r t h a n t h e
t e m p o ra l a rt e ry b io p sie d
• De sp it e b e in g t h e p re fe rre d d ia g n o st ic t e st , fa lse n e g a t ive s in t e m p o ra l a rt e ry
b io p sie s a re co m m o n (a b o u t 15% o f ca se s)
• Te m p o ra l a rt e ry b io p sie s sh o u ld b e p e rfo rm e d a s so o n a s p o ssib le . Ho w e ve r,
t h e y ca n b e u se fu l e ve n a ft e r 4 w e e ks o f g lu co co rt ico id t h e ra p y
s
p rom is e of ot h e r va s cu la r be d s t h rou gh im a gin g, a n d gu id in g t re a t m e n t d e ci-
e
s
a
s ion s on t h e ba s is of clin ica l s ym p t om s a n d t h e ove ra ll leve l of s u s p icion for
e
s
GCA.
i
D
Po ly m ya lgia r h e u m a t ic a h a s n o s p e c i c d ia gn o s t ic m a r k e r s a n d t h e
c
i
t
a p p r o a ch is e s s e n t ia lly clin ica l. Sim ila r t o GCA, t h e in a m m a t o ry m a r k e r s
a
CLINICAL POINTS
m
a r e u s u a lly e le va t e d , b u t t h e re is n o t h r e s h o ld t h a t ca n d iffe r e n t ia t e t h e t w o
u
• Po lym ya lg ia rh e u m a t ica
e
co n d it io n s . Th e u s e o f u lt ra s o u n d o r m a gn e t ic re s o n a n ce im a gin g t o id e n -
h
is a clin ica l d ia g n o sis,
R
a n d t h e re fo re , t h e re is t ify t h e p e r ia r t icu la r b u r s it is o f t h e s h o u ld e r a n d h ip s t h a t a re ch a ra ct e r is t ic
c
n o co n rm a t o ry t e st . o f t h e co n d it io n h a s b e e n a d vo ca t e d . How e ve r, t h e s e p r o ce d u re s h a ve fa ile d
i
c
e
t o d e m o n s t ra t e a cle a r d iffe re n t ia t io n w it h o t h e r co n d it io n s t h a t ca n re s e m -
p
• Cra n ia l a rt e rit is is t h e
S
b e t t e r re co g n ize d fo rm o f b le PMR.
3
GCA. Ho w e ve r, o t h e r clin i-
N
O
ca l p re se n t a t io n s in clu d e
I
DIFFERENTIAL DIAGNOSES
T
w a st in g syn d ro m e s, PMR,
C
E
a o rt it is, a n d p e rip h e ra l Th e Am e r ica n Co lle ge o f Rh e u m a t o logy d eve lo p e d cla s s i ca t io n cr it e r ia fo r
S
a rt e ria l o cclu sio n s. Th e se
a re o ft e n m isse d , a n d GCA in 1990 (Ta ble 15.3 ) (5 ). As m o s t cla s s i ca t io n crit e ria , t h e s e w e re cre a t e d
clin icia n s sh o u ld m a in t a in in ord e r t o h e lp t o in clu d e p a t ie n t s in s t u d ie s in a u n iform fa s h ion a n d s h ou ld
a h ig h in d e x o f su sp icio n . n o t be a p p lie d t o t h e d ia gn o s is o f in d ivid u a l p a t ie n t s . Th e s e crit e ria p e rfo rm
• Te m p o ra l a rt e ry b io p sy is re a s on a bly w e ll in d iffe re n t ia t in g GCA from ot h e r va s cu lit id e s , bu t t h e ir u s e -
t h e g o ld st a n d a rd fo r t h e fu ln e s s is d im in is h e d w h e n t ryin g t o d iffe re n t ia t e it fro m co n d it io n s o t h e r
d ia g n o sis in m o st ca se s o f t h a n va s cu lit id e s . Th e s e crit e ria focu s h e a vily on t h e cra n ia l a rt e rit is p re s e n t a -
GCA. It sh o u ld b e p u rsu e d t ion p a t t e rn , a n d ot h e r p re s e n t a t ion p a t t e rn s cou ld be m is s e d w h e n t h e s e a re
w h e n e ve r p o ssib le , e ve n u t ilize d .
a ft e r t h e p a t ie n t h a s b e e n
e xp o se d t o g lu co co rt ico id s.
• Wh e n t h e re is su sp icio n
o f visu a l sym p t o m s re la t e d Table 15.3 Tradit ional Format of t he 1990 American College
t o GCA, h ig h -d o se g lu co -
co rt ico id t h e ra p y sh o u ld
of Rheumat ology Crit eria for t he Classi cat ion
b e in it ia t e d a s so o n a s of Giant Cell Art erit is a
p o ssib le . Th is sh o u ld n o t b e
d e la ye d w h ile w a it in g fo r • Ag e a t d ise a se o n se t e q u a l t o o r o ld e r t h a n 50 ye a rs
a t e m p o ra l a rt e ry b io p sy. • Ne w o n se t o f o r n e w t yp e o f h e a d a ch e
• Pa t ie n t s o n h ig h -d o se • Te m p o ra l a rt e ry t e n d e rn e ss t o p a lp a t io n o r d e cre a se d p u lsa t io n (u n re la t e d t o
g lu co co rt ico id t h e ra p y a t h e ro scle ro sis)
fo r GCA sh o u ld b e clo se ly • Eryt h ro cyt e se d im e n t a t io n ra t e g re a t e r t h a n 50 m m /h
m o n it o re d a n d t re a t e d fo r • Bio p sy o f t h e t e m p o ra l a rt e ry sh o w in g va scu lit is co n sist e n t w it h g ia n t ce ll
e xp e ct e d co m p lica t io n s o f a rt e rit is
t h e ra p y, m o st n o t a b ly b o n e
m a ss lo ss, h yp e rg lyce m ia , Ad a p t e d fro m re fe re n ce 5.
a
a n d h yp e rt e n sio n . Th e p re se n ce o f t h re e o r m o re crit e ria yie ld s a se n sit ivit y o f 93.5% a n d a sp e ci cit y o f 91.2% .
146 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
s
e
Tre a tme nt
s
a
e
s
i
To d a t e, glu cocort icoid t h e ra py is t h e on ly a p p roa ch t h a t h a s be e n p rove d t o be
D
c
e ffe ct ive in bot h PMR a n d GCA. Th e in it ia l d os e of glu cocort icoid s in GCA w it h -
i
t
a
ou t cu rre n t or re ce n t n d in gs s u gge s t ive of vis ion los s is of 40 t o 60 m g/d ay of
m
p re d n is on e or it s glu cocort icoid e q u iva le n t . In ca s e s of im p e n d in g vis ion los s ,
u
e
h igh d o s e s of in t ra ve n ou s glu cocort icoid s (1,000 m g of in t ra ve n o u s m e t h yl-
h
R
p re d n is olon e for 3 d a ys follow e d by 60 m g a d a y of p re d n is on e ) is a com m on
c
i
a p p roa ch a lt h ou gh cle a r evid e n ce of it s be n e t ove r p re d n is on e 40 t o 60 m g/
c
e
d a y is la ckin g. Eve n t h is a ggre s s ive a p p roa ch ve ry ra re ly s a lva ge s vis ion w h e n
p
S
m o re t h a n 24 h ou rs h a ve e la p s e d s in ce t h e vis ion los s . For t h is re a s o n , it is
3
N
im p o r t a n t t o e m p h a s iz e t h e e m e rge n t n a t u re o f t h is a ggre s s ive t re a t m e n t
O
w h e n p re m on it ory s ign s of vis ion los s a re p re s e n t . If a t e m p ora l a rt e ry biop s y
I
T
C
ca n n ot be obt a in e d w it h in a few h ou rs , glu cocort icoid t h e ra py s h ou ld be s t a rt e d
E
S
a n d follow e d by a biop s y a s s oon a s p os s ible. Ap a rt from vis ion los s , s ym p t om s
of GCA u s u a lly re s p on d d ra m a t ica lly w it h in 48 h ou rs , bu t it m a y t a ke u p t o
PATIENT ASSESSMENT 5 d ays in s om e ca s e s .
Th e t r e a t m e n t o f PMR s h o u ld b e in it ia t e d a t a d o s e o f 10 t o 20 m g o f
• Po lym ya lg ia rh e u m a t ica p r e d n is o n e o r it s glu c o c o r t ic o id e q u iva le n t p e r d a y. As w it h GCA, t h e
a n d g ia n t ce ll a rt e rit is a re re s p o n s e is u s u a lly s o d ra m a t ic t h a t s o m e u s e it a s a co n r m a t o ry d ia gn o s -
se e n in p e o p le o ld e r t h a n t ic e le m e n t . In b o t h PMR a n d GCA, t a p e r in g o f glu c o co r t ic o id s s h o u ld b e
50 ye a rs. s lo w, s t a r t in g s o m e w h e r e b e t w e e n 2 a n d 4 w e e k s a ft e r t h e in it ia t io n o f
• Ele va t e d se d im e n t a t io n t r e a t m e n t , a n d o n ly a ft e r t h e r eve r s ib le m a n ife s t a t io n s o f t h e d is e a s e h a ve
ra t e s a n d /o r C-re a ct ive re s p o n d e d a n d in a m m a t o ry m a r k e r t it e r s h a ve n o r m a liz e d . Re co m m e n d a -
p ro t e in le ve ls a re fo u n d in t io n s fo r glu co co r t ico id t a p e r in g ca n b e fo u n d in Ta b le 15.5 (3 ). Th e r o le o f
a la rg e m a jo rit y b u t n o t
a ll ca se s.
in a m m a t o r y m a r k e r s in t h e t a p e r in g o f glu co co r t ico id s is s u p p o r t ive , a n d
t r e a t m e n t d e cis io n s a r e p r im a r ily b a s e d o n t h e p re s e n ce o r a b s e n ce o f clin -
• Ot h e r a b n o rm a l, b u t ica l m a n ife s t a t io n s . Pa t ie n t s w h o a re a s ym p t o m a t ic b u t s e e t h e ir ESR o r CRP
le ss sp e ci c, la b o ra t o ry
t it e r s in cre a s e s h o u ld h a ve t h e ir glu co co r t ico id t a p e r s low e d d ow n , b u t m a y
n d in g s a re m icro cyt ic
a n e m ia , t h ro m b o cyt o sis, n o t n e e d t o h a ve t h e ir glu co co r t ico id d o s a ge in cre a s e d a ga in . On t h e o t h e r
le u ko cyt o sis, e le va t e d h a n d , p a t ie n t s w it h n o r m a l ESR o r CRP b u t w it h clin ica l m a n ife s t a t io n s o f
a lka lin e p h o sp h a t a se a n d re la p s e n e e d t o h a ve t h e ir glu co co r t ico id d o s e in cr e a s e d a ga in . Pa t ie n t s t yp -
t ra n sa m in a se , a n d ica lly s t a y o n glu co co r t ico id s a n a ve ra ge o f 2 ye a r s , a n d m o s t o f t h a t p e r io d
h yp o a lb u m in e m ia .
s h o u ld b e a t low d o s e s . Ca r e give r s s h o u ld m o n it o r a n d a ggr e s s ive ly t r e a t
• Te m p o ra l a rt e ry b io p sy c o m p lic a t io n s o f glu c o c o r t ic o id t h e r a p y, in c lu d in g b u t n o t lim it e d t o
sp e cim e n s m u st b e o f glu co co r t ico id -in d u ce d o s t e o p o r o s is , d ia b e t e s , h yp e r lip id e m ia , d e p re s s io n ,
su f cie n t le n g t h , a t le a st
a n d p e p t ic u lce r d is e a s e . La rge d o s e s o f in t ra ve n o u s glu co co r t ico id s a s a
1 cm a n d p re fe ra b ly 3 cm ,
t o a vo id sa m p lin g e rro r. s t a n d a rd in d u ct io n t h e ra p y in p a t ie n t s w it h GCA co u ld le a d t o a m o re ra p id
re s p o n s e a n d d e cre a s e t h e fu t u re n e e d fo r o ra l glu co co r t ico id s t o t re a t t h e
148 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Table 15.5 Recommendat ions for Glucocort icoid Tapering in Polymyalgia Rheumat ica
and Giant Cell Art erit is
Ad a p t e d fro m re fe re n ce 3.
a
Do e s n o t a p p ly t o o p t ic isch e m ia , w h e re h ig h d o se s o f in t ra ve n o u s g lu co co rt ico id s a re p re fe rre d .
b
Pro ce e d a n d co n t in u e t a p e rin g o n ly if t h e p a t ie n t re m a in s a sym p t o m a t ic. Dise a se re la p se s a re co m m o n fo r b o t h g ia n t ce ll a rt e rit is a n d p o lym ya lg ia
rh e u m a t ica d u rin g t h is p h a se .
NOT TO BE MISSED
c o n d it io n . Fa ilu r e t o r e s p o n d t o glu c o c o r t ic o id t h e r a p y s h o u ld p r o m p t a
• Eld e rly p a t ie n t s w it h re a s s e s s m e n t o f t h e d ia gn o s is .
m a rke d fu n ct io n a l d e clin e Ace t yls a licylic a cid (a s p irin ), a t a d os e be t w e e n 81 a n d 325 m g/d a y, is a n
a n d d if cu lt y ca rin g fo r im p ort a n t a d ju va n t t h e ra p y in p a t ie n t s w it h GCA w h o d o n ot h a ve con t ra in d i-
t h e m se lve s m a y h a ve PMR
ca t io n s t o it . St u d ie s s u p p o rt it s ro le in p reve n t in g vis u a l lo s s a n d is ch e m ic
o r GCA a s t h e u n d e rlyin g
d ia g n o sis. com p lica t ion s , bu t it s m e ch a n is m of a ct ion is u n cle a r a s t h rom bos is d oe s n ot
p lay a big role in va s cu la r occlu s ion s ca u s e d by GCA. Tria ls of glu cocort icoid -
• Ja w cla u d ica t io n is a
s p a r in g a ge n t s h a ve b e e n u n s u cce s s fu l. Az a t h io p r in e , a n t im a la r ia ls , cyclo -
re la t ive ly sp e ci c sym p t o m
o f t h e d ise a se a n d sh o u ld p h os p h a m id e, d a p s on e, a n d s t a t in s a ll h a d d is a p p oin t in g re s u lt s in ke e p in g
b e a ske d a b o u t d u rin g t h e d is e a s e in re m is s ion a n d in t h e ir glu cocort icoid -s p a rin g e ffe ct . De s p it e in i-
t h e e va lu a t io n o f p a t ie n t s t ia l e n t h u s ia s m w it h m e t h ot re xa t e, it s e f ca cy in m a in t a in in g re m is s ion a n d
su sp e ct e d o f h a vin g GCA. a s a glu cocort icoid -s p a rin g a ge n t cou ld n ot be con rm e d in a la rge ra n d om ize d
• Visio n lo ss is t h e m o st con t rolle d t ria l (6 ). A s im ila r d is a p p oin t in g re s u lt w a s obt a in e d w it h t h e t u m or
fe a re d co m p lica t io n o f n e cro s is fa ct o r re ce p t o r a n t ib o d y in ix im a b, w h ich s h ow e d n o e ffe ct a s a
GCA. Sym p t o m s su g g e st ive glu cocort icoid -s p a rin g a ge n t (7 ). In con clu s ion , t h e cu rre n t a p p roa ch re m a in s
of o ph t h a lm ic co m prom ise
t o ke e p t h e low e s t d os e of glu cocort icoid s for t h e s h ort e s t p e riod of t im e, in
sh ould a lwa ys be e xplo re d;
th e se m a inly inclu de blu rry ord e r t o avoid s id e e ffe ct s .
vision, tra nsie nt visua l loss,
visua l ha llucina tion s, a nd
diplo pia .
• A t h o ro u g h p e rip h e ra l
Clinica l Co urse a nd Co nclusio ns
va scu la r e xa m in a t io n Th e p rogn os is for t h e gre a t m a jorit y of p a t ie n t w it h PMR is good , a s t h e d is e a s e
(p u lse s a n d b lo o d is u s u a lly t re a t m e n t re s p on s ive a n d m os t p a t ie n t s d is con t in u e glu cocort icoid s
p re ssu re ) sh o u ld a lw a ys
a ft e r 1 t o 2 ye a rs . A s u bs e t of p a t ie n t s cou ld d eve lop a s e ron ega t ive in a m m a -
b e p e rfo rm e d in p a t ie n t s
su sp e ct e d o f h a vin g PMR t ory p olya rt h rit is re q u irin g a t re a t m e n t a p p roa ch s im ila r t o rh e u m a t oid a rt h ri-
o r GCA a s t h is m a y re ve a l t is , bu t t h is a rt h rit is is n ot a ggre s s ive or e ros ive.
n d in g s in d ica t ive o f Th e m os t om in ou s m a n ife s t a t ion s of GCA a re t h e d eve lop m e n t of vis io n
a o rt it is o r p e rip h e ra l lo s s o r o t h e r cra n ia l is ch e m ic m a n ife s t a t io n s , p rin cip a lly s t ro k e s . If t h is is
a rt e ria l o cclu sio n s.
avoid e d , p a t ie n t s re s p on d w e ll t o h igh -d os e glu cocort icoid t h e ra p y. Th e m a in
• The p re sen ce of n orma l lon g-t e rm m orbid it y is s e con d a ry t o a p rolon ge d e xp os u re t o glu cocort icoid s . A
in a mma tory ma rke rs (ESR m a jorit y of p a t ie n t s h ave a t le a s t on e re la p s e of d is e a s e, u s u a lly in t h e form of
a n d/o r CRP), w h ile u nlike ly,
PMR. No cle a r p ict u re a bou t life e xp e ct a n cy in GCA h a s be e n obt a in e d , w it h
does no t e xclu de th e
diagn osis o f PMR or GCA. con t ra d ict in g s t u d ie s s u p p ort in g bot h a p re m a t u re m ort a lit y a n d a n orm a l life
e xp e ct a n cy.
Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 149
s
e
su rg e o n s. Sp e ci ca t io n s 7. Hoffm a n GS, Cid MC, He llm a n n DB, e t a l. In ixim a b for m a in t e n a n ce of glu cocort icos t e roid -in d u ce d
s
a
re m is s io n of gia n t ce ll a rt e rit is : A ra n d om ize d t ria l . A nn Intern Med 2007 ;146 (9 ):621 –630 .
a b o u t t h e b io p sy sp e cim e n
e
s
m a n a g e m e n t sh o u ld b e
i
D
p ro vid e d .
c
i
t
a
• Pa tie nt suspe cte d of havin g
m
GCA w it h visio n sym p t o m s
u
e
should se e an ophtha lmol-
h
R
ogist a s so on as po ssib le for
c
a fu n d o sco p ic e xa m in a t io n
i
a n d t o ru le o u t o t h e r
c
e
re ve rsib le ca u se s o f visio n
p
S
lo ss.
3
N
• Pa t ie n t s w it h PMR w h o
O
h a ve sym p t o m re cu rre n ce
I
T
a ft e r a n a p p ro p ria t e
C
E
g lu co co rt ico id co u rse a n d
S
t a p e r sh o u ld b e re fe rre d
t o a rh e u m a t o lo g ist .
CHAPTER
16 Overla p Syndromes
a nd Uncla ssi ed or
Undifferentia ted
Connective Tissue
Disea se
Iris Navarro-Millán and Graciela S. A larcón
s
Th e rh e u m a t ologic com m u n it y h a s n ot va lid a t e d t h e e xis t e n ce of s u ch d is or-
e
s
a
d e r; t h u s , ACTD is n ot d is cu s s e d .
e
s
Th e t e rm in ology or n om e n cla t u re u s e d in t h is ch a p t e r is s u m m a rize d in
i
D
Ta ble 16.1 .
c
i
t
a
CLINICAL POINTS
m
u
• Wh ile t h e re a re p a t ie n t s The Ove rla p Syndro me s
e
h
w it h a n a u t o im m u n e rh e u -
R
m a t ic d ise a se w h o m a y Th e follow in g ove rla p s yn d rom e s h a ve be e n d e s cribe d in t h e lit e ra t u re : rh u p u s
c
d e ve lo p m a n ife st a t io n s o f
i
o r t h e ove r la p b e t w e e n r h e u m a t o id a r t h r it is (RA) a n d s ys t e m ic lu p u s e ry-
c
e
a n o t h e r, t h e re a re so m e
p
t h e m a t o s u s (SLE); s cle ro d e r m a t o m yo s it is (o r s cle ro m yo s it is ) o r t h e ove rla p
S
p a t ie n t s w h o fu lly d e ve lo p
be t w e e n s cle rod e rm a a n d m yos it is ; a n d MCTD or t h e ove rla p be t w e e n p oly/
3
t w o o r m o re d ise a se s sim u l-
N
t a n e o u sly o r se q u e n t ia lly. d e rm a t om yos it is , s cle rod e rm a , SLE, a n d RA in t h e p re s e n ce of a n t i-U1RNP a n t i-
O
bod ie s a n d HLA-DR4. Ot h e r “ove rla p s ” a re con s id e re d s u bs e t s of d e n e d CTDs
I
T
• Th e se p a t ie n t s m a y b e
C
ra t h e r t h a n ove rla p s ; s u ch is t h e ca s e for p a t ie n t s w it h SLE or RA w h o a ls o h ave
E
cla ssi e d a s h a vin g a n
S
o ve rla p syn d ro m e . m yos it is or va s cu lit is , a s w e ll a s for p a t ie n t s w it h SLE w h o h ave clin ica l a n d
• Co m m o n o ve rla p syn - la bora t ory fe a t u re s of t h e a n t ip h os p h olip id a n t ibod y s yn d rom e (APS). Ot h e r
d ro m e s in clu d e rh u p u s, p a t ie n t s w it h a d e n e d CTD p re s e n t ove rla p p in g m a n ife s t a t ion s w it h n on -CTD
scle ro d e rm a t o m yo sit is o r d is ord e rs ; s u ch is t h e ca s e of p a t ie n t s w it h lu p os cle ros is a s t h e ove rla p p in g
scle ro m yo sit is, a n d MCTD. clin ica l s yn d rom e of SLE, a n d m u lt ip le s cle ros is h a s be e n ca lle d . Fin a lly, p a t ie n t s
• Mixe d co n n e ct ive t issu e w it h p rim a ry APS m ay a ls o p re s e n t w it h m a n ife s t a t ion of m u lt ip le s cle ros is .
d ise a se is a t e rm co in e d Ta ble 16.2 s u m m a rize s t h e s e d iffe re n t con d it ion s by ca t egorie s .
n e a rly 40 ye a rs a g o t o re fe r Th e rs t t h re e ove rla p s yn d rom e s a re n ow d e s cribe d in s om e d e t a il.
t o p a t ie n t s w it h fe a t u re s
o f m o re t h a n o n e d ise a se
(a rt h rit is, scle ro d e rm a , RHUPUS
lu p u s, m yo sit is) w it h h ig h
a n t i-U1RNP a n t ib o d ie s; Art h ra lgia s a n d a rt h rit is a re ra t h e r com m on in p a t ie n t s w it h SLE; h ow eve r, in
w it h t im e , h o w e ve r, t h e se s om e p a t ie n t s w it h SLE, t h e m os t p rom in e n t clin ica l m a n ife s t a t ion is a s ym -
p a t ie n t s u su a lly e vo lve in t o m e t ric p olya rt h rit is . Th e s e p a t ie n t s m a y o r m a y n ot h a ve a p os it ive RF. Th a t
a m o re d e n e d CTD.
w a s t h e ca s e o f o u r p a t ie n t w h o s e clin ica l p re s e n t a t io n w a s a s ym m e t r ic
• Th e re is n o co n se n su s o n in a m m a t ory a rt h rit is w it h ra d iogra p h ic evid e n ce of e ros ion s t h a t re s e m ble
h o w t o d ia g n o se u n cla ssi- RA, ye t h e r s e ro logie s w e re m ore s u gge s t ive o f SLE. Pa t ie n t s w it h RA m a y
e d o r u n d iffe re n t ia t e d
p re s e n t s om e e xt ra -a rt icu la r fe a t u re s a n d a p os it ive ANA t e s t t h a t m ay s u gge s t
CTD; su ch a la b e l m a y re p -
re se n t t h e p ro d ro m e o f t h e d ia gn os is of SLE. Th e t e rm rh u p u s , h ow eve r, is re s e rve d for t h os e p a t ie n t s
lu p u s; h o w e ve r, so m e o f w h o cle a rly m e e t crit e ria for bot h SLE a n d RA, a n d w h o p re s e n t ch a ra ct e ris t ic
t h e se p a t ie n t s m a y re m a in clin ica l fe a t u re s of bot h t h e d is ord e rs . Th e s e p a t ie n t s u s u a lly h ave a s e rop os i-
u n d iffe re n t ia t e d o r in co m - t ive, e ros ive, s ym m e t ric p olya rt h rit is , w h ich a n t e d a t e s t h e on s e t of u n e q u ivo-
p le t e o r e vo lve in t o a b ro -
ca l clin ica l fe a t u re s of SLE. Th ey a ls o p re s e n t a u t oa n t ibod ie s ch a ra ct e ris t ic of
m ya lg ia -like syn d ro m e w it h
ANA p o sit ivit y. bot h t h e d is ord e rs ; t h e s e in clu d e IgM-RF, ANA, a n t i-d s DNA, a n d in a bou t h a lf
t h e p a t ie n t s , a n t ibod ie s t o Ro. Mos t re ce n t ly h igh ly s p e ci c a n t ibod ie s for RA
152 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
PATIENT ASSESSMENT Table 16.2 Overlap Connect ive Tissue Diseases and
Relat ed Syndromes
• Ou r p a t ie n t h a d sym m e t ric
p o lya rt h rit is in a rh e u m a - Re co g nize d o ve rlap CTDs
t o id -like d ist rib u t io n w it h
se ro lo g ie s t h a t w e re m o re SLE/RA : Rh u p u s
co n sist e n t w it h SLE ra t h e r M yo sit is/scle ro d e rm a: Scle ro d e rm at o m yo sit is o r scle ro m yo sit is
t h a n w it h RA. M yo sit is/scle ro d e rm a/RA /SLE: M CTD
• Ha n d s a n d fe e t ra d io - Subse ts w ithin de ne d CTDs
g ra p h s d e m o n st ra t e d a n
SLE/m yo sit is
e ro sive a rt h rit is h ig h ly
RA /m yo sit is
su g g e st ive o f RA.
SLE/A PS
• Th e re w a s b io p sy-p ro ve n RA /vascu lit is
p o lym yo sit is. SLE/vascu lit is
• Scle ro d a ct yly a n d ILD Ove rlap CTD and a no nrhe umatic diso rde r
su g g e st e d t h e d ia g n o sis o f
SLE/m u lt ip le scle ro sis
syst e m ic scle ro sis (SSc).
Ove rlap CTD-like and a no nrhe umatic diso rde r
• Th e se n d in g s re p re se n t
t h e o ve rla p o f fo u r rh e u - A PS/m u lt ip le scle ro sis
m a t ic d ise a se s: RA, SLE,
SSc, a n d p o lym yo sit is; CTD, co n n e ct ive t issu e d ise a se ; SLE, syst e m ic lu p u s e ryt h e m a t o su s; RA, rh e u m a t o id a rt h rit is; APS,
h o w e ve r, sh e la cke d a n t i- a n t ip h o sp h o lip id a n t ib o d y syn d ro m e .
U1RNP a n t ib o d ie s, t h e
h a llm a rk o f MCTD.
SCLERODERMATOMYOSITIS OR SCLEROMYOSITIS
Th ese a re p a tien ts w ith m a n ifesta tion s of sclerod erm a a n d p oly/d erm a tom yositis
t h a t e xh ibit va ria ble cu t a n e ou s , m u s cu la r, a n d orga n s ys t e m m a n ife s t a t ion s ;
a lt h ou gh t h is ove rla p s yn d rom e w a s origin a lly d e s cribe d in a d u lt s , p e d ia t ric
ca s e s h a ve a ls o be e n rep ort e d . Com m on m a n ife s t a t ion s ch a ra ct e ris t ic of SSc
a re a ls o fre q u e n t ly fou n d in s cle rod e rm a t om yos it is or s cle rom yos it is , in clu d -
s
e
in g Rayn a u d ’s p h e n om e n on , m ya lgia s or a rt h ra lgia s , d ys p h a gia , a n d in a bou t
s
a
30% of t h e p a t ie n t s , ILD. Fe a t u re s of d e rm a t om yos it is s u ch a s p e riorbit a l e d e m a
e
s
i
a n d e ryt h e m a , Go t t ro n ’s p a p u le s , a n d e ryt h e m a t o u s a n d p o ik ilo d e r m a t ou s
D
c
le s ion s on t h e t ru n k a n d a rm s or t h e “s h a w l s ign ” m ay occu r ove r t h e cou rs e of
i
t
a
t h e d is e a s e (7 ). W h ile t h e re a re a u t h ors w h o s t re s s t h e im p ort a n ce of t h e p re s -
m
e n ce of “m e ch a n ic’s h a n d s ” (h yp e rke ra t ot ic ch ron ic e cze m a of t h e h a n d s ) (8 ),
u
e
h
ot h e rs s u gge s t t h a t t h is m igh t be p re s e n t in a ll t yp e s of m yop a t h ie s a n d t h u s
R
t h is n d in g is n ot s p e ci c for s cle rod e rm a t om yos is t is or s cle rom yos it is . Ou r
c
i
ow n e xp e rie n ce w it h t h is ra re d is ord e r, h ow eve r, is q u it e d iffe re n t ; t h e p a t ie n t s
c
e
(ch ild re n a n d a d u lt s ) w e h ave follow e d h ave h a d s eve re a n d ge n e ra lize d s kin
p
S
in volvem e n t w it h t h e con s eq u en t occu rren ce of exion con t ra ctu res . Pu lm on a ry,
3
N
ga s t roin t e s t in a l, a n d re n a l in volve m en t , a s t h e on e d e scribe d in s clerod e rm a , is
O
ch a ra ct e r is t ica lly m ild , b u t s eve re m e ga co lo n a n d re s t r ict ive lu n g fu n ct io n
I
T
C
h a ve be e n d e s cribe d .
E
S
Pa t ie n t s w it h s cle rod e rm a t om yos it is u s u a lly e xh ibit h igh ANA t it e rs in a
h om oge n e ou s p a t t e rn , w h ich corre s p on d t o t h e p re s e n ce of t h e PM-Scl a n t ige n
(a n u cle ola r a n t ige n ic com p le x of 11 t o 16 p olyp ep t id e s ); a n t i-U1RNP a n t ibod ie s
a re ch a ra ct e ris t ica lly a bs e n t . PM-Scl a n t ibod ie s a re n ot , h ow eve r, s p e ci c for
s cle rom yos is t is , bu t in d iffe re n t ca s e s e rie s , t h ey h ave be e n t h e m os t fre q u e n t ly
fou n d a n t ibod ie s ; in fa ct , t h ey h a ve be e n d e s cribe d in u p t o 83% of p a t ie n t s
w it h t h is d is e a s e, bu t on ly in 10% t o 17% w it h ot h e r CTDs (9 ). From t h e im m u -
n oge n e t ic p oin t of view, p a t ie n t s w it h s cle rod e rm a t om yos it is a re e it h e r HLA-
DR3 h om ozygou s or HLA-DR3/DR4 h e t e rozygou s . Th ey a re t h u s q u it e d iffe re n t
from p a t ie n t s w it h MCTD.
Th e freq u en cy of th is d isord er is la rgely u n kn ow n ; a s w ith rh u p u s, m ost p u b-
lica tion s on sclerod erm a tom yositis com e from tertia ry ca re fa cilities a n d in clu d e
sm a ll ca se series a n d ca se rep orts; th u s, p op u la tion -ba sed gu res a re u n ava ilable.
Th e t re a t m e n t of t h e s e p a t ie n t s s h ou ld be a im e d a t con t rollin g t h e in a m -
m a t ory p ro ce s s in m u s cle s a n d ot h e r t is s u e s in volve d . W h ile SSc a s s o cia t e d
w it h m yos it is is u s u a lly a ve ry s eve re form of t h e d is e a s e, s cle rom yos it is h a s ,
in ge n e ra l, a p rot ra ct e d a n d ra t h e r be n ign cou rs e . Th e d iffe re n ce lie s on it s
vis ce ra l in volve m e n t a n d n ot in fre q u e n t ly by t h e vis u a l s ign s of d e rm a t om y-
os it is (7 ). Mu s cle in a m m a t ion is u s u a lly m ild a n d s t e roid re s p on s ive. Aggre s -
s ive t re a t m e n t s u ch a s t h e on e u s e d in SSc a n d d e rm a t om yos it is cou ld be m ore
h a rm fu l t h a n t h e d is e a s e it s e lf, a n d is ra re ly re q u ire d (7 ). Th is is a n im p ort a n t
re a s on for re cogn izin g p a t ie n t s w it h t h is ove rla p s yn d rom e. Th e p rogn os is of
p a t ie n t s w it h t h is ove rla p s yn d rom e d ep e n d s on t h e d egre e of orga n s ys t e m
in volve m e n t t h ey h a ve, bu t ove ra ll, t h e p rogn os is is m ore favora ble t h a n SSc or
d e rm a t om yos it is by t h e m s e lve s (9 ).
154 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Table 16.3 Clinical and Laborat ory Feat ures of Mixed Connect ive
Tissue Disease
MAJOR MINOR
Sw o lle n n g e rs a n d /o r h a n d s Art h rit is
Ra yn a u d ’s p h e n o m e n o n Alo p e cia
Eso p h a g e a l d ysm o t ilit y Myo sit is
Scle ro d a ct yly Trig e m in a l n e u ro p a t h y
Myo sit is Cyt o p e n ia s
Se ro sit is
Pu lm o n a ry in vo lve m e n t
An t i-U1RNP a n t ib o d ie s
Ne g a t ive a n t i-Sm a n t ib o d ie s
Ch a p te r 16 Ove rla p Syn d ro m e s a n d Un cla s s i e d or Un d iffe re n t ia t e d Con n e ct ive Tis s u e Dis e a s e 155
s
e
w it h is ola t e d Rayn a u d ’s p h e n om e n on , (b) t h os e w it h u n e xp la in e d p olya rt h rit is
s
a
(p a t ie n t s q u it e n ot m e e t in g crit e ria for t h e d ia gn os is of RA), a n d (c) t h os e w it h
e
s
i
t ru ly u n d e n e d m a n ife s t a t ion s (a s p rovid e d in Ta ble 16.4 ). It ca n be a rgu e d t h a t
D
c
n ot a ll p a t ie n t s e n t e rin g t h e u n d e n e d ca t egory w ou ld h ave be e n in clu d e d a s
i
t
a
s u ch t o d a t e ; in d e e d s om e of t h e s e p a t ie n t s p roba bly cou ld h ave be e n con s id -
m
e re d a s h a vin g a n ANA-p os it ive, brom ya lgia -like s yn d rom e a s d e s cribe d by
u
e
ou r grou p s eve ra l ye a rs a go. Th is m u lt ice n t ric grou p a ls o con s t it u t e d a s e con d
h
R
coh ort of p a t ie n t s w it h w e ll-d e n e d CTDs t h a t s e rve d a s a com p a ris on for t h e
c
i
u n cla s s i e d p a t ie n t s .
c
e
Pa t ie n t s in t h is s t u d y w e re follow e d lon git u d in a lly in a n e ffort t o d e t e rm in e
p
S
t h e p a t ie n t s ’ n a l d ia gn os is . Ye a rly vis it s w e re d on e d u rin g t h e rs t 5 ye a rs ; a n
3
N
a d d it ion a l vis it w a s con d u ct e d a t 10 ye a rs . Th e p rot ocol re q u ire d on ly a n u p d a t e
O
in t e rva l h is t o ry, a p h ys ica l e x a m in a t io n , a n d a co re o f la b o ra t o ry t e s t s . An y
I
T
C
ot h e r la bora t ory t e s t or m ore s op h is t ica t e d a n cilla ry p roce d u re re q u ire d t h e
E
S
p re s e n ce of clin ica l m a n ife s t a t ion s t h a t cou ld ju s t ify ord e rin g or p e rform in g
t h e m . Th e re s u lt s of t h is s t u d y a re w ort h d is cu s s in g. Firs t , t h e ove rw h e lm in g
m a jorit y of p a t ie n t s e n t e rin g t h e s t u dy a s d e n e d CTDs kep t t h e s a m e d ia gn os is
a t a la t e r t im e p oin t ; t h is con t ra s t s w it h le s s t h a n 50% for t h os e w it h u n d iffe r-
e n t ia t e d d is e a s e t h a t kep t t h e s a m e d ia gn os is . Am on g t h os e w it h u n cla s s i e d
d is e a s e s , t h e re w e re s o m e d iffe re n ce s d e p e n d in g o n t h e s u b gro u p w it h in
t h is coh ort a t e n rollm e n t . Of t h os e w h o s t a rt e d a s u n e xp la in e d p olya rt h rit is ,
Unclassified or
undifferentiated
CTD
n = 213
Defined CTDs
n = 19(2)
NA
n = 47
Undefined CTDs
n = 35(6)
Figure 16.2 Ten-yea r follow-up dia gnoses of pa tients with uncla ssi ed or undifferentia ted connective tissue disea se
(CTD); UPA, unexpla ined polya rthritis; NA, nona va ila ble; RP, Ra yna ud’s phenomenon. a One pa tient developed psoria tic
a rthritis; b one pa tient ea ch developed psoria tic a rthritis, sa rcoidosis, a nd mya sthenia gra vis. Modi ed from Ala rcón (1).
s
is t o b e le sse n e d .
e
t h e t h e ra p ie s u t ilize d .
s
a
e
Re fe r to Patie nt Education
s
i
D
c
i
t
a
ICD9
m
u
710.9 Co nne ctive tissue , diffuse
e
h
R
c
i
c
Re fe re nce s
e
p
S
1. Ala rcon G. Un cla s s i e d o r u n d iffe re n t ia t e d con n e ct ive t is s u e d is e a s e . In : Koop m a n W J, Bou lw a re DW,
3
He u d e be rt GR, e d s . Clinical Prim er of Rheum atology. Lip p in cot t Willia m s a n d W ilkin s . 2003 :213 –219 .
N
2. Am e zcu a -Gu e rra LM , Sp rin ga ll R, Ma rq u e z-Ve la s co R, e t a l. Pre s e n ce of a n t ibod ie s a ga in s t cyclic cit -
O
I
ru llin a t e d p e p t id e s in p a t ie n t s w it h “rh u p u s ”: A cros s -s e ct ion a l s t u d y. A rthritis Res Ther 2006 ;8 (5 ):R144 .
T
C
3. Ro d r igu e z-Reyn a TS, Ala rcon -Segovia D. Ove rla p s yn d rom e s in t h e con t e xt of s h a re d a u t oim m u n it y.
E
Autoim m unity 2005 ;38 (3 ):219 –223 .
S
4. Pip ili C, Sfrit ze ri A, Ch olon git a s E. De fo rm in g a rt h rop a t h y in SLE: Review in t h e lit e ra t u re a p rop os of on e
ca s e . Rheum atol Int 2009 ;29 (10 ):1219 –1221 .
5. Levin e D, Sw it lyk SA, Got t lie b A. Cu t a n e ou s lu p u s e ryt h e m a t os u s a n d a n t i-TNF-a lp h a t h e ra py: A ca s e
re p ort w it h review of t h e lit e ra t u re . J Drugs Derm atol 2010 ;9 (10 ):1283 –1287 .
6. Soforo E, Ba u m ga rt e r M , Fra n cis L, e t a l. In d u ct ion of s ys t e m ic lu p u s e ryt h e m a t os u s w it h t u m or n e cro-
s is fa ct or blocke rs . J Rheum atol 2010 ;37 (1 ):204 –205 .
7. Ja blon s ka S, Bla s zyk M . Scle rom yos it is (s cle rod e rm a /p olim yos it is ove rla p ) is a n e n t it y. J Eur A cad Derm atol
Venereol 2004 ;18 (3 ):265 –266 .
8. Torok L, Da kó K, Cs e rin G, e t a l. PM-SCL a u t oa n t ibod y p os it ive s cle rod e rm a w it h p olym yos it is (m e ch a n -
ic’s h a n d : clin ica l a id in t h e d ia gn os is ). J Eur A cad Derm atol Venereol 2004 ;18 (3 ):356 –359 .
9. Ja blon s ka S, Bla s zczyk M . Scle rom yos it is : A s cle rod e rm a /p olym yos it is ove rla p s yn d rom e . Clin Rheum atol
1998 ;17 (6 ):465 –467 .
10. Zold E, Szod oray P, Ka p p e lm a ye r J, e t a l. Im p a ire d regu la t ory T-ce ll h om e os t a s is d u e t o vit a m in D d e -
cie n cy in u n d iffe re n t ia t e d con n e ct ive t is s u e d is e a s e . Scand J Rheum atol 2010 ;39 :490 –497 .
CHAPTER
17 Fibromya lgia
Graciela S . A larcón
Intro ductio n
A 40-ye ar-o ld o b e se , se d e n -
Fib ro m ya lgia (FM) is a co n d it io n
S
t ary, Cau casian w o m an
E
C
a ffe c t in g p r e fe r e n t ia lly m id d le -
T
p re se n t s t o a rh e u m at o lo g ist
I
a ge d w h it e w om e n ; m e n , ch ild re n
O
N
w it h a 6-m o n t h h ist o ry o f of e it h e r ge n d e r, a n d old e r a d u lt s
3
g e n e raliz e d m yalg ias, ca n be a ffe ct e d , h ow eve r (1 ). Fibro-
S
p
m ya lgia h a s be e n re cogn iz e d p r i-
e
art h ralg ias, sw e llin g o f sm all
c
m a r ily in t h e m id d le a n d u p p e r
i
h an d jo in t s, an d m o rn in g
c
s ocioe con om ic s t ra t a . W h e t h e r t h is
R
st iff n e ss o f u n sp e ci e d d u ra- re e ct s on ly a cce s s t o h e a lt h ca re
h
e
u
t io n . He r p rim ary care p h ysi- or t ru e d iffe re n ce s in t h e in cid e n ce
m
a n d p r e va le n ce o f t h e d is o rd e r
a
cian h ad ru n so m e t e st s an d
t
i
a m on g d is a d va n t a ge d p op u la t ion s
c
re f e rre d h e r f o r p o ssib le
D
h a s n ot be e n d e t e rm in e d .
i
s
e
rh e u m at o id art h rit is (RA ). Th e tru e in cid en ce a n d p reva -
a
s
(Ig M rh e u m at o id f act o r w as len ce of FM is u n kn ow n . Pop u la tion -
e
s
ba sed stu d ies a re d if cu lt to in ter-
p o sit ive at 24 u n it s.) Ot h e r
pret; issu es su ch a s th e criteria u sed
sym p t o m s e licit e d b y t h e t o d ia gn os e FM, w h e t h e r p rim a ry
rh e u m at o lo g ist in clu d e d a n d secon d a ry ca ses a re in clu d e d ,
f at ig u e , u n re f re sh e d sle e p , a n d th e d em ogra p h ic ch a ra cteristics
of th e p op u la tion th a t is bein g su r-
in t e rm it t e n t ab d o m in al
veyed n eed to be con sid ered . Stu d ies
p ain , an d in cre ase d u rin ary from Nort h Am e rica a n d Eu rop e,
f re q u e n cy. M o rn in g st iff n e ss last e d ab o u t 30 m in u t e s. Ph ysical im p e rfe ct a s t h ey m ay be, reve a l
e xam in at io n re ve ale d an o b e se w h it e w o m an in n o d ist re ss. Th e re overa ll p reva len ce ra tes betw een 1%
a n d 5%, bu t gu res a s h igh a s 13%
w e re m u lt ip le t e n d e r are as o ve r t h e u p p e r an d lo w e r b ack , an d
h ave been rep orted . Th es e p op u la -
aro u n d t h e sh o u ld e r an d p e lvic g ird le s. Th e h an d s w e re p u ff y tion -ba sed stu d ies con rm th e gen -
(f at ), b u t n o syn o vit is w as d e t e ct e d in an y o f t h e jo in t s. A co m - d e r d is t r ib u t io n (p re d o m in a n t ly
p le t e b lo o d co u n t an d a u rin alysis w e re n o rm al. Rad io g rap h s o f fem a le) of th e FM syn d rom e. In th e
clin ica l settin g, th e freq u en cy of FM
t h e aff e ct e d are as w e re n o t o b t ain e d .
d ep en d s, to a certa in exten t, on th e
degree of aw a ren ess abou t th is con -
d ition . Figu res betw een 2% a n d 4% h ave been rep orted in th e p rim a ry ca re settin g.
In rh eu m a tology clin ics, th e freq u en cy of FM u ctu a tes betw een 3% a n d 20%. Th ese
gu res p robably re ect th e rh eu m a tologists’ in terest in FM a n d th e level of aw a re-
n ess abou t th is con d ition a m on g com m u n ity ph ysicia n s a n d th e p u blic a t la rge (1 ).
Like m a n y ot h e r rh e u m a t ic d is ord e rs , t h e e t iop a t h oge n e s is of FM is p rob-
a bly m u lt ifa ct oria l (1 ). Su s cep t ible in d ivid u a ls m a y d eve lop FM a s a re s u lt of t h e
158
Ch a p te r 17 Fibrom ya lgia 159
s
e
viru s B19 (1 ). In fe ct ion s w it h Borrelia burgdorferi (Lym e d is e a s e ) h ave a ls o be e n
s
a
re cogn iz e d a s ca p a ble o f p re cip it a t in g FM. It s h ou ld be n ot e d t h a t , u n fo rt u -
e
s
i
n a t e ly, m a n y ca s e s of p os t -Lym e FM a re e rron e ou s ly d ia gn os e d a s ch ron ic Lym e
D
c
d is e a s e a n d p a t ie n t s a re s u bje ct e d t o cos t ly, u n n e ce s s a ry, a n d le n gt h y t re a t -
i
t
a
m e n t s (s e e Ch a p t e rs 27 t o 30).
m
u
e
h
R
Clinica l Pre se nta tio n
c
i
c
Fibrom ya lgia is a ch ron ic m u s cu los ke le t a l d is ord e r ch a ra ct e rize d by ge n e ra l-
e
p
S
ize d p a in a n d t e n d e rn e s s a t s p e ci c a n a t om ic s it e s , ca lle d tender points (1 ).
3
Fibrom ya lgia ca n occu r in is ola t ion or in t h e s e t t in g of ot h e r m u s cu los ke le t a l
N
O
or rh e u m a t ic d is ord e r (p rim a ry vs . s e con d a ry FM) (1 ). In fa ct , in s om e p a t ie n t s
I
T
w it h rh e u m a t oid a rt h rit is (RA) or s ys t e m ic lu p u s e ryt h e m a t os u s (SLE), t h e ove r-
C
E
w h e lm in g clin ica l m a n ife s t a t ion s a re t h os e of FM, a n d n ot t h e on e s w e t yp ica lly
S
a t t ribu t e t o e it h e r RA or SLE. Th es e FM s ym p t om s a re, by a n d la rge, u n re s p on s ive
t o t h e ra p ies com m on ly u s e d for t h e t re a t m e n t of t h e u n d e rlyin g con d it ion .
MUSCULOSKELETAL MANIFESTATIONS
Pa t ie n t s w it h FM o ft e n p r e s e n t t o t h e ir p h ys icia n s co m p la in in g o f d iffu s e
a r t h ra lgia s a n d m ya lgia s a s w e ll a s o f jo in t s w e llin g, p a r t icu la r ly in t h e s m a ll
jo in t s o f t h e h a n d s a n d fe e t (1 ). So m e p a t ie n t s a ls o co m p la in o f m o r n in g
s t iffn e s s , la s t in g fro m m in u t e s t o h o u r s ; o t h e r s e x h ib it jo in t h yp e r m o b ilit y.
It s h o u ld b e n o t e d , h ow e ve r, t h a t jo in t s w e llin g is n o t p r e s e n t in t h e s e
PATIENT ASSESSMENT p a t ie n t s .
• Th e d ia g n o sis is clin ica l. A
co m p le t e h ist o ry a n d a
p h ysica l e xa m in a t io n a re OTHER CLINICAL MANIFESTATIONS
n e ce ssa ry. Mu lt ip le t e n d e r Pa t ie n t s w it h FM m ay e xp e rie n ce n u m e rou s ot h e r clin ica l m a n ife s t a t ion s . In
p o in t s a re u su a lly p re se n t , fa ct , t h e s e ot h e r m a n ife s t a t ion s m ay be t h e on e s t h a t brin g t h e s e p a t ie n t s t o
w h e re a s jo in t sw e llin g is s e e k m e d ica l h e lp . Sym p t om s re fe rre d t o a ll orga n s ys t e m s h ave be e n d e s cribe d .
co n sp icu o u sly a b se n t .
In s om e ca s e s , t h e s e ot h e r m a n ife s t a t ion s , ra t h e r t h a n p a in , m a y be t h e p re -
• Ext e n sive (a n d e xp e n sive ) d om in a n t on e s .
a n cilla ry t e st s a re n o t
re co m m e n d e d .
Fatig ue
• Tre a t m e n t is m u lt id iscip li-
Pa t ie n t s w it h FM oft e n com p la in of s om e d egre e of fa t igu e ; ra re ly, h ow eve r, is
n a ry w it h m e d ica t io n s
b e in g o n ly o n e e le m e n t . fa t igu e s o in t e n s e a s t o be t h e fa ct or d e t e rm in in g in ca p a cit a t ion , u n like t h e
s it u a t ion of p a t ie n t s w it h ch ron ic fa t igu e s yn d rom e (CFS) (1 ). In t u rn , p a t ie n t s
160 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Sle e p Disturbance s
Pa t ie n t s w it h FM, rega rd le s s of t h e in t e n s it y of t h e ir p a in , u s u a lly com p la in of
p oor s le e p ; t h ey m ay h a ve d if cu lt y fa llin g a s le ep or m ay w a ke u p t h rou gh ou t
t h e n igh t . As a re s u lt , t h ey aw a ke in t h e m orn in g u n re fre s h e d a n d t ire d . Som e
in ve s t iga t ors h a ve p os t u la t e d t h a t t h e m u s cu los ke le t a l p a in in FM re s u lt s from
s le e p d e p riva t io n . Sle e p s t u d ie s co n d u ct e d in p a t ie n t s w it h FM h a ve in d e e d
s h ow n a bn orm a l re cord in gs d u rin g d e ep s le e p . Th is p a t t e rn , ca lle d “n on –ra p id
eye m ove m e n t a n o m a ly,” is ch a ra ct e rize d by a re la t ive fa s t fre q u e n cy (a lp h a
w a ve s ) s u p e rim p o s e d in a s low e r d e lt a fre q u e n cy (1 ). Sim ila r n d in gs h a ve
b e e n o b t a in e d in n o r m a l in d ivid u a ls s u b je ct e d t o s le e p d e p r iva t io n ; t h e s e
a bn orm a lit ie s a re n e it h e r s p e ci c n or s e n s it ive for FM. An o t h e r a bn orm a lit y,
s le ep a p n e a , d e s cribe d in s om e p a t ie n t s w it h FM, p rim a rily ove rw e igh t m e n ,
S
ca n be con s id e re d a m a rke r for t h is d is ord e r. How eve r, on ly a ca re fu l a s s e s s -
E
C
m e n t of s le ep (in clu d in g t h e s p ou s e or be d p a rt n e r) m a y u n cove r t h e p re s e n ce
T
I
O
a n d s eve rit y of s le ep a p n e a .
N
3
S
Othe r Manife statio ns
p
e
Ta ble 17.1 p rovid e s ot h e r clin ica l m a n ife s t a t ion s d e s cribe d in p a t ie n t s w it h FM.
c
i
Th e s e p a t ie n t s m ay be u n d e r t h e ca re of d iffe re n t p h ys icia n s for t h e ir va riou s
c
R
s ym p t om s a n d m a y be s u bje ct e d t o e xt e n s ive, e xp e n s ive, a n d eve n in va s ive
h
e
t e s t s a n d p roce d u re s in ord e r t o ru le ou t m ore s e riou s or d iffe re n t d is ord e rs .
u
m
Im a gin g a n d n u cle a r m e d icin e s t u d ie s , e n d os cop ie s , a n d e xp lora t ory s u rge rie s
a
t
a re, u n fort u n a t e ly, n ot u n com m on ly p e rform e d . Ta ble 17.1 p rovid e s p roce d u re s
i
c
a n d t e s t s com m on ly obt a in e d in p a t ie n t s w it h FM.
D
i
s
Rh e u m a t o logis t s s e e p a t ie n t s w it h p o s s ible FM in con s u lt a t ion in d iffe r-
e
a
e n t s it u a t io n s . On e s ce n a r io is t h a t o f p a t ie n t s w it h FM w h o h a ve fa ile d
s
e
n u m e ro u s t re a t m e n t s a n d w h o co m e s e e k in g a cu re fo r t h e ir a ilm e n t . A s e c-
s
o n d s ce n a r io is t h a t o f p a t ie n t s w h o w a n t t o le git im iz e t h e ir d ia gn o s is fo r
le ga l p u r p o s e s (e .g., w o r k m a n ’s co m p e n s a t io n o r d is a b ilit y d e t e r m in a t io n ) (1 ).
St ill o t h e r s a re p a t ie n t s w it h d iffe re n t m u s cu lo s k e le t a l d is o rd e r s , w h o h a d
b e e n d ia gn o s e d a s h a vin g FM b u t w h o s e d ia gn o s e s h a ve b e e n ove r lo o k e d .
Ex a m p le s in clu d e s p in a l s t e n o s is , p e r ip h e ra l n e u ro p a t h ie s , s ys t e m ic va s cu li-
t is , m yo s it is , a n d p o lym ya lgia r h e u m a t ica , a m o n g o t h e r s . A fo u r t h s ce n a r io is
t h a t o f p a t ie n t s w h o h a ve b e e n d ia gn o s e d a s h a vin g “re fra ct o ry RA” a n d h a ve
re ce ive d m u lt ip le m e d ica t io n s , b u t h a ve s ign i ca n t jo in t co m p la in t s (p a in
p r im a r ily). If p a t ie n t s a re o b e s e , t h e d iffe re n t ia t io n b e t w e e n p u ffy o r fa t t y
h a n d s a n d t r u e a rt h r it is m a y n o t be re a d ily evid e n t t o t h e n o n r h e u m a t o logis t .
La s t ly, o t h e r p a t ie n t s h a ve b e e n d ia gn o s e d a s h a vin g SLE o r re fe rre d fo r eva l-
u a t io n o f p o s s ible SLE. Th ey p re s e n t FM-lik e m a n ife s t a t io n s a n d a p o s it ive
t e s t fo r a n t in u cle a r a n t ibo d ie s (ANA). Th ey m a y a ls o h a ve s u bje ct ive , b u t n o t
o b je ct ive , clin ica l m a n ife s t a t io n s t h a t re n d e r t h e d ia gn os is o f SLE p la u s ible ,
u n t il t h e h is t o ry is e xa m in e d m o re cr it ica lly (1 ). Fo r e x a m p le , p a t ie n t s m a y
p re s e n t a ft e r h a vin g h a d ora l or n a s a l u lce r s , p h o t os e n s it ivit y, a n d p h o t o s e n -
s it ive ra s h e s . Sim ila r ly, t h ey m a y co m p la in o f Ra yn a u d ’s p h e n o m e n o n –lik e
m a n ife s t a t io n s , a lo p e cia , ch e s t p a in (w h ich w o r s e n s in in s p ira t io n ), a n d o f
co u r s e , a r t h ra lgia s a n d m ya lgia s . A p o s it ive ANA in t h is s e t t in g re in fo rce s t h e
d ia gn o s is of SLE a n d , u n fo rt u n a t e ly, m a y p ro m p t t h e in it ia t io n o f p o t e n t ia lly
t o x ic p h a r m a co lo gic co m p o u n d s . Alt h o u gh it is n eve r p o s s ib le t o b e s u re
w h e t h e r s u ch p a t ie n t s m a y eve n t u a lly d eve lo p SLE, it is p re fe ra ble t o w a it
u n t il o b je ct ive e vid e n ce o f SLE b e co m e s e vid e n t a n d t o n o t a la r m t h e s e
p a t ie n t s u n d u ly.
Ch a p te r 17 Fibrom ya lgia 161
Table 17.1 Sympt oms, Diagnost ic Test s or Procedures, and Diagnoses in Pat ient s wit h
Fibromyalgia Seeking Healt h Care
s
e
s
En d o crin o lo g ist We a kn e ss, fa in t n e ss Fa st in g b lo o d su g a rs, se ru m Hyp o g lyce m ia
a
e
h o rm o n e le ve ls
s
i
D
Rh e u m a t o lo g ist Mya lg ia s, a rt h ra lg ia s, Se ro lo g ic t e st s, e le ct ro p h ysio - “ La t e n t ,” “ va ria n t ,”
c
i
t
Ra yn a u d ’s p h e n o m e n o n , lo g ic st u d ie s o r “ p re lu p u s” ; co st o ch o n -
a
m
w e a kn e ss, n e ck a n d /o r b a ck d rit is; p o lym ya lg ia
u
p a in , fa t ig u e rh e u m a t ica ; “ u n d iffe re n t i-
e
h
a t e d ” CTD
R
c
De rm a t o lo g ist Pru rit u s, h ive s, skin ra sh e s, Skin b io p sie s De rm a t it is
i
c
“ p h o t o se n sit ivit y”
e
p
S
Alle rg ist “ Alle rg ie s” Skin t e st s, su p p re ssio n t e st s Alle rg ie s
3
Mu lt ip le ch e m ica l
N
O
se n sit ivit ie s
I
T
C
Ne u ro lo g ist Dizzin e ss, d yse st h e sia s, CT sca n s a n d /o r MRIs, MR Mig ra in e , re st le ss le g
E
ve rt ig o , h e a d a ch e , syn co p e , a n g io g ra m s, e le ct ro p h ysio lo g - syn d ro m e , d ysa u t o n o m ia ,
S
se izu re s ic st u d ie s, lu m b a r p u n ct u re , a n xie t y
b io p sie s
Gyn e co lo g ist Polyuria, dysuria, dyspareunia, Cyst o sco p ie s, co lp o sco p ie s UTI, cyst it is, va g in it is,
“ va g in it is,” p e lvic p a in e n d o m e t rio sis
Ot o rh in o la ryn g o lo g ist Tin n it u s, co u g h , h e a d a ch e , Au d io g ra m s, CT sca n s o r MRIs, Rh in it is, sin u sit is, Me n iè rie ,
h o a rse n e ss, sn o rin g , ve rt ig o , p o lyso m n o g ra m sle e p a p n e a
d izzin e ss
Ort h o p e d ist Ne ck a n d /o r b a ck p a in Ra d io g ra p h s, MRIs, a n d /o r CT “ Art h rit is”
sca n s
Ne u ro su rg e o n He a d a ch e , n e ck a n d /o r CT sca n s a n d /o r MRIs, e le ct ro - Sp in a l st e n o sis, ra d icu lo -
b a ck p a in , d yse st h e sia s p h ysio lo g ic st u d ie s pathy
Op h t h a lm o lo g ist Dry e ye s, b lu rre d visio n , Sch irm e r t e st , u o re sce in t e st Sicca syn d ro m e
d o u b le visio n
Psych ia t rist Anxiety, depression, insomnia, MMPI, n e u ro co g n it ive e va lu a - An xie t y, d e p re ssio n , a b u se
d e cre a se d m e m o ry, se xu a l t io n , o t h e r p sych o lo g ic t e st s (se xu a l a n d /o r p h ysica l)
a n d /o r p h ysica l a b u se
De n t ist Dry m o u t h Sa liva ry g la n d b io p sy Sicca syn d ro m e
Mo d i e d fro m Ala rcó n GS. Fib ro m ya lg ia : Disp e llin g d ia g n o st ic a n d t re a t m e n t m yt h s. W m n He alt h Pri Care (Ort h Ed ) 1999 ;2 :11 –22 .
CT, co m p u t e rize d t o m o g ra p h y; CTD, co n n e ct ive t issu e d ise a se ; ECG, e le ct ro ca rd io g ra m s; GI, g a st ro in t e st in a l; MMPI, Min n e so t a Mu lt ip h a sic
Pe rso n a lit y In ve n t o ry; MR, m a g n e t ic re so n a n ce ; MRI, MR im a g in g ; UTI, u rin a ry t ra ct in fe ct io n .
a
So m e o f t h e se d ia g n o se s re p re se n t t ru e a sso cia t io n s. Ot h e rs, u n fo rt u n a t e ly, a re g ive n t o p a t ie n t s in a n e ffo rt t o e xp la in t h e ir sym p t o m s, b u t la ck
org a n ic b a sis.
162 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
Crite ria
A p a t ie n t sa t is e s d ia g n o st ic crit e ria fo r b ro m ya lg ia if t h e fo llo w in g t h re e co n d it io n s a re m e t :
1. Wid e sp re ad Pa in In d e x (WPI) 7 a n d Sym pt o m Se ve rit y (SS) sca le sco re 5 o r WPI 3–6 a nd SS sca le sco re 9
2. Sym p t o m s h a ve b e e n p re se n t a t a sim ila r le ve l fo r a t le a st 3 m o n t h s
3. Th e p a t ie n t d o e s n o t h a ve a d iso rd e r t h a t w o u ld o t h e rw ise e xp la in t h e p a in
Asce rtainme nt
1. If WPI: n o t e t h e n u m b e r o f a re a s in w h ich t h e p a t ie n t h a s h a d p a in o ve r t h e la st w e e k. In h o w m a n y a re a s
h a s t h e p a t ie n t h a d p a in ? Sco re w ill b e b e t w e e n 0 a n d 19
Sh o u ld e r g ird le , le ft Hip (b u t t o ck, t ro ch a n t e r), le ft Ja w, le ft Up p e r b a ck
Sh o u ld e r g ird le , rig h t Hip (b u t t o ck, t ro ch a n t e r), rig h t Ja w, rig h t Lo w e r b a ck
Up p e r a rm , le ft Up p e r le g , le ft Ch e st Ne ck
Up p e r a rm , rig h t Up p e r le g , rig h t Ab d o m e n
Lo w e r a rm , le ft Lo w e r le g , le ft
Lo w e r a rm , rig h t Lo w e r le g , rig h t
2. SS sca le sco re :
s
e
Fa t ig u e
s
a
Wa kin g u n re fre sh e d
e
Co g n it ive sym p t o m s
s
i
D
Fo r t h e e a ch o f t h e t h re e sym p t o m s a b o ve , in d ica t e t h e le ve l o f se ve rit y o ve r t h e p a st w e e k u sin g t h e fo llo w in g
c
i
t
sca le :
a
m
0—n o p ro b le m
u
1—slig h t o r m ild p ro b le m s, g e n e ra lly m ild o r in t e rm it t e n t
e
h
2—m o d e ra t e , co n sid e ra b le p ro b le m s, o ft e n p re se n t a n d /o r a t a m o d e ra t e le ve l
R
3—se ve re : p e rva sive , co n t in u o u s, life -d ist u rb in g p ro b le m s
c
i
c
Co n sid e rin g so m a t ic sym p t o m s in g e n e ra l, in d ica t e w h e t h e r t h e p a t ie n t h a s:
e
p
0—n o sym p t o m s
S
1—fe w sym p t o m s
3
2—a m o d e ra t e n u m b e r o f sym p t o m s
N
O
3—a g re a t d e a l o f sym p t o m s
I
T
C
Th e SS sca le sco re is t h e su m o f t h e se ve rit y o f t h e t h re e sym p t o m s (fa t ig u e , w a kin g u n re fre sh e d , co g n it ive
E
S
sym p t o m s) p lu s t h e e xt e n t (se ve rit y) o f so m a t ic sym p t o m s in g e n e ra l. Th e n a l sco re is b e t w e e n 0 a n d 12
Tre a tme nt
Give n t h a t w e a re ju s t be gin n in g t o u n d e rs t a n d t h is d is ord e r, it s h ou ld n o t
com e a s a s u rp ris e t h a t w e h ave lim it e d e ffe ct ive t h e ra p ie s t o m a n a ge t h e s e
p a t ie n t s . Prim a ry ca re p h ys icia n s h a ve t h e t re m e n d ou s re s p on s ibilit y of s t e e r-
in g p a t ie n t s a w a y from u n p rove d (a n d oft e n ris ky) t re a t m e n t s . Pa t ie n t s w it h
FM n e e d t o rs t be lieve t h a t w e, t h e ir h e a lt h ca re p rovid e rs , a ckn ow le d ge t h a t
164 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
s
e
1999;2:11–22. t io n s in a ll p a t ie n t s w it h FM is n o n e x is t e n t , o t h e r
s
a
t h a n p e r h a p s “n e e d lin g” t h e s e p a t ie n t s in m u ch t h e
e
s
i
s a m e w a y a s is d on e w it h a cu p u n ct u re , n ow a re cogn iz e d a lt e rn a t ive t re a t -
D
c
m e n t fo r FM (1 ). Th e ro le o f s o ft -t is s u e m a s s a ge s , h yp n o t h e ra p y, re la x a t io n ,
i
t
a
a n d s p in a l m a n ip u la t ion s for t h e t re a t m e n t of FM is u n d e t e rm in e d for n ow.
m
Cla im s h a ve a p p e a re d on t h e In t e rn e t of t h e s u cce s s fu l t re a t m e n t of FM
u
e
w it h d e com p re s s ive s u rge ry of t h e cra n ioce rvica l ju n ct ion (1 ). Th is s u rge ry is
h
R
WHEN TO REFER b a s e d on t h e re p o rt e d p os s ible a s s o cia t ion of FM w it h Ch ia ri m a lfo rm a t io n
c
i
(p rot ru s ion of t h e t on s ils be low t h e leve l of t h e fora m e n m a gn u m ). Alt h ou gh w e
c
e
• Wh e n t h e d ia g n o sis is in re cogn ize t h a t p a t ie n t s w it h ce rvica l s p in a l s t e n os is m ay e xh ibit s om e FM-like
p
S
d o u b t a n d a m o re se rio u s m a n ife s t a t ion s , s e a rch in g fo r t h is a s s o cia t io n s h ou ld be d on e on ly if clin ica l
3
rh e u m a t ic d iso rd e r is
m a n ife s t a t ion s a re in d ica t ive of ca n a l s t e n os is a n d com p re s s ive m ye lop a t h y,
N
b e in g co n sid e re d .
O
bu t n ot ot h e rw is e (1 ). Un fort u n a t e ly, t h e In t e rn e t h a s favore d t h e d is s e m in a t ion
I
T
• Wh e n t h e p a t ie n t w o u ld
C
of u n lt e re d in form a t ion ca p a ble of d ire ct ly re a ch in g m a n y m ore p a t ie n t s t h a n
E
like t o h a ve a se co n d
S
o p in io n t o co n rm
w it h m e t h od s u s e d in t h e p a s t . (Million s of We b s it e s a re fou n d .) PCPs s h ou ld
d ia g n o sis. be p rop e rly in form e d s o t h a t p a t ie n t s re ce ive a d e q u a t e cou n s e lin g a n d u n n e c-
e s s a ry a n d ris ky s u rgica l p roce d u re s a re avoid e d .
Clinica l Co urse
Alt h o u gh p a t ie n t s w it h FM d o n o t d eve lo p o bvio u s p h ys ica l d e fo r m it ie s o r
im p a irm e n t s , t h is d is ord e r ca n a ffe ct s eve ra l d om a in s of t h e ir live s (p a in , ia t ro-
ge n e s is , e m p loym e n t , a n d n a n cia l a n d fa m ily s t a bilit y) (1, 6, 7 ). Pa t ie n t s w h o
re m a in e m p loye d , p h ys ica lly a ct ive, a n d t rim ; t a ke few m e d ica t ion s ; a n d h ave
a d e q u a t e cop in g s kills a n d a s u p p ort ive fa m ily t e n d t o d o be t t e r t h a n t h os e
w h o a re p h ys ica lly in a ct ive, u n e m p loye d , ove rw e igh t , a n d a lre a d y t a kin g m a n y
m e d ica t ion s .
Co nclusio ns
Alth ou gh w e d o n ot com p letely u n d ersta n d a ll th e m ech a n ism s in volved in th e
m u s cu los ke let a l p a in p a t ien t s w it h FM h ave, w e h ave m a d e s ign i ca n t st rid e s
tow a rd u n d ersta n d in g th em . Draw in g from ou r stu d ies a n d th ose of oth er in ves-
tiga tors, w e h ave p u t togeth er a testa ble p a in m od el. Th e con tribu tion s of p erip h -
era l a n d cen tra l fa ctors to th e p a th ogen esis of p a in in FM a re sh ow n in Figu re 17.3 ,
w h ich is a n itera tion of th e m od el ou r grou p h a s p u blish ed before (1 ). Th is m od el
sh ou ld be m od i ed a s n ew evid e n ce e m erge s from re s ea rch con d u ct e d w orld -
w id e. Figu re 17.4 su m m a rizes th e m a in p oin ts d iscu ssed in th is ch a p ter.
166 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
*Fibromyalgia is not a psychiatric disorder. The misconception that fibromyalgia may be an affective
disorder arose from the fact that patients seen in tertiary care centers (patients included in most clinical
trials and studies) often have a concomitant psychiatric illness. However, they are not typical of all
persons with fibromyalgia.
*Criteria for the classification of fibromyalgia (2000) patients include widespread and persistent
musculoskeletal pain and the presence of soft tissue tender points in at least 11 of 18 anatomic sites
called “tender points” (See Figure 20.1). However, these criteria were developed for research and not so
much for clinical practice. In fact, a new set of criteria have been proposed (2010) which do not include
these tender points but, in addition to widespread pain, include a symptom severity scale (See Table
20.1).
*The following findings help support the diagnosis of fibromyalgia (and some of them are considered in
the symptom severity scale of the 2010 preliminary diagnostic criteria, as noted in Table 20.1): fatigue,
difficulty sleeping, arthralgias, headache, chest, abdominal, pelvic and/or perineal pain, cognitive
impairment, weakness, and dysesthesias.
*Why patients with fibromyalgia experience chronic pain remains unknown, although evidence points
out to aberrations in CNS processing of stimuli. Abnormalities of the endocrine system, sleep
disturbances, altered cerebral blood flow to the thalamus and caudate nucleus, bilateral activation of
the somatosensory cortices on painful stimulation, increase resting brain activity within multiple brain
networks and altered neuropeptide serum and CSF levels are seen in these patients (See Fig. 17.3 for
a model of fibromyalgia etiopathogenesis).
*Although the etiology of fibromyalgia remains unknown, several triggers have been identified: bacterial
S
E
(i.e., Borrelia
Burgdorferi) or viral (i.e., Parvovirus) infections, physical and/or emotional trauma, and
C
sleep deprivation. However, in some patients the onset of fibromyalgia is insidious, and no triggers can
T
I
be identified. A genetic predisposition is supported by studies in twins and siblings.
O
N
*Managing patients with fibromyalgia is challenging. A combination of pharmacological and non-
3
pharmacological options is recommended. Non-pharmacological options include cognitive-behavioral
S
therapy, exercise (combined with periods of rest). Newer pharmacological options including the double
p
e
reuptake inhibitors and pregabalin have been shown to be beneficial. Antidepressants, in general, have
c
shown to be beneficial as well.
i
c
*NSAIDs and glucocorticoids are not indicated for the treatment of patients with fibromyalgia except
R
under specific circumstances (localized area of pain of clear inflammatory nature). However, NSAIDs can
h
e
be used sporadically for their analgesic effects. Narcotic analgesics and other psychotropic drugs should
u
m
be avoided if at all possible.
a
t
i
c
Figure 17.4 Importa nt pra ctica l issues in bromya lgia . Modi ed from Ala rcón GS. Wmn Hea lth Pri Ca re (Orth
D
Ed) 1999;2:11–22.
i
s
e
a
s
e
ICD9
s
729.1 Fibro myalg ia
Re fe re nce s
1. Ala rcon G. Fibrom ya lgia . In : Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Lip p in cot t Willia m s a n d
Wilkin s ; 2003 :226 –235 .
2. Wolfe F, Cla u w DJ, Fit zch a rle s MA, e t a l . Th e Am e rica n College of Rh e u m a t ology p re lim in a ry d ia gn os t ic
crit e ria fo r brom ya lgia a n d m e a s u re m e n t of s ym p t om s eve rit y. A rthritis Care Res 2010 ;62 :600 –610 .
3. Be rn a rdy K, Fü be r N , Kölln e r V, e t a l. Ef ca cy of cogn it ive -be h aviora l t h e ra p ie s in brom ya lgia s yn d rom e —
a s ys t e m a t ic review a n d m e t a -a n a lys is of ra n d om ize d con t rolle d t ria ls . J Rheum atol 2010 ;37 :1991 –2005 .
4. Wa n g C , Sch m id CH , Ro n e s R, e t a l . A ra n d o m ize d t r ia l o f t a i ch i fo r b ro m ya lgia . N Engl J Med
2010 ;363 (8 ):743 –754 .
5. Be n n e t t RM , Jon e s J, Tu rk DC, e t a l . An in t e rn e t s u rvey of 2,596 p e op le w it h brom ya lgia . BMC Muscu-
loskelet Disord 2007 ;8 :27 .
6. Wolfe F, Ha s s e t t AL, Wa lit t B, e t a l . Mort a lit y in brom ya lgia : An 8,186 p a t ie n t s t u dy ove r 35 ye a rs . A rthri-
tis Care Res 2011 ;63 :94 –101 .
7. Dreye r L, Ke n d a ll S, Da n n e s kiold -Sa m s ø e B, e t a l . Mort a lit y in a coh ort of Da n is h p a t ie n t s w it h brom y-
a lgia : In cre a s e d fre q u e n cy of s u icid e . A rthritis Rheum 2010 ;62 :3101 –3108 .
8. Gold e n be rg DL, Cla u w DJ, Pa lm e r RH , e t a l . Du ra bilit y o f t h e ra p e u t ic re s p on s e t o m iln a cip ra n t re a t m e n t
fo r bro m ya lgia . Re s u lt s o f a ra n d om ize d , d o u ble -blin d , m o n o t h e ra p y 6-m on t h e xt e n s io n s t u d y. Pain
Med 2010 ;11 :180 –194.
9. Hä u s e r W, Be rn a rd y K, Uçeyle r N , e t a l . Tre a t m e n t of brom ya lgia s yn d rom e w it h a n t id ep re s s a n t s : A
m e t a -a n a lys is . JA MA 2009 ;301 :198 –209 .
10. Crofford LJ, Row bot h a m MC, Me a s e PJ, e t a l . Prega ba lin for t h e t re a t m e n t of brom ya lgia s yn d rom e :
Re s u lt s of a ra n d om ize d , d ou ble -blin d , p la ce bo-con t rolle d t ria l . A rthritis Rheum 2005 ;52 :1264 –1273 .
11. Cro fford LJ, Me a s e PJ, Sim p s on SL, e t a l . Fibrom ya lgia re la p s e eva lu a t ion a n d e f ca cy for d u ra bilit y of
m e a n in gfu l re lie f (FREEDOM): A 6-m o n t h , d ou ble -blin d , p la ce bo -con t ro lle d t ria l w it h p rega b a lin . Pain
2008 ;136 :419 –431 .
CHAPTER
18 Pregna ncy a nd
Rheuma tic Disea ses
Michael Lockshin
s
Th a t t h e p a t ie n t h a s n o t be e n in
e
ing rheum atoid arthritis, w hich she
s
m e d ica l co n t a ct d e s p it e o n go in g
a
e
believes is now quiescent, consults you
s
d is e a s e is a m a t t e r of con ce rn . He r
i
D
because she is planning a pregnancy. ch oice m ay re e ct m is u n d e rs t a n d -
c
i
t
She has not been under regular m edical in g a bou t h e r illn e s s , con ict s w it h
a
m
h e r p h ys icia n s , s o cia l o r n a n cia l
u
care, but instead has taken ibuprofen
e
is s u e s , d e n ia l, o r o t h e r is s u e s .
h
or naproxen on an as-needed basis for
R
W h a t eve r t h e re a s o n , h e r e a r lie r
c
joint pain. A prior pregnancy 3 years ch oice t o avoid m e d ica l ca re ra is e s
i
c
e
earlier w as successfully delivered at a gs fo r m a n a ge m e n t of a fu t u re
p
S
p regn a n cy.
term . She com es now at the insistence of her colleague. She asks for
3
N
your advice regarding risks to her and her potential child, particular-
O
I
EXAMINATION
T
ly those im parted by treatm ent. You point out that anti-in am m ato-
C
E
ry m edications interfere w ith cilial m otion that transports the ovum Im m e d ia t e t h in gs t o a s s e s s in clu d e
S
ca re fu l join t e xa m in a t ion , focu s in g
through the Fallopian tube and, thus, m odestly inhibits fertility.
e s p e c ia lly o n jo in t in s t a b ilit y,
Yo u r e valu at io n sh o w s m o d e rat e ly act ive syn o vit is in h e r w rist s be ca u s e of p ot e n t ia l w ors e n in g a s
(w it h sig n s o f e arly carp al t u n n e l syn d ro m e ), e lb o w s, an d k n e e s. p regn a n cy-a s s ocia t e d re la xin loos -
He r lab o rat o ry st u d ie s sh o w st ro n g p o sit ive rh e u m at o id f act o r, e n s liga m e n t s in la t e p re gn a n cy.
Ce r v ica l s p in e s u b lu x a t io n a n d
an t icyclic cit ru llin at e d p e p t id e , an d an t i-Sjo g re n ’s syn d ro m e A
C1 t o C2 in s t a b ilit y a re e s p e cia lly
(SSA ), also k n o w n as an t i-Ro . A n t i-Sjo g re n ’s syn d ro m e B (SSB) an t i- im p o r t a n t b e ca u s e o f p o t e n t ia l
b o d ie s, also k n o w n as an t i-La, an t icard io lip in , an t i- 2 -g lyco p ro t e in cord in ju ry. It m ay be n e ce s s a ry t o
I, an d lu p u s an t ico ag u lan t t e st s are n e g at ive . Lat e ral ce rvical sp in e p rovid e t h e p a t ie n t w it h a rigid col-
la r d u rin g la t e p regn a n cy a n d d u r-
x-ray in e xio n an d e xt e n sio n sh o w s 11-m m d isp lace m e n t o f t h e
in g d e live ry, w h e n in t u ba t ion is a
o d o n t o id p ro ce ss f ro m t h e an t e rio r arch o f t h e at las in e xio n . p os s ib ilit y. Liga m e n t lo o s e n in g a t
t h e h ip a n d kn e e m a y ca u s e ga it
p roble m s a s p regn a n cy p rogre s s e s .
Ca rp a l t u n n e l s ym p t om s t yp ica lly w ors e n in la t e p regn a n cy.
s
sh o u ld b e fo llo w e d b y
e
e s p e cia lly h igh for p a t ie n t s w it h h ip rep la ce m e n t s .
s
a n e xp e rie n ce d t e a m o f
a
A n orm a l la bor m ay t a ke 18 or m ore h ou rs , d u rin g w h ich t h e p a t ie n t m a y
e
h ig h -risk o b st e t ricia n s a n d
s
i
n ot be a ble t o t a ke h e r n orm a l m e d ica t ion s . Es p e cia lly for m a in t e n a n ce cort i-
D
t h e p h ysicia n t re a t in g t h e
c
rh e u m a t ic d ise a se . cos t e roid s , t h e rh e u m a t ologis t s h ou ld re m in d t h e obs t e t ric s t a ff t o give t h e s e
i
t
a
m e d ica t ion s in t rave n ou s ly.
m
• Po st p a rt u m co m p lica t io n s
u
sh o u ld b e a n t icip a t e d ,
e
h
p a rt icu la rly t h o se
R
co n ce rn in g t h e m o t h e r’s CONCLUSIONS
c
a b ilit y t o ca re fo r h e r
i
c
ch ild . Po s t p a rt u m is s u e s in clu d e re la t ive ly s low re cove ry b e ca u s e o f t h e m o t h e r ’s
e
p
ch ron ic illn e s s . (Th e con t e m p ora ry “in -a n d -ou t in 1 d a y” p ra ct ice for d e live ry
S
s h ou ld be avoid e d .) Me d ica t ion s s h ou ld be re s u m e d q u ickly, w it h a t t e n t ion t o
3
N
t h os e m e d ica t ion s a ccep t a ble for bre a s t -fe e d in g if t h e m ot h e r ch oos e s t o d o
O
I
t h is . (Seve ra l s ou rce s of in form a t ion a bou t a ccep t a ble m e d ica t ion s a re a va ila -
T
C
ble ; 8, 9 .) Mot h e rs w it h u p p e r e xt re m it y a rt h rit is m ay be u n a ble t o cra d le a ba by
E
S
for n u rs in g. Mot h e rs w it h a n y ch ron ic illn e s s m ay be u n a ble t o bre a s t -fe e d or
ca re for t h e ir in fa n t s in t h e w ay t h ey w is h , p ot e n t ia lly le a d in g t o d ep re s s ion or
fa m ily con ict or bot h .
Be ca u s e fa m ilia rit y w it h t h e m a n y p ot e n t ia l com p lica t ion s of rh e u m a t ic
WHEN TO REFER d is e a s e p regn a n cy is n ot w id e s p re a d , re fe rra l t o a n e xp e rt in t h e e ld for con -
s u lt a t ion a t le a s t on ce is a d vis a ble. Som e p a t ie n t s , for in s t a n ce t h os e w it h n o
• All p a t ie n t s w it h rh e u m a t - s e ro logic w a r n in g s ign s o r a n a t o m ic r is k s , m a y b e co n s id e re d low r is k a n d
ic d ise a se o u g h t t o co n su lt n e e d n o fu rt h e r eva lu a t ion . Th os e w it h a n t ip h os p h olip id a n t ibod ie s , a n t i-SSA/
a n e xp e rt a t le a st o n ce fo r Ro a n d a n t i-SSB/La a n t ibod ie s , w it h p rior fe t a l los s or com p lica t e d p regn a n cie s ,
e va lu a t io n o f risk fa ct o rs
a n a t o m ic d is a bilit ie s , re n a l or ca rd iop u lm on a ry d is e a s e , t h ro m bo cyt o p e n ia ,
t o t h e m o t h e r o r ch ild .
a n d re q u irin g p ot e n t ia lly t oxic m e d ica t ion s s h ou ld a ll re ce ive s p e cia lize d ca re.
• Pa t ie n t s w it h se ro lo g ic
m a rke rs o f risk (a n t ip h o s-
p h o lip id o r a n t i-SSA/Ro
a n d a n t i-SSB/La a n t ib o d - Re fe re nce s
ie s).
1. Bru ca t o A, Cim a z R, Ca p ora li R, e t a l. Pregn a n cy ou t com e s in p a t ie n t s w it h a u t oim m u n e d is e a s e s a n d
• Pa t ie n t s w it h se ve re jo in t a n t i-Ro/SSA a n t ibod ie s . Clin Rev A llergy Im m unol 2011;40 (1 ):27 –41 .
d ise a se , ca rd io p u lm o n a ry 2. Bu yon JP, Cla n cy RM , Frie d m a n DM . Ca rd ia c m a n ife s t a t ion s of n e on a t a l lu p u s e ryt h e m a t o s u s : Gu id e lin e s
o r re n a l d ise a se , o r t h ro m - t o m a n a ge m e n t , in t egra t in g clu e s from t h e be n ch a n d be d s id e . Nat Clin Pract Rheum atol 2009 ;5 (3 ):139 –148 .
b o cyt o p e n ia . [Review ]
3. Frie d m a n DM , Lla n os C, Izm irly PM , e t a l. Eva lu a t ion of fe t u s e s in a s t u d y of in t rave n ou s im m u n oglobu -
• Pa t ie n t s w it h p rio r p re g - lin a s p reve n t ive t h e ra p y fo r co n ge n it a l h e a r t block : Re s u lt s of a m u lt ice n t e r, p ro s p e ct ive, o p e n -la b e l
n a n cy co m p lica t io n s. clin ica l t ria l . A rthritis Rheum 2010 ;62 (4 ):1138 –1146 .
4. Izm irly PM , Kim MY, Lla n os C, e t a l. Eva lu a t ion of t h e ris k of a n t i-SSA/Ro-SSB/La a n t ibod y-a s s ocia t e d
• Pa t ie n t re q u irin g t re a t - ca rd ia c m a n ife s t a t io n s o f n e o n a t a l lu p u s in fe t u s e s o f m o t h e r s w it h s ys t e m ic lu p u s e ryt h e m a t o s u s
m e n t w it h p o t e n t ia lly e xp os e d t o h yd roxych loroq u in e . A nn Rheum Dis 2010 ;69 (10 ):1827 –1830, e p u b May 6, 2010 .
fe t o t o xic m e d ica t io n s. 5. Sa lm on J, Gira rd i G, Locks h in MD . Th e a n t ip h os p h olip id s yn d rom e —a d is ord e r in it ia t e d by in a m m a t ion :
Im p lica t ion s for t h e ra py of p regn a n t p a t ie n t s . Nat Clin Pract Rheum atol 2007 ;3 (3 ):140 –147 .
170 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
171
CHAPTER
19 Osteoa rthritis
Mary S. W alton , Carlos J. Loz ada, and Seth M. Berney
Intro ductio n
e
A 60-ye ar-o ld m ale f o rm e r
n
o
Os t e o a r t h rit is (OA), a ls o re fe r re d t o a s
B
p ro f e ssio n al f o o t b all p laye r
c
d e ge n e ra t ive join t d is e a s e (DJD), is t h e
i
l
w it h a h ist o ry o f m u lt ip le k n e e
o
m o s t com m on fo rm of join t d is e a s e in
b
in ju rie s co m p lain s o f b ilat e ral
a
h u m a n s . Be ca u s e o f p h ys icia n vis it s ,
t
e
M
k n e e p ain f o r 10 ye ars. Th e m e d ica t ion s , s u rgica l in t e rve n t ion , a n d
t im e m is s e d from w ork, OA a p p e a rs t o
d
p at ie n t also co m p lain s o f
n
co s t a s m u ch a s 30 t im e s m o re t h a n
a
b ilat e ral w rist p ain an d 15 t o
s
rh e u m a t oid a rt h rit is (RA) (1 ).
i
t
i
r
20 m in u t e s o f m o rn in g st iff - Os t e oa rt h rit is w a s on ce t h ou gh t t o
h
t
r
n e ss. He d e n ie s jo in t sw e llin g , be t h e re s u lt of a gin g. How eve r, w e n ow
a
o
b e lie ve t h a t it d e ve lo p s a s a co n s e -
e
Rayn au d ’s p h e n o m e n a, sicca sym p t o m s, f e ve r, o r ch ills.
t
s
q u e n ce o f m u lt ip le fa ct o r s , in clu d in g
O
On p h ysical e xam in at io n , h e is a n o n –ill-ap p e arin g m ale bioch e m ica l a n d biom e ch a n ica l a bn or-
4
w it h a n o n t e n d e r n o d u le o n t h e rig h t in d e x d ist al in t e r-
N
m a lit ie s , a s w e ll a s ge n e t ic p re d is p os i-
O
t ion s m a n ife s t in g clin ica lly a s OA.
I
p h alan g e al (DIP) jo in t an d b o n y e n larg e m e n t o f rig h t lo n g
T
C
E
an d le f t rin g p ro xim al in t e rp h alan g e al (PIP) an d DIP jo in t s.
S
He also h as t e n d e rn e ss o n p alp at io n at t h e b ase o f b ilat e ral EPIDEMIOLOGY
t h u m b s’ carp o m e t acarp al (CM C) jo in t s an d e n larg e m e n t o f Os t e o a r t h r it is ca n b e d e n e d ra d io -
h is b ilat e ral k n e e s w it h p ain an d cre p it u s o n p assive ran g e gra p h ica lly o r clin ica lly (ra d io gra p h s
p lu s clin ica l s ym p t om s or s ign s ). Ut iliz-
o f m o t io n . His w rist s, m e t acarp o p h alan g e al (M CP) jo in t s,
in g ra d iogra p h ic crit e ria , 30% of in d ivid -
e lb o w s, h ip s, an d an k le s are n o rm al (Fig . 19.1 ). u a ls be t w e e n t h e a ge s of 45 a n d 65 a re
a ffe ct e d , a n d m ore t h a n 80% a re a ffe ct e d
by t h e ir e igh t h d e ca d e of life.
Th e p reva le n ce of OA in cre a s e s in bot h m e n a n d w om e n a s t h ey a ge, bu t
ge n d e r d iffe re n ce s e xis t . Os t e oa rt h rit is a ffe ct s m e n m ore com m on ly a m on g
p a t ie n t s you n ge r t h a n 45 ye a rs a n d w om e n m ore com m on ly a m on g p a t ie n t s
o ld e r t h a n 55 ye a rs . Ad d it ion a lly, DIP OA is t e n t im e s m ore like ly in w om e n
t h a n in m e n . Mot h e rs a n d s is t e rs of w om e n w it h DIP OA a re t w o t o t h re e t im e s
m ore like ly t o be a ffe ct e d by it (2 ).
Obe s it y in w om e n h a s be e n lin ke d t o OA of t h e kn e e s a n d h ip (3 ) a n d is
p roba bly a ls o a ris k fa ct or for kn e e OA in m e n Obe s it y is a ls o a ris k fa ct or for
h a n d OA in bot h ge n d e rs . Th e m e ch a n is m s for t h is h ave n ot be e n cle a rly e lu -
cid a t e d a n d m a y in clu d e in cre a s e in bod y m a s s , a lt e re d biom e ch a n ics of ga it ,
ge n e t ic p re d is p os it ion , a n d /or a lt e re d m e t a bolis m . We a ls o ca n n ot a d e q u a t e ly
e xp la in t h e a s s ocia t ion be t w e e n obe s it y a n d OA of n on –w e igh t -be a rin g join t s
s u ch a s t h e s t e rn oclavicu la r a n d DIP join t s .
173
174 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
PATHOGENESIS
In it ia lly t h ou gh t of a s a d is e a s e on ly of a rt icu la r ca rt i-
la ge , OA in vo lve s t h e e n t ir e jo in t , in clu d in g t h e
s u b ch o n d ra l b o n e. Be ca u s e t h e ro le o f in a m m a t io n
in OA w it h in cre a s e d e xp re s s ion of cyt okin e s a n d m e t -
a llop rot e in a s e s in s yn oviu m a n d ca rt ila ge is be com in g
m ore re cogn ize d , t h e t e rm degenerativ e joint disease is
n o lon ge r a p p rop ria t e w h e n re fe rrin g t o OA. Fu rt h e r-
m ore, t h e con t e n t ion t h a t OA is “n on in a m m a t ory” is
in co r re ct , w h ile “m ild ly in a m m a t o ry” w o u ld b e a
m ore a ccu ra t e d e s crip t ion .
Th e e t iop a t h oge n e s is of OA h a s be e n d ivid e d in t o
t h re e s t a ge s (5 ). Du rin g s t a ge 1, in cre a s e d p rod u ct ion
of p ro t e olyt ic e n z ym e s s u ch a s m e t a llo p rot e in a s e s
(e.g., colla ge n a s e a n d s t rom e lys in ) d e s t roys t h e ca rt i-
la ge m a t rix. Du rin g s t a ge 2, t h e ca rt ila ge s u rfa ce e rod e s
S
a n d brilla t e s , re le a s in g p rot e oglyca n s a n d colla ge n
E
Figure 19.1 Sta nding (weight-bea ring) view of the knees indica tes
C
signi ca nt bila tera l media l joint spa ce na rrowing, modera te bila tera l fra gm e n t s in t o t h e s yn ovia l u id . Fin a lly, in s t a ge 3,
T
I
O
la tera l compa rtment joint spa ce na rrowing, a nd media l a nd la tera l joint t h e s e ca rt ila ge bre a kd ow n p rod u ct s in d u ce a ch ron ic
N
osteophyte forma tion. in a m m a t ory re s p on s e in t h e s yn oviu m , ch a ra ct e rize d
4
by m a crop h a ge p rod u ct ion of in t e rle u kin 1 (IL-1), t u m or
O
s
n e cros is fa ct or (TNF- α), a n d m e t a llop rot e in a s e s . Th e s e
t
e
s u bs t a n ce s p ro ba bly in cre a s e t h e ca r t ila ge u lce ra t io n s a n d m a y s t im u la t e
o
a
ch on d rocyt e s t o p rod u ce m ore m e t a llop rot e in a s e s , re s u lt in g in ca rt ila ge los s
r
t
h
a n d bon y ebu rn a t ion a n d u lt im a t e ly s u bch on d ra l bon e os t e op h yt e form a t ion .
r
i
t
i
s
a
n
d
Clinica l Pre se nta tio n
M
e
t
Th e in it ia l goa l of t h e h e a lt h ca re p rofe s s ion a l w h e n s e e in g a p a t ie n t w it h join t
a
b
p a in is t o d iffe re n t ia t e OA from m ore in a m m a t ory a rt h rit id e s , s u ch a s RA.
o
l
i
In con t ra s t t o OA, RA p rim a rily a ffe ct s t h e w ris t s , MCP join t s , a n d PIP join t s
c
B
(PIP), a n d s p a re s t h e DIP join t s a n d t h ora cic a n d lu m bos a cra l s p in e. Rh e u m a -
o
n
t oid a rt h rit is is a ls o t yp ica lly a s s ocia t e d w it h in a m m a t ory m orn in g s t iffn e s s
e
(m ore t h a n 1 h ou r) a n d ra d iogra p h ic n d in gs of bon e los s (p e ria rt icu la r os t e o-
p e n ia ; m a rgin a l e ros ion s of bon e ) ra t h e r t h a n bon e form a t ion .
Sym p t om a t ic h ip OA is u s u a lly in s id iou s in on s e t a n d m ay ca u s e d im in is h e d
in t e rn a l rot a t ion , a lim p, a n d groin or bu t t ock p a in . How eve r, n ot u n com m on ly,
p a t ie n t s m ay exp e rie n ce low ba ck p a in or m e d ia l kn e e p a in , rep re s e n t in g p a in
re fe rre d from t h e h ip . Pa in in t h e la t e ra l a s p e ct of t h e t h igh , a rou n d t h e gre a t e r
t roch a n t e r t h a t is u s u a lly rep rod u cible on p a lp a t ion , u s u a lly rep re s e n t s gre a t e r
t roch a n t e ric bu rs it is , n ot OA.
CLINICAL POINTS
Os t e oa rt h rit is of t h e lu m ba r s p in e ca n ca u s e s p in a l s t e n os is . Th e s e s ym p -
• Wh a t Diffe re n t ia t e s OA t om s m a y in clu d e p s e u d ocla u d ica t ion w it h in t e rm it t e n t or con s t a n t p a in in
Fro m RA t h e legs w ors e n e d by e xe rt ion (p a rt icu la rly w h e n t h e p a t ie n t s t a n d s s t ra igh t u p
• Asym m e t ric jo in t or h yp e re xt e n d s t h e ba ck, s u ch a s d e s ce n d in g s t a irs ) a n d re lieve d by e xin g t h e
in vo lve m e n t ba ck, s it t in g, or w a lkin g u p s t a irs .
• Bo n y jo in t e n la rg e m e n t Eros ive OA, a d is ord e r occu rrin g p rim a rily in w om e n , ca u s e s in a m m a t ion
(n o t jo in t sw e llin g ) of t h e DIP or PIP join t s , re s u lt in g in a ce n t ra l join t e ros ion (d e s cribe d a s “s e a gu lls ”
• Ne w b o n e fo rm a t io n on ra d iogra p h ).
(o st e o p h yt e s) Mu lt ip le ca u s e s of s e con d a ry OA e xis t , in clu d in g join t t ra u m a (fra ct u re s or
s u rge rie s ), p rior in a m m a t ory a rt h rop a t h y, Pa ge t d is e a s e, h e m op h ilia , m u lt ip le
• Mo rn in g st iffn e ss 45 t o
60 m in u t e s e n d ocrin op a t h ie s , n e u rop a t h ic or Ch a rcot join t s , a n d con ge n it a l or h yp e rm o-
bilit y d is ord e rs .
• In vo lve m e n t o f DIP jo in t s, Th e d is e a s e p rogre s s ion is ch a ra ct e ris t ica lly s low, ove r ye a rs or d e ca d e s .
PIP jo in t s, a n d /o r sp in e ;
sp a rin g MCP jo in t s Eve n t u a lly, t h e s e eve n t s a lt e r t h e join t a rch it e ct u re, a n d a d d it ion a l bon e grow s
a s it re m od e ls t o s t a bilize t h e join t .
Ch a p te r 19 Os t e o a rt h rit is 175
PATIENT ASSESSMENT
• Hist o ry: p a in w it h o u t
sw e llin g (syn o vit is) a n d
m o rn in g st iffn e ss 45
m in u t e s
• Ph ysica l e xa m in a t io n
ndings: bony enlargement
without synovitis commonly
involving DIP, PIP, rst CMC
joints, AC joint of shoulder,
h ip s, kn e e s, rst MTP
jo in t s, fa ce t jo in t s o f t h e
ce rvica l a n d lu m b a r sp in e
• La b o ra t o ry: No rm a l
la b o ra t o ry st u d ie s;
jo in t e ffu sio n w ill b e
n o n in a m m a t o ry w it h Figure 19.2 Bony joint enla rgement of the right thumb interpha la ngea l
e
n
2,000 WBC/m m 3 joint, bila tera l index a nd long nger proxima l interpha la ngea l (PIP) joints,
o
B
a nd multiple dista l interpha la ngea l (DIP) joints with a ngula tions a t the
• Ra d io g ra p h ic: Asym m e t ric
c
right ring nger DIP, long nger PIP a nd DIP, index nger PIP a nd DIP, a nd
i
l
jo in t sp a ce n a rro w in g ;
o
the left index nger PIP a nd DIP joints.
b
a sym m e t ric jo in t
a
t
in vo lve m e n t ; o st e o p h yt e s
e
M
d
n
a
Exa mina tio n
s
i
t
i
r
h
Th e p h ys ica l e xa m in a t ion n d in gs a re lim it e d t o t h e a ffe ct e d join t s . On in s p e c-
t
r
a
t ion , t h e re m ay be bon y e n la rge m e n t a n d m a la lign m e n t (s u ch a s a n gu la t ion of
o
e
t h e PIP, DIP, or kn e e join t s ) d ep e n d in g on d is e a s e s eve rit y. He be rd e n ’s a n d /or
t
s
O
Bou ch a rd ’s n od e s (com p re s s e d broge la t in ou s cys t s ) ove rlyin g t h e DIP a n d PIP
4
join t s , re s p e ct ive ly, m ay d eve lop a n d in a m e (Fig. 19.2 ).
N
A n on in a m m a t ory join t e ffu s ion (d e n e d a s a W BC cou n t of 200 t o 2,000
O
I
W BC/m m 3 ) m ay occu r, u s u a lly w it h ou t s ign i ca n t join t e ryt h e m a or w a rm t h .
T
C
E
Pa t ie n t s h ave p a in on a ct ive or p a s s ive ra n ge of m ot ion of t h e a ffe ct e d join t s .
S
Cre p it u s (a gra t in g or grin d in g s e n s a t ion t h a t occu rs a s t h e join t is m ovin g) is
ch a ra ct e ris t ic of la rge r join t s , s u ch a s t h e kn e e s . Lim it a t ion of join t m ot ion m ay
b e p re s e n t in m ore a d va n ce d ca s e s , a s w e ll a s p e ria rt icu la r m u s cle a t rop h y
s e con d a ry t o d is u s e.
Physical Me asure s
A va rie t y of p h ys ica l m od a lit ie s a re va lu a ble for im p rovin g t h e s ym p t om s of
OA, a n d in clu d e e xe rcis e, s u p p ort ive d evice s , a lt e ra t ion s in a ct ivit ie s of d a ily
livin g, a n d t h e rm a l m od a lit ie s (Ta ble 19.1 ).
e
n
e xt e n s ion of t h e s p in e , a s in sw im m in g). Ad d it ion a lly, w e n o lon ge r re co m -
o
B
m e n d be d re s t for p a t ie n t s w it h a cu t e or ch ron ic low ba ck p a in .
c
i
l
Supportiv e dev ices a re a ls o h e lp fu l be ca u s e t h ey p a rt ia lly u n loa d t h e w e igh t
o
b
from join t s , a n d m ay d e cre a s e p a in a n d im p rove ba la n ce a n d m obilit y. Th e s e
a
t
e
d evice s in clu d e ca n e s , cru t ch e s , w a lke rs , cors e t s , colla rs , a n d ort h ot ic d evice s
M
for s h oe s . Ca n e s , w h e n p rop e rly u s e d , ca n in cre a s e t h e ba s e of s u p p ort , d e cre a s e
d
n
loa d in g, a n d re d u ce d e m a n d s on t h e low e r lim b a n d it s join t s . Th e t ot a l le n gt h
a
o f a p ro p e rly m e a s u re d ca n e s h o u ld e q u a l t h e d is t a n ce b e t w e e n t h e u p p e r
s
i
t
i
bord e r of t h e gre a t e r t roch a n t e r of t h e fe m u r a n d t h e bot t om of t h e h e e l of t h e
r
h
t
s h oe. Th is s h ou ld re s u lt in e lbow e xion of a bou t 20 d egre e s a n d be h e ld in t h e
r
a
o
h a n d con t ra la t e ra l t o a n d m ove d t oge t h e r w it h t h e a ffe ct e d lim b.
e
t
Prop e r foot w e a r a n d ort h ot ic s h oe s ca n be of gre a t va lu e. A s h ort leg t h a t
s
O
a cce n t u a t e s lu m ba r s colios is m ay be h e lp e d t h rou gh a u n ila t e ra l h e e l or a s ole
4
lift . An ort h ot ic d evice, or s h oe in s e rt , m a y h e lp t h e p a t ie n t w it h s u blu xe d m e t -
N
O
a t a rs o p h a la n ge a l jo in t s . A p a t ie n t ’s w a lk in g a b ilit y a n d p a in in t h e m e d ia l
I
T
com p a rt m e n t of t h e kn e e m a y im p rove w it h a la t e ra l h e e l-w e d ge d in s ole. At h -
C
E
le t ic s h oe s w it h good m e d ia l a n d la t e ra l s u p p ort , a s w e ll a s good m e d ia l a rch
S
s u p p ort , a n d ca lca n e a l cu s h ion ca n be of be n e t .
Kn e e bra ce s m ay be of u s e in s om e p a t ie n t s w it h t ibiofe m ora l d is e a s e, e s p e -
cia lly t h os e w it h la t e ra l in s t a bilit y a n d a t e n d e n cy for t h e kn e e t o “give ou t .”
Join t s u p p ort s a n d ort h ot ic d evice s a llow t h e p a t ie n t t o p a rt icip a t e in m ore
a ct ivit ie s , im p rove co m p lia n ce , a n d re t a in fu n ct io n a l in d e p e n d e n ce . Th e s e
d evice s s h o u ld b e fre q u e n t ly m o n it o re d t o e n s u re p ro p e r u s e , s u ch a s t h e
p rop e r s izin g a n d orie n t a t ion of t h e ce rvica l colla r. Ca n e a n d cru t ch t ip s s h ou ld
be ch a n ge d w h e n w orn in ord e r t o avoid s lip p in g on s m oot h or w e t s u rfa ce s .
Pa t ie n t s m ay n eed t o a lt er s om e of t h e ir activities of daily living be ca u se s im p le
a d ju st m en ts m ay d ecrea s e t h eir s ym p t om s . For exa m p le, p a tien t s w it h ba ck p a in
s h ou ld avoid s it t in g on s oft cou ch e s or re clin e rs , or lyin g in be d w it h a p illow
u n d er th e kn ee s. In s t ea d th ey s h ou ld s it in s t ra igh t -ba ck ch a irs w it h good st ru c-
t u ra l s u p p ort (cu s h ion s a llow ed ). Ra is in g t h e leve l of a ch a ir or t oilet s ea t ca n be
h elp fu l, beca u s e th e h ip a n d kn ee s a re s u bject ed to t h e h igh e st p res s u res d u rin g
t h e in it ia l p h a se of ris in g from t h e s ea t ed p os it ion . How eve r, lift ch a irs a re very
ra rely h elp fu l or n eces sa ry. Th e p a t ie n t s h ou ld a lso u s e a rm m a t tres s, p erh a p s
w ith a bed boa rd , a n d avoid s lou ch in g, even w h e n d rivin g. Th e ca r s ea t sh ou ld be
p la ce d forw a rd s o t h a t t h e kn ees a re exed d u rin g d rivin g.
Therm al m odalities ca n h e lp d e cre a s e a p a t ie n t ’s p a in . Th e u s e of h e a t , cold ,
or a lt e rn a t in g h e a t a n d cold is ba s e d on t h e p a t ie n t ’s p re fe re n ce. Tra d it ion a lly,
t h e m ore a cu t e t h e p roce s s , t h e m ore like ly cold a p p lica t ion s w ill be of be n e t .
He a t ca n be s u bd ivid e d in t o s u p e r cia l a n d d e e p , w it h n o p rove n a d va n t a ge of
on e ove r t h e ot h e r. Th e t h e ra p e u t ic va lu e of a p p lyin g h e a t in clu d e s d e cre a s in g
178 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
To pical Ag e nts
Top ica l a ge n t s ca n be u s e fu l a d ju n ct s in t h e t re a t m e n t of OA. Ca p s a icin , d e rive d
from ca p s icu m , t h e com m on p e p p e r p la n t , is ava ila ble w it h ou t p re s crip t ion . It
in t e rfe re s w it h s u bs t a n ce P–m e d ia t e d p a in t ra n s m is s ion by reve rs ibly d ep le t -
in g s t ore s of s u bs t a n ce P in u n m ye lin a t e d C- be r a ffe re n t n e u ron s . Un t il t h e
n e rve e n d in gs a re d ep le t e d of s u bs t a n ce P, ca p s a icin (a p p lie d t w o t o fou r t im e s
d a ily) m a y ca u s e a bu rn in g s e n s a t ion w h e re it is a p p lie d . If n ot u s e d con t in u -
ou s ly, t h e n e rve e n d in gs re n ew t h e ir s u p p ly of a n d s e n s it ivit y t o s u bs t a n ce P.
Wa rn p a t ie n t s t o a vo id in a d ve rt e n t ly ge t t in g ca p s a icin in t h e eye s , b e ca u s e
e
n
t h e ir eye s w ill bu rn t re m e n d ou s ly.
o
B
A va rie t y of ot h e r t o p ica l a n a lge s ics e x is t of q u e s t io n a ble be n e t . Th e s e
c
i
l
in clu d e m e n t h ol- a n d s a licyla t e -ba s e d ove r-t h e -cou n t e r t op ica l p rep a ra t ion s ,
o
b
a s w e ll a s t op ica l n on s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs ).
a
t
e
M
Syste mic Oral Ag e nts
d
n
No n –a n t i-in a m m a t o r y analgesics in clu d e d r u gs s u ch a s a ce t a m in o p h e n .
a
De s p it e m a n y ye a rs of re s e a rch , t h e m e ch a n is m s of a ct ion of a ce t a m in op h e n
s
i
t
i
a re s t ill n ot a d e q u a t e ly u n d e rs t ood . In a n im a ls , t h e a ct ion s a p p e a r t o a ct a t t h e
r
h
t
s p in a l co rd a n d ce re bra l leve ls a n d in t e rfe re w it h a t le a s t cyclooxyge n a s e -3.
r
a
o
Neve rt h e le s s , a ce t a m in op h e n m a y be a s e ffe ct ive a s ibu p rofe n for t h e t re a t -
e
t
m e n t o f kn e e OA p a in (9 ). Fu r t h e r m o re , a ce t a m in o p h e n is s a fe r t h a n NSAIDs
s
O
b e ca u s e it d o e s n o t a p p e a r t o ca u s e ga s t ro p a t h y o r n e p h ro p a t h y a t co n ve n -
4
t io n a l d o s e s , b u t h e p a t o t o x icit y ca n o ccu r w h e n in ge s t e d a t h igh d o s e s .
N
O
Tra m a d ol is a ls o a n e ffe ct ive a n a lge s ic by m ild ly s u p p re s s in g t h e µ-op ioid
I
T
re ce p t o r a n d in h ib it in g t h e u p t a k e o f n o re p in e p h r in e a n d s e ro t o n in . It ca n
C
E
ca u s e n a u s e a a n d ce n t ra l n e rvou s s ys t e m s id e e ffe ct s t h a t ca n be re d u ce d by
S
s t a rt in g w it h 50 m g t w ice d a ily for 3 d ays a n d s low ly e s ca la t in g t h e d os e t o t h e
m a xim u m re com m e n d e d d os e of 50 m g QID or u n t il t h e d e s ire d p a in re lie f is
a ch ieve d .
Th e OA p a in is ge n e ra lly re s p on s ive t o n a rcot ic a n a lge s ics . Mild ly p ot e n t
a n d m in im a lly a d d ict ive n a rcot ic a n a lge s ics , s u ch a s cod e in e, h ave be e n e ffe c-
t ive in p a t ie n t s w it h OA, e s p e cia lly in com bin a t ion w it h n on n a rcot ic a n a lge s ics
(e.g., a ce t a m in op h e n a n d /or NSAIDs ). Be ca u s e of t h e a d d ict ive p ot e n t ia l of t h e
s t ron ge r op ia t e s a n d op ioid s , t h e ris ks of oxycod on e a n d h yd rocod on e s h ou ld
b e com p a re d w it h t h e b e n e t s of t h e p a in re lie f a ch ieve d . A nti-in am m atory
drugs , of w h ich NSAIDs a re t h e m os t com m on ly p re s cribe d , a re u s e d for t re a t in g
bot h p a in a n d m ild in a m m a t ion in OA. Wit h m os t t ra d it ion a l NSAIDs , a n a lge -
s ia ca n be a ch ieve d a t s m a lle r d os e s t h a n a re n e e d e d fo r a n t i-in a m m a t ory
e ffe ct s . How eve r, for m os t NSAIDs , t h e gre a t e r t h e d os e, t h e gre a t e r t h e a n t i-
in a m m a t ory e ffe ct (a ls o t h e gre a t e r ris k of a n a d ve rs e re a ct ion ). Mos t rh e u -
m a t o logis t s re cogn ize t h a t a t t h e ra p e u t ic d o s e s , a ll NSAIDs a p p e a r e q u a lly
e ffe ct ive a t p rovid in g a n a lge s ia .
Th e m a jor p ot e n t ia l a d ve rs e e ffe ct s of n on s e le ct ive NSAIDs a re ga s t rop a -
t h y (p e p t ic u lce r d is e a s e a n d ga s t r it is ) a n d re n a l d ys fu n ct io n (in t e r s t it ia l
n e p h r it is a n d p ro s t a gla n d in -in h ib it io n –re la t e d re n a l in s u f cie n cy). Th e s e
a d ve rs e e ffe ct s a re m ore p reva le n t in t h e e ld e rly.
Effe ct ive s t ra t egie s h a ve be e n d eve lop e d t o m it iga t e t h e ga s t ro in t e s t in a l
(GI) t oxicit y of t h e NSAIDs : u s e of low e r d os e s , n on a ce t yla t e d s a licyla t e, con -
com it a n t u s e of m is op ros t ol (200 µg BID t o QID), or a p rot on p u m p in h ibit or, u s e
180 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Adjuvant Ag e nts
An y a n a lge s ic p rogra m ca n be s u p p le m e n t e d w it h tricyclic antidepressants o r
selectiv e serotonin reuptake inhibitors. Not on ly t h ey m ay a cce n t u a t e t h e e ffe ct of
t h e ot h e r a n a lge s ics , t h ey m ay e xe rt p a rt of t h e ir be n e t in t h os e p a t ie n t s h a v-
in g s le e p d is t u rba n ce s be ca u s e of n oct u rn a l m yoclon u s a n d brom ya lgia -like
S
E
com p la in t s .
C
T
A ntispasm odics a re u s e fu l in re d u cin g m u s cle p a in a n d s p a s m in OA. Pa in
I
O
N
a s s ocia t e d w it h m u s cle s p a s m m a y be re d u ce d w it h a n in je ct ion of lid oca in e,
4
w it h or w it h ou t a d ep ocort icos t e roid .
O
s
t
e
Intra-Articular The rapy
o
a
Ora l cort icos t e roid s a re n ot in d ica t e d for t h e t re a t m e n t of OA. How eve r, intra-
r
t
h
articular corticosteroids m ay re lieve t h e p a t ie n t ’s p a in . Th ey h ave n ot be e n con -
r
i
t
s is t e n t ly h e lp fu l in fa ce t join t s for t re a t m e n t of ch ron ic low ba ck p a in , bu t h ave
i
s
a
b e e n u s e fu l in m a n y p a t ie n t s a s e p id u ra l in je ct ion s fo r s ym p t om a t ic s p in a l
n
d
s t e n os is . De s p it e t h e clin ica l im p re s s ion t h a t t h ey m ay be of va lu e, n o con s is t -
M
e n t clin ica l p re d ict ors of re s p on s e t o in t ra -a rt icu la r d e p ocort icos t e roid s h ave
e
t
be e n fou n d t o a id in p a t ie n t s e le ct ion for t h is t h e ra py.
a
b
In ge n e ra l, d e p ocort icos t e ro id in je ct ion s s h ou ld be lim it e d t o fou r in je c-
o
l
i
t ion s t o a n y s in gle join t p e r ye a r (t yp ica lly n o m ore fre q u e n t ly t h a n a t 3-m on t h
c
B
in t e rva ls ). How eve r, if p a t ie n t s re q u ire m u lt ip le in je ct ion s , t h ey p roba bly re q u ire
o
n
ort h op e d ic s u rgica l in t e rve n t ion .
e
Com p lica t ion s of in t ra -a rt icu la r d e p ocort icos t e roid s , s u ch a s s ep t ic a rt h ri-
t is , a re ra re if p rop e r a s e p t ic t e ch n iq u e is e m p loye d . Dep ocort icos t e roid s a re
crys t a llin e a n d ca n in d u ce a t ra n s ie n t s yn ovit is or “p os t in je ct ion in a m m a t ory
re a ct ion .” Th is re a ct ion occu rs w it h in s eve ra l h ou rs of t h e in je ct ion , in con t ra s t
t o a join t in fe ct ion , w h ich m os t oft e n h a p p e n s 24 t o 72 h ou rs a ft e r t h e p roce -
d u re . Th e a p p lica t io n o f co ld co m p re s s e s o ft e n re d u ce s t h e p a in u n t il t h e
in a m m a t ion re s o lve s . Th e s u s p icion o f in fe ct ion s h ou ld p ro m p t im m e d ia t e
a s p ira t io n w it h s u b s e q u e n t Gra m s t a in a n d cu lt u re s . Fu r t h e rm o re , fre q u e n t
in t ra -a rt icu la r cort icos t e roid s m ay d a m a ge ca rt ila ge a n d bon e, a n d m ay eve n
con t ribu t e t o t h e d eve lop m e n t of ava s cu la r n e cros is .
Syn t h e t ic a n d n a t u ra lly occu rrin g hyaluronic acid derivativ es a re a d m in is t e re d
in t ra -a rt icu la rly. Th e s e v iscosupplem ents a re p rep a re d in a va rie t y of m ole cu la r
w e igh t s (ra n ge 100,000 t o 1,000,000 Sve d be rg u n it s ) a n d m ay re d u ce p a in a n d
im p rove m obilit y for p rolon ge d p e riod s of t im e. Th e m e ch a n is m (s ) of a ct ion is
u n kn ow n . How eve r, s om e evid e n ce e xis t s , s u gge s t in g a n a n t i-in a m m a t ory
e ffe ct (p a rt icu la rly t h e h igh -m ole cu la r-w e igh t p rep a ra t ion ), a s h ort -t e rm lu bri-
ca n t e ffe ct , a n a n a lge s ic e ffe ct by d ire ct ly bu ffe rin g s yn ovia l n e rve e n d in gs , a n d
a s t im u la t in g e ffe ct on s yn ovia l lin in g ce lls in t o p rod u cin g n orm a l h ya lu ron ic
a cid , p e rh a p s t h rou gh bin d in g t o t h e s yn ovia l ce ll CD44H re cep t ors .
Th e vis co s u p p le m e n t s in clu d e Syn vis c (HYLAN GF 20) a d m in is t e re d a s
t h re e w e e kly in je ct ion s , Hya lga n (h ya lu ron a t e s od iu m ) a d m in is t e re d a s t h re e
t o ve w e e kly in je ct io n s , a n d Or t h ovis c (h ya lu ro n a n ) a d m in is t e re d a s t h re e
w e e kly in je ct ion s .
Ch a p te r 19 Os t e o a rt h rit is 181
Clinica l Co urse
W it h a d e q u a t e p a in re lie f, p a t ie n t s s h ou ld h a ve a n u n co m p lica t e d clin ica l
cou rs e. Th e re is n o good ep id e m iologic d a t a t h a t OA s h ort e n s life exp e ct a n cy a s
e
n
RA a n d s ys t e m ic lu p u s e ryt h e m a t a s u s (SLE) h ave cle a rly be e n d e m on s t ra t e d t o
o
B
d o. W h ile ove ra ll s u rviva l is n ot a ffe ct e d by t h is con d it ion , t h e d is e a s e t e n d s t o
c
i
h ave a s low, p rogre s s ive cou rs e oft e n cu lm in a t in g in t h e n e e d for in va s ive ort h o-
l
o
b
p e d ic p roce d u re s t o a ch ieve p a in con t rol. As s u ch , a ggre s s ive m a n a ge m e n t of
a
t
m od i a ble ris k fa ct ors , s u ch a s w e igh t con t rol a n d s u p e rvis e d exe rcis e p rogra m s ,
e
M
a re of p a ra m ou n t im p ort a n ce t o le n gt h en t h e t im e for a n ort h op e d ic p roce d u re.
d
n
a
s
ICD9
i
t
i
r
h
715.9 Oste o athritis – (se e also Ost e o a rt h ro sis) •
t
r
a
Use t h e f o llo w in g f t h -d ig it
o
e
su b classi cat io n w it h cat e g o rie s 715:
t
s
O
0 sit e u n sp e ci e d
4
1 sh o u ld e r re g io n
N
2 u p p e r arm
O
I
T
3 f o re arm
C
E
4 h an d
S
5 p e lvic re g io n an d t h ig h
6 lo w e r le g
7 an k le an d f o o t
8 o t h e r sp e ci e d sit e s e xce p t sp in e
9 m u lt ip le sit e s
715.9 Oste o arthro sis (d e g e n e rat ive ) (h yp e rt ro p h ic) •
715.0 [0,4,9] g e n e raliz e d
715.3 lo caliz e d •
715.1 id io p at h ic •
715.1 p rim ary •
715.2 se co n d ary •
715.89 m u lt ip le sit e s, (n o t g e n e raliz e d )
715.09 p o lyart icu lar
721.90 sp in e (se e also Sp o n d ylo sis)
524.6 t e m p o ro m an d ib u lar jo in t
Re fe re nce s
1. Kra m e r JS, Ye lin EH , Ep s t e in W V. Socia l a n d e con om ic im p a ct s of fou r m u s cu los ke le t a l con d it ion s : A
s t u d y u s in g n a t ion a l com m u n it y-ba s e d d a t a . J Rheum atol 1983 ;26 :901 –907 .
2. Law re n ce JS. Ge n e ra lize d os t e oa rt h ros is in a p op u la t ion s a m p le . A m J Epidem iol 1969 ;90 :381 –389 .
3. Fe ls on DT. Th e ep id e m iology of kn e e os t e oa rt h rit is : Re s u lt s from t h e Fra m in gh a m os t e oa rt h rit is s t u d y.
Sem in A rthritis Rheum 1990 ;20 :42 –50 .
4. Pe lle t ie r JP, Ma rt e l-Pe lle t ie r J, How e ll DS. Et iop a t h oge n e s is of os t e oa rt h rit is . In : Koop m a n W J, e d . A rthritis
and A llied Conditions: A Textbook of Rheum atology. 13t h e d . Ba lt im ore : Willia m s & Wilkin s , 1997 :1969 –1984 .
182 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
e
A 65-ye ar-o ld p at ie n t w it h
n
o
Gou t is t h e clin ica l m a n ife s t a t ion from
B
p o o rly co n t ro lle d d iab e t e s,
c
t h e t is s u e d e p os it ion of m on os od iu m
i
l
h yp e rt e n sio n , h e art f ailu re ,
o
u ra t e (MSU) crys t a ls . Th e d is e a s e h a s
b
an d a p rio r d iag n o sis o f g o u t
a
becom e m ore p reva le n t in Wes te rn p op -
t
e
M
is h o sp it aliz e d b e cau se o f an u la t ion s , s p e ci ca lly in ce rt a in p a t ie n t
grou p s s u ch a s tra n sp la n t recip ien ts . It is
d
e xace rb at io n o f h e art f ailu re
n
on e of t h e few m e d ica l con d it ion s for
a
w it h w o rse n in g e d e m a an d
s
w h ich p h ys icia n s h ave a n ea rly com p lete
i
t
i
r
p ro g re ssive d ysp n e a. On h o s- u n d e rs t a n d in g of t h e ca u s a t ive a n d n e c-
h
t
r
p it al st ay d ay n u m b e r 2, sym p - es sa ry fa ctor for its d evelop m e n t , in t h is
a
o
ca se a s eru m u ra te con ce n t ra tion a bove
e
t o m s le ad in g t o ad m issio n
t
s
t h e s a t u ra t ion t h re s h old , or h yp e ru ri-
O
w e re sig n i can t ly im p ro ve d . Ho w e ve r in t h e p rio r 12 h o u rs, ce m ia . Th is u n d e rs t a n d in g of t h e e t iol-
4
h e h as d e ve lo p e d a re d , w arm , sw o lle n , an d e xt re m e ly
N
ogy a n d t h era p eu t ic t a rge t of t h e d is ea se
O
h a s n ot t ra n s la t e d in t o a d e q u a t e m a n -
I
t e n d e r rig h t an k le .
T
C
a ge m e n t fo r t h e m a jo rit y o f p a t ie n t s
E
A n art h ro ce n t e sis o f t h e aff e ct e d jo in t yie ld s clo u d y u id
S
w it h gou t be ca u s e of a com bin a t ion of
t h at is p o sit ive f o r t h e p re se n ce o f n e g at ive ly b ire f rin g e n t fa ctors, in clu d in g in com p le te kn ow le d ge
n e e d le -sh ap e d cryst als (Fig . 20.1 ). A jo in t g lu co co rt ico id of th e ba s ic t h era p e u tic p rin cip les of t h e
in je ct io n w as d e laye d an d o n ly an alg e sic t re at m e n t alo n g d is e a s e a n d t h e grow in g com p le xit y of
p a t ie n t s w it h gou t , d rive n by m u lt ip le
w it h lo w -d o se o ral co lch icin e w as p ro vid e d . A t 48 h o u rs t h e
co m o rb id it ie s o r p o lyp h a r m a cy. Un t il
syn o vial u id cu lt u re w as re p o rt e d p o sit ive f o r g ro w t h o f recen t ly, a s ca rcity of th era p eu tic op tion s
Kle b sie lla sp p . Th e p at ie n t im p ro ve d w it h an t ib io t ic for gou t a d d e d t o t h e s e ch a lle n ge s , bu t
t h e rap y, re p e at e d jo in t asp irat io n s, lo w -d o se co lch icin e , th a t p a n ora m a h a s s t a rt ed t o ch a n ge.
an d an alg e sics.
EPIDEMIOLOGY
Go u t is t h e m o s t co m m o n in a m m a -
t ory a rt h rit is in t h e Un it e d St a t e s : a ccord in g t o t h e m os t re ce n t e s t im a t e by t h e
Na t ion a l Art h rit is Da t a Wo rkgrou p , u s in g 1996 d a t a from t h e Na t io n a l He a lt h
In t e rview Su rvey (NHIS) a n d Na t io n a l He a lt h a n d Nu t rit ion Exa m in a t io n Su r-
vey (NHANES), 3.0 m illio n a d u lt s old e r t h a n 18 ye a rs h a d go u t in t h e p revio u s
ye a r a n d 6.1 m illion a d u lt s old e r t h a n 20 ye a rs h a d gou t a t s om e p o in t of t h e ir
live s . Th e fre q u e n cy ra t e s h a ve cle a r ly b e e n in cre a s in g in t h e la s t d e ca d e s ,
w it h a cu rre n t e s t im a t e d p reva le n ce a t 940 p e r 100,000 a d u lt s old e r t h a n 18
ye a rs (1 ).
183
184 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
HYPERURICEMIA
Figure 20 .1 Needle-shaped monosodium urate crystals showing charac- Uric a cid , fou n d in s e ru m a s u ra t e , is t h e e n d p ro d u ct
teristic negative birefringence. (Axis of the polarizer points at four O’clock of p u r in e m e t a bo lis m in h u m a n s . Th e a ccu m u la t io n
and crystals are predominantly yellow at that direction; perpendicular crys-
o f u ra t e b e yo n d it s s o lu b ilit y p o in t o f 6.8 m g/ d L
tals are predominantly blue.) Courtesy of H. Ralph Schumacher, Jr., M.D.,
and Janet Dinnella, University of Pennsylvania (http:/ / www.med.upenn. d e n e s h yp e r u rice m ia , a n e ce s s a ry bu t n ot s u f cie n t
edu/ synovium. Accessed June 6, 2011). fa ct o r for t h e d eve lop m e n t o f gou t . Gou t is t h e clin i-
ca l m a n ife s t a t io n o f t h e d e p o s it io n o f MSU crys t a ls in
t is s u e s .
CLINICAL POINTS
Th e im p ort a n ce of h yp e ru rice m ia a s a ca u s a t ive fa ct or for gou t h a s be e n
• Ea rly in t h e d ise a se co u rse , corrobo ra t e d in p ro s p e ct ive s t u d ie s . As p a rt of t h e Norm a t ive Agin g St u d y, a
g o u t is ch a ra ct e rize d b y
coh ort of 2,046 m e n w a s follow e d for 15 ye a rs (2 ). Th e ris k for gou t follow e d a
a cu t e a t t a cks o f a rt h rit is
( a re s) a n d a sym p t o m a t ic gra d ie n t d ep e n d in g on t h e in it ia l u ra t e leve l: w it h a n in it ia l leve l of m ore t h a n
in t e rva ls. If t h e d ise a se 9 m g/d L, t h e a n n u a l in cid e n ce ra t e w a s 4.9%. W h e n t h e in it ia l leve l w a s be t w e e n
g o e s u n t re a t e d , it m o rp h s 7.0 a n d 8.9 m g/d L, t h e a n n u a l in cid e n ce ra t e w a s 0.5%, a n d n a lly, it w a s 0.1%
in t o a ch ro n ic d e fo rm in g w it h u ra t e leve ls le s s t h a n 7.0 m g/d L. Th e im p ort a n ce of h yp e ru rice m ia in p re -
a rt h rit is w it h t o p h i.
d ict in g gou t a t t a cks is lim it e d n ot on ly t o t h e in it ia l d ia gn os is , bu t a ls o t o t h e
• Common precipitants of m a n a ge m e n t , a s it h a s be e n d e m on s t ra t e d t h a t low s e ru m u ra t e leve ls p re d ict
gout ares include acute fre e d om from re cu rre n ce of gou t a re s .
illnesses, alcohol intake, star-
Uric a cid is s yn t h e s ize d in t h e live r from p u rin e com p ou n d s p rovid e d by
vation, excessive intake of
purines, and use of certain d ie t a n d t h e e n d o ge n o u s p a t h w a y o f p u r in e s yn t h e s is d e n ovo. It is t h e n
medications (allopurinol, re le a s e d in t o t h e circu la t ion a lm os t e xclu s ive ly in it s s olu ble -form MSU, w h ich
diuretics, cyclosporine). is re a d ily a va ila ble fo r lt ra t io n in t h e p rox im a l t u b u le s o f t h e k id n ey. Tw o
• Go u t a re s in it ia lly in vo lve m e ch a n is m s e xis t t h rou gh w h ich a n in d ivid u a l cou ld d eve lop h yp e ru rice m ia :
t h e lo w e r e xt re m it y jo in t s ove rp rod u ct ion (e xcre t ion of m ore t h a n 600 m g/d a y in t h e u rin e w h ile on a
a n d p e a k in in t e n sit y p u rin e -fre e d ie t , a ccou n t in g for 10% t o 15% of ca s e s ) a n d u n d e re xcre t ion (e xcre -
w it h in 24 h o u rs. t ion of le s s t h a n 400 m g/d a y, a ccou n t in g for 85% t o 90% of ca s e s ). In bot h ca s e s
• When starting urate-lowering t h e p roble m cou ld be p rim a ry (s e con d a ry t o e n zym a t ic in h e rit e d d is ord e rs of
t h e ra p y fo r g o u t , it sh o u ld u ra t e p rod u ct ion or d e fe ct s in re n a l e xcre t ion ) or s e con d a ry t o e xce s s ive p u rin e
a lw a ys b e a cco m p a n ie d b y t u rn ove r (d ie t , m a lign a n cie s ), m e d ica t ion s , or t oxin s . For a n e xp a n d e d ove r-
p ro p h yla ct ic t h e ra p y fo r
view of ca u s e s of h yp e ru rice m ia , s e e Ta ble 20.1 .
g o u t a re s (n o n st e ro id a l
a n t i-in a m m a t o ry d ru g s Aft e r a n e a rly com p le t e lt ra t io n in t h e glom e ru lu s , u ra t e u n d e rgoe s a n
(NSAIDs), g lu co co rt ico id s, e xt e n s ive re a bs orp t ion in t h e p roxim a l t u bu le la rge ly m e d ia t e d by a s p e ci c
o r lo w -d o se co lch icin e ). orga n ic a n ion t ra n s p ort e r. Aft e r t h e rs t rou n d of re a bs orp t ion , a s e con d cycle
• Ca lciu m p yro p h o sp h a t e of s e cre t ion a n d fu rt h e r re a bs orp t ion occu rs in t h e d is t a l p ort ion s of t h e p rox-
d e p o sit io n d ise a se ca n im a l t u bu le s . Th e s e n a l s t ep s d e t e rm in e t h e n e t u ra t e e xcre t ion , t yp ica lly 8%
p re se n t a s a cu t e a rt h rit is t o 12% of t h e in it ia lly lt e re d loa d .
(p se u d o g o u t ), a n in a m - On ce h yp e ru rice m ia e n s u e s , t h e p roba bilit y of d eve lop in g gou t d e p e n d s on
m a t o ry su b a cu t e p o lya r-
t h e con ce n t ra t ion of u ra t e in t h e t is s u e or join t a n d ot h e r p re d is p os in g fa ct ors
t h rit is (p se u d o rh e u m at o id
art h rit is), d e g e n e ra t ive s u ch a s a low p H, low t e m p e ra t u re, p reviou s t ra u m a t o t h e join t , a n d la ck of
jo in t d ise a se (p se u d o - m obilit y (e.g., d u rin g s le ep , w h e n t h e re is a n in cre a s e d w a t e r re a bs orp t ion , a n d
o st e o art h rit is), sp in a l con ce n t ra t ion of u ra t e ). Re ce n t a d va n ce s in u n d e rs t a n d in g h ow MSU crys t a ls
d ise a se , a n d a d e st ru ct ive ca u s e t h e ch a ra ct e ris t ic gou t in a m m a t o ry re s p o n s e h ave be e n m a d e. Alon g
a rt h rit is re se m b lin g a
w it h ot h e r crys t a ls , s u ch a s ca lciu m pyrop h os p h a t e, s ilica , a n d a s be s t os , MSU
n e u ro p a t h ic a rt h rit is.
is in t e rn a lize d in t o p h a gocyt e s a n d s e n s e d by t h e in n a t e im m u n e s ys t e m a s a
Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 185
e
n
o f ch ro n ic kid n e y d ise a se
o
B
Increased purine nucleotide turnover: In h ib it io n o f t u b u la r u ra t e se cre t io n
c
i
l
myeloproliferative and lymphoprolif- (o rg a n ic a cid o sis): la ct ic a cid o sis, ke t o -
o
b
erative diseases, psoriasis a cid o sis, e t h a n o l, p re e cla m p sia
a
t
e
Acce le ra t e d a d e n o sin e t rip h o sp h a t e In h ib it io n o f t u b u la r u ra t e se cre t io n
M
(ATP) d e g ra d a t io n : e t h a n o l in t a ke , (d ru g s): sa licyla t e s, t h ia zid e s,
d
t issu e h yp o xia , g lyco g e n st o ra g e cyclo sp o rin e , e t c.
n
a
d ise a se s En h a n ce d t u b u la r u ra t e re a b so rp t io n :
s
i
d e h yd ra t io n , d iu re t ic u se , in su lin
t
i
r
re sist a n ce
h
t
r
Un kn o w n m e ch a n ism : ch ro n ic le a d
a
o
e xp o su re , h yp e rt e n sio n , h yp e rp a ra t h y-
e
t
ro id ism , sa rco id o sis, b e ryllio sis
s
O
4
N
O
I
T
d a n ge r s ign a l in d ica t ive of t is s u e d a m a ge a n d re cogn ize d by a s e rie s of s op h is -
C
E
t ica t e d cyt os olic re cep t ors (3 ).
S
Th e e ffe ct o f d ie t a s a ris k fa ct o r fo r h yp e r u r ice m ia a n d go u t h a s b e e n
cla ri e d by ep id e m iologic evid e n ce. Cros s -s e ct ion a l a n a lys e s reve a l t h a t t ot a l
b e e r, liq u o r, m e a t , a n d s e a fo o d co n s u m p t io n w e re a s s o cia t e d w it h h igh e r
s e ru m u ric a cid leve ls . How eve r, t h e m a gn it u d e of t h e in cre a s e in s e ru m u ra t e
in m os t in d ivid u a ls p e r u n it o f in t a ke is re la t ive ly s m a ll. W in e, t ot a l p rot e in ,
a n d d a iry in t a ke h ave n ot be e n fou n d t o be a s s ocia t e d w it h h igh e r s e ru m u ra t e
leve ls . Th e e ffe ct of a lcoh ol in t a ke in in d u cin g a re s in p a t ie n t s w it h e s t a b-
lis h e d gou t is s ign i ca n t .
Fru ct os e in t a ke h a s ga t h e re d m u ch a t t e n t ion a s a fa ct or a s s ocia t e d w it h
h igh e r leve ls of s e ru m u ra t e, re n a l d is e a s e, a n d t h e d eve lop m e n t of h yp e rt e n -
s ion . Fru ct os e m a y in d u ce h yp e ru rice m ia t h rou gh d ep le t ion of a d e n os in e t ri-
p h os p h a t e a n d it s ra p id con ve rs ion in t o a d e n os in e m on op h os p h a t e, w h ich w ill
be la t e r ca t a bolize d in t o u ric a cid . Ep id e m iologic s t u d ie s h a ve e s t a blis h e d a n
a s s ocia t ion be t w e e n fru ct os e in t a ke a n d h yp e ru rice m ia a n d gou t .
Th e re a re s eve ra l m e d ica t ion s a n d t oxin s t h a t in u e n ce t h e re n a l h a n d lin g
of u ric a cid . As p irin h a s a d u a l e ffe ct on s e ru m u ric a cid leve ls , w it h h igh leve ls
of in t a ke (m ore t h a n 3 g/d ay) be in g u ricos u ric a n d low e r leve ls of in t a ke (75 t o
2,000 m g/d a y) p rom ot in g u ric a cid re t e n t ion . Diu re t ics (bot h loop a n d t h ia zid e s )
a re w e ll k n ow n t o b e a s s o cia t e d w it h h igh e r s e r u m u ra t e leve ls , p o s s ibly
t h rou gh volu m e con t ra ct ion a n d con cu rre n t s t im u la t ion of u ra t e re a bs orp t ion
a t t h e leve l of t h e u ra t e a bs orp t ion re ce p t or in t h e p roxim a l t u bu le s . Cyclos p orin e
a n d t a crolim u s a re w id e ly u s e d d ru gs for p os t t ra n s p la n t im m u n os u p p re s s ion
a n d a re s t ron gly a s s ocia t e d w it h t h e d eve lop m e n t of h yp e ru rice m ia a n d gou t ;
186 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Flares occur
more often
n
i
a
P
Intercritical
segments decrease
Persistent pain
and stiffness
Asymptomatic Acute Flares Advanced
Hyperuricemia Time Gout
Adapted from Klippel et al, eds. In: P rim e r o n th e Rh e u m a tic Dis e a s e s . 12th ed.
Arthritis Foundation; 2001:313.
Studie s
Th e d ia gn os is of gou t is s t ron gly s u p p ort e d by t h e com bin a t ion of a cla s s ica l
clin ica l p re s e n t a t ion (m on oa rt h rit is a n d t op h i) a lon g w it h evid e n ce of h yp e ru ri-
ce m ia a n d clin ica l re s p on s e t o colch icin e, NSAIDs , or glu cocort icoid s . How eve r,
it is ve ry im p ort a n t t o e m p h a s ize t h a t e a ch on e of t h e s e d ia gn os t ic con s id e ra -
t ion s a re im p e rfe ct a n d t h a t t h e d ia gn os is ca n on ly be re lia bly e s t a blis h e d by t h e
id e n t i ca t ion of n ega t ive ly bire frin ge n t n e e d le -s h a p e d MSU crys t a ls from a n
e
a ffe ct e d join t or t is s u e.
n
o
Th e m os t com m on w ay of id e n t ifyin g MSU crys t a ls in p a t ie n t s s u s p e ct e d
B
c
of h a vin g a gou t a re is t h rou gh s yn ovia l u id a s p ira t ion from a n a ffe ct e d join t .
i
l
o
Th e u id obt a in e d from join t s a ffe ct e d by gou t is u s u a lly t u rbid w it h a ye llow
b
a
t in ge, bu t in e xt re m e ca s e s , it is t h ick a n d ch a lky, w it h a w h it e colora t ion . Th e
t
e
M
ce ll cou n t s a re u s u a lly in t h e in a m m a t ory ra n ge from 3,000/m m 3 u p t o gre a t e r
t h a n 50,000/ m m 3 , m o re t h a n 90% o f t h e s e ce lls b e in g p o lym o r p h o n u cle a r.
d
n
Oft e n , n e e d le -s h a p e d MSU crys t a ls ca n be id e n t i e d u n d e r s t a n d a rd ligh t
a
s
m icros cop y. How eve r, t h e op t im a l w a y t o vis u a lize MSU is t h rou gh p o la rize d
i
t
i
r
ligh t m icro s co p y, in w h ich n e e d le -s h a p e d MSU crys t a ls w ill a p p e a r w it h a
h
t
r
b righ t -ye llow or blu e co lo ra t ion (d e p e n d in g on if t h e a xis of t h e p o la rize r is
a
o
p a ra lle l or p e rp e n d icu la r t o t h e crys t a l) a ga in s t a p u rp le ba ckgrou n d (Fig. 20.1 ).
e
t
s
Ma n y t im e s t h e MSU crys t a ls a re fou n d in s id e a le u kocyt e t h a t is a t t e m p t in g
O
p h a gocyt os is . De s p it e be in g t h e s t a n d a rd w ay of d e t e rm in in g t h e p re s e n ce of a
4
N
go u t a re , s yn ovia l u id a n a lys is w it h crys t a l id e n t i ca t io n h a s s o m e d ra w -
O
I
ba cks . For e xa m p le, p a t ie n t s w it h gou t a n d h yp e ru rice m ia t h a t a re n ot h a vin g
T
C
a gou t a re cou ld h a ve MSU crys t a ls in t h e ir join t s yn ovia l u id (u s u a lly in t h e
E
S
con t e xt of a n on in a m m a t ory ce ll cou n t ). Als o, t h e a s p ira t ion of s m a ll join t s
co u ld be t e ch n ica lly ch a lle n gin g a n d t h e p ro ce d u re cou ld be d if cu lt t o p e r-
form for u n t ra in e d p ra ct it ion e rs . An ot h e r p ot e n t ia l is s u e is t h a t s yn ovia l u id
h a s t o be p ro m p t ly a n a lyze d a s ce lls co u n t s d e clin e a n d crys t a ls d ege n e ra t e
w h e n s a m p le p roce s s in g is d e laye d . Fin a lly, t h e id e n t i ca t ion of MSU crys t a ls
in p a rt ia lly t re a t e d p a t ie n t s or t h os e in w h ich t h e gou t a re is re s olvin g ca n be
ch a lle n gin g a n d re q u ire s lot s of p a t ie n ce on p a rt of t h e e xa m in e r. Bu rs a l u id ,
t op h i a s p ira t e s , a n d t is s u e s a m p le s ca n a ls o be a n a lyze d w it h t h e p u rp os e of
id e n t ifyin g MSU crys t a ls .
Me a s u re m e n t of s e ru m u ra t e is a n u n re lia ble p re d ict or of gou t a re s a n d
s h ou ld n o t be u s e d w it h d ia gn o s t ic p u rp o s e s a s u p t o 40% o f ca s e s o f a cu t e
gou t occu r in t h e s e t t in g of n orm ou rice m ia . On t h e ot h e r h a n d , h yp e ru rice m ia
is fre q u e n t in t h e ge n e ra l p op u la t ion a n d cou ld be p re s e n t in t h e s e t t in g of a n
a cu t e a rt h rit is s e con d a ry t o rh e u m a t oid d is e a s e, p s oria s is , in fe ct ion , a n d s o on .
Ot h e r a n cilla ry in ve s t iga t ion s s u ch a s t h e m e a s u re m e n t of u rin e u ra t e e xcre -
t ion a n d p la in ra d iogra p h s h ave a lim it e d role in d ia gn os t ic a n d m a n a ge m e n t
d e cis ion s .
Th e Am e rica n College of Rh e u m a t ology (form e rly Am e rica n Rh e u m a t is m
As s o cia t io n ) p ro p o s e d p re lim in a ry cr it e r ia fo r t h e d ia gn o s is o f a cu t e go u t y
a rt h rit is in 1977 (Ta ble 20.2 ; 4 ). De s p it e t h e ir w id e ly a d op t e d u s e a n d cit a t ion ,
t h os e w e re n eve r va lid a t e d , a n d im p or t a n t lim it a t io n s in t h e ir p e rform a n ce
h a ve be e n re cogn ize d . More re ce n t ly, t h e Eu rop e a n Le a gu e Aga in s t Rh e u m a -
t is m h a s p rop os e d re com m e n d a t ion s for t h e d ia gn os is of gou t t h a t t ra n s la t e
188 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Table 20.2 Rules for t he Classi cat ion and Diagnosis of Gout
ARA PRELIMINARY
CLASSIFICATION CRITERIA EULAR EVIDENCE-BASED DIAGNOSIS OF GOUT IN
FOR ACUTE GOUTY RECOMMENDATIONS FOR PATIENTS WITH ACUTE
ARTHRITIS (1977) GOUT DIAGNOSIS (2006) MONOARTHRITIS (2010)
Co n t e xt Acu t e a rt h rit is ( a re s) An y g o u t Community-based undiagnosed
monoa rthritis
Ru le o r 1. Mo n o so d iu m u ra t e cryst a ls 1. Ra p id (6–12 h o u rs) 1. Ma le se x (2 p o in t s)
recommendations in t h e jo in t u id ; o r d e ve lo p m e n t o f se ve re 2. Pre vio u s p a t ie n t
2. To p h u s p ro ve n t o co n t a in p a in , sw e llin g , e ryt h e m a re p o rt e d —a t t a ck (2 p o in t s)
u ra t e cryst a ls; o r is h ig h ly su g g e st ive , b u t 3. On se t w it h in 1 d a y
3. Six o f t h e fo llo w in g : n o t sp e ci c fo r g o u t (0.5 p o in t s)
• Mo re t h a n o n e a t t a ck o f 2. Fo r t yp ica l p re se n t a tio n s, 4. Jo in t re d n e ss (1 p o in t )
a cu t e a rt h rit is clin ica l d ia g n o sis is 5. First MTP in vo lve m e n t
• Ma xim a l in a m m a t io n re a so n a b ly a ccu ra t e (2.5 p o in t s)
d e ve lo p e d w it h in 1 d a y 3. MSU cryst a ls in syn o via l 6. Hyp e rt e n sio n o r 1 cardio-
• At t a ck o f m o n o a rt icu la r u id o f t o p h u s co n rm s vascular diseasesa (1.5 points)
S
E
a rt h rit is gout 7. Se ru m u ra t e 5.88 m g /d L
C
T
• Jo in t re d n e ss 4. Ro u t in e se a rch fo r MSU (3.5 p o in t s)
I
O
• First MTP jo in t p a in fu l cryst a ls in d ia g n o se d • Le ss t h a n 4 p o in t s: g o u t
N
o r sw o lle n jo in t s is re co m m e n d e d p re va le n ce 2.8%
4
• Un ila t e ra l a t t a ck in vo lv- 5. Id e n t i ca t io n o f MSU • More t ha n 4 t o 8 p oin t s:
O
in g rst MTP jo in t crystals from asymptomatic go ut pre va len ce 27%
s
t
e
• Su sp e ct e d t o p h u s joints allows diagnosis in • Mo re t h a n 8 p o in t s: g o u t
o
• Hyp e ru rice m ia intercritical periods p re va le n ce 80.4%
a
r
• Asym m e t ric sw e llin g 6. Gra m st a in a n d cu lt u re
t
h
r
w it h in a jo in t (ra d io - sh o u ld b e d o n e in jo in t s
i
t
i
g ra p h s) su sp e ct e d t o h a ve g o u t
s
a
• Su b co rt ica l cyst s w it h o u t 7. Se ru m u ra t e d o n o t
n
e ro sio n s (ra d io g ra p h s) co n rm o r e xclu d e g o u t
d
M
• Ne g a t ive cu lt u re s d u rin g 8. Re n a l u ra t e e xcre t io n
e
a cu t e e p iso d e sh o u ld b e co n sid e re d in
t
a
ce rt a in p a t ie n t s
b
o
9. Ra d io g ra p h s se ld o m a re
l
i
c
n o t u se fu l in a cu t e g o u t
B
10. Risk fa ct o rs a n d co m o rb id -
o
n
it ie s sh o u ld b e a sse sse d
e
Pe rfo rm a n ce Se n sit ivit y 88% No t p ro vid e d Are a u n d e r t h e cu rve 0.87
Sp e ci cit y 80%
ARA, Am e rica n Rh e u m a t ism Asso cia t io n (cu rre n t ly Am e rica n Co lle g e o f Rh e u m a t o lo g y); EULAR, Eu ro p e a n Le a g u e Ag a in st Rh e u m a t ism ; MSU,
m o n o so d iu m u ra t e ; MTP, m e t a t a rso p h a la n g e a l.
a
An g in a p e ct o ris, m yo ca rd ia l in fa rct io n , h e a rt fa ilu re , ce re b ro va scu la r a ccid e n t , t ra n sie n t isch e m ic a t t a ck, o r p e rip h e ra l va scu la r d ise a se .
Ta b le a d a p t e d fro m re fe re n ce s 4 –6 .
DIFFERENTIAL DIAGNOSIS
Gou t a re s ca n be m im icke d by ot h e r in a m m a t ory a n d in fe ct iou s con d it ion s ,
m a in ly s e p t ic a rt h rit is (Ta ble 20.3 ). Th e clin ica l d iffe re n t ia t ion be t w e e n t h e s e
con d it ion s ca n be d if cu lt in t h e im m u n e -s u p p re s s e d , e ld e rly, or s u bje ct s w it h
m u lt ip le com orbid it ie s . In t h e s e s e t t in gs , bot h con d it ion s ca n be p olya rt icu la r
a n d a s s ocia t e d w it h p rom in e n t s ys t e m ic m a n ife s t a t ion s s u ch a s feve r, ch ills ,
Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 189
e
sym p t o m s, in clu d in g
n
s a m e p a t ie n t , a s join t a s p ira t e s con t a in in g gou t or p s e u d ogou t crys t a ls h a ve
o
fe ve r a n d ch ills.
B
a ls o b e e n re p o r t e d p o s it ive fo r b a ct e r ia l cu lt u re s . Se p t ic a r t h r it is ca n a ls o
c
• Medica tio n nonco mpliance
i
p re s e n t in p a t ie n t s w it h e s t a blis h e d gou t , m im ickin g a n ew a re of t h e d is e a s e.
l
o
is a very frequ ent ca use of
b
For t h is re a s on , gra m s t a in a n d cu lt u re s a re re com m e n d e d a s p a rt of t h e rou -
a
gou t that is re sistan t to
t
t in e la bora t o ry w ork-u p o f s yn ovia l u id a s p ira t e d from a p a t ie n t in w h om
e
ura te -low ering the rap y.
M
gou t is s u s p e ct e d .
d
Ot h e r con d it ion s t h a t ca n m im ic gou t a re s in clu d e t ra u m a , p s e u d ogou t
n
a
a n d ot h e r crys t a l a rt h rit id e s , or a re s of ot h e r in a m m a t ory a rt h rit id e s , s u ch
s
i
t
a s s e ron ega t ive s p on d yloa rt h rop a t h ie s a n d rh e u m a t oid a rt h rit is . Ch ron ic gou t
i
r
h
co u ld b e d if cu lt t o d iffe re n t ia t e fro m o t h e r in a m m a t o ry a rt h rit id e s , m o s t
t
r
a
n ot a bly rh e u m a t oid a rt h rit is . Top h i cou ld be m is t a ke n a s rh e u m a t oid n od u le s
o
e
in t h a t s a m e co n t e x t . In e ld e r ly p a t ie n t s w it h e x t re m e d is a b ilit y ca u s e d by
t
s
O
ch ron ic p olya rt icu la r gou t , t h e clin ica l p ict u re cou ld be con fu s e d w it h p olym y-
4
a lgia rh e u m a t ica , s e ron ega t ive a rt h rit is , or d ep re s s ion .
N
O
I
T
C
Tre a tme nt
E
S
Th e m a n a ge m e n t goa ls in gou t d iffe r d ep e n d in g on t h e s e t t in g. In a cu t e gou t t h e
t re a t m e n t is a im e d a t re s olvin g t h e a re s of p rom in e n t p a in a n d in a m m a t ion .
In t h e in t e rcrit ica l p e riod s t h e goa ls a re t o m a in t a in u ric a cid a t s u bs a t u ra t ion
leve ls , p reve n t in g t h e occu rre n ce of n ew a re s a n d t h e d eve lop m e n t of ch ron ic
t op h a ce ou s gou t . A lis t of t h e a ge n t s ava ila ble for m a n a ge m e n t of gou t is p re -
s e n t e d in Ta ble 20.4 .
e
n
u s u a lly p re s e n t s w it h in 8 t o 12 h ou rs a ft e r t h e in je ct ion a n d h a s be e n d e s cribe d
o
B
m ore fre q u e n t ly in a s s ocia t ion w it h t ria m cin olon e h e xa ce t on id e p rep a ra t ion s .
c
i
l
Th e d ia gn os is ca n be s u p p ort e d by a s p ira t ion of s yn ovia l u id a n d vis u a liza t ion
o
b
of la rge, irregu la r, in t e n s e ly bire frin ge n t , irregu la r crys t a ls . Th e con d it ion is s e lf-
a
t
e
lim it e d , u s u a lly s u bs id in g w it h in 24 t o 48 h ou rs a ft e r t h e in je ct ion . An a lge s ics ,
M
NSAIDs , a n d ice p a cks cou ld be u s e d a s s ym p t om a t ic t h e ra p y.
d
n
Co r t ico t ro p in (ACTH) s h a re s t h e s a m e p ro le o f in d ica t io n s a s s ys t e m ic
a
glu co co r t ico id s , n a m e ly p o lya r t icu la r a re s in w h ich NSAIDs a re n o t e ffe ct ive
s
i
t
i
o r co n t ra in d ica t e d . How eve r, ACTH is co s t ly co m p a re d w it h glu co co r t ico id s
r
h
t
a n d n o t w id e ly a va ila ble . It s m e ch a n is m o f a ct io n s e e m s t o b e t h ro u gh s t im -
r
a
o
u la t io n o f e n d o ge n o u s a d r e n a l h o r m o n e s , b u t d ir e ct a n t i- in a m m a t o r y
e
t
e ffe ct s a t t h e a ffe ct e d s it e co u ld a ls o b e im p lica t e d . Th e d r u g is a va ila ble fo r
s
O
s u b cu t a n e o u s o r in t ra m u s cu la r a d m in is t ra t io n , a n d a s in gle d o s e o f 40 IU h a s
4
b e e n fo u n d t o b e ra p id , e f cie n t , a n d w e ll t o le ra t e d eve n in p a t ie n t s t h a t a re
N
O
t a k in g m o d e r a t e d o s e s o f glu c o c o r t ic o id s . Ad ve r s e e ffe c t s in c lu d e m ild
I
T
h yp o k a le m ia , u id re t e n t io n , h yp e rglyce m ia , a n d t h e d eve lo p m e n t o f re b o u n d
C
E
go u t a re s , t h e la t t e r b e in g co n t ro lle d by t h e a d m in is t ra t io n o f o t h e r p ro p h y-
S
la ct ic t h e ra p y.
e
n
m os t w id e ly u s e d u ricos u ric; u s u a lly in it ia t e d a t a d os e of 500 m g ora lly t w ice a
o
B
d ay, t h e d os a ge ca n be s low ly in cre a s e d u p t o 3 g/d ay. Ad ve rs e e ffe ct s in clu d e
c
i
l
ga s t roin t e s t in a l in t o le ra n ce, ra s h , h e p a t ot oxicit y, gou t a re s , n e p h ro lit h ia s is ,
o
b
a n d n ep h rot ic s yn d rom e.
a
t
e
Ura t e ox id a s e (u rica s e ) is a p o t e n t e n z ym e p re s e n t in a ll m a m m a ls b u t
M
h igh e r p rim a t e s a n d h u m a n s , w h ich con ve rt s s e ru m u ra t e in t o m ore s o lu ble
d
n
a lla n t oin . Non re com bin a n t (obt a in e d from A spergillus av us ) a n d re com bin a n t
a
fo rm s (o bt a in e d from Saccharom y ces cerev isiae) h a ve be e n u s e d e ffe ct ive ly a s
s
i
t
i
in t ra ve n o u s in fu s io n s in t h e p reve n t io n a n d t re a t m e n t o f t u m o r lys is s yn -
r
h
t
d ro m e. How eve r, t h e ir com p lica t e d d os in g s ch e m e s , s eve re a d ve rs e re a ct ion s ,
r
a
o
a n d s e co n d a ry lo s s o f e f ca cy s eve re ly re s t r ict e d t h e ir u s e fo r t re a t m e n t -
e
t
re fra ct ory ca s e s of gou t .
s
O
A p olye t h yle n e glycol (PEG)–lin ke d u rica s e (p eglot ica s e ) h a s be e n a p p rove d
4
a s s e con d -lin e t re a t m e n t for gou t . Th e d ru g is a d m in is t e re d a s a n in t rave n ou s
N
O
in fu s ion of 8 m g eve ry 2 w e e ks , a n d re q u ire s p re m e d ica t ion w it h a n t ih is t a -
I
T
m in e s a n d glu cocort icoid s . In clin ica l t ria ls it p rove d t o be h igh ly e ffe ct ive a n d
C
E
p ot e n t in a ch ievin g m a rke d s e ru m u ra t e re d u ct ion s . It is im p ort a n t t o n ot e t h a t
S
a b o u t 40% o f p a t ie n t s d id n o t re s p o n d t o t h e d ru g p rim a rily o r d eve lo p e d a
s e con d a ry los s of re s p on s e. Ma n y p a t ie n t s h a d p a rt ia l or com p le t e re s olu t ion
of t h e ir t op h i bu rd e n . Us e of t h e m e d ica t ion w a s lim it e d by in cre a s e in t h e
fre q u e n cy o f go u t a re s a n d in fu s ion re a ct ion s (in clu d in g ca s e s o f a n a p h y-
la xis ). It s ca rd iova s cu la r s a fe t y w a s ca lle d in t o q u e s t ion , bu t s h ort -t e rm clin ica l
t ria ls d id n ot ra is e a n y cle a r s a fe t y s ign a ls . Cle a rly, p os t m a rke t in g s u rve illa n ce
s t u d ie s a re n e ce s s a ry.
PHYSIOLOGIC
• Ag in g
INJURY-RELATED
• Tra u m a
• Prio r su rg e ry t o a ffe ct e d jo in t
• Po st su rg ica l st a t e a
RHEUMATOLOGIC
• Ost e o a rt h rit is
• Go u t
• Ne u ro p a t h ic a rt h rit is
ENDOCRINE
• Hyp e rp a ra t h yro id ism a
• He m o ch ro m a t o sis
• Hyp o t h yro id ism
e
n
• Acro m e g a ly
o
B
METABOLIC
c
i
l
• Hyp o m a g n e se m ia
o
b
• Hyp o p h o sp h a t e m ia
a
t
e
MISCELLANEOUS
M
• Wilso n ’s d ise a se
d
• Och ro n o sis
n
a
s
i
a
t
Hyp e rp a ra t h yro id e ct o m y su rg e ry is a co m m o n p re d isp o sin g fa ct o r.
i
r
h
t
r
a
o
e
t
s
O
4
fa ct o r s , o n e p re cip it a n t is p a ra t h yro id e ct o m y s u rge ry. In a d d it io n
N
O
t o go u t , t h e p s e u d o go u t fo r m o f CPPD n e e d s t o b e d iffe r e n t ia t e d
I
T
fr o m s e p t ic a r t h r it is t h r o u gh s y n ovia l u id a n a ly s e s . Go u t a n d
C
E
p s e u d o go u t ca n co e x is t in t h e s a m e jo in t .
S
Ca lciu m pyrop h os p h a t e d ih yd ra t e d ep os it ion d is e a s e ca n a ls o
p re s e n t w it h a d va n ce d d ege n e ra t ive join t d is e a s e, in a form kn ow n
a s pseu do-osteoarthritis . As w it h p r im a ry o s t e o a rt h rit is , t h is fo rm
in volve s p a in , p rogre s s ive s t iffn e s s , a n d fu n ct ion a l lim it a t ion . Th e
p a t t e rn of join t in volve m e n t ca n be a t yp ica l for p rim a ry os t e oa r-
t h rit is , a s it u s u a lly a ffe ct s , in a d d it ion t o t h e t yp ica l join t s s u ch a s
t h e kn e e s , n on –w e igh t -be a rin g join t s s u ch a s t h e w ris t s , e lbow s ,
a n d s h o u ld e r s . A va lgu s k n e e d e fo rm it y is h igh ly s u gge s t ive of
CPPD. Th e d iffe re n t ia t io n fro m p r im a ry o s t e o a r t h r it is is o ft e n
d if cu lt .
A p r e s e n t a t io n clo s e ly r e s e m b lin g r h e u m a t o id a r t h r it is is
k n ow n a s pseu dorheu m atoid arthritis . It in vo lve s p a in , s t iffn e s s ,
sw e llin g, a n d m ild e leva t io n in in a m m a t o ry m a r k e rs in a s ym -
m e t r ic fa s h io n a n d u s u a lly in vo lvin g s m a ll jo in t s . Mild s yn ovia l
p ro life ra t io n a n d e ro s io n s co u ld m a k e t h e d iffe re n t ia t io n w it h
r h e u m a t o id a r t h r it is eve n m o re ch a lle n gin g. In e ld e r ly p a t ie n t s ,
p o lym ya lgia r h e u m a t ica w it h p e r ip h e ra l a r t h r it is ca n p re s e n t in a
s im ila r w a y.
Ad d it io n a l p re s e n t a t io n s o f CPPD in clu d e s eve re d e s t r u ct ive
Figure 20 .4 Synovial uid showing rectangular and a r t h rit id e s re s e m blin g n e u ro p a t h ic a r t h ro p a t h ie s a n d a x ia l s k e l-
irregularly sha ped calcium pyrophosphate dihydrate
e t o n d is e a s e w it h low b a ck o r n e ck p a in . Th e la t t e r co u ld b e a cu t e
crystals at a magni cation of 400×. (Courtesy of H. Ralph
Schumacher, Jr., M.D., and Janet Dinnella, University of a n d s e ve r e , e ve n m im ick in g m e n in git is o r in a m m a t o r y b a ck
Pennsylvania (http:/ / www.med.upenn.edu/ synovium)). p a in s .
196 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Studie s
Th e d ia gn os is of CPPD ca n be re in force d w h e n in t h e
righ t clin ica l con t e xt , a n a lys is of s yn ovia l u id d e m on -
s t ra t e s t h e p re s e n ce of s m a ll, w e a kly p os it ive bire frin -
ge n t crys t a ls on a p ola rizin g ligh t m icros cop ic e xa m i-
n a t ion (blu e w h e n t h e la rge r a xis of t h e crys t a l is
p a ra lle l t o t h e a xis of t h e p ola rize r; s e e Fig. 20.4 ). Th e s e
a re u s u a lly re ct a n gu la r, bu t cou ld a ls o be s q u a re d ,
oblon g, or h ave ot h e r irregu la r s h a p e s . An in a m m a -
t ory s yn ovia l u id a ls o s u p p ort s t h e role of t h e crys t a ls
in t h e in a m m a t ory a rt h rit is . An a d d it ion a l im p ort a n t
re a s on t o e xa m in e s yn ovia l u id , m a in ly in p a t ie n t s
w it h a cu t e a rt h rit is in w h ich p s e u d ogou t is in t h e d if-
fe re n t ia l, is t o ru le ou t s ep t ic a rt h rit is a n d gou t . Lim it a -
t ion s of s yn ovia l u id a n a lys is t o e s t a blis h a d ia gn os is
of p s e u d o go u t in clu d e t h e t e ch n ica l ch a lle n ge s t o
S
E
id e n t ify t h e crys t a ls (t h e s e a re oft e n s m a ll a n d ca n e a s -
C
T
ily be m is s e d ) a n d t h e fa ct t h a t ca lciu m pyrop h os p h a t e
I
O
N
crys t a ls ca n be p re s e n t in join t s n ot a ffe ct e d by CPPD.
4
An ot h e r u s e fu l a p p roa ch in t h e w ork-u p of CPPD
O
is t h rou gh ra d iologic s t u d ie s d e m on s t ra t in g t h e p re s -
s
t
e
Figure 20 .5 Anteroposterior ra diogra ph of the wrist, showing ca lci ca tion e n ce of ch on d roca lcin os is in s u s p iciou s join t s . Ch on -
o
a
of the ca rtila ginous a rticula r disc a nd a ne line of ca lci ca tion pa ra llel to d roca lcin os is a p p e a rs a s a n e, p u n ct a t e, d is cre t e, or
r
t
h
the radiodensity of the underlying bone, indica tive of a rticula r cartilage lin e a r ra d io -o p a cit y in ca rt ila gin o u s a re a s (Fig. 20.5 ).
r
i
calci cation (arrow ). (Reproduced with permission from Koopma n WJ,
t
Com m on ly in volve d a re t h e kn e e s , w ris t s , a n d h ip s a t
i
s
Morela nd LW, eds. Arthritis a nd Allied Conditions: A Textbook of
t h e leve ls of t h e s ym p h ys is p u bis . Ch on d roca lcin os is
a
Rheumatology. 15th ed. Phila delphia : Lippincott Willia ms & Wilkins; 2005.)
n
is a co m m o n n d in g in ra d io logic s t u d ie s in e ld e rly
d
M
in d ivid u a ls , s o it s n d in g s h o u ld b e in t e r p re t e d a s
e
s u p p o rt ive o f t h e d ia gn o s is o f CPPD in t h e righ t clin ica l co n t e x t . Dia gn o s t ic
t
a
b
crit e ria for CPPD h ave be e n p u blis h e d a n d a re p re s e n t e d in Ta ble 20.6 .
o
l
i
c
B
o
n
Table 20.6 Diagnost ic Crit eria and Cat egories for Calcium Pyrophosphat e Dihydrat e
e
Cryst al Deposit ion Disease (Revised Version)
e
n
o
B
c
Clinica l Co urse
i
l
o
b
a
Acu t e a re s o f go u t a n d CPPD ca n b e s e lf-lim it e d ; u s e o f a n t i-in a m m a t o ry
t
e
M
a ge n t s ca n h a s t e n re cove ry. A s m a ll n u m be r of p a t ie n t s w it h gou t ca n con t in u e
t o h ave s om e d is com fort d u rin g t h e in t e rcrit ica l p e riod s . Th e ch ron ic form of
d
n
gou t ca n be d e form in g a n d ca u s e s ign i ca n t d is a bilit y. Un like gou t , CPPD ca n
a
s
fre q u e n t ly p re s e n t a s a p o lya r t icu la r a r t h ro p a t h y re s e m blin g r h e u m a t o id
i
t
i
r
a rt h rit is a n d os t e oa rt h rit is re s p e ct ive ly; t h e s e form s of CPPD t e n d t o h a ve a
h
t
r
le s s e ros ive a n d d e s t ru ct ive cou rs e t h a n t h a t of rh e u m a t oid a rt h rit is . Ep id e -
a
o
m io logic evid e n ce lin k in g h yp e ru r ice m ia t o a n a d ve r s e ca rd iova s cu la r o u t -
e
t
s
com e s is in t rigu in g a n d m e rit s fu rt h e r eva lu a t ion .
O
4
N
O
I
T
C
E
ICD9
S
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
d u e t o o r asso ciat e d w it h cryst als
275.49 [712.1] d icalciu m p h o sp h at e
275.49 [712.2] p yro p h o sp h at e
275.49 [712.8] sp e ci e d NEC
274.00 g o u t y
274.01 acu t e
275.49 [712.3] Cho ndrocalcino sis (art icu lar) (cryst al de p o sit io n ) (d ih yd rat e )
due to
275.49 [712.2] calciu m p yro p h o sp h at e
275.49 [712.1] d icalciu m p h o sp h at e cryst als
275.49 [712.2] p yro p h o sp h at e cryst als
274.9 Go ut , g o u t y
274.00 art h rit is
274.01 acu t e
274.00 art h ro p at h y
274.01 acu t e
274.02 ch ro n ic (w it h o u t m e n t io n o f t o p h u s (t o p h i))
274.03 w it h t o p h u s (t o p h i)
274.03 t o p h i
274.81 e ar
274.82 sp e ci e d sit e NEC
198 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Re fe re nce s
1. La w re n ce RC, Fe ls on DT, He lm ick CG, e t a l. Es t im a t e s of t h e p reva le n ce of a rt h rit is a n d ot h e r rh e u m a t ic
con d it ion s in t h e Un it e d St a t e s . Pa rt II. A rthritis Rheum 2008 ;58 26 –5835 .
2. Ca m p ion EW, Glyn n RJ, De La bry LO . As ym p t om a t ic h yp e ru rice m ia . Ris ks a n d con s e q u e n ce s in t h e Nor-
m a t ive Agin g St u d y. A m J Med 1987 ;82 :421 –426 .
3. Ma rt in on F. Me ch a n is m s of u ric a cid crys t a l-m e d ia t e d a u t oin a m m a t ion . Im m unol Rev 233 :218 –232 .
4. Wa lla ce SL, Robin s on H , Ma s i AT, e t a l. Pre lim in a ry crit e ria for t h e cla s s i ca t ion of t h e a cu t e a rt h rit is of
p rim a ry gou t . A rthritis Rheum 1977 ;20 :895 –900.
5. Zh a n g W, Doh e rt y M , Pa s cu a l E, e t a l. EULAR evid e n ce ba s e d re com m e n d a t ion s for go u t . Pa rt I: Dia gn os is .
Rep ort of a t a s k force of t h e St a n d in g Com m it t e e for In t e rn a t ion a l Clin ica l St u d ie s In clu d in g Th e ra p e u -
t ics (ESCISIT). A nn Rheum Dis 2006 ;65 :1301 –1311 .
6. Ja n s s e n s HJ, Fra n s e n J, va n d e Lis d on k EH , e t a l. A d ia gn os t ic ru le for a cu t e go u t y a rt h rit is in p rim a ry ca re
w it h ou t join t u id a n a lys is . A rch Intern Med 2010 ;170 :1120 –1126.
7. Te rke lt a u b RA, Fu rs t DE, Be n n e t t K, e t a l. High ve rs u s low d os in g of ora l colch icin e for e a rly a cu t e gou t
a re : Tw e n t y-fou r-h ou r ou t com e of t h e rs t m u lt ice n t e r, ra n d o m ize d , d ou ble -blin d , p la ce bo-con t rolle d ,
p a ra lle l-grou p , d os e -com p a ris on colch icin e s t u d y. A rthritis Rheum 2010 ;62 :1060 –1068.
8. Be cke r MA, Sch u m a ch e r HR, Jr., Wo rt m a n n RL, e t a l. Fe bu xo s t a t com p a re d w it h a llop u rin ol in p a t ie n t s
w it h h yp e ru rice m ia a n d gou t . N Engl J Med 2005 ;353 :2450 –2461.
9. Fe ig DI, Ka n g DH, Joh n s on RJ. Uric a cid a n d ca rd iova s cu la r ris k . N Engl J Med 2008 ;359 :1811 –1821.
S
E
C
T
I
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N
4
O
s
t
e
o
a
r
t
h
r
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t
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a
n
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M
e
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B
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e
CHAPTER
21 Osteopenic Bone
Disea ses a nd
Osteonecrosis
Kenneth G. Saag, Gregory A . Clines, and Sarah L. Morgan
e
n
A 75-year-old m ale seen for com pression fractures. He relates a strong
o
B
fam ily history of m etabolic bone disease or fractures; his m other had
c
i
l
o
severe osteoporosis, tw o sisters have osteoporosis, and his father had
b
a
t
com pression fractures, w hich com plicated his em physem a. He presents
e
M
w ith records docum enting com pressions fractures at thoracic vertebra
d
n
11 (T11), T12 and lum bar vertebra 4 (L4) and L5. He has undergone a
a
s
i
kyphoplasty at L5. All com pression fractures occurred w ithout know n
t
i
r
h
traum a. He w as initially treated w ith injectable calcitonin and has
t
r
a
o
been on alendronate for approxim ately 10 years. He is referred because of concern for future fractures and
e
t
s
w orsening restrictive long disease in the setting of glucocorticoid-dependent obstructive lung disease.
O
He in dicat e s t hat he has a hist ory of in f e rt ilit y and p ro ble m s w it h im po t e nce . He has a lon g h ist o ry o f
4
N
in hale d glu co cort ico id use . Th e re is no hist ory o f an abo lic st e roid use an d n o hist ory of t h yro id d ise ase .
O
I
T
He g re w u p d rin k in g m ilk , b u t cu rre n t ly d rin k s n o m ilk an d e at s 2 o z o f ch e e se p e r w e e k . He co n -
C
E
S
su m e s n o calciu m -f o rt i e d f o o d s. He g e n e rally d o e s n o t g e t an y sig n i can t su n e xp o su re . He co n su m e s
15 g lasse s o f w in e p e r w e e k an d 2 o z o f h ard liq u o r p e r w e e k .
His p ast m e d ical h ist o ry is re m ark ab le f o r at h e ro scle ro t ic h e art d ise ase , e m p h yse m a, h yp e rlip id e m ia,
an d o st e o art h rit is. His cu rre n t m e d icat io n s in clu d e ale n d ro n at e 70 m g /w e e k , calciu m carb o n at e p lu s
vit am in D t w ice a d ay, ib u p ro f e n t w o t ab le t s d aily f o r b ack p ain , m o n t e lu k ast 10 m g o rally d aily, ip rat -
ro p iu m b ro m id e an d alb u t e ro l su lf at e in h ale r t w o p u ff s f o u r t im e s a d ay, in h ale d .
On p h ysical e xam in at io n , h e is 68 in . t all (d rive r’s lice n se h e ig h t is 74 in .), h is w e ig h t is 238 lb , vit al
sig n s are n o rm al. M P’s p o st u re is n o t ab le , h e ad b o w e d f o rw ard w it h a slig h t ly p ro t u b e ran t ab d o m e n .
He is w e arin g an e xt e n sio n b race . Eye s, n o b lu e scle ra. M o u t h , n o e xp o se d b o n e . Th e t h yro id is p alp ab le
w it h o u t m asse s.
Lo w e r t h o racic k yp h o sis, n o p o in t p ain t o p alp at io n . Ch e st , cle ar an d card iac e xam in at io n m u rm u r.
A b d o m e n , n o o rg an o m e g aly o r p ain . Ne u ro lo g ic, n o n f o cal.
Laboratory data. Chem istry pro le norm al, calcium = 8.7, alkaline phosphatase = 99, PTH = 67 (nl 12 to 90).
CBC, IFE, PSA all norm al. Anti tissue transglutam inase (TTG) 5. 25-OH vitam in D total = 43. Calcium /creatinine
ratio on a spot urine = 0.10.
Th e p at ie n t is st art e d o n t e rip arat id e as an an ab o lic ag e n t f o r h is b o n e . Th e re w as n o h ist o ry o f
b o n e t u m o rs, rad iat io n t h e rap y, an d im p lan t ab le rad iat io n t o p o se an ab so lu t e co n t rain d icat io n . Th e
b ase lin e alk alin e p h o sp h at e s an d b ase lin e b o n e -sp e ci c alk alin e p h o sp h at ase w e re n o rm al.
199
200 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
CATEGORY DEFINITION
No rm a l BMD b e t t e r t h a n 1 SD b e lo w t h e m e a n va lu e
o f p e a k b o n e m a ss in yo u n g w h it e w o m e n
Ost e o p e n ia (lo w b o n e m a ss) BMD b e t w e e n 1.0 a n d 2.5 SD b e lo w t h e
m e a n p e a k va lu e
Ost e o p o ro sis BMD m o re t h a n 2.5 SD b e lo w t h e p e a k va lu e
Se ve re o st e o p o ro sis BMD crit e ria fo r o st e o p o ro sis a n d fra ct u re
Intro ductio n
S
E
C
Os te op oros is is a syst em ic s kelet a l d ise a s e ch a ra ct erized by low bon e m a ss a n d
T
I
m icroa rch it e ct u ra l d e t e riora t ion of bon e t is s u e w it h a con s e q u e n t in cre a s e in
O
N
bon e fra gilit y a n d s u s cep t ibility t o fra ctu re. Th e World Hea lt h Orga n iza tion (W HO)
4
d e n it ion s of ost eop oros is a re ba s ed on ep id em iologic d a ta t h a t rela t e fra ct u re
O
s
in cid en ce to bon e m in era l d en s it y (BMD) in Ca u ca s ia n w om en (Ta ble 21.1 ).
t
e
By a ge 60 t o 70 ye a rs , o n e of t h re e n on -His p a n ic Ca u ca s ia n w om e n w ill
o
a
h ave os t e op oros is a n d t h e re m a in d e r, os t e op e n ia (a s t a t e of low bon e m a s s in
r
t
h
be t w e e n n orm a l a n d os t e op orot ic BMD); by a ge 80 ye a rs , 70% w ill h ave os t e -
r
i
t
i
op oros is . Figu re 21.1 s h ow s t h e p reva le n ce of os t e op oros is a n d os t e op e n ia in
s
a
Am e rica n w om e n bot h n ow a n d in t o t h e fu t u re.
n
d
Th e e s t im a t e d n u m be r of fra ct u re s a m on g Nort h Am e rica n w om e n w a s
M
200,000 in 1990 a n d is e s t im a t e d t o in cre a s e t o n e a rly 500,000 in 2025. Th e
e
t
a
p rop ort ion of fra ct u re s a t t ribu t a ble t o os t e op oros is is le s s for n on w h it e s t h a n
b
o
w h it e s a n d le s s for m e n t h a n w om e n . Th e in cid e n ce ra t e for h ip fra ct u re s is
l
i
c
a p p roxim a t e ly 2 p e r 1,000 p a t ie n t -ye a rs a t a ge 65 t o 69 in Ca u ca s ia n a n d n on -
B
o
Ca u ca s ia n w om e n , a n d in cre a s e s t o a bou t 26 p e r 1,000 p a t ie n t -ye a rs a t a ge 80
n
e
t o 84. Th e in cid e n ce a n d p reva le n ce of ve rt e bra l fra ct u re s is low p rior t o a ge
50 yea rs a n d ris e s a lm os t e xp on e n t ia lly t h e re a ft e r (Ta ble 21.2 ). Am on g Am e rica n
w om e n , t h e in cid e n ce of w ris t fra ct u re s in cre a s e s ra p id ly a t t h e t im e of m e n o-
p a u s e a n d p la t e a u s a t a bou t 700 p e r 100,000 p e rs on -ye a rs a ft e r a ge 60.
Th e life t im e ris k of a n y fra ct u re in t h e h ip , s p in e, or d is t a l fore a rm is a bou t
50% in Ca u ca s ia n w om e n of a ge 50 a n d 20% in Ca u ca s ia n m e n of s im ila r a ge.
Th e re a re s p e cia l p op u la t ion s , s u ch a s a p op u la t ion of in d ivid u a ls w it h h u m a n
10
Figure 21.1 Preva lence of low bone mass and osteoporosis in women a ged 50 yea rs a nd older.
(Na tiona l Osteoporosis Founda tion, a va ila ble a t: http:/ / www.nof.org/ a dvoca cy/ preva lence.)
Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 201
CLINICAL POINTS Table 21.2 Est imat ed Lifet ime Fract ure Risk in 50-Year-Old
Whit e Women and Men a
• Lifetime risk of osteoporotic
fracture in Caucasian males
is 20% . WOMEN %, (95% MEN %, (95%
SITE CONFIDENCE INTERVAL ) CONFIDENCE INTERVALb )
b
• Ob t a in in fo rm a t io n o f
h e ig h t lo ss o ve r t im e fro m Pro xim a l fe m u r 17.5 (16.8, 18.2) 6.0 (5.6, 6.5)
a d rive r’s lice n se . Ve rt e b ra l fra ct u re 15.6 (14.8, 16.3) 5.0 (4.6, 5.4)
• Un u su a l z-sco re s o n DEXA Dist a l fo re a rm fra ct u re 16.0 (15.2, 16.7) 2.5 (2.2, 3.1)
sca n ca n re p re se n t b o n e
m in e ra l d iso rd e r o t h e r An y fra ct u re 39.7 (38.7, 40.6) 13.1 (12.4, 13.7)
t h a n o st e o p o ro sis.
a
Ag e 50 ye a rs w a s ch o se n b e ca u se t h is is a b o u t t h e a ve ra g e o f m e n o p a u se in w o m e n .
• Ost e o n e cro sis o f t h e ja w is b
Usin g in cid e n ce o f clin ica lly d ia g n o se d fra ct u re s o n ly.
a d e va st a t in g co m p lica t io n Fro m Me lt o n LJ, Ch risch ille s EA, Co o p e r C, e t a l. Ho w m a n y w o m e n h a ve o st e o p o ro sis? J Bo n e M in e r
from use of bisphosphonates Re s 1992 ;7 :1005 –1010 , w it h p e rm issio n .
a n d is a sso cia t e d w it h
d e n t a l p ro ce d u re s.
e
n
• Diffu se b o n e p a in ca n
o
im m u n o d e cie n cy vir u s (HIV) w h e re a h igh p reva le n ce a n d p rogre s s io n o f
B
b e a m a n ife st a t io n o f
o s t e op o ros is o r os t e o p e n ia h a s b e e n d ocu m e n t e d . It is a n t icip a t e d t h a t t h e
c
o st e o m a la cia .
i
l
o
p reva le n ce of os t e op oros is a n d like ly fra ct u re s w ill grow in t h is p op u la t ion .
b
• Ost e o n e cro sis ca n b e
a
a sso cia t e d w it h a lco h o l Osteoporosis a n d con seq u en t fra ctu res a re m a jor p u blic h ea lth con cern s in th e
t
e
Un ited Sta tes. Th e econ om ic costs of osteop orotic fra ctu res a re la rge a n d som ew h a t
M
a b u se , p ro lo n g e d u se
o f co rt ico st e ro id s, a n d d if cu lt to a ssess beca u se th e tota l in clu des expen ses for su rgery a n d h osp ita liza -
d
n
m a n y m e d ica l co n d it io n s tion , reh a bilita tion , lon g-term ca re costs, loss of p rod u ctivity, a n d m ed ica tion s.
a
in clu d in g sickle ce ll d ise a se
s
Oth er bu rd en s a ssocia ted w ith fra ctu re in clu d e p oor resu lta n t fu n ction a l sta tu s,
i
t
a n d syst e m ic lu p u s e ry-
i
r
p a in , a d im in ish ed qu a lity of life, loss of in d ep en d en ce, fea r, a n d d ep ression .
h
t h e m a t o sis (SLE).
t
r
Hip fra ct u re s re s u lt in m ore t h a n 7 m illion d ays of re s t rict e d a ct ivit y a n d
a
o
6,000 a d m is s ion s t o n u rs in g h om e s a n n u a lly in t h e Un it e d St a t e s ; n e a rly t h re e
e
t
s
q u a rt e rs of a ll n u rs in g h om e a d m is s ion s a re re la t e d t o os t e op oros is . For h ip
O
fra ct u re s , a bo u t h a lf o f t h e h e a lt h ca re co s t s re e ct n u rs in g h om e e xp e n s e s .
4
N
Th e re is a n a p p roxim a t e ly 20% m ort a lit y w it h in 1 ye a r of h ip fra ct u re, a n d 50%
O
of s u rvivors n eve r fu lly re cove r. Th e m ort a lit y a s s ocia t e d w it h ve rt e bra l fra c-
I
T
C
t u re s is a ls o gre a t e r t h a n e xp e ct e d in t h e ge n e ra l p op u la t ion , w h e re a s t h e m or-
E
S
t a lit y of p a t ie n t s w it h w ris t fra ct u re s is s im ila r.
Figu re 21.2 sh ow s t h e lifet im e a ccru a l a n d los s of BMD in m e n a n d w om en .
Pea k BMD is t h e m a xim u m p os s ible w ith n orm a l grow t h a n d rep res en ts a gen et -
ica lly a n d e n viron m e n t a lly d e t e rm in e d a p ex from w h ich fu t u re los s e s occu r.
Mos t s ke let a l d e n s it y (bot h tra becu la r a n d cort ica l) is a ccu m u la t ed by a ge 18. In
1,600 cort ica l bon e, a s low p h a s e of loss begin s a t a ge
40, ra n gin g from 0.3 t o 0.5% p e r ye a r in m e n
a n d w om en . At m e n op a u s e in w om en n ot t a k-
in g h orm on e rep la cem en t t h e ra py, los s es aver-
y
1,200
t
si
a ge a bou t 1% p er yea r, bu t m ay a p p roa ch 3% t o
n
e
D
5% p e r ye a r. Aft e r t h is a cce le ra t e d los s for
l
a
800 a bo u t 8 t o 10 ye a rs , t h e ra t e d e cre a s e s in
r
e
n
a n ot h e r s low p h a s e. Th e cu m u la t ive life t im e
i
M
Men Women
e
loss es of bon e m ay be a s m u ch a s 30% t o 40%
n
o
400 of p ea k BMD in w om e n a n d 20% t o 30% in m en .
B
0
0 10 20 30 40 50 60 70 80 Clinica l Pre se nta tio n
Years of Age
Th e clin ica l eva lu a tion of osteop orosis sh ou ld
Figure 21.2 Age-rela ted bone minera l density for men and women. From Christenson id en tify lifestyle risk fa ctors a n d p ertin en t p h ys-
RH. Biochemica l ma rkers of bone meta bolism: An overview. Clin Biochem 1997;30:573–
593, with permission. (Reprinted in Sa a g KG, Morga n SL, Ca o X, et al. Bone in hea lth
ica l n d in gs, a n d a ss es s s econ d a ry ca u se s of
and disea se. In: Koopma n WJ, ed. Arthritis a nd Allied Condition: A Textbook of osteop en ia . Table 21.3 p rovid es con d ition s a sso-
Rheuma tology. 15th ed. Phila delphia : Lippincott Willia ms & Wilkins; 2005:2449–2541.) cia ted w ith osteop en ia or osteop orosis.
202 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Table 21.3 Diseases and Drug Therapies Associat ed wit h Ost eopenia and Fract ure
Un iq u e t o w o m e n Exce ssive p ro t e in in t a ke
Na t u ra l m e n o p a u se Im m o b iliza t io n o r m icro g ra vit y
Pre g n a n cy Lo w ca lciu m o r vit a m in D in t a ke
Hyp o g o n a d ism Se d e n t a ry life st yle
Ag o n ist fo r g o n a d o t ro p in -re le a sin g h o rm o n e o r Sm o kin g
De p o - Pro ve ra
Ma lig n a n cy
Go n a d a l d ysg e n e sis (e .g ., Tu rn e r’s syn d ro m e )
En d o m e t rio sis Lym p h o p ro life ra t ive a n d m ye lo p ro life ra t ive
d ise a se s (lym p h o m a a n d le u ke m ia )
Un iq u e t o m e n
Mu lt ip le m ye lo m a
Hyp o g o n a d ism
Syst e m ic m a st o cyt o sis
Co n st it u t io n a l d e la y o f p u b e rt y
Tu m o r se cre t io n o f p a ra t h yro id h o rm o n e –re la t e d
He m o ch ro m a t o sis (d u e t o e it h e r in lt ra t io n
p e p t id e
o f t e st e s (h yp e rg o n a d o t ro p ic) o r p it u it a ry
(h yp o g o n a d o t ro p ic) Nu t rit io n a l d iso rd e rs
Kallman’s syndrome (isolated gonadotropin
de ciency) Ea t in g d iso rd e rs, su ch a s a n o re xia n e rvo sa
S
Klin e fe lt e r’s syn d ro m e (g e n o t yp e XXY) Ost e o m a la cia
E
Ma la b so rp t io n syn d ro m e s
C
Orch it is, vira l
T
Pa re n t e ra l n u t rit io n
I
O
M e n an d w o m e n Pe rn icio u s a n e m ia
N
Ag e -re la t e d b o n e lo ss Ba ria t ric su rg e ry (e sp e cia lly Ro u x-e n -Y b yp a ss)
4
Co n n e ct ive t issu e d ise a se s
O
An kylo sin g sp o n d ylit is Ot h e r d ise a se s
s
t
Ch ro n ic o b st ru ct ive p u lm o n a ry d ise a se (o ft e n
e
Ost e o g e n e sis im p e rfe ct a
o
Rh e u m a t o id a rt h rit is se co n d a ry t o g lu co co rt ico id u sa g e )
a
Ch ro n ic re n a l fa ilu re
r
Sp in a l co rd in ju ry
t
h
Co n g e n it a l p o rp h yria
r
i
t
En d o crin e ca u se s He m o ch ro m a t o sis
i
s
Acro m e g a ly He m o p h ilia
a
n
Ad re n a l t ro p h y a n d Ad d iso n ’s d ise a se Ho m o cyst in u ria
d
Cu sh in g ’s syn d ro m e Hyp o p h o sp h a t a sia
M
Dia b e t e s m e llit u s t yp e 1 Th a la sse m ia
e
t
Glu co co rticoid e xce ss (e n do g e n o us a n d e xo g e n o us)
a
M e d icat io n s
b
Go n a d o t ro p h ce ll a d e n o m a
o
Alu m in u m
l
Hyp e rp a ra t h yro id ism (p rim a ry a n d se co n d a ry)
i
c
Hyp e rp ro la ct in e m ia (a s a ca u se o f h yp o g o n a d ism ) An t ie p ile p t ics (so m e )
B
Ch e m o t h e ra p e u t ic a g e n t s t h a t ca u se ch e m ica l
o
Hyp e rt h yro id ism
n
ca st ra t io n
e
Hyp e rca lcit o n in e m ia ?
Hyp o g o n a d ism (p rim a ry, se co n d a ry, o r su rg ica l) Cyclo sp o rin e A a n d t a cro lim u s
Pa n h yp o p it u it a rism Cyt o t o xic d ru g s
Th yro t o xico sis Glu co co rt ico id s a n d a d re n o co rt ico t ro p in
He p a rin (p e rh a p s le ss se ve re w it h lo w -m o le cu la r-
Ga st ro in t e st in a l d ise a se s w e ig h t co m p o u n d s)
Ch o le st a t ic live r d ise a se (e sp e cia lly p rim a ry b ilia ry Lit h iu m
cirrh o sis) Me t h o t re xa t e
Ga st re ct o m y Ta m o xife n (p re m e n o p a u sa l u se )
In a m m a t o ry b o w e l d ise a se (e sp e cia lly re g io n a l Th yro id h o rm o n e (in e xce ss)
e n t e rit is) Se le ct ive se ro t o n in re u p t a ke in h ib it o rs
Po st g a st re ct o m y Pro t o n p u m p in h ib it o rs
Th io g lit a zo n e s
Life st yle /g e n e t ic fa ct o rs
Exce ssive a lco h o l
Exce ssive ca ffe in e ?
Exce ssive e xe rcise (im p a irm e n t o f h yp o t h a la m ic–
p it u it a ry a xis)
e
• Lo ss in h e ig h t . e rin g h e igh t los s . Los s of 2 in . or m ore is a fa irly s e n s it ive in d ica t or of ve rt e bra l
n
o
com p re s s ion . Th e s p in e s h ou ld be e xa m in e d for con form a t ion a n d s p in a l a n d
B
• Hist o ry o f fra ct u re s o f a ll
c
ca u se s. p a ra s p in ou s t e n d e rn e s s . If kyp h os is is p re s e n t , t h e p os s ibilit y of p u lm on a ry
i
l
o
co m p ro m is e s h o u ld b e co n s id e re d . A “b u ffa lo h u m p ,” e a s y b ru is a b ilit y, a n d
b
• Life t im e a n d cu rre n t
a
s t r ia e s u gge s t Cu s h in g’s s yn d ro m e . Blu e s cle ra e m a y in d ica t e o s t e oge n e s is
t
co n su m p t io n o f ca lciu m ,
e
M
vit a m in D, so d iu m , a n d im p e rfe ct a . Th e n u m be r of m is s in g t e e t h h a s be e n corre la t e d t o t h e s eve rit y of
d
ca ffe in e . los s in BMD. A join t a s s e s s m e n t m ay s u gge s t rh e u m a t ologic ca u s e s of low BMD.
n
Th e n e u rologic e xa m in a t ion is im p ort a n t be ca u s e m u s cu la r w e a kn e s s p re d is -
a
• Me d ica t io n u se .
s
p os e s t o fa lls a n d a n u n d e rlyin g n e u rologic p roble m m ay be d is cove re d .
i
t
i
r
h
t
r
a
Studie s
o
e
t
s
O
LABORATORY EVALUATION
4
Ro utine Labo rato ry Te sting
N
O
Th e la b ora t ory a s s e s s m e n t s e e k s p os s ible s e con d a ry ca u s e s o f los s o f BMD.
I
T
Ta ble 21.4 p rovid e s t e s t s t h a t m a y be a p p rop ria t e. Ma n y a re n ot cos t -e ffe ct ive
C
E
if obt a in e d for eve ry p a t ie n t . In t a ct PTH con ce n t ra t ion , for e xa m p le, s h ou ld be
S
Table 21.4 Laborat ory Evaluat ion of Decreased Bone Mass
FORMATION RESORPTION
Fro m o st e o b last s, in se ru m Fro m o st e o clast s
Bo n e a lka lin e p h o sp h a t a se Ta rt ra t e -re sist a n t a cid p h o sp h a t a se
Ost e o ca lcin
Fro m b o n e m at rix, in se ru m
Pro co lla g e n I C-t e rm in a l p ro p e p t id e N-te rm in al t elopep tide o f type I collagen
Pro co lla g e n I N-t e rm in a l p ro p e p t id e C-termina l te lop e pt id e o f t yp e I collage n
Fro m b o n e m at rix, in u rin e
Pyrid in o lin e a n d d e o xyp yrid in o lin e
cro ss-lin ks
N-terminal telopeptide of type I collagen
Hyd ro xyp ro lin e fro m co lla g e n
d e g ra d a t io n
Fro m Ro sa lki SB. Bio ch e m ica l m a rke rs o f b o n e t u rn o ve r. In t J Clin Pract 1998 ;52 :256 , w it h p e rm issio n .
S
E
C
T
I
O
N
m e a s u re d if t h e ca lciu m con ce n t ra t ion is e leva t e d a n d t h e p h os p h oru s con ce n -
4
O
t ra t ion is low or if clin ica l s u s p icion is h igh for h yp e rp a ra t h yroid is m .
s
t
e
o
Spe ci c Bo ne Turno ve r Marke rs
a
r
Bio ch e m ica l m a r ke r s o f bo n e t u r n ove r a re s o m e t im e s u s e d in t h e m a n a ge -
t
h
r
m e n t of o s t e o p o ro s is . W h ile bo n e fo r m a t io n a n d re s or p t io n a re u s u a lly “co u -
i
t
i
s
p le d ,” n e t im b a la n ce s ca n be eva lu a t e d w it h t h e s e a s s a ys . Ta ble 21.5 p rovid e s
a
n
b o n e t u r n ove r m a r k e r s t h a t ca n be cla s s i e d a s in d ice s o f b o n e fo r m a t io n o r
d
r e s o r p t io n . “Bo n e b a la n ce ” is t h e n e t d iffe r e n ce b e t w e e n fo r m a t io n a n d
M
e
re s o r p t io n .
t
a
b
o
l
i
Ima g ing
c
B
o
n
Du a l-e n e rgy x -ra y a b s o r p t io m e t ry (DXA) is cu r re n t ly t h e “go ld s t a n d a rd ” fo r
e
p a t ie n t ca re a n d clin ica l in ve s t iga t io n fo r o s t e o p o ro s is . On DXA, b o n e m a s s
is r e p o r t e d a s a n a b s o lu t e va lu e in g/ cm 2 , a co m p a r is o n t o a ge - a n d s e x -
m a t ch e d re fe re n ce ra n ge (t h e Z-s co re ), a n d a co m p a r is o n t o m e a n b o n e m a s s
o f yo u n g a d u lt n o r m a l in d ivid u a ls (t h e T-s co re o r yo u n g-a d u lt Z-s co re ; s e e
Fig. 21.3 ). T-s co re s a re u s e d t o p re d ict fra ct u re r is k a n d cla s s ify d is e a s e s t a -
t u s . A ch a n ge o f o n e s t a n d a rd d evia t io n in t h e T- o r Z-s co re co r re la t e s t o a
ch a n ge o f a p p r o x im a t e ly 0.06 g/ cm 2 , o r a b o u t 10% o f BMD. Alt h o u gh t h e
Z-s co re is o f le s s clin ica l va lu e t h a n t h e T-s co re , Z-s co re s s ign i ca n t ly d evia t -
in g fro m n o r m a l m a y in d ica t e a lt e r n a t ive ca u s e s o f m e t a b o lic b o n e d is e a s e .
Du a l-e n e rgy x -ra y a b s o r p t io m e t ry s ca n s a ls o p ro d u ce a d e n s it y-b a s e d im a ge
u s e fu l in in t e r p re t in g s ca n q u a lit y (s e e Fig. 21.3 a n d b e low ). Th e s e re a d in gs
a r e co m p a r e d t o t h e Na t io n a l He a lt h a n d Nu t r it io n Ex a m in a t io n Su r ve y
(NHANES) III d a t a b a s e .
Du a l-e n e rgy x-ray a bs orp t iom e t ry m e a s u re s BMD a t ce n t ra l a n d p e rip h e ra l
s it e s . Th e ch oice of s it e (s ) s ca n n e d s h ou ld d e p e n d on t h e a n t icip a t e d ra t e s of
ch a n ge in bon e m a s s w it h in t h e s e s ke le t a l loca t ion s a n d p re cis ion of t h e t e s t -
in g d evice a t t h e s e s it e s . Th e ce n t ra l DXA s it e s of t h e h ip a n d s p in e, follow e d
by p e rip h e ra l s it e s o f t h e w ris t a n d h e e l, a re t h e m os t d e s ire d im a gin g loca -
t ion s . Ce n t ra l DXA of t h e s p in e a n d h ip h a s e xce lle n t p re cis ion a n d good a ccu -
ra cy. Ce n t ra l DXA is ge n e ra lly p re fe rre d be ca u s e t h e q u a n t it y of ca n ce llou s
bon e of ce n t ra l s it e s is h igh ly in d ica t ive of t h e os t e op oros is bu rd e n a n d fra c-
t u re ris k. In os t e op oros is , t h e e a rlie s t bon e los s begin s in ca n ce llou s bon e. A
h igh e r p rop ort ion of e a rly p os t m e n op a u s a l w om e n h ave low e r ca n ce llou s BMD
Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 205
e
B
n
o
C
B
c
Figure 21.3 Dua l-energy x-ra y a bsorptiometry (DXA) printout. For a 70-yea r-old white woma n. A: DXA of this pa tient’s lumba r spine
i
l
o
showing ima ging windows for vertebra e L1 to L4. Estima ted vertebra l a rea s, bone minera l content (BMC), a nd bone minera l density
b
(BMD) a re shown (middle ). Bone minera l density is plotted a ga inst a lumba r spine reference da ta ba se showing the pa tient’s current
a
t
e
va lue a s well a s previous rea dings indica ted by crosses (right, top ). The da rk (top ) ba r of the gra ph indica ted 2 sta nda rd devia tions
M
a bove norma l a nd the lighter (bottom ) ba r 2 sta nda rd devia tions below pea k bone ma ss. T-scores (pea k bone ma ss ma tched) show
d
tha t the pa tient is well below the World Hea lth Orga niza tion’s de nition of osteoporosis (T-score −2.5) a t ea ch vertebra l level a nd for
n
a
the lumba r spine overa ll. The Z-score is a n a ge-ma tched mea surement. B: Simila r pa ra meters a re shown for the left hip, a nd ba sed
s
on T-scores , there is osteoporosis a t both the femora l neck a nd the tota l hip. C: At both the hip a nd lumba r spine, there ha s been
i
t
i
r
signi ca nt 3-yea r improvement in BMD. The seria l plot (left ) a nd ta ble show a nea rly 12% increa se a t the left hip. The a sterisk signi es
h
t
a signi ca nt increa se of decline between two va lues. An 18.4% increa se in BMD wa s a lso seen a t the lumba r spine (da ta not shown).
r
a
(From Sa a g KG, Morga n SL, Ca o X, et a l. Bone in hea lth a nd disea se. In: Koopma n WJ, ed. Arthritis a nd Allied Condition: A Textbook of
o
e
Rheuma tology. 15th ed. Phila delphia : Lippincott Willia ms & Wilkins; 2005:2449–2541.)
t
s
O
4
N
O
t h a n cort ica l BMD. Ap p roxim a t e ly a t h ird of t h e s p on gy t ra be cu la r bon e of t h e
I
T
h ip a n d s p in e re m od e ls e a ch ye a r a s op p os e d t o on ly 3% t u rn ove r of com p a ct
C
E
co rt ica l b o n e co m p ris in g a gre a t e r p ro p o rt io n o f p e rip h e ra l s k e le t o n . At t h e
S
s p in e, DXA re p ort s m e a s u re m e n t s of a n in d ivid u a l ve rt e bra a s w e ll a s ave ra ge
BMD of t h e L1 t o L4 (s e e Fig. 21.3 ). At t h e h ip , fe m ora l n e ck, a n d t h e t ot a l h ip
a re t h e t h re e m e a s u re m e n t s it e s of gre a t e s t clin ica l in t e re s t . Ce n t ra l m e a s u re -
m e n t s a re u s e d t o d ia gn os e os t e op oros is , a s s e s s fra ct u re ris k, a n d follow u p t h e
re s p on s e t o a n t ios t e op orot ic t h e ra p ie s .
Pe rip h e ra l DXA of t h e fore a rm is m od e ra t e ly corre la t e d w it h ce n t ra l DXA
re s u lt s a n d ca n , t h u s , be u s e d a s a n a lt e rn a t ive t o p re d ict fra ct u re ris k. He e l
DXA corre la t e s w e ll w it h ot h e r h e e l im a gin g t e ch n ologie s a n d a d e q u a t e ly d is -
cr im in a t e s o s t e o p o ro t ic fro m n o r m a l yo u n g s u b je ct s . How eve r, t h e m u ch
s low e r ra t e of bon e re m od e lin g a t s it e s s u ch a s t h e h e e l lim it s t h is t e ch n ology
for m on it orin g t h e re s p on s e t o t h e ra p y. Th e e n h a n ce d p ort a bilit y of d e d ica t e d
p e rip h e ra l bon e m a s s m e a s u re m e n t in s t ru m e n t s a n d t h e ir low e r cos t re n d e rs
t h e m in cre a s in gly a t t ra ct ive for com m u n it y os t e op oros is s cre e n in g.
Ve rt e bra l fra ct u re a n a lys is (VFA) is a p oin t of s e rvice e xa m in a t ion t h a t ca n
be p e rform e d on m a n y DXA s ca n n e rs . Ve rt e bra l fra ct u re a n a lys is con ce n t ra t e s
on t h e m orp h om e t ry of in d ivid u a l ve rt e bra l bod ie s for t h e p u rp os e of id e n t ify-
in g ve rt e bra l com p re s s ion fra ct u re s .
Bon e m in e ra l d e n s it y m e a s u re d by DXA is a good p re d ict or of t h e ris k of
h ip a n d s p in a l fra ct u re s . Sp in a l fra ct u re is in ve rs e ly p rop ort ion a l t o bon e m in -
e ra l con t e n t . For e a ch d e clin e of a bou t 1 s t a n d a rd d evia t ion of bon e m a s s , t h e re
is a 1.3- t o 2.5-fold in cre a s e in fra ct u re ris k of a n y s it e. Alt h ou gh fra ct u re ris k
a t a n y s it e ca n be a ccu ra t e ly a s s e s s e d u s in g a va rie t y of n on in va s ive bon e m a s s
m e a s u re m e n t s d on e a t a n y s it e, BMD a t t h e fe m ora l n e ck is be t t e r t h a n BMD a t
206 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
1. Age (between 40-90 years) or Date of birth 11. Alcohol 3 more units per day No Yes
Age: Date of birth: 12. Femoral neck BMD
Y: M: D: Select
2. Sex Male Female Clear Calculate
S
3. Weight (kg)
E
C
4. Height (cm)
T
I
5. Previous fracture No Yes
O
N
6. Parent fractured hip No Yes
4
7. Current smoking No Yes
O
8. Glucocorticoids No Yes
s
t
9. Rheumatoid arthritis No Yes
e
o
a
r
t
h
r
i
t
i
s
Figure 21.4 The FRAX WHO Fra cture Risk Assessment Tool. Ca lcula tes the 10-yea r proba bility of hip a nd ma jor osteoporotic* fra cture in previously
a
untrea ted pa tients. Ma jor osteoporotic fra cture is de ned a s vertebra l, hip, forea rm, or humerus fra cture. (Na tiona l Osteoporosis Founda tion. Clinicia n’s
n
Guide to Prevention a nd Trea tment of Osteoporosis . Wa shington, DC: Na tiona l Osteoporosis Founda tion; 2008. FRAX® WHO Fra cture Risk Assessment
d
M
Tool. Ava ila ble a t: www.shef.a c.uk/ FRAX/ tool.jsp.)
e
t
a
b
o
l
i
c
t h e s p in e, ra d iu s , a n d ca lca n e u s t o p re d ict h ip fra ct u re. De cre a s e s of 2 s t a n d a rd
B
d evia t ion s in ra d ia l a n d ca lca n e a l bon e m a s s a re a s s ocia t e d w it h 4- t o 6-fold
o
n
in cre a s e s in ris k for ve rt e bra l fra ct u re. In cre a s in g a ge a n d d e cre a s in g BMD of
e
t h e ra d iu s p re d ict s u b s e q u e n t n o n s p in a l fra ct u re s . It is e s t im a t e d t h a t a
50-ye a r-old w om a n h a s a 19% life t im e ris k of fra ct u re if ra d ia l bon e m a s s is in
t h e 10t h p e rce n t ile com p a re d w it h a n 11% life t im e ris k if t h e m e a s u re m e n t is
in t h e 90t h p e rce n t ile. Abs olu t e fra ct u re ris k for t h e n e xt 10 ye a rs ca n be ca l-
cu la t e d by in co rp o ra t in g clin ica l in fo rm a t io n o n fra ct u re ris k w it h BMD a n d
u s in g t h e FRAX t o ol a va ila ble on t h e We b (h t t p ://w w w.s h e f e ld .a c.u k /FRAX/;
s e e Fig. 21.4 ).
NONPHARMACOLOGIC PREVENTION
Exe rcise
Mod era t e t o in ten s ive w eigh t-bea rin g exercise ca n lea d to m od est in crea ses of
abou t 1% to 3% in BMD. For a n exercise to be effective in a lterin g BMD, it m u st
stra in th e skeleta l site bein g eva lu a ted . For exa m p le, bon e m a ss ga in s a re p a rticu -
la rly n otable in th e tibia in ru n n ers a n d in th e sp in e a m on g w eigh t lifters. Old er
w om en m ay d em on stra te lu m ba r BMD ga in s w ith regu la r vigorou s w eigh t-bea rin g
exe rcis e p e rform e d m u lt ip le t im e s p e r w e e k. Con t in u e d p h ys ica l a ct ivit y is
req u ired to m a in ta in observed BMD ga in s. Sp in a l exten sion exercises a re p referred
e
n
over exion m a n eu vers, w h ich m ay lea d to sp in a l com p ression d eform ities.
o
B
c
i
l
Hip Pro te cto rs
o
b
Protective h ip p a d s w orn in sp ecia lized u n d erga rm en ts h ave effectively red u ced
a
t
e
fra ct u re ra t e s in n u rs in g h om e p a t ie n t s in s om e s t u d ie s . Ad h e re n ce t o t h e s e
M
d evices is p roblem a tic a n d oth er stu d ies h ave n ot been su p p ortive of th eir ef ca cy.
d
n
a
s
i
PHARMACOLOGIC PREVENTION
t
i
r
h
t
Calcium and Vitamin D
r
a
o
Ca lciu m a lo n e m a y s o m ew h a t re d u ce, b u t n o t fu lly p reve n t , b o n e lo s s e a rly
e
t
a ft e r m e n o p a u s e . In p o s t m e n o p a u s a l w o m e n , s u f cie n t ca lciu m p rovid e d
s
O
t h rou gh d ie t a ry a n d e xoge n ou s s ou rce s d e cre a s e s a p p e n d icu la r s ke le t a l bon e
4
los s by 1% t o 3% com p a re d t o w om e n w h o d o n ot con s u m e a d e q u a t e ca lciu m .
N
O
Ca lciu m m a y be m os t be n e cia l for w om e n la t e r a ft e r m e n op a u s e. How eve r,
I
T
eve n a m on g you n ge r w om e n a n d m e n , ca lciu m s u p p le m e n t a t io n p reve n t s
C
E
bon e los s a t va riou s s ke le t a l s it e s .
S
Va ryin g a m ou n t s of e le m e n t a l ca lciu m a re fou n d in d iffe re n t food grou p s
a n d n u t rit ion a l s u p p le m e n t s . Ca lciu m is e q u a lly w e ll a bs orbe d (25% t o 30%)
from e it h e r m ilk p rod u ct s or ca lciu m ca rbon a t e. Alt h ou gh s om e s t u d ie s s u g-
ge s t t h a t ca lciu m cit ra t e h a s s ligh t ly h igh e r a bs or p t ion t h a n ot h e r p re p a ra -
t ion s , ot h e r in ve s t iga t ion s in d ica t e t h a t t h ey a re e q u a lly w e ll a bs orbe d .
On e a re a o f co n t rove r s y co n ce r n s t h e u s e o f ca lciu m s u p p le m e n t s in
p a t ie n t s w it h a h is t o ry o f n e p h ro lit h ia s is . High in t a k e o f d ie t a ry ca lciu m
a p p e a rs t o d e cre a s e t h e ris k of s t on e s , w h e re a s in t a ke of h igh d os e s of s u p -
p le m e n t a l ca lciu m m a y m od e s t ly in cre a s e ris k. Die t a ry ca lciu m m a y be n e -
cia lly bin d oxa la t e, t h e p rim a ry com p on e n t in m os t re n a l s t on e s .
Alt h ou gh ca lciu m s u p p le m e n t s a re w e ll t ole ra t e d by m a n y, con s t ip a t ion (in
a bou t 10% of u s e rs ) a n d d ys p ep s ia lim it lon g-t e rm a d h e re n ce. In d ivid u a l t ria ls
of d iffe re n t p rep a ra t ion s a n d t im e s of a d m in is t ra t ion m a y m a xim ize p a t ie n t
s a t is fa ct ion . In s t it u t e of Me d icin e 2010 Con s e n s u s re com m e n d a t ion s for d a ily
d os e s of e le m e n t a l ca lciu m a re p rovid e d in Ta ble 21.6. Th e in cre a s in g va rie t ie s
of food a n d beve ra ge p rod u ct s a va ila ble in t h e Un it e d St a t e s t h a t a re ca lciu m
fort i e d h ave re d u ce d t h e re lia n ce on e xoge n ou s ca lciu m s a lt s u p p le m e n t s t o
a ch ieve d a ily re q u ire m e n t s . Th e re is evid e n ce from s om e, bu t n ot ot h e r, s t u d ie s
t h a t e xce s s ive ca lciu m s u p p le m e n t a t ion m a y in cre a s e ca rd iova s cu la r eve n t s ,
s u ch a s m yoca rd ia l in fa rct ion , in ce rt a in p op u la t ion s .
Vit a m in D is a grou p of fa t -s olu ble s t e rols t h a t in clu d e s e rgoca lcife rol (vit a -
m in D 2 ) a n d ch ole ca lcife rol (vit a m in D 3 ); vit a m in D 3 is m ore p ot e n t t h a n vit a -
m in D 2 . Th e s e in a ct ive p roh orm on e s a re h yd roxyla t e d in t h e live r a n d kid n ey
208 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Calcito nin
W h e n u s e d for p reve n t ion or t re a t m e n t of os t e op oros is , s yn t h e t ic ca lcit on in
(d e rive d from s a lm on ) is a d m in is t e re d e it h e r s u bcu t a n e ou s ly (u p t o 100 IU d a ily
e
n
for os t e op oros is ) or m ore com m on ly in t ra n a s a lly (200 IU d a ily). Ca lcit on in s h ou ld
o
B
be give n w it h a d e q u a t e ca lciu m (a t le a s t 1 g) a n d vit a m in D (400 IU d a ily). Ra n -
c
i
l
d om ize d con t rolle d t ria ls of in je ct a ble a n d in t ra n a s a l ca lcit on in for t re a t m e n t of
o
b
e s t a blis h e d p os t m e n op a u s a l os t e op oros is h ave con s is t e n t ly s h ow n e it h e r s t a bi-
a
t
e
liza t ion of BMD or s m a ll, bu t s ign i ca n t , in cre a s e s in ve rt ebra l BMD. Be n e cia l
M
BMD e ffe ct s a t t h e h ip h ave n ot ye t be e n rep ort e d . A 5-ye a r m u lt ice n t e r s t u d y of
d
n
ca lcit on in n a s a l s p ra y s h ow e d a 36% re d u ct ion in ve rt e bra l fra ct u re s in t h e
a
200 IU, bu t n ot in t h e 100 or 400 IU grou p s . In t e rp re t a t ion of s t u d y w a s lim it e d
s
i
t
i
by a n a p p roxim a t e ly 50% d rop ou t ra t e. Na s a l ca lcit on in is ge n e ra lly w e ll t ole r-
r
h
t
a t e d , ot h e r t h a n occa s ion a l rh in it is m in im ize d by a lt e rn a t in g n os t rils e a ch d ay.
r
a
o
He a d a ch e, u s h in g, n a u s e a , a n d d ia rrh e a h ave be e n rep ort e d m ore com m on ly
e
t
w it h s u bcu t a n e ou s t h a n w it h in t ra n a s a l ca lcit on in . On t h e ba s is of it s w e a k
s
O
a n t ire s orp t ive e ffe ct s a n d t h e ava ila bilit y of a grow in g a rm a m e n t a riu m of ot h e r
4
a n t ios t e op oros is a ge n t s , t h e u s e of ca lcit on in h a s d e clin e d ove r t im e a n d is cu r-
N
O
re n t ly re lega t e d t o a s e con d - or t h ird -lin e op t ion .
I
T
C
E
Bispho spho nate s
S
Bis p h os p h on a t e s com p ris e a cla s s of a n t ire s orp t ive a ge n t s ch a ra ct e rize d by a
p h os p h oru s –ca rbon –p h os p h oru s bon d . Th ey a re re cogn ize d a s p ot e n t in h ibi-
t ors of bon e re s orp t ion a n d re d u ce ris ks for fra ct u re s w h e n a d m in is t e re d ora lly
o r by in t ra ve n o u s in fu s io n . Va r ia t io n s in t h e s t r u ct u re o f t h e ir a m in o s id e
ch a in s a lt e r t h e p h a r m a co lo gic a ct ivit y. Bis p h o s p h o n a t e s va r ia bly s u p p re s s
o s t e o cla s t s a n d / o r le a d t o p re m a t u re d e a t h of o s t e o cla s t s a s t h e ir p rim a ry
m e ch a n is m of a ct ion . Ora l bis p h os p h on a t e s a re p oorly a bs orbe d w it h bioava il-
a bilit y of le s s t h a n 1% a n d a re bou n d by d iva le n t ca t ion s . Th u s , w it h t h e e xcep -
t ion of on e p rep a ra t ion of ris e d ron a t e t h a t is d e e m e d a cce p t a ble t o t a ke w it h
foo d , t h ey s h o u ld be t a ke n o n a n e m p t y s t o m a ch t o m a xim iz e a bs or p t io n .
Bisp h osp h on a tes tigh tly bin d to h yd roxya p a tite crysta ls in th e resorp tion la cu n a e
of bon e w h ere th ey h ave a lon g s keleta l reten tion (a bou t 10 yea rs for a len d ron a te).
Th is p rop e rt y re s u lt s in p rot ra ct e d p a rt ia l s u p p re s s ion of bon e re m od e lin g for
m on th s to yea rs a fter t h e m ed ica tion s a re d iscon tin u ed .
Fou r bis p h os p h on a t e s a le n d ron a t e, ris e d ron a t e, iba n d ron a t e, a n d zole d ron ic
a cid a re lice n s e d in t h e Un it e d St a t e s for t re a t m e n t of os t e op oros is . Pot e n t ia l
m od e s of a d m in is t ra t ion of t h e s e a ge n t s va ry s om ew h a t a s give n in Ta ble 21.7 .
Ale n d ron a t e in h ibit s bon e re s orp t ion w it h ou t d e t rim en t a l e ffect s on m in e r-
a liza t ion ove r t h e s h ort t o m od e ra t e t e rm . St u d ie s of p os t m e n op a u s a l w om e n
re ceivin g 10 m g/d ay s h ow e d t h a t lu m ba r s p in e BMD in cre a s e d u p t o 9% ove r a
2-ye a r p e riod . In a la rge US s t u dy of old er w om en w it h a t le a s t on e p rior ve rt ebra l
fra ct u re a n d low fe m ora l n eck BMD, a le n d ron a t e s ign i ca n t ly re d u ce d ve rt ebra l
a n d h ip fra ct u re s by 47% a n d 51%, re s p e ct ive ly. In s u bje ct s w it h ou t p reva le n t
210 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
e
review: bisphosphona tes a nd osteonecrosis of the ja ws. Ann Intern Med
n
zoled ron ic acid stu d ies or w ith oth er bisp h osp h on a tes.
o
2006;144:753–761.)
B
W h ile b is p h o s p h o n a t e s a fe t y ove ra ll h a s b e e n
c
i
l
a ccep t a ble in clin ica l t ria ls , beyon d clin ica l t ria ls , t h e re h ave be e n n u m e rou s
o
b
ca s e rep ort s lin kin g a le n d ron a t e, a n d t o a le s s e r d egre e, ot h e r bis p h os p h on a t e s
a
t
e
w it h a va rie t y of a d ve rs e e ffe ct s t h a t cou ld p ot e n t ia lly re s u lt from p rolon ge d or
M
s ign i ca n t s u p p re s s ion of bon e re m od e lin g.
d
n
Os t e on e cros is of t h e jaw (ONJ) h a s be e n a s s ocia t e d w it h bis p h os p h on a t e
a
e xp os u re a n d is d e n e d a s a n a re a of ba re a lve ola r bon e occu rrin g a n yw h e re
s
i
t
i
in t h e m ou t h (s e e Fig. 21.5 ). It occu rs m os t com m on ly follow in g d e n t a l m a n ip -
r
h
t
u la t ion s u ch a s t oot h e xt ra ct ion . Os t e on e cros is of t h e ja w h a s be e n rep ort e d in
r
a
o
u p t o 10% of p e rs on s w h o re ce ive h igh -d os e bis p h os p h on a t e s (p re d om in a t e ly
e
t
in t ra ve n ou s ly) for t h e t re a t m e n t of m a lign a n t con d it ion s . Th e in cid e n ce in p e r-
s
O
s o n s w it h o s t e o p o ro s is t a k in g b is p h o s p h o n a t e s a p p e a rs t o b e m u ch low e r,
4
a lt h ou gh e xa ct ra t e s a re u n kn ow n .
N
O
A n ew e r con ce rn is t h e d eve lop m e n t of a t yp ica l fra ct u re s in t h e s u bt ro -
I
T
ch a n t e ric (s e e Fig. 21.6A) a n d m ore d is t a l region s of t h e h ip a n d fe m u r t h a t a re
C
E
S
A B
Figure 21.6 Ra diogra phs of a typica l femora l fra ctures. A: Fra cture demonstra ting cha ra cteristic tra nsverse
pa ttern in subtrocha nteric region with media l bone “bea king.” B: Contra la tera l femur showing a rea of stress
rea ction over la ter femora l cortex. This pa ttern is commonly a ssocia ted with hip pa in.
212 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
De no sumab
De n os u m a b is a m on oclon a l a n t ibod y t h a t is s olu ble re cep t or t h a t bin d s a n d
in h ibit s RANKL. RANKL is a s ign a lin g m ole cu le p rod u ce d by os t e obla s t s t h a t
a re re s p on s ible for d iffe re n t ia t ion a n d a ct iva t ion of os t e ocla s t s a n d t h e ir p re -
cu rs o rs . De n o s u m a b is p ot e n t in h ibit o r of bo n e re s o rp t ion w it h a ve ry ra p id
on s e t a n d a n e q u a lly q u ick offs e t of a ct ion , re s e m blin g t h e d egre e of ch a n ge s
in bo n e t u rn ove r s e e m w it h s e x s t e ro id a d m in is t ra t ion a n d d is con t in u a t io n .
Mu lt is it e clin ica l t ria ls d e m on s t ra t e d it s s ign i ca n t im p a ct on bon e d e n s it y
a n d it s 68% a n d 40% re d u ct ion in s p in e a n d h ip fra ct u re s , re s p e ct ive ly. A s m a ll
in cre a s e in in fe ct ion s h a s be e n s e e n w it h d e n os u m a b in s om e, bu t n ot in a ll,
clin ica l t ria ls . It is u n ce rt a in if it s p ow e rfu l a n t ire s orp t ive e ffe ct s w ill be a s s oci-
a t e d in t h e fu t u re w it h ja w os t e on e cros is or a t yp ica l fra ct u re s t h a t h ave be e n
p u t a t ive ly lin ke d w it h t h e bis p h os p h on a t e s .
e
m a t e ly 2 ye a rs o f glu co co r t ico id t h e ra p y, ra t e o f b o n e lo s s s low s in m a n y
n
o
p a t ie n t s . How eve r, BMD con t in u e s t o be los t a t a ra t e h igh e r t h a n t h a t w it h n or-
B
c
m a l a gin g. St u d ie s of s t e roid -d os e e ffe ct s a re con fou n d e d by t h e va ria ble t im in g
i
l
o
of glu cocort icoid a d m in is t ra t ion , d iffe rin g d is e a s e p roce s s e s , va ria ble a lt e rn a -
b
a
t ive os t e op oros is ris k fa ct ors (in d ep e n d e n t of glu cocort icoid u s e ), a n d t h e fa ct
t
e
M
t h a t fra ct u re ris k is u lt im a t e ly d e t e rm in e d by fa ct ors ot h e r t h a n on ly BMD. Glu -
d
cocort icoid s in cre a s e t h e ris k of fra ct u re s rou gh ly by t w ofold , in d ep e n d e n t of
n
a ge, ge n d e r, a n d rh e u m a t oid a rt h rit is (RA). Wom e n w it h RA t a kin g low -d os e
a
s
p re d n is on e h ave a n e a rly 33% ch a n ce of s e lf-rep ort in g a clin ica l fra ct u re a ft e r
i
t
i
r
5 yea rs. Alt h ou gh s a fer for bon e th a n ora l or en tera l glu cocorticoid s , even n on s ys-
h
t
r
tem ica lly a d m in istered glu cocorticoid s m ay h ave biologica l effects on bon e.
a
o
Th e e t iology of GIOP is m u lt ifa ct oria l a n d occu rs , in m a n y ca s e s , con com i-
e
t
s
t a n t ly w it h n orm a l a ge - a n d m e n op a u s e -a s s ocia t e d bon e los s . Th e re a re t w o
O
m a jor p a t h w ays by w h ich p a t ie n t s on glu cocort icoid s d eve lop a bn orm a lit ie s in
4
N
bon e m e t a bolis m : re d u ce d bon e form a t ion a n d in cre a s e d bon e re s orp t ion . W h ile
O
I
a cce le ra t ion of bon e re s orp t ion is cle a rly a n im p ort a n t p a t h w ay, t h e p re d om i-
T
C
n a n t p roble m in glu cocort icoid -in d u ce d os t e op o ros is m a y be s u p p re s s io n of
E
S
bon e form a t ion via a d ire ct t oxic e ffe ct on os t e obla s t s a n d os t e ocyt e s in bon e.
re ce ive d a com bin a t ion con t a in in g ca lcit riol, ca lciu m , a n d ca lcit on in e xp e ri-
e n ce d s ign i ca n t ly le s s bon e los s in t h e s p in e t h a n t h os e re ce ivin g ca lciu m
a lon e. In a ct iva t e d vit a m in D p re p a ra t ion s a ls o h ave m e rit . Be ca u s e of im p a ir-
m e n t in ca lciu m a b s o r p t io n m e d ia t e d by glu co co r t ico id s a n d t h e co m m o n
occu rre n ce of vit a m in D d e cie n cy a m on g h ou s e bou n d p a t ie n t s s u ffe rin g w it h
ch ron ic in a m m a t ory con d it ion s , vit a m in D s h ou ld be p re s cribe d for a ll glu co-
cort icoid u s e rs . Th is ca n be a ccom p lis h e d w it h 800 IU/d ay vit a m in D 3 , ava ila ble
in m a n y m u lt ivit a m in s a n d vit a m in D–s u p p le m e n t e d ca lciu m p re p a ra t io n s .
W it h ca re fu l u s e o f e x oge n o u s ca lciu m a n d m o n it o rin g o f u rin e a n d s e ru m
ca lciu m , vit a m in D ca n be a d m in is t e re d a lt e rn a t ive ly a s ca lcit riol.
Yes No
Figure 21.7 Trea tment a lgorithm for the ma na gement of glucocorticoid-a ssocia ted
bone disease. Asterisks indicate during the rst 2 years of therapy and then less regularly.
(Adapted from Rosen HN, Rosenblatt M. Prevention and treatment of glucocorticoid-induced
osteoporosis. In: Rose B, ed. UptoDate . Vol. 6, No. 3. Wellesley, MA: UpToDa te. Reprinted
in, Saag KG, Morgan SL, Cao X, et al. Bone in health and disease In: Koopman WJ, ed.
Arthritis and Allied Condition: A Textbook of Rheumatology. 15th ed. Phila delphia: Lippincott
Williams & Wilkins; 2005:2449–2541.)
Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 215
Ma le Oste o po ro sis
INTRODUCTION
Os t e op oros is in m e n is com m on : a bou t 20% of a ll os t e op orot ic fra ct u re s occu r
in m e n . As t h e p o p u la t io n a ge s , o s t e o p o ro s is in m e n is b e co m in g a n eve n
gre a t e r p u blic h e a lt h p roble m .
In Nort h Am e rica , m e n a ge d 50 ye a rs h a ve a n a p p roxim a t e 13% life t im e
ris k for fra ct u re of t h e h ip , s p in e, or fore a rm . In t h e Un it e d St a t e s , t h e in cid e n ce
of h ip fra ct u re in m e n old e r t h a n 65 ye a rs is 4 t o 5 in 1,000; a bou t h a lf t h a t in
w om e n of s im ila r a ge. In cid e n ce of h ip fra ct u re in m e n d iffe rs be t w e e n d iffe r-
e n t e t h n ic grou p s . Africa n -Am e rica n m e n h ave a ra t e a bou t h a lf t h a t of Ca u ca -
s ia n s , a n d Ja p a n e s e m e n livin g in Ja p a n or Haw a ii m ay h a ve a low e r fre q u e n cy
t h a n Ca u ca s ia n Am e rica n m e n . Os t e op o rot ic ve r t e bra l fra ct u re s in m e n a re
m ore com m on in t h e low t h ora cic region , bu t m ay occu r a t a n y leve l. Eld e rly
m e n le s s oft e n fra ct u re m ore t h a n on e ve rt e bra l bod y. Mos t fra ct u re s a re t h e
a n t e r io r co m p re s s io n t yp e ; cr u s h fra ct u re s o ccu r le s s co m m o n ly t h a n in
w om e n , t h e re by a ccou n t in g for le s s kyp h os is in m e n .
e
n
o
Th e gre a t e r bon e m a s s in m e n t h a n in w om e n is m os t ly re la t e d t o bod y
B
s ize, w it h t h e e xcep t ion of a few s it e s s u ch a s t h e ra d iu s . Aft e r a t t a in in g p e a k
c
i
l
o
bon e m a s s , m e n m a in t a in a s t a ble BMD d u rin g m id d le a ge a n d t h e n los e bon e
b
a t a n a cce le ra t in g ra t e in t o old a ge. Th is ra t e m ay re a ch 5% t o 10% p e r d e ca d e,
a
t
e
a n d is gre a t e r in t ra be cu la r t h a n cort ica l bon e. As m a n y a s 20% t o 40% of m e n
M
w it h a n os t e op orot ic fra ct u re h ave n o id e n t i a ble m e d ica l con d it ion or ris k fa c-
d
n
t or a s s ocia t e d w it h os t e op oros is ; t h ey a re d e s ign a t e d a s h a vin g p rim a ry os t e -
a
s
op oros is t o d is t in gu is h t h e m from m e n w h o h a ve los t s u bs t a n t ia l bon e m a s s
i
t
i
r
s e con d a ry t o a n y of va riou s con d it ion s .
h
t
r
a
o
e
HISTORY AND PHYSICAL EXAMINATION
t
s
O
In m e n w it h clin ica l fe a t u re s or n d in gs s u gge s t ive of m e t a bolic bon e d is e a s e
4
(s u ch a s ra d iogra p h ic os t e op e n ia , low -t ra u m a fra ct u re s , or d is ord e rs a s s ocia t e d
N
O
w it h bon e los s ), m e a s u re m e n t of BMD s h ou ld be con s id e re d . Th e s e m e a s u re -
I
T
m e n t s m ay be u s e d t o con rm low bon e m a s s , ga u ge it s s eve rit y, a n d s e rve a s a
C
E
ba s e lin e t o a s s e s s t h e p rogre s s ion of d is e a s e or t h e ra p e u t ic re s p on s e. Crit e ria t o
S
d e n e os t e op oros is in m e n a re n ot a s cle a r a s for w om e n . Es t im a t e s of fra ct u re
ris k d e rive d from m e a s u re m e n t s of w om e n m ay n ot a p p ly t o m e n . Low e r bon e
d e n s it y is a s s ocia t e d w it h a n in cre a s e d ris k for fra ct u re a n d m e a s u re m e n t s ca n
be u s e d t o m on it or s e ria l ch a n ge s in bon e m a s s .
Th e in it ia l h is t ory a n d p h ys ica l e x a m in a t io n s h o u ld be u n d e rt a ke n w it h
kn ow le d ge of con d it ion s a s s ocia t e d w it h os t e op oros is . Sp e cia l a t t e n t ion s h ou ld
be give n t o s ign s of ge n e t ic, n u t rit ion a l, a n d life s t yle fa ct ors (a lcoh ol or t oba cco),
s ys t e m ic illn e s s , a n d m e d ica t ion u s a ge. If t h e ca u s e of os t e op oros is re m a in s
u n d e n e d , m e a s u re m e n t of s e ru m t h yroid -s t im u la t in g h orm on e, a n d 24-h ou r
u rin a ry ca lciu m a n d cort is ol s h ou ld be con s id e re d .
TREATMENT
To a ch ieve m a xim a l a d u lt bon e m a s s , a d ole s ce n t boys s h ou ld be e n cou ra ge d t o
in ge s t 1,300 m g ca lciu m d a ily in t h e ir d ie t s , p a rt icip a t e in regu la r w e igh t -be a rin g
exe rcis e, m a in t a in id e a l bod y w e igh t , a n d avoid u s e of t oba cco a n d exce s s ive
a lcoh ol. Ext e n d in g t h is a p p roa ch in t o a d u lt h ood , it is re com m e n d e d t h a t m e n
a ge d 19 t o 50 con s u m e 1,000 m g ca lciu m d a ily a n d t h a t m e n old e r t h a n 50 ye a rs
con s u m e 1,000 t o 1,200 m g d a ily (s e e Ta ble 21.6 ).
Te s t os t e ron e in cre a s e s BMD in h yp ogon a d a l m e n or t h os e on glu cocort i-
coid t h e ra py, a n d h a s be e n u s e d e m p irica lly in e u gon a d a l m e n , a lbe it in s h ort -
t e rm t ria ls . Th e goa l of t h e ra p y is a p h ys iologic t e s t os t e ron e p ro le. Sid e e ffe ct s
ge n e ra lly a re n ot s e riou s , a lt h ou gh lon g-t e rm s a fe t y is n ot w e ll e s t a blis h e d .
216 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
STUDIES
La bora t ory fe a t u re s of vit a m in D–d e cie n cy os t e om a la cia a re low or n orm a l
s e ru m ca lciu m leve l, h yp op h os p h a t e m ia , in cre a s e d s e ru m a lka lin e p h os p h a t a s e
e
leve l, a n d a low s e ru m 25-h yd roxyvit a m in D. Se con d a ry h yp e ra p a ra t h yroid is m
n
o
e n s u e s t o ra is e s e ru m ca lciu m t o n e a r n orm a l. Hyp op h os p h a t e m ia is t h e re s u lt
B
of p h os p h a t e w a s t in g be ca u s e of e leva t e d PTH a s w e ll a s re d u ce d gu t a bs orp -
c
i
l
o
t io n fro m vit a m in D d e cie n cy. In d ivid u a lly, e leva t e d PTH a n d h yp o p h o s -
b
p h a t e m ia s t im u la t e re n a l s yn t h e s is of 1,25-d ih yd roxyvit a m in D t o m a in t a in
a
t
e
n orm a l s e ru m leve ls . Urin e ca lciu m is a ls o exp e ct e d ly low. Ca lciu m -d e cie n cy
M
os t e om a la cia is a s s ocia t e d w it h s im ila r la bora t ory n d in gs e xcep t t h a t vit a m in
d
n
D a n d s e ru m p h os p h oru s a re oft e n n orm a l.
a
s
In o s t e o m a la cia b e ca u s e o f h yp o p h o s p h a t e m ic s t a t e s a s s o cia t e d w it h
i
t
i
r
h yp e rp h os p h a t u ria , s e ru m ca lciu m , PTH, a n d 25-h yd roxyvit a m in D a re n orm a l,
h
t
r
s e ru m a lka lin e p h o s p h a t a s e leve ls a re u s u a lly in cre a s e d , s e ru m p h os p h o ru s
a
o
a n d 1,25-d ih yd roxyvit a m in D leve ls a re low, a n d u rin a ry p h os p h oru s e xcre t ion
e
t
is ve ry h igh . Pa t ie n t s w it h t yp e II re n a l t u bu la r a cid os is h a ve d e fe ct ive re a b-
s
O
s o rp t io n o f b ica rb o n a t e a n d m a n ife s t h yp e rch lo re m ic h yp o k a le m ic a cid o s is
4
w it h h yp o p h o s p h a t e m ia b e ca u s e o f a u gm e n t e d p h o s p h a t u r ia . Low s e r u m
N
O
1,25-d ih yd roxyvit a m in D leve ls in s om e p a t ie n t s m ay be t h e con s e q u e n ce of
I
T
C
a bn orm a l p roxim a l t u bu la r m e t a bolis m . Hyp op h os p h a t a s ia is a ra re a u t os om a l-
E
S
d o m in a n t d is ord e r w it h d e cre a s e d s e r u m bon e a lk a lin e p h o s p h a t a s e leve l;
s e ru m ca lciu m , p h os p h oru s , 25-h yd roxyvit a m in D, a n d 1,25-d ih yd roxyvit a m in D
leve ls a re n ot re d u ce d .
TREATMENT
Tre a t m e n t is ba s e d on t h e u n d e rlyin g d is ord e r. Vit a m in D–d e cie n t os t e om a la -
cia re q u ire s h igh d o s e s o f vit a m in D t o re s t o re p ro p e r b o n e m in e ra liza t io n .
Ergoca lcife rol, or vit a m in D 2 , s h ou ld be a d m in is t e re d a t a d o s e of 50,000 IU
t w ice a w e e k for a t le a s t 8 w e e ks be fore re a s s e s s m e n t of s e ru m ca lciu m a n d
vit a m in D. Vit a m in D leve ls gre a t e r t h a n 30 n g/m L h ave be e n p rop os e d t o be
a s s ocia t e d w it h op t im a l bon e h e a lt h . On ce t h a t leve l h a s be e n a ch ieve d , s ev-
e ra l vit a m in D m a in t e n a n ce regim e n s a re a va ila ble, in clu d in g ch ole ca lcife rol
(vit a m in D 3 ) 1,000 t o 2,000 IU d a ily or e rgoca lcife rol 50,000 IU eve ry 2 t o 4 w e e ks .
In p a t ie n t s w it h gu t m a la bs orp t ion , eve n h igh e r d os e s m a y be re q u ire d . Ge n e r-
a lly, t h e a ct ive form of vit a m in D (1,25-d ih yd roxyvit a m in D) s h ou ld be avoid e d
a s it h a s a s h ort h a lf-life a n d is a s s ocia t e d w it h a h igh e r ris k of h yp e rca lce m ia .
Su n ligh t is a n ot h e r m e t h od t o m a in t a in vit a m in D s t ore s in p a t ie n t s w h o a re
n ot p ron e t o s u n bu rn or s kin ca n ce r. Su p p le m e n t a l ca lciu m , 1,000 t o 2,000 m g/
d ay, is n e ce s s a ry for bot h vit a m in D– a n d ca lciu m -d e cie n t os t e om a la cia .
In p a t ie n t s w it h re n a l t u b u la r a cid o s is , re s t o ra t io n o f t h e s e r u m b ica r b o -
n a t e leve l t o n o r m a l u s in g s o d iu m o r p o t a s s iu m cit ra t e s u p p le m e n t s reve r s e s
b o n e re s o r p t io n a n d h yp e rca lciu r ia . Pa t ie n t s w it h o s t e o m a la cia b e ca u s e o f
h y p e r p h o s p h a t u r ia r e q u ir e o r a l p h o s p h a t e s u p p le m e n t s , ge n e r a lly 1 t o
218 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
TREATMENT
Th e cu re for p rim a ry h yp e rp a ra t h yroid is m is s u rgica l re m ova l of t h e p a ra t h y-
ro id a d e n om a o r ca rcin o m a , o r m o s t of t h e h yp e rp la s t ic t is s u e, a ft e r w h ich
bon e m a s s oft e n in cre a s e s for s eve ra l ye a rs . Th e ge n e ra l gu id e lin e s for re com -
m e n d in g s u rge ry in p a t ie n t s w it h ou t ca rcin om a a re a s e ru m ca lciu m con ce n -
t ra t ion gre a t e r t h a n 1 m g/d L a bove t h e u p p e r lim it of n orm a l, a cre a t in in e cle a r-
a n ce le s s t h a n 60 m L/m in u t e, a DXA T-s core e q u a l t o or le s s t h a n −2.5 in t h e h ip ,
s p in e, or d is t a l ra d iu s a n d a ge le s s t h a n 50. Ra re ly, p os t op e ra t ive h yp oca lce m ia ,
h yp o p h o s p h a t e m ia , a n d h yp o m a gn e s e m ia , o r “h u n gry bo n e ” s yn d ro m e, ca n
Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 219
e
d ie t a ry ca lciu m , glu cocort icoid t h e ra py, fa t m a la bs orp t ion , loop d iu re t ic t h e ra py,
n
o
a n d re n a l in s u f cie n cy m ay ca u s e s e con d a ry h yp e rp a ra t h yroid is m . Tre a t m e n t
B
c
in clu d e s ca lciu m s u p p le m e n t s a n d vit a m in D rep la ce m e n t . In ch ron ic kid n ey
i
l
o
d is e a s e, con ve r s ion o f vit a m in D t o t h e a ct ive 1,25-d ih yd roxyvit a m in D is
b
a
im p a ire d , s o rep la ce m e n t w it h t h e a ct ive vit a m in D is in d ica t e d . Th e ca lcim i-
t
e
M
m e t ic a ge n t cin a ca lce t is e ffe ct ive in m a n a gin g s e con d a ry h yp e rp a ra t h yroid is m
d
be ca u s e of ch ron ic kid n ey d is e a s e.
n
a
s
i
Oste o g e ne sis Impe rfe cta
t
i
r
h
t
r
a
Occa s ion a lly a n a d u lt w it h m u lt ip le fra ct u re s , e s p e cia lly in t h e lon g bon e s of
o
e
t h e legs , a n d ra d iogra p h ic os t e op e n ia h a s os t e oge n e s is im p e rfe ct a . A ge n e t i-
t
s
O
ca lly d e t e rm in e d in a bilit y t o form q u a n t it a t ive ly or q u a lit a t ive ly n orm a l colla -
4
ge n ch a ra ct e rize s t h is grou p of d is ord e rs . Seve ra l m u t a t ion s in t h e ge n e for t yp e
N
1 p rocolla ge n h ave be e n id e n t i e d ; a ll re s u lt in form a t ion of u n s t a ble colla ge n
O
I
T
h e lice s . Mos t p a t ie n t s d eve lop fra ct u re s in ch ild h ood . Som e in d ivid u a ls a re d e a f
C
E
or h ave blu e s cle ra , bu t ot h e rs h ave on ly os s e ou s m a n ife s t a t ion s .
S
If n o p h en otyp ic ch a ra ct e ris t ic of os t e oge n e s is im p erfe ct a is p res e n t excep t
for fra gile bon e s , d ia gn osis ca n be d if cu lt . A p os it ive fa m ily h is tory a n d a h is t ory
of m u lt ip le fra ct u re s in ch ild h ood a re su gges t ive. Ra d iogra p h s s h ow t h in n in g of
cortica l a n d t ra becu la r a re a s of bon e s , es p ecia lly m et a ca rp a ls a n d m e t a ta rs a ls .
Pla t yba s ia of t h e s ku ll a n d bon e is la n d s in t h e cra n iu m s u gge s t os t e oge n e s is
im p erfe ct a . Bon e biop s y s h ow s d im in is h e d q u a n t ities of os t eoid a n d exce s s ive
os t e ocyt e n u m be rs . Th e ra py w it h gon a d a l h orm on e s , bis p h os p h on a t e s , a n d
a n e cd ota l u s e of t erip a ra t id e h a s be en a dvoca t ed . Bis p h os p h on a t e s m ay re d u ce
th e su bs e q u e n t fra ct u re ra t es .
Table 21.8 Pot ent ial Et iologic Fact ors for Ost eonecrosis
TRAUMATIC
NONTRAUMATIC (LESS RARE) NONTRAUMATIC (RARE)
St e ro id s Co a g u lo p a t h y
Alco h o l Pa n cre a t it is
Syst e m ic lu p u s e ryt h e m a t o sis Ga u ch e r’s d ise a se
Org a n t ra n sp la n t Ch ro n ic kid n e y d ise a se
Sickle ce ll d ise a se Pre g n a n cy
Hyp e rlip id e m ia
Ca isso n ’s d ise a se
Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 221
e
n
o
B
Figure 21.9 Osteonecrosis on ma gnetic resona nce ima ging. “Double-line
c
i
l
sign” on T2 ima ges with periphera l ma rgin da rk surrounding bright inner
o
b
line. (Mitchell DG, Ra o VM, Da linka MK, et a l: Femora l hea d a va scula r
a
t
Figure 21.8 Hip radiogra ph demonstra ting crescent sign. Area of colla pse necrosis: correla tion of MR ima ging, ra diogra phic sta ging, ra dionuclide
e
M
of subchondra l bone with a ccompa nying ra diolucency. ima ging, and clinica l ndings. Ra diology 1987;162:709–715.)
d
n
a
im a gin g (MRI) in 5% t o 10% of re n a l t ra n s p la n t re cip ie n t s w it h in 3 t o 6 m o n t h s
s
i
t
i
r
o f e n gra ft m e n t . Os t e o n e cro s is m a y a cco m p a n y HIV d is e a s e , p a r t icu la r ly in
h
t
r
t h e s e s e t t in g o f lip o d ys t rop h y. Ot h e r s om ew h a t com m o n a n d le s s co m m o n
a
o
fa ct ors e t iologica lly a s s ocia t e d w it h os t e on e cros is a re p rovid e d in Ta ble 21.8 .
e
t
Th e r e a r e m u lt ip le p a t h o ge n ic m e ch a n is m s t h a t m a y co n t r ib u t e t o
s
O
os t e on e cros is , in clu d in g com p rom is e of t h e bon ey va s cu la t u re (m os t com m on
4
w it h t ra u m a ) a n d a s p rogra m m e d ce ll d e a t h (a p op t os is ) of t h e os t e obla s t s a n d
N
O
os t e ocyt e s . Th e la t t e r m e ch a n is m m ay p re d om in a t e in glu cocort icoid -m e d ia t e d
I
T
C
os t e on e cros is .
E
S
STUDIES/ IMAGING
Pla in ra d iogra p h s ca n yie ld clu e s , bu t s u ffe r from p o or s e n s it ivit y fo r e a rly
le s ion s . Ch a ra ct e ris t ic ra d iogra p h ic a p p e a ra n ce s of bon e colla p s e a n d s u bch on -
d ra l fra ct u re a re s e e n in la t e r s t a ge d is e a s e (s e e Fig. 21.8 ). Bon e s cin t igra p h y
(b o n e s ca n s ) is u s e fu l in t h e e a rly d ia gn os is a n d d e m o n s t ra t e s d e cre a s e d o r
NOT TO BE MISSED a b s e n t ra d io t ra ce r a ct ivit y s u rro u n d e d by in cre a s e d a ct ivit y (“d o n u t le s io n ”)
be ca u s e of reva s cu la riza t ion . W h ile bon e s ca n h a s con s id e ra ble s e n s it ivit y, it
On w he n to pre scribe anti-
h a s low s p e ci cit y for d iffe re n t ia t in g os t e on e cros is from in fe ct ion , m ye lom a ,
o ste o po ro sis the rapy
a n d m e t a s t a t ic d is e a s e . Ma gn e t ic re s o n a n ce im a gin g is t h e m o s t s e n s it ive
• A h ist o ry o f a h ip o r m od a lit y for e a rly d ia gn os is a n d s t a gin g. A “d ou ble -lin e ” s ign is evid e n t , a n d
ve rt e b ra l fra ct u re .
in ve rs ion re cove ry p rot on d e n s it y im a gin g m ay p rovid e a s e n s it ive m e a n s t o
• T-sco re 2.5 in t h e d e t e ct e a rly le s ion s (s e e Fig. 21.9 ).
fe m o ra l n e ck o r sp in e . A s im ila r a p p e a r in g, b u t s e lf-lim it in g, e n t it y is t ra n s ie n t re gio n a l o s t e -
• T-sco re 1.0 a n d a FRAX op oros is (TRO) of t h e h ip . Ma gn e t ic re s on a n ce im a ge s for TRO a re ve ry s im ila r
10-ye a r p ro b a b ilit y o f a t o os t e on e cros is , bu t t h is con d it ion com m on ly re s olve s in 6 t o 12 m on t h s . It
h ip fra ct u re 3% in US m os t com m on ly follow s p regn a n cy, bu t is a ls o obs e rve d in m id d le -a ge d m e n .
p o p u la t io n s.
• T-sco re 1.0 a n d a FRAX
10-ye a r p ro b a b ilit y o f a TREATMENT
m a jo r o st e o p o ro sis-re la t e d Th e re is n o p rove n s t a n d a rd t h e ra p y for e ffe ct ive ly m a n a gin g o s t e o n e cro s is
fra ct u re 20% in US
p o p u la t io n s. on ce it d eve lop s . Ma n y p a t ie n t s go on t o bon ey colla p s e a n d re q u ire t ot a l join t
re p la ce m e n t , in join t s w h e re t h is is p os s ible. Wit h d raw a l of a n y in cit in g a ge n t s
222 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
e
n
o
B
c
Endo crine Dise a se s
i
l
o
A 60-ye ar-o ld Cau casian
b
w ith Asso cia te d
a
t
g e n t le m an w it h lo n g -
e
Arthro pa thie s
M
st an d in g p o o rly co n t ro lle d
d
n
t yp e 2 d iab e t e s m e llit u s DIABETES MELLITUS
a
s
Dia b e t e s is a n in cre a s in gly co m -
i
p re se n t s t o yo u r o f ce
t
i
r
m o n m e d ic a l c o n d it io n in t h e
h
w it h sym pt om s of sw e lling
t
r
Un it e d St a t e s , w it h a p reva le n ce of
a
o
an d m o d e rat e p ain in h is m o r e t h a n 23 m illio n p e o p le ,
e
t
s
rig h t m id f o o t o ve r t h e in c lu d in g b o t h d ia gn o s e d a n d
O
u n d ia gn os e d ca s e s , or o n e in t e n
4
p ast 3 w e e k s. He is u n ab le
N
a d u lt s (2 ). He a lt h ca re p rovid e r s
O
t o re call an y sp e ci c t rau -
m u s t be fa m ilia r w it h t h e m yr ia d
I
T
C
m at ic e ve n t . On e xam in at io n , t h e f o o t is w arm , sw o lle n , t e n d e r, of e xt ra gla n d u la r com p lica t ion s of
E
S
an d e ryt h e m at o u s (Fig . 22.1 ). Yo u r d iff e re n t ial in clu d e s ce llu lit is, t h e d is e a s e . It is t h ou gh t t h a t t h e
acu t e g o u t y art h rit is, o st e o m ye lit is, an d f ract u re . A n im p o rt an t a s s ocia t e d a rt h rop a t h ie s a re d u e t o
co m p lica t io n s o f d ia b e t e s , in clu d -
ad d it io n t o t h is d iff e re n t ial is co n sid e rat io n o f acu t e Ch arco t
in g n e u rop a t h y a n d m icrova s cu la r
n e u ro art h ro p at h y (CN). To ru le o u t u n d e rlyin g in f e ct io n , t h e b e st d is e a s e . Fu r t h e r m o r e , a h igh -
im ag in g st u d y is co m b in at io n o f a t h re e -p h ase b o n e scan w it h a glu co s e a n d in s u lin e n viro n m e n t
lab e le d w h it e b lo o d ce ll (W BC) scan . h a s be e n s h ow n t o h ave p a t h ologic
e ffe c t s o n m a n y k e y ce lls a n d
Jo in t p ain is o n e o f t h e m o st co m m o n re aso n s f o r a p at ie n t
m a t r ix co m p o n e n t s o f co n n e ct ive
t o se e h is o r h e r p rim ary care p ro vid e r. Of ce visit s in t h e Un it e d t is s u e s (3 ). Alt h o u gh r e la t ive ly
St at e s f o r m u scu lo sk e le t al p ain in 2000 acco u n t e d f o r 280 visit s u n com m on , ch a rcot n e u roa rt h rop -
p e r 1,000 p e o p le , an d w e re e ve n ly d ivid e d b e t w e e n acu t e an d a t h y is a n im p o r t a n t p ro ble m t o
re cogn ize a s it le a d s t o s ign i ca n t
ch ro n ic sym p t o m s (1 ). A lt h o u g h n o t in clu sive , t h is ch ap t e r aim s
d e fo r m it y a n d jo in t d e s t r u ct io n .
t o co ve r asso ciat io n s b e t w e e n a varie t y o f syst e m ic d ise ase s an d Co n ve rs e ly, a d h e s ive ca p s u lit is o f
t h e ir re lat e d m u scu lo sk e le t al m an if e st at io n s. t h e s h ou ld e r is q u it e com m on , bu t
o ft e n im p rove s w it h co n s e rva t ive
m a n a ge m e n t . Bo t h a re d is cu s s e d
in m o re d e t a il b e low. Ot h e r n o t a ble a rt h rop a t h ie s a s s o cia t e d w it h d ia b e t e s
m e llit u s in clu d e d iffu s e id iop a t h ic s ke le t a l h yp e ros t os is (DISH), ca rp a l t u n n e l
s yn d rom e, a n d os t e oa rt h rit is .
223
224 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
CHARCOT NEUROARTHROPATHY
Clinical Pre se ntatio n
Th e in cid e n ce of CN is rep ort e d a t a p p roxim a t e ly 1 in
333 p a t ie n t s w it h d ia be t e s (4 ). Th e e xa ct p a t h oge n ic
m e ch a n is m of CN is in com p le t e ly u n d e rs t oo d ; h ow -
eve r, a com bin a t ion of bot h n e u rova s cu la r a n d n e u ro-
t ra u m a t ic t h e orie s is ge n e ra lly a cce p t e d (4 ). Cu rre n t
h yp ot h e s is s u gge s t s t h a t s om a t ic a n d a u t on om ic n e u -
ro p a t h y le a d s t o in cre a s e d blo o d ow t o t h e jo in t ,
re s u lt in g in bon e re s orp t ion a n d s u s cep t ibilit y t o m in or
t ra u m a . Con t in u e d m e ch a n ica l s t re s s occu rs be ca u s e
of los s of p rot e ct ive p a in s e n s a t ion , a n d m a jor d e s t ru c-
t ive ch a n ge s re s u lt in fra ct u re s a n d d e form it ie s .
Pa tien ts w ith CN ca n p resen t w ith a n a cu te or ch ron ic
p rocess. In a cu te CN, th e ea rliest sym p tom s a re p ersist-
en t sw ellin g a n d p a in , a lth ou gh sen sory d e cits m ay p re-
Figure 22.1 Subluxa tion of the na vicula r a nd soft tissue swelling a s
S
clu d e a ssocia ted d iscom fort. A h istory of tra u m a m ay be
E
a n ea rly ma nifesta tion of a neuropa thic joint (Courtesy of Gera ld F.
C
p resen t, a lth ou gh on e stu dy sh ow ed th a t n ea rly 75% of
T
Moore, MD.)
I
O
p a tien ts d id n ot reca ll a n y p recip ita tin g even t. Progres-
N
sion from a cu te to ch ron ic n eu roa rth rop a th y ca n be ra p id , w ith irreversible d a m -
4
age seen in less th a n 6 m on th s. Pa tien ts w ith ch ron ic CN ca n p resen t w ith estab-
O
s
lish ed d eform ity a n d m ay com p la in of a ssocia ted d if cu lties w ith a m bu la tion .
t
e
o
a
Examinatio n
r
t
h
On p h ys ica l exa m in a t ion , a foot w it h a cu t e CN is t yp ica lly w a rm , sw olle n , a n d
r
i
t
i
t e n d e r. Mod e ra t e -t o-m a rke d e ryt h e m a m ay a ls o be p re s e n t (4 ). Th e m id foot is
s
a
m os t com m on ly in volve d a n d h a s a be t t e r p rogn os is t h a n h in d foot in volve m e n t
n
d
be ca u s e of w e igh t d is t ribu t ion e ffe ct s . Typ ica l d e form it ie s in clu d e a colla p s e d
M
a rch a n d rocke r-bot t om foot w it h ca llu s form a t ion a n d p os s ible u lce ra t ion s .
e
t
a
b
Studie s
o
l
i
Dia gn os is is p rim a rily m a d e by clin ica l h is t ory a n d e xa m in a t ion . Pla in
c
B
ra d iogra p h s a re in exp e n s ive a n d ca n s h ow a n a t om ic bon y d e form it ie s ,
o
n
d e m in e ra liza t ion , a n d p e rios t e a l re a ct ion . W h e n s eve re, CN ca n re s u lt in
e
fra gm en ta tion of t h e m eta ta rs a l h ea d s, or even “p en cil a n d cu p ” d eform ities
of th e MTP join t s . Ra d iogra p h ic p rogre ss ion ca n occu r ra p id ly, oft en tim e s
w ith in severa l w eeks of a n orm a l x-ray (Fig. 22.2 ) (4 ).
It is crit ica l t o ru le ou t in fe ct ion in t h e d ia gn os t ic w ork-u p of CN. Ra d i-
ogra p h s a re n eit h e r s e n s it ive n or s p eci c for d iffe ren t ia t in g in fe ct ion from
CN. Th e com bin a t ion of a t h re e -p h a s e bon e s ca n w it h a t a gge d W BC s ca n
h a s a s en s it ivit y a n d s p e ci cit y of 80% t o 90%. In a cu t e CN, a t h re e -p h a s e
bon e s ca n s h ou ld be p os it ive in a ll t h ree p h a s e s , re e ct in g in crea s ed bon e
t u rn ove r, a n d a t a gge d W BC s ca n s h ou ld be n ega t ive in t h e a bs e n ce of
in fe ct ion . How eve r, fa ls e p os it ive W BC s ca n s ca n occu r in t h e s e t t in g of ve ry
ra p id ly a d va n cin g CN. Fu rt h e r im a gin g ca n be d on e w it h com p le m en t a ry
m a rrow s ca n n in g, w h ich if p os it ive in t h e s a m e a re a , in d ica t e s a cu t e n eu -
roa rt h rop a t h ic ch a n ge s a n d n ot in fe ct ion (4 ). Alt h ou gh m a gn e t ic re s on a n ce
im a gin g (MRI) d oe s n ot d iffe re n t ia t e CN from in fe ct ion , it give s exce lle n t
a n a t o m ic d e n it io n , d o e s n o t re q u ire ga d o lin iu m t o s e e e d e m a t o u s
ch a n ge s , a n d m ay be u s e fu l for m on it orin g p rogre s s ion of d is e a s e (4 ).
Tre atme nt
Th e m a n a ge m e n t of CN is lim it e d a n d m a in ly con s is t s o f re d u ct io n in
w e igh t -b e a r in g a ct ivit y. Pla s t e r ca s t in g fo r s eve ra l w e e k s t o a llow t h e
Figure 22.2 Destruction of midfoot joints in
a cu t e p h a s e t o re s olve, follow e d by t ot a l-con t a ct ca s t a p p lica t ion s t h a t
Cha rcot neuroa rthropa thy. (Courtesy of Gera ld a llow for be t t e r a m bu la t ion , is com m on ly u t ilize d . Ot h e r s p e cia lize d foot -
F. Moore, MD.) w e a r for a cu t e CN a p p lica t ion s in clu d e Ch a rcot re s t ra in t ort h ot ic w a lke rs ,
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 225
Clinical Co urse
Ea rly d ia gn os is of CN ca n p ot e n t ia lly p reve n t com p lica t ion s in clu d in g s eve re
d e form it y, u lce ra t ion s , a n d eve n lim b a m p u t a t ion . Be ca u s e CN is a re la t ive ly
u n com m on co n d it ion , re fe rra l t o a s p e cia lis t w it h a m u lt id is cip lin a ry t e a m
a p p roa ch is p re fe rre d .
ADHESIVE CAPSULITIS
e
n
Clinical Pre se ntatio n
o
B
Com p a re d t o 2% t o 5% of t h e ge n e ra l p op u la t ion , a p p roxim a t e ly 20% of p e op le
c
i
l
w it h d ia be t e s a re a ffe ct e d a t s om e t im e by a d h e s ive ca p s u lit is of t h e s h ou ld e r.
o
b
Th is re la t ive ly com m on con d it ion is d e n e d a s t h e in s id iou s on s e t of s h ou ld e r
a
t
p a in w it h a gra d u a l los s of bot h a ct ive a n d p a s s ive ra n ge of m ot ion (ROM) (5 ).
e
M
Th e n a t u ra l h is t o ry o f a d h e s ive ca p s u lit is is a p rogre s s ion t h rou gh fou r
d
n
s e q u e n t ia l a n d d e s crip t ive s t a ge s : (a ) p re a d h e s ive s t a ge (d iffu s e gle n oh u m e ra l
a
s yn ovit is s e e n on a rt h ros copy); (b) fre e zin g s t a ge (h yp e rt rop h ic a n d h yp e rva s -
s
i
t
i
cu la r s yn ovit is w it h ca p s u la r brop la s ia a n d s ca r form a t ion ); (c) froze n s t a ge
r
h
t
(s ign i ca n t h yp e r t ro p h y a n d h yp e r va s cu la r it y w it h d e n s e ca p s u la r s ca r );
r
a
(d ) t h a w in g p h a s e (a p p a re n t re m od e lin g w it h ou t s yn ovit is ) (5 ). Pa in is in it ia lly
o
e
t
s eve re a n d im p rove s w it h d e cre a s in g s yn ovit is in la t e r s t a ge s . A p rogre s s ive
s
O
d e clin e in ROM is n ot a ble u n t il s t a ge 4, or t h aw in g occu rs .
4
Sle e p -d is t u rbin g p a in is oft e n a m ot iva t in g fa ct or for p a t ie n t s t o s e e k m e d -
N
O
ica l a t t e n t ion . Ce rt a in e le m e n t s of t h e h is t ory ca n h e lp d e t e rm in e w h e re e a ch
I
T
p a t ie n t re s id e s on t h e co n t in u u m (Ta ble 22.1 ). For e xa m p le, a p a t ie n t w h o is
C
E
u n a ble t o s le ep t h rou gh t h e n igh t , h a s s ign i ca n t lim it a t ion s in ROM, a n d s u f-
S
fe rs from on goin g p a in is like ly in s t a ge 2, or a ct ive fre e zin g.
Examinatio n
Sign i ca n t lim it a t io n o f bo t h a ct ive a n d p a s s ive a bd u ct io n o f t h e s h o u ld e r
e xis t ; h ow eve r, t h e e xt e n t of re s t rict ion is s t a ge d ep e n d e n t . Act ive ROM t h a t is
a ccom p a n ie d by s ca p u la r m ove m e n t is a clu e t o d ia gn os is . Pa t ie n t s oft e n d is -
p lay t ra n s ie n t s eve re p a in w it h a bru p t or e n d -ra n ge m ove m e n t s . Alt h ou gh n or-
m a l s t re n gt h h a s be e n con s id e re d a cla s s ic n d in g, re ce n t s t u d ie s u s in g h a n d -
h e ld d yn a m om e t ry h ave d e m on s t ra t e d w e a kn e s s in t h e in t e rn a l a n d e xt e rn a l
rot a t ors , a bd u ct ors , a n d e leva t ors (5 ).
DURATION SLEEP
STAGE (MONTHS) PAIN DISRUPTION STIFFNESS
Pre a d h e sive 0–3
Fre e zin g 3–9
Fro ze n 9–15
Th a w in g 15–24
226 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Studie s
His t ory a n d p h ys ica l e xa m in a t ion a lon e a re oft e n a d e q u a t e t o d ia gn os e a d h e -
s ive ca p s u lit is . How eve r, im a gin g s t u d ie s ca n h e lp ru le o u t o t h e r p a t h o logy.
Pla in ra d iogra p h s a re lim it e d t o n d in g bon y p a t h ology. Ma gn e t ic re s on a n ce
im a gin g ca n d iffe re n t ia t e s o ft -t is s u e a b n o r m a lit ie s o f t h e ro t a t o r cu ff a n d
la bru m . Ult ra s on ogra p h y h a s a ls o p rove d t o be u s e fu l in d e cip h e rin g a d h e s ive
ca p s u lit is from rot a t or cu ff t e n d in op a t h y (5 ).
Tre atme nt
Dis cu s s ion s w it h t h e p a t ie n t s h ou ld in clu d e e d u ca t ion rega rd in g t h e n a t u ra l
h is t ory of a d h e s ive ca p s u lit is , p re p a ra t ion for a n e xt e n d e d re cove ry, a n d a lle -
via t ion of fe a r of a m ore s e riou s d is e a s e. A h om e e xe rcis e p rogra m ou t lin e d by
a p h ys ica l t h e ra p is t ca n be e ffe ct ive in re lievin g s ym p t om s , a n d a ls o p la ce s t h e
p a t ie n t in a n a ct ive role. Gle n oh u m e ra l cort icos t e roid in je ct ion , e xe rcis e, a n d
join t m obiliza t ion a ll le a d t o im p rove d s h ort - a n d lon g-t e rm ou t com e s . Cort i-
cos t e roid in je ct ion s h a ve be e n s h ow n t o re s u lt in m ore ra p id im p rove m e n t s a t
4- t o 6-w e e k in t e rva ls a n d a re t h e re fore a re a s on a ble op t ion for p a t ie n t s w it h
S
E
m o re s eve re s ym p t o m s , w h o h a ve n o t re s p o n d e d w e ll t o re h a b ilit a t io n (5 ).
C
T
How eve r, t h e re is co n ce r n fo r p o t e n t ia lly e leva t e d s e r u m glu co s e leve ls in
I
O
p a t ie n t s w it h d ia be t e s w h o re ce ive in t ra -a rt icu la r cort icos t e roid s . If con s e rva -
N
4
t ive m a n a ge m e n t is u n s u cce s s fu l, obs t in a t e froze n s h ou ld e r m a y be fu rt h e r
O
m a n a ge d w it h m a n ip u la t ion u n d e r a n e s t h e s ia or s u rgica l ca p s u la r re le a s e.
s
t
e
o
Clinical Co urse
a
r
t
Ad h e s ive ca p s u lit is is u s u a lly s e lf-lim it e d , la s t in g 12 t o 24 m on t h s . How eve r,
h
r
i
m ild s ym p t om s ca n p e rs is t for ye a rs , d e p e n d in g on t h e e xt e n t of brop la s ia s .
t
i
s
Som e s t u d ie s re p ort t h a t u p t o h a lf of p a t ie n t s h a ve lim it e d ROM m ore t h a n
a
n
3 ye a rs a ft e r s ym p t om on s e t .
d
M
e
t
HYPOTHYROIDISM
a
b
o
Sym m e t rica l a rt h rop a t h y w it h s t iffn e s s of t h e h a n d s a n d kn e e s is a com m on
l
i
c
in it ia l p re s e n t a t ion of p a t ie n t s w it h h yp ot h yroid is m . Exa m in a t ion in clu d in g
B
o
p a lp a t ion of in volve d join t s m a y reve a l s yn ovit is . Syn ovia l u id is t yp ica lly
n
e
n on in a m m a t ory w it h h igh leve ls of h ya lu ron ic a cid .
Hyp ot h yroid is m is a ls o a s s ocia t e d w it h ca lciu m pyrop h os p h a t e d ep os it ion
(CPPD), w h ich w ou ld re s u lt in a n in a m m a t ory s yn ovia l u id w it h w e a kly p os -
it ive ly bire frin ge n t rh om boid a l crys t a ls s e e n u n d e r p ola rize d ligh t m icros cop y
(Fig. 22.3 ). In d e e d , m u lt ip le s ys t e m ic d is e a s e s a re a s s ocia t e d w it h CPPD a rt h rop -
a t h y (Ta ble 22.2 ). Ca rp a l t u n n e l s yn d rom e ca n a ls o be
a n in it ia l p re s e n t a t io n in u p t o 7% o f p a t ie n t s w it h
h yp ot h yroid is m .
Ch ro n ic a u t oim m u n e t h yro id it is , or Ha s h im o t o ’s
t h yro id it is , h a s a va r ie t y o f a s s o cia t e d r h e u m a t ic
m a n ife s t a t ion s , s u ch a s m ild n on e ros ive a rt h rit is , p ol-
ya rt h ra lgia , m ya lgia , a n d s icca s yn d rom e. Mos t m a n i-
fe s t a t ion s a re s e co n d a ry t o h yp ot h yroid is m a n d d o
n o t re s olve u n t il a e u t h yroid s t a t e is a ch ieve d . How -
eve r, in t re a t e d or e u t h yroid Ha s h im ot o’s t h yroid it is ,
a r t h rop a t h ie s m a y be d u e t o a n a s s ocia t e d a u t o im -
m u n e e t iology, s u ch a s Sjogre n ’s s yn d rom e, rh e u m a -
t oid a rt h rit is , or s ys t e m ic lu p u s e ryt h e m a t os u s .
HYPERTHYROIDISM
Hyp erth yroid ism , in clu d in g Grave’s d isea se, ca n p resen t
Figure 22.3 Ca lcium pyrophospha te deposition crysta l. (Courtesy of a s p retibia l m yxed em a a n d op h th a lm op a th y. Digita l soft-
Gera ld F. Moore, MD.) tissu e sw ellin g w ith p eriostitis of m eta ca rp op h a la n gea l
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 227
e
ca n a ls o le a d t o os t e o p oros is . Tre a t m e n t go a ls in clu d e n o rm a liza t ion of t h y-
n
o
roid -s t im u la t in g h orm on e a n d im p rove m e n t in bon e m in e ra l d e n s it y a s m e a s -
B
u re d by d e n s it om e t ry.
c
i
l
o
b
a
t
HYPERPARATHYROIDISM AND HYPOVITAMINOSIS D
e
M
Ca lciu m h o m e o s t a s is w it h b o n e m e t a b o lis m a n d re m o d e lin g a re in t r ica t e ly
d
n
con t rolle d by p a ra t h yroid h orm on e (PTH), vit a m in D, a n d ca lcit on in leve ls . Pri-
a
m a ry h yp e r p a ra t h yro id is m is o ft e n s e co n d a ry t o a p a ra t h yro id a d e n o m a ,
s
i
t
i
r
w h e re a s s e con d a ry d is e a s e is m os t com m on ly re la t e d t o re n a l fa ilu re, vit a m in
h
t
r
D d e cie n cy, a n d os t e om a la cia . Art h ra lgia s a re com m on in bot h p rim a ry a n d
a
o
s e con d a ry d is e a s e, a n d ca n in volve s m a ll join t s of t h e h a n d s , oft e n s p a rin g t h e
e
t
p roxim a l in t e rp h a la n ge a l (PIP) join t s . Ra d iogra p h ic ch a n ge s in clu d e os t e it is b-
s
O
ro s a cys t ica , e ro s io n s , p h a la n ge a l s u b p e r io s t e a l re s o r p t io n a lo n g t h e ra d ia l
4
e d ge s , a n d eve n d is t a l t u ft re s orp t ion . Rh e u m a t oid fa ct or is t yp ica lly n ega t ive
N
O
a n d e ryt h rocyt e s e d im e n t a t ion ra t e n orm a l. Ca lciu m p yrop h os p h a t e d e p os i-
I
T
C
t ion is a s s ocia t e d w it h h yp e rp a ra t h yroid is m , a n d a cu t e gou t a t t a cks ca n a ls o
E
occu r (Ta ble 22.2 ). Eit h e r ca lciu m p yrop h os p h a t e or u ric a cid crys t a ls ca n be
S
fou n d in a s p ira t e d join t u id from a n a cu t e ly in a m e d join t of a p a t ie n t w it h
h yp e r p a ra t h yro id is m . Brow n t u m o rs (Fig. 22.4 ), w h ich a re lyt ic b o n e le s io n s ,
ca n be s e e n on ra d iogra p h s a n d rep re s e n t loca lize d a re a s of brou s t is s u e w it h
in cre a s e d os t e ocla s t ic a ct ivit y.
ACROMEGALY
Acrom ega ly is a ra re con d it ion w it h a n es t im a t e d a n n u a l in cid e n ce of 4 ca s e s p er
m illion p e rs on s a n d is typ ica lly d u e t o h yp e rse cre tion of grow t h h orm on e s e c-
on d a ry to a ben ign p itu it a ry a d en om a (6 ). W h ile ca rd iova s cu la r d is ea s e a ccou n ts
for t h e m a jorit y of m ort a lit y in t h e s e p a t ien t s , a rt icu la r m a n ifes t a t ion s a re t h e
le a d in g ca u s e of m orbid ity. Acrom ega lic a rth rop a t h y a ffect s bot h th e a xia l a n d
a p p e n d icu la r s ke le t on , w it h t h e kn e e s be in g t h e m os t com m on ly in volve d
p e rip h e ra l join t . Non in a m m a t ory a rt h rit is w it h join t s t iffn e s s a n d sw e llin g is
com m on . Art icu la r w id e n in g w it h s oft -t is s u e h yp e rtrop h y a n d join t h yp erm obil-
it y p red om in a t es in ea rly s t a ges w h en con trol of grow t h h orm on e a n d in s u lin -
like grow t h fa ct or 1 (IGF-1) m ay revers e t h e a rt h rop a t h y (6 ). La t er s t a ge s m a n ife s t
in ca rtila ge u lce rs , s u bch on d ra l cys t form a t ion , a rt icu la r t h icke n in g, lim it e d ROM,
a n d u ltim a t ely s eve re d ege n e ra t ive a rth ritis . Ra d iogra p h ic a bn orm a lit ie s in clu d e
d is ta l t u ft in g of t h e p h a la n ge s , os t eop h yt e form a t ion , es p ecia lly a t th e ba s e of
Figure 22.4 Brown tumors hyperpa r-
d is ta l p h a la n ge s , a n d su bch on d ra l cys t form a t ion . Up to on e h a lf of p a t ien t s h ave
a thyroid. (Courtesy of Gera ld F. Moore, sym p t om a t ic ca rp a l t u n n el s yn d rom e ; h ow eve r, t h is is like ly rela t ed t o m e d ia n
MD.) n e rve ed e m a ra t h e r t h a n ext rin s ic com p re s s ion in t h e s e p a t ie n ts .
228 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Tre atme nt
As ym p t o m a t ic p a t ie n t s d o n o t re q u ire s p e ci c t re a t m e n t fo r
HOA. No n s t e ro id a l a n t i-in a m m a t o ry d r u gs (NSAIDs ) m a y b e
u s e fu l fo r s ym p t o m s o f p a in . Ca s e s t u d ie s h a ve re p o r t e d
im p rove d p a in con t rol in re fra ct ory ca s e s w it h a d m in is t ra t ion
of in t rave n ou s bis p h os p h on a t e t h e ra p y (7 ).
Clinical Co urse
In ge n e ra l, t h e clin ica l con d it ion is m o s t d e p e n d e n t on t re a t -
m e n t of t h e u n d e rlyin g s ys t e m ic d is e a s e. For e xa m p le, clu bbin g
ca n im p rove or eve n re s olve w it h ch e m ot h e ra py or re s e ct ion of
t h e a s s ocia t e d m a lign a n cy.
CARCINOMATOUS POLYARTHRITIS
Figure 22.6 Periostitis in hypertrophic osteoa rthropa thy. Ge n e ra lly a s e ron ega t ive p olya rt h ro p a t h y, ca rcin om a t o u s p ol-
(Courtesy of Gera ld F. Moore, MD.) ya r t h rit is re p re s e n t s a co n d it io n t h a t ca n m im ic rh e u m a t o id
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 229
e
n
s ion a n d PIP e xion or e xt e n s ion . Con ve rs e ly, e xion of bot h MCP a n d PIP join t s ,
o
B
or cle n ch e d s t , m ay s u gge s t m a lin ge rin g (8 ). Ot h e r s ign s a n d s ym p t om s m ay
c
i
l
in clu d e s t iffn e s s , loca l os t e op e n ia , a t rop h y of n a ils a n d h a ir, s kin h yp e rt rop h y,
o
b
a n d n e m ot or d if cu lt ie s . Ma gn e t ic re s on a n ce im a gin g a n d t h re e -p h a s e bon e
a
t
s ca n ca n be p os it ive in la t e d is e a s e, s h ow in g in cre a s e d p e ria rt icu la r u p t a ke in
e
M
in vo lve d jo in t s . A m u lt id is cip lin a ry a p p ro a ch t o m a n a ge m e n t is im p o rt a n t ,
d
n
w it h in p u t from a n in t e rn is t , s u rge on , p a in s p e cia lis t , p h ys ica l t h e ra p is t , p s y-
a
ch ologis t or p s ych ia t ris t , a n d rh e u m a t ologis t . Ph a rm a cologic t h e ra py in clu d e s
s
i
t
i
a n t id e p re s s a n t s , a n t icon vu ls a n t s , ca lciu m ch a n n e l blocke rs , a d re n e rgic com -
r
h
t
p ou n d s , a n d cort icos t e roid s , a s w e ll a s a n t i-in a m m a t ory a n d a n a lge s ic a ge n t s .
r
a
A com bin a t ion of a ge n t s w it h con cu rre n t h a n d t h e ra py is m os t be n e cia l (8 ).
o
e
t
s
O
MULTICENTRIC RETICULOHISTIOCYTOSIS
4
N
A ra re d is ord e r w it h u n kn ow n p a t h oge n e s is , m u lt ice n t ric re t icu loh is t iocyt os is
O
I
T
(MR) is ch a ra ct e rize d by p rogre s s ive e ros ive p olya rt h rit is a n d n od u la r s kin a n d
C
E
m u cos a l le s ion s (Fig. 22.7 ). Mu lt ice n t ric re t icu loh is t iocyt os is h a s be e n rep ort e d
S
in a s s ocia t ion w it h s eve ra l m a lign a n cie s , m os t oft e n bre a s t a n d s t om a ch ca r-
cin om a . Mid d le -a ge d w om e n a re m os t com m on ly a ffe ct e d , w it h a rt h ra lgia s fol-
low e d by s kin m a n ife s t a t ion s m on t h s t o ye a rs la t e r. Th e lon g clin ica l cou rs e
m a ke s d ia gn os is d if cu lt . Con rm a t ion is by h is t ologic p re s e n ce of m on on u -
cle a r h is t iocyt e s a n d m u lt in u cle a t e d gia n t ce lls . Sym m e t rica l a rt h rop a t h y p ri-
m a rily a ffe ct s t h e in t e rp h a la n ge a l jo in t s o f t h e h a n d s a n d ca u s e s m o d e ra t e
p a in , s t iffn e s s , a n d s w e llin g. Dis t a l in t e r p h a la n ge a l
(DIP) join t in volve m e n t ca n h e lp d is t in gu is h t h e p roc-
e s s fro m o t h e r d is e a s e s , a lt h o u gh a n y jo in t ca n b e
a ffe ct e d . Na t u ra l p rogre s s ion le a d s t o s eve re d e s t ru c-
t io n a n d d is gu ra t io n . Aggre s s ive t r e a t m e n t w it h
im m u n os u p p re s s ive m e d ica t ion s is im p ort a n t in s u ch
ca s e s (9 ).
Tre atme nt
Acu t e t h e ra py for s ickle ce ll cris is in clu d e s h yd ra t ion
a n d p a in co n t ro l. Co n s e rva t ive m a n a ge m e n t ve r s u s
s u rgica l in t e rve n t ion for os t e on e cros is is ba s e d on t h e
p a t ie n t a n d s t a gin g of s eve rit y. Core d e com p re s s ion ,
s t ru ct u ra l bon e gra ft in g, os t e ot om y, a n d a rt h rop la s t y
a re a va ila ble op t ion s . Con s e rva t ive m e a s u re s in clu d e
lim it a t io n s in w e igh t b e a rin g a n d p a in co n t ro l w it h
a n a lge s ic a ge n t s (11 ).
Clinical Co urse
Progre s s ion a n d p rogn os is of os t e on e cros is is d ep e n d -
e n t o n t h e s ize a n d lo ca t io n o f t h e in fa rct e d le s io n .
Ra n ge of m ot ion t yp ica lly d e clin e s s low ly ove r t im e .
Figure 22.8 Osteonecrosis of left femora l hea d. (Courtesy of Gera ld F. Eve n t u a lly, colla p s e ca n occu r. Th e re fore m on it orin g is
Moore, MD.) w a rra n t e d .
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 231
HEMOPHILIA
Join t d is e a s e is on e of t h e m os t im p ort a n t ca u s e s of m orbid it y in p a t ie n t s w it h
s eve re h e m op h ilia . Re cu rre n t ble e d in g in t o t h e join t le a d s t o ca rt ila ge d a m a ge,
s yn ovia l h yp e rt rop h y, n a rrow e d join t s p a ce, a n d eve n a lt e ra t ion s in bon e s t ru c-
t u re (12 ). Pa t ie n t s m ay p re s e n t w it h p a in , sw e llin g, s t iffn e s s , or “lockin g” w it h
in s t a bilit y of t h e kn e e s or e lbow s . Ma gn e t ic re s on a n ce im a gin g is a s e n s it ive
t ool s h ow in g low s ign a l in t e n s it y on T 1 - or T 2 -w e igh t e d im a ge s w h e re p e rs is t -
e n t h e m os id e rin d ep os it ion occu rs from rep e a t e d in t ra -a rt icu la r h e m orrh a ge.
Ph ys ica l t h e ra p y a n d re h a b ilit a t io n —in clu d in g p h ys io t h e ra p y, h yd ro t h e ra p y,
s p lin t in g, a n d ort h ot ics —a re im p ort a n t in bot h t h e t re a t m e n t a n d t h e p reve n -
t ion of h e m op h ilic a rt h rop a t h y (12 ). Syn ove ct om y a n d join t rep la ce m e n t a re
a d d it ion a l op t ion s .
e
n
HEMOCHROMATOSIS
o
B
Clinical Pre se ntatio n
c
i
l
o
He re d it a ry h e m och rom a t os is is a re la t ive ly com m on a u t os om a l-re ce s s ive d is -
b
a
ord e r w it h a p p roxim a t e ly 1 in 200 p e rs on s a ffe ct e d . A s u bs t it u t ion of t yros in e
t
e
M
for cys t e in e a t a s p e ci c loca t ion on e a ch a lle le re s u lt s in in cre a s e d in t e s t in a l
iron a bs orp t ion a n d eve n t u a l iron ove rloa d . Th e a rt h rop a t h y a s s ocia t e d w it h
d
n
h e m och rom a t os is is w e ll re cogn ize d a n d rep ort e d in u p t o 81% of p a t ie n t s (13 ).
a
s
Fa t igu e a n d a rt h ra lgia s a re com m on n on s p e ci c e a rly s ym p t om s , w h ile cla s s ic
i
t
i
r
bron ze d ia be t e s , CHF, a n d cirrh os is a re a m u ch le s s com m on p re s e n t a t ion , a n d
h
t
r
s u gge s t e n d -s t a ge d is e a s e (14 ).
a
o
Pa in fu l a rt h ra lgia s a re a m a jor ca u s e of m orbid it y, d is a bilit y, a n d re d u ce d
e
t
s
q u a lit y o f life fo r p a t ie n t s w it h h e re d it a ry h e m o ch ro m a t o s is . It ca n a ffe ct
O
n e a rly a n y join t , bu t m os t com m on ly in volve s t h e MCP a n d ra d ioca rp a l join t s ,
4
N
a n kle s , h ip s , e lbow s , kn e e s , a n d s h ou ld e r s (13 ). Lo n g-s t a n d in g u n e xp la in e d
O
jo in t p a in o r o s t e o a r t h r it is in a p a t ie n t yo u n ge r t h a n 55
I
T
C
ye a rs o f a ge s h o u ld w a rra n t s u s p icio n o f p o s s ible h e m o -
E
S
ch rom a t os is (14 ).
Examinatio n
Bon y sw e llin g ca n be s ign i ca n t a n d re s e m ble os t e oa rt h ri-
t is . In volve m e n t of t h e s e con d a n d t h ird MCP join t s in a
s ym m e t rica l p a t t e rn is a h a llm a rk (15 ).
Studie s
Se ru m leve ls of iron , t ot a l iron -bin d in g ca p a cit y (TIBC), a n d
fe rrit in s h ou ld be obt a in e d . If iron s a t u ra t ion is gre a t e r t h a n
50%, o r a n e leva t e d fe rr it in leve l p re s e n t , ge n e t ic t e s t in g
s h ou ld fo llow (14 ). Re fe rra l t o a ga s t ro e n t e ro logis t is w a r-
ra n t e d . Ra d iogra p h ic ch a n ge s in clu d e broa d e n in g of m e t a -
ca rp a l h e a d s w it h cla s s ic “h ook-like ” os t e op h yt e s a n d join t
s p a ce n a rrow in g (Fig. 22.9 ). Se co n d a ry CPPD d is e a s e fro m
h e m och rom a t os is ca n a ls o reve a l crys t a ls on a rt h roce n t e -
s is of in volve d join t s .
Tre atme nt
Tre a t m e n t op t ion s a re lim it e d , w it h on ly s ym p t om a t ic t h e r-
a p ie s a va ila ble for m a n a ge m e n t of a r t h rop a t h y. Un fo rt u -
Figure 22.9 Joint spa ce na rrowing with “hook” osteophytes a nd
n a t e ly, regu la r p h le bot om y w it h s ys t e m ic iron d ep le t ion is
hypertrophic cha nges seen in Hemochroma tosis. (Courtesy of s e ld om h e lp fu l for join t s ym p t om re lie f, a n d h a s n o e ffe ct
Gera ld F. Moore, MD.) on t h e p rogre s s ive d e t e riora t ion of join t s t ru ct u re (13 ).
232 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Clinical Co urse
Alth ou gh ea rly d ia gn osis a n d trea tm en t h ave little effect on th e a rth rop a th y, m ore
seriou s com p lica tion s secon d a ry to system ic iron overloa d , n otably cirrh osis, CHF,
a n d d ia betes m ellitu s, m ay be avoid ed .
WILSON’S DISEASE
Wils on ’s d is e a s e is a ra re, bu t t re a t a ble, a u t os om a l-re ce s s ive d is ord e r ca u s e d
by a m u t a t ion in cop p e r-t ra n s p ort in g ATPa s e. Th is re s u lt s in a n a ccu m u la t ion
of fre e cop p e r in orga n s in clu d in g t h e live r, bra in , a n d join t s . Ne u rologic m a n i-
fe s t a t ion s in clu d e d ys a rt h ria , d ys t on ia , a n d t re m or. Pa t ie n t s m ay com p la in of
p a in a n d s t iffn e s s , e s p e cia lly in volvin g t h e kn e e s , w ris t s , or ot h e r la rge join t s .
Mu s cu los ke le t a l p a in m ay be t h e on ly p re s e n t in g s ym p t om a n d is like ly s e c-
on d a ry t o s yn ovia l in a m m a t ion a n d bon e d e m in e ra liza t ion (16 ).
ALKAPTONURIA (OCHRONOSIS)
S
E
Alka p t on u ria is a ra re m e t a bolic a u t os om a l-re ce s s ive d is e a s e w it h e s t im a t e d
C
T
in cid e n ce of 1 in 250,000 t o 1 m illion live birt h s . A d e cie n cy of h om oge n t is a t e
I
O
N
1,2-d ioxyge n a s e e n zym e re s u lt s in e xce s s h om oge n t is ic a cid . Och ron ot ic p ig-
4
m e n t d ep os it s in t is s u e, p a rt icu la rly join t s , ca u s in g in a m m a t ion a n d a rt icu la r
O
d ege n e ra t ion (17 ). A ch ild ’s rs t s ym p t om s ca n in clu d e d a rke n e d or bla ck u rin e.
s
t
e
How eve r, p a t ie n t s ca n b e u n d ia gn o s e d a n d p re s e n t a s a n a d u lt w it h lo n g-
o
a
s t a n d in g ba ck p a in a s t h e ir on ly com p la in t . Seve re s p on d yloa rt h rop a t h y is t h e
r
t
h
m os t com m on p re s e n t a t ion of och ron ot ic a rt h rop a t h y. Clin ica l re s e m bla n ce t o
r
i
t
a n kylos in g s p on d ylit is e xis t s ; h ow eve r, s a croilia c join t s a re t yp ica lly s p a re d .
i
s
Arth rop a th y begin s in th e th ird or fou rth d eca d e of life a n d resu lts in ROM
a
n
lim ita tion s, effu sion s, a n d even tu a lly ch ron ic p a in . Kn ee, h ip, or sh ou ld er rep la ce-
d
M
m e n t s a re com m on . Sp in a l in volve m e n t le a d s t o kyp h os is , h e igh t los s , a n d
e
d ecrea sed lu m ba r exion . Den sely ca lci ed in tervertebra l d iscs a re ch a ra cteristic
t
a
b
on im agin g stu d ies. Th era p ies in clu d e vita m in C beca u se of a n tioxid a n t p rop erties
o
l
i
a n d p rote in rest riction in a n a t tem p t t o d ecrea s e h om ogen tis ic a cid excretion .
c
B
How ever, ef ca cy h a s n ot bee n p roved . In gen era l, su rveilla n ce for ca rd ia c a n d
o
n
ren a l com p lica tion s a n d a tten tion to p a in con trol a re m ost p ra ctica l (17 ).
e
HEREDITARY DISORDERS OF CONNECTIVE TISSUES
Polya rt icu la r h yp e rm obilit y is p re s e n t in u p t o 30% t o 40% of you n g m e n a n d
w om e n , re s p e ct ive ly. For m os t , h ow eve r, h yp e rm obilit y is of n o m e d ica l con s e -
q u e n ce a n d t e rm e d benign hyperm obility syndrom e. Con d it ion s in clu d in g Eh le rs –
Da n lo s s yn d ro m e , o s t e o ge n e s is im p e r fe ct a , a n d Ma r fa n s yn d ro m e in vo lve
a bn orm a lit ie s of colla ge n , brillin , a n d m a t rix p rot e in s w it h s ign i ca n t m u s cu -
los ke le t a l m a n ife s t a t ion s . Pa t ie n t s w it h t h e s e d is e a s e s ca n p re s e n t w it h loca l-
ize d or d iffu s e a rt h ra lgia , m ya lgia s , t e n d in op a t h ie s , re cu rre n t join t d is loca t ion ,
s u blu x a t io n s , fra gilit y fra ct u re s , liga m e n t o r ca p s u la r p a t h o logy, e a r ly o n s e t
os t e oa rt h rit is , a n d fa t igu e (18 ). Pa in is t h e m os t com m on re a s on t h e s e p a t ie n t s
s e e k m e d ica l a t t e n t ion . In m os t ca s e s t h e re is n o evid e n ce of s ign i ca n t d a m -
a ge t o join t s , m u s cle s , or s u rrou n d in g s t ru ct u re s t o a ccou n t for t h e w id e s p re a d
p a in . Ph ys ica l a n d o ccu p a t io n a l t h e ra p y m e t h o d s n e e d t o b e m o d i e d t o
a ccou n t for la xit y of t is s u e s , in clu d in g s p lin t s t o p rot e ct u n s t a ble join t s , d eve l-
op m e n t of m u s cle s re s p on s ible for core s t a bilit y, re s t ora t ion of p rop riocep t ion ,
a n d ort h ot ics t o corre ct m e ch a n ica l d is crep a n cie s (18 ).
For m os t h e rit a ble d is ord e rs , re fe rra l t o a ge n e t icis t is w a rra n t e d for a p p ro-
p ria t e re p rod u ct ive ris k s t ra t i ca t ion a n d cou n s e lin g. Alt h ou gh m u s cu los ke le -
t a l m a n ife s t a t ion s a re d is cu s s e d h e re , in h e rit e d d is e a s e s oft e n h a ve a w id e
a rray of s ys t e m ic a n d m u lt iorga n in volve m e n t n e ce s s it a t in g in t e rd is cip lin a ry
a p p roa ch t o m a n a ge m e n t .
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 233
e
n
Th e “s h o u ld e r p a d ” s ign is t h e m o s t cla s s ic a r t icu la r m a n ife s t a t io n o f AL
o
B
a m yloid os is a n d is d u e t o in lt ra t ion of t e n d on s a n d ca p s u la r s t ru ct u re s of
c
i
l
t h e s h ou ld e r, le a d in g t o sw e llin g a n d m ot ion lim it a t ion . W h e n cou p le d w it h
o
b
m a croglo s s ia a n d p e r io r b it a l cu t a n e o u s e cch ym o s is (“ra cco o n eye s ”), t h e
a
t
e
s h o u ld e r p a d s ign is co n s id e re d n e a r ly p a t h ogn o m o n ic. Pa t ie n t s w it h AL
M
a m yloid os is h ave t h e w ors t p rogn os is s e con d a ry t o a s s ocia t ion s w it h h e a rt
d
n
fa ilu re. Tre a t m e n t focu s e s on re d u ct ion of a m yloid oge n ic p rot e in con ce n t ra -
a
t ion by ch e m ot h e ra py.
s
i
t
i
• A A am yloidosis: An y ch ron ic in a m m a tory p rocess th a t ca u ses p ersisten t eleva -
r
h
t
tion of a cu te-p h a se rea ct a n ts ca n lea d to d ep osition of seru m a m yloid A (SAA)
r
a
o
p rotein a n d res u lt in AA a m yloid osis. Rh eu m a tic d is ea ses in clu d in g rh eu m a -
e
t
t oid a rt h rit is , a n kylos in g s p on d ylit is , p s oria t ic a rt h rit is , ju ve n ile id iop a t h ic
s
O
a rth ritis, a n d fa m ilia l Med iterra n ea n fever (FMF) a ccou n t for 70% of AA a m yloi-
4
d osis (19 ). Pa tien ts h ave a m u ch better p rogn osis th a n th ose w ith AL a m yloid osis,
N
O
w it h a m e d ia n s u rviva l of 4 t o 10 ye a rs , d ep e n d in g on ca rd ia c in volve m e n t .
I
T
Th era py focu ses on trea tin g th e u n d erlyin g d isord er to su p p ress ch ron ic in a m -
C
E
m a t io n a n d t h u s re d u ce circu la t in g leve ls o f SAA
S
p rot e in . Colch icin e is h igh ly e ffe ct ive in p reve n t in g
th e AA a m yloid osis of fa m ilia l Med iterra n ea n fever.
• 2 -m icroglobulin ( 2M) am yloidosis: Pa t ie n t s on lon g-
term h em od ia lysis a re a t risk of d evelop in g a m yloid o-
sis ca u sed by d ep osition of brilla r 2M p rotein . Pa th o-
gen es is is u n kn ow n bu t felt to be m u ltifa ctoria l a n d
a s s ocia t e d w it h a ge a n d d u ra t ion of h e m od ia lys is .
Ea rly m a n ifesta tion s in clu d e ca rp a l tu n n el syn d rom e
a n d ch ron ic a rth ra lgia , com m on ly in volvin g th e sh ou l-
d ers. Un fortu n a tely, a n erosive a n d d isablin g a rth rop a -
th y of la rge join ts ca n d evelop. Ra d iogra p h ic sign s of
a xia l in volve m e n t in clu d e e ros ion s of ve rt ebra l cor-
n ers a n d severe in tervertebra l sp a ce n a rrow in g. Mag-
n etic reson a n ce im a gin g ca n sh ow a m yloid d ep osits
a s w e ll (Fig. 22.10 ). Ap p ro xim a t e ly 50% t o 60% o f
p a tien ts receivin g h em od ia lysis for m ore th a n 10 yea rs
w ill h ave s u bch on d ra l ra d iolu cen t bon e cys t s in t h e
sh ou ld er, h ip s, w rists, or vertebra e on im agin g. Bon y
cys t s ca n a ccou n t for fra ct u re s of t h e fe m ora l n e ck
a n d vertebra e. Th era py a im s a t p rom otin g clea ra n ce of
2M p rotein a n d p reven tin g a m yloid d ep osition ; h ow -
Figure 22.10 Ma gnetic resona nce ima ging of a myloid in ltra ting right ever, th e u se of h igh - u x d ia lysis m em bra n es h a s n ot
femora l hea d. (Courtesy of Gera ld F. Moore, MD.) been p roved to be effective (19 ).
234 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
SARCOIDOSIS
WHEN TO REFER
Sa rcoid os is is a p oorly u n d e rs t ood d is e a s e of n on ca s e a t in g gra n u lom a d eve lop -
• Fo r a ssist a n ce in d if cu lt m e n t , t yp ica lly in t h e lu n gs a n d lym p h n od e s . It a ffe ct s virt u a lly a n y orga n ,
d ia g n o se s a lt h ou gh p a t ie n t s m ay be com p le t e ly a s ym p t om a t ic. Mu s cu los ke le t a l m a n ife s -
• Wh e n co n se rva t ive m e a s-
t a t ion s in clu d e in a m m a t ory a rt h rit is , t e n os yn ovit is , d a ct ylit is , p e ria rt icu la r
u re s a re n o t h e lp fu l s o ft -t is s u e s w e llin g, m yo p a t h y, a n d gra n u lo m a t o u s b o n e in lt ra t io n (20 ).
Löfgre n ’s s yn d rom e is bila t e ra l h ila r a d e n op a t h y w it h a cu t e e ryt h e m a n od os u m ,
• Whe n t h e clin ica l p ict u re
n o lo ng e r t s t he dia g no sis
a n d m ay in clu d e feve r, a n t e rior u ve it is , a n d a rt h rit is , e s p e cia lly of t h e a n kle s .
Tw o t yp e s of a rt h rit is a re re cogn ize d . Acu t e s a rcoid a rt h rit is is s e lf-lim it e d a n d
• Fo r m a n a g e m e n t o f im m u - re s olve s w it h ou t p e rm a n e n t s e q u e la e . Ch ron ic a rt h rit is is le s s com m on a n d
n o su p p re ssa n t m e d ica t io n s
ca n p ro gre s s t o jo in t d e fo r m it y b e ca u s e o f p ro life ra t ive a n d in a m m a t o ry
• For therapeutic measures ch a n ge s in t h e s yn oviu m . Non s t e roid a l a n t i-in a m m a t ory d ru gs , cort icos t e r-
including special procedures oid s , colch icin e, a n t im a la ria ls , a n d /or im m u n os u p p re s s ive m e d ica t ion s h a ve
a ll be e n u s e d a s d ru g t h e ra py of s a rcoid a rt h rit is (20 ).
S
E
ICD9
C
T
726.90 Capsulitis (jo in t )
I
O
726.0 ad h e sive (sh o u ld e r)
N
4
250.0 Diabe te s, diabe tic (b rit t le ) (co n g e n it al) (f am ilial) (m e llit u s)
O
(se ve re ) (slig h t ) (w it h o u t co m p licat io n )
s
t
e
244.9 Hypo thyro idism (acq u ire d )
o
a
715.9 Oste o arthro pathy
r
t
h
757.39 ch ro n ic id io p at h ic h yp e rt ro p h ic
r
i
t
757.39 f am ilial id io p at h ic
i
s
731.2 h yp e rt ro p h ic p u lm o n ary
a
n
731.2 se co n d ary
d
M
757.39 id io p at h ic h yp e rt ro p h ic
e
731.2 p rim ary h yp e rt ro p h ic
t
a
b
731.2 p u lm o n ary h yp e rt ro p h ic
o
l
i
731.2 se co n d ary h yp e rt ro p h ic
c
B
716.59 Po lyarthritis, po lyarthro pathy NEC
o
n
714.9 in am m at o ry
e
Re fe re nce s
1. Ca u d ill-Slo s b e rg MA, Sch w a r t z LM , Wolo s h in S. Of ce vis it s a n d a n a lge s ic p re s cr ip t ion s for m u s cu -
lo s ke le t a l p a in in US: 1980 vs . 2000 . Pain 2004 ;109 (3 ):514 –519 .
2. Preve n t ion , C.f.D. C. a ., National Diabetes Fact Sheet: General Inform ation and National Estim ates on Diabetes
in the United States, 2007. US Dep a rt m e n t of He a lt h a n d Hu m a n Se rvice s ; 2008 .
3. Bu rn e r TW , Ros e n t h a l AK. Dia be t e s a n d rh e u m a t ic d is e a s e s . Curr Opin Rheum atol 2009 ;21 (1 ):50 –54 .
4. Ra jbh a n d a ri SM , Je n kin s RC, Davie s C, e t a l. Ch a rcot n e u roa rt h rop a t h y in d ia be t e s m e llit u s . Diabetologia
2002 ;45 (8 ):1085 –1096 .
5. Kelley MJ, McClu re PW, Leggin BG. Frozen sh ou ld er: Evid e n ce a n d a p rop os ed m od el gu id in g reh a bilit a t ion .
J Orthop Sports Phys Ther 2009 ;39 (2 ):135 –148 .
6. Cola o A, Fe ron e D, Ma rzu llo P, e t a l. Sys t e m ic com p lica t ion s of a crom ega ly: Ep id e m io logy, p a t h oge n e s is ,
a n d m a n a ge m e n t . Endocr Rev 2004 ;25 (1 ):102 –152 .
7. Ya o Q , Alt m a n RD, Bra h n E. Pe rios t it is a n d h yp e rt rop h ic p u lm on a ry os t e oa rt h rop a t h y: Rep ort of 2 ca s e s
a n d review of t h e lit e ra t u re . Sem in A rthritis Rheum 2009 ;38 (6 ):458 –466 .
8. Li Z , Pa t e rs on Sm it h B, Sm it h TL, e t a l. Dia gn os is a n d m a n a ge m e n t of com p lex region a l p a in s yn d rom e
com p lica t in g u p p e r e xt re m it y re cove ry. J Hand Ther 2005 ;18 (2 ):270 –276 .
9. Trot t a F, Ca s t e llin o G, Lo Mo n a co A. Mu lt ice n t ric re t icu loh is t io cyt os is . Best Pract Res Clin Rheu m atol
2004 ;18 (5 ):759 –772 .
10. Ke e n a n RT, Ha m a lia n GM , Pillin ge r MH . RS3PE p re s e n t in g in a u n ila t e ra l p a t t e rn : Ca s e rep ort a n d review
of t h e lit e ra t u re . Sem in A rthritis Rheum 2009 ;38 (6 ):428 –433 .
11. Ejin d u VC, Hin e AL, Ma s h aye kh i M, e t a l. Mu s cu lo s ke le t a l m a n ife s t a t ion s of s ickle ce ll d is e a s e . Radio-
graphics 2007 ;27 (4 ):1005 –1021 .
12. Bo s s a rd D, Ca r r illo n Y, St ie lt je s N, e t a l. Ma n a ge m e n t o f h a e m o p h ilic a r t h r o p a t h y. Haem ophilia
2008 ;14 (Su p p l 4 ):11 –19 .
13. Ca rro ll G, Bre id a h l W H, Bu ls a ra MK, e t a l. He re d it a ry h a e m o ch rom a t o s is (HH) is ch a ra ct e riz e d by a
clin ica lly d e n a ble a rt h rop a t h y t h a t corre la t e s w it h iron loa d . A rthritis Rheum 2011;63(1):286–94 .
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 235
e
n
o
B
c
i
l
o
b
a
t
e
M
d
n
a
s
i
t
i
r
h
t
r
a
o
e
t
s
O
4
N
O
I
T
C
E
S
SECTION
5
Infectious Arthritis
237
CHAPTER
23 Ba cteria l Arthritis
A rthur Kavanaugh and Maika Onishi
A 30-ye ar-o ld
Intro ductio n
Ba ct e r ia l a r t h r it is is a t ru e r h e u m a t o -
m ale p re se n t in g
logic e m e rge n cy t h a t ca n le a d t o irre -
w it h acu t e -o n se t
s
ve r s ib le jo in t d e s t r u ct io n , in cr e a s e d
i
t
i
le f t k n e e p ain ,
r
m o r b id it y, a n d a cce le ra t e d m o r t a lit y,
h
t
r
w arm t h , an d w it h o u t p ro m p t d ia gn o s is a n d t re a t -
A
m e n t . Alt h ou gh m a n y in fe ct iou s a ge n t s
s
sw e llin g (Fig . 23.1 ).
u
m ay ca u s e a rt h rit is , ba ct e ria l a rt h rit is is
o
i
t
c
t h e m os t s ign i ca n t be ca u s e of it s ra p -
e
f
id ly p rogre s s ive a n d h igh ly d e s t ru ct ive
n
I
n a t u re. De s p it e re ce n t a d va n ce s in a n t i-
5
N
m icro b ia l t h e ra p y, d ia gn o s t ic t e s t in g,
O
I
a n d ge n e ra l m e d ica l ca re, t h e p rogn os is
T
C
for p a t ie n t s w it h ba ct e ria l a rt h rit is con t in u e s t o be gu a rd e d w it h 25% t o 50% of
E
S
p a t ie n t s s u ffe rin g p e rm a n e n t join t d a m a ge a n d a n e s t im a t e d 5% t o 15% ca s e
fa t a lit y s e con d a ry t o com p lica t ion s in clu d in g s ep s is . Pe rh a p s t h e m os t im p or-
t a n t fa ct o r rega rd in g t h e o u t com e o f p a t ie n t s w it h ba ct e ria l a rt h rit is is t h e
s p e e d w it h w h ich a p p rop ria t e t h e ra py is in s t it u t e d . Th e re fore, it re m a in s t ru e
Figure 23.1 Pla in ra diogra ph of septic a rthritis. Media l a nd la tera l x-ra ys of the left knee showing mild joint
effusion, but is otherwise norma l.
239
240 Se ctio n 5 In fe ct iou s Art h rit is
a t t h e s t a rt o f t h e n ew m ille n n iu m a s it h a s fo r m o re t h a n h a lf a ce n t u ry;
clin ica l s u s p icion of t h e d ia gn os is of ba ct e ria l a rt h rit is is t h e m os t crit ica l con -
s id e ra t ion for t h e clin icia n .
Ba ct e ria l a rt h rit is e n s u e s w h e n fore ign orga n is m s in va d e t h e s yn oviu m or
join t s p a ce. In t h e m a jority of ca ses , in fect ion is in trod u ced via h e m a togen ou s
sp re a d from a d is ta n t s ite. Less com m on ly, ba cte ria l p a t h ogen s rea ch t h e join t
s p a ce via d ire ct in ocu la t ion t h rou gh a p e n e t ra t in g t ra u m a or p roce d u re (e.g.,
a rt h roce n t e s is , s u rge ry) or via con t igu ou s s p re a d from a d ja ce n t s oft -t is s u e or
bon e in fection s , in clu d in g cellu lit is, osteom yelitis , a n d bu rsitis . Up on en t ry in t o
th e join t sp a ce, ba cteria in d u ce a n a cu te in a m m a tory resp on s e, w h ich ra p id ly
p rogresses to s yn ovia l h yp erp la sia a n d in ltra t ion by in a m m a tory cells. With ou t
p rom p t trea tm en t in itia t ion , th is ca n lea d to en zym a tic a n d cytokin e-m ed ia ted
ca rtila ge a n d bon e d egra d a tion w it h in d ays . Ad d it ion a lly, in ba cteria l a rth ritis, th e
u rgen cy of t rea tm en t is fu rth er h eigh ten ed beca u s e of p oten tia l in fection w ith
ba cteria l stra in s w ith viru len ce fa ct ors (e.g., toxin s, a d h esin s ), w h ich a re a s soci-
a ted w it h in crea s ed p a th ogen icit y a n d d isea s e severity (1 ).
Th e t w o m a jor cla s s e s of ba ct e ria l a rt h rit is a re n on gon ococca l a n d gon o-
cocca l a rt h rit is (d is cu s s e d be low ), w it h n on gon ococca l a rt h rit is a ccou n t in g for
t h e m a jorit y of ca s e s a cros s a ll a ge a n d ris k grou p s . Staphylococcus aureus is t h e
m os t com m on orga n is m in fe ct in g n a ïve join t s in 60% t o 70% of ca s e s . Be ca u s e
S
E
it is s u ch a fre q u e n t ca u s e of ba ct e ria l a rt h rit is , t h e in cre a s in g p reva le n ce of
C
T
com m u n it y- a n d h os p it a l-a cq u ire d m e t h icillin -re s is t a n t Staph. aureus (MRSA)
I
O
is a n im p ort a n t con s id e ra t ion w h e n in it ia lly t re a t in g ba ct e ria l a rt h rit is . Ad d i-
N
5
t ion a lly, s t a p h ylococci in fe ct ion s a re a s s ocia t e d w it h h igh e r ra t e s of fu lm in a n t
I
n
d is e a s e a n d re s id u a l join t d a m a ge, t h u s n e ce s s it a t in g p rom p t d ia gn os is a n d
f
e
a ggre s s ive t re a t m e n t .
c
t
i
Th e m a in re m a in in g ca u s e s of ba ct e ria l a rt h rit is in clu d e s t rep t occci, gra m -
o
u
s
n ega t ive ba cilli, a n d a n a e robe s . Hos t –p a t h oge n a s s ocia t ion s m ay be h e lp fu l in
A
gu id in g in it ia l a n t im icrobia l t re a t m e n t . St rep t ococci (e.g., Streptococcus v iridans ,
r
t
h
Strep. pneum oniae, grou p A a n d B s t rep t ococci) a ccou n t for 15% t o 20% of n on -
r
i
t
i
gon ococca l a rt h rit is a n d m ay be p re ce d e d by p rim a ry s kin or s oft -t is s u e in fe c-
s
t ion s . Grou p A s t re p t ococci a re t h e m os t com m on s t re p t ococca l s p e cie s a n d a re
oft e n is ola t e d a ft e r d e n t a l p roce d u re s . Gra m -n ega t ive ba cilli in fe ct ion s (e.g.,
Pseudom onas aeruginosa , Escherichia coli, Proteus m irabilis ) a re re s p on s ible for 5%
t o 25% of ca s e s , a n d a re a s s ocia t e d w it h ch ron ic s ys t e m ic illn e s s , im m u n os u p -
p re s s ion , in t ra ve n ou s d ru g u s e , a n d a d va n cin g a ge (e.g., in e ld e rly p a t ie n t s ).
Th e s e in fe ct ion s m ay begin a s u rin a ry t ra ct or s kin in fe ct ion s w it h s u bs e q u e n t
h e m a t oge n ou s s p re a d t o a join t . La s t ly, a n a e ro bic ba ct e ria (e .g., Bacteroides ,
Clostridium , Fusobacterium ) a ccou n t for 1% t o 5% of ba ct e ria l a rt h rit is , a lt h ou gh
t h is m ay be a n u n d e re s t im a t e a s a n a e robe s h ave h is t orica lly be e n m ore d if -
cu lt t o is o la t e. W h ile m o s t b a ct e ria l a rt h rit is in fe ct io n s a re m o n o m icro b ia l,
a n a e ro b ic in fe ct io n s m a y b e p o lym icro b ia l in n a t u re . Pre d is p o s in g fa ct o r s
in clu d e d ia b e t e s m e llit u s , im m u n o co m p ro m is e d s t a t e s , a n d p o s t o p e ra t ive
w ou n d in fe ct ion s . Su s p icion for a n a n a e robic a ge n t s h ou ld be ra is e d in t h e ca s e
of fou l-s m e llin g s yn ovia l u id or p la in ra d iogra p h s d ep ict in g ga s in t h e join t
s p a ce. Ad e q u a t e d ra in a ge of t h e join t is a key a d ju n ct t o a n t im icrobia l t h e ra py
in t h e ca s e of a n a e robic in fe ct ion .
Le s s co m m o n ly, ot h e r o rga n is m s m a y a ls o b e a s s ocia t e d w it h ba ct e r ia l
a rt h rit is . On e w ort h m e n t ion in g is t h e Brucella s p e cie s (e.g., B. m elitensis ), w h ich
is be com in g m ore p reva le n t w orld w id e (2 ). Ris k fa ct ors in clu d e con s u m p t ion of
u n p a s t e u rize d m ilk or ch e e s e or d ire ct con t a ct w it h in fe ct e d a n im a ls . Pre s e n -
t a t ion is u s u a lly ch a ra ct e rize d by m on oa rt h rit is of t h e h ip or kn e e, a lt h ou gh
o ligo a rt h r it is , s a cro iliit is , o r s p on d ylit is m a y a ls o b e s e e n . Fu r t h e r w o rk -u p
s h ou ld be gu id e d by t h e clin ica l s e t t in g if on e of t h e com m on e t iologic a ge n t s
is n ot id e n t i e d .
Go n o co cca l a rt h rit is is t h e m os t co m m on ca u s e o f ba ct e r ia l a r t h rit is in
you n g, s e xu a lly a ct ive in d ivid u a ls w it h ou t a h is t ory of join t d is e a s e. Wom e n
Ch a p te r 23 Ba ct e ria l Art h rit is 241
s
i
t
cu lt u re t e ch n iq u e (e.g., ch ocola t e a ga r, ra p id p la t in g), gra m s t a in s a n d cu lt u re s
i
r
h
of s yn ovia l u id a re p os it ive in few e r t h a n 40% of ca s e s , a n d blood cu lt u re s a re
t
r
A
a lm os t a lw ays n ega t ive (3 ). Mu cos a l cu lt u re s of t h e u re t h ra , p h a ryn x, ce rvix, a n d
s
u
re ct u m s h ou ld be p e rform e d in a ll p a t ie n t s , s in ce t h ey h ave a h igh e r yie ld a n d
o
i
t
m ay be p os it ive eve n in t h e a bs e n ce of s ym p t om s . More s e n s it ive t e ch n iq u e s for
c
e
id e n t i ca t ion of gon ococci, s u ch a s p olym e ra s e ch a in re a ct ion , a re cu rre n t ly n ot
f
n
I
rou t in e ly u s e d , bu t m ay p rovid e a d d it ion a l d ia gn os t ic va lu e in t h e fu t u re.
5
Alt h o u gh m os t p a t ie n t s re s p o n d d ra m a t ica lly t o a n t ibio t ics w it h in 24 t o
N
O
48 h ou rs a n d n e a rly a ll m a ke a com p le t e re cove ry, w h e n gon occoca l a rt h rit is is
I
T
C
s u s p e ct e d , p a t ie n t s s h o u ld b e co n s id e re d fo r h o s p it a l a d m is s io n t o co n rm
E
d ia gn os is , e xclu d e co m p lica t ion s s u ch a s m e n in git is a n d e n d o ca rd it is , a n d
S
re ce ive p a re n t e ra l t h e ra p y.
CLINICAL POINTS
• Clin ica l su sp icio n o f t h e
d ia g n o sis o f b a ct e ria l Clinica l Pre se nta tio n
a rt h rit is is t h e m o st
im p o rt a n t co n sid e ra t io n Clin ica l s u s p icion for ba ct e ria l a rt h rit is s h ou ld be ra is e d in p a t ie n t s w it h u n d e r-
fo r t h e clin icia n . lyin g jo in t d is e a s e, co m p ro m is e d im m u n e fu n ct io n , a n d in cre a s e d in fe ct io n
ris k, a ll of w h ich a re key ris k fa ct ors for join t in fe ct ion . Join t s t h a t h ave be e n
• Ext e n sive , ra p id jo in t
d e st ru ct io n m a y o ccu r d a m a ge d by a r t h r it is (e .g., r h e u m a t o id a r t h r it is , o s t e o a r t h r it is , crys t a llin e
w it h o u t p ro m p t in it ia t io n a rt h rit is ) or t ra u m a a re m ore s u s cep t ible t o in fe ct ion t h a n n orm a l join t s . Th is
o f a p p ro p ria t e a n t ib io t ics. m ay be s e con d a ry t o s t ru ct u ra l d a m a ge, n e ova s cu la riza t ion , or loca l fa ct ors . As
• Acu t e m o n o a rt icu la r a rt h ri- t h e s yn oviu m s e rve s a n im p or t a n t p rot e ct ive role in join t d e fe n s e, p a t ie n t s
t is sh o u ld b e co n sid e re d w it h rh e u m a t oid a rt h rit is a re p a rt icu la rly s u s ce p t ible. Pa t ie n t s w it h im p a ire d
b a ct e ria l a rt h rit is u n t il h os t d e fe n s e s be ca u s e of e xt re m e s of a ge, s ys t e m ic illn e s s (e.g., d ia be t e s m e l-
p ro ve n o t h e rw ise . lit u s , m a lign a n cy, live r or kid n ey d is e a s e ), im m u n os u p p re s s ive m e d ica t ion s , or
• Jo in t d ra in a g e a n d im m u n o co m p ro m is e d co n d it io n s (e .g., HIV/ AIDs ) a re a ls o a t in cre a s e d ris k .
a n t ib io t ic t h e ra p y a re Likew is e, it follow s t h a t ris k fa ct ors for in fe ct ion s u ch a s p ros t h e t ic join t s in
t h e ke y co m p o n e n t s o f w h ich fore ign bod ie s s e rve a s a n id u s for in fe ct ion , in t ra -a rt icu la r join t in je c-
t re a t m e n t . t ion s , s kin in fe ct ion s , a n d in t rave n ou s d ru g a bu s e m ay p re d is p os e p a t ie n t s t o
• St ap h ylo co ccu s au re u s ba ct e ria l a rt h rit is . As a clin icia n , obt a in in g a t h orou gh h is t ory rega rd in g t h e s e
is t h e m o st co m m o n ris k fa ct ors p lays a n im p ort a n t role in d ia gn os is a n d t re a t m e n t .
o rg a n ism a cro ss a ll a g e s
a n d risk g ro u p s, w h ile
Ne isse ria g o n o rrh o e ae
a cco u n t s fo r m o st ca se s Exa mina tio n
a m o n g yo u n g , se xu a lly
a ct ive in d ivid u a ls. Th e cla s s ic p re s e n t a t ion for ba ct e ria l a rt h rit is is a cu t e m on oa rt icu la r join t p a in
w it h sw e llin g, w a rm t h , a n d e ryt h e m a . On exa m in a t ion , p a t ie n t s t yp ica lly e xh ibit
242 Se ctio n 5 In fe ct iou s Art h rit is
PATIENT ASSESSMENT Table 23.1 Different ial Diagnosis of Bact erial Art hrit is
• Th e cla ssic p re se n t a t io n Ot h e r in fe ct io u s a rt h rit id e s
is a cu t e m o n o a rt icu la r Vira l a rt h rit is
jo in t p a in w it h sw e llin g , Myco b a ct e riu m a rt h rit is
w a rm t h , a n d e ryt h e m a . Fu n g a l a rt h rit is
Lym e d ise a se
• Pa t ie n t s w it h g o n o co cca l
a rt h rit is m a y e xh ib it Cryst a llin e a rt h rit is
m ig ra t o ry p o lya rt h ra lg ia s, Go u t
t e n o syn o vit is, a n d Pse u d o g o u t
ch a ra ct e rist ic skin le sio n s.
Sp o n d ylo a rt h ro p a t h ie s
• Jo in t a sp ira t io n sh o u ld b e Re it e r’s syn d ro m e
p e rfo rm e d in a ll p a t ie n t s An kylo sin g sp o n d ylit is
w it h su sp e ct e d b a ct e ria l
a rt h rit is p rio r t o st a rt in g Re a ct ive a rt h rit is (e .g ., p o st st re p t o co cca l)
e m p iric a n t ib io t ic t h e ra p y. No n a rt h rit ic co n d it io n s
• Syn o via l u id w ill b e Ce llu lit is
in a m m a t o ry w it h w h it e Bu rsit is
b lo o d ce ll (WBC) co u n t Tra u m a /fra ct u re
2,500/m m 3 a n d 75% Fo re ig n b o d y re a ct io n
n e u t ro p h ils; in fe ct io u s
a rt h rit is m a y b e a sso cia t e d
w it h ve ry h ig h WBC
co u n t s in t h e syn o via l obviou s join t e ffu s ion , t e n d e rn e s s t o p a lp a t ion , a n d re s t rict e d ra n ge of m ot ion .
u id , fo r e xa m p le , WBC La rge join t s a re m ore com m on ly a ffe ct e d t h a n s m a ll join t s , a n d in u p t o 70% of
co u n t 50,000/m m 3 .
ca s e s , t h e kn e e or h ip is in volve d . In t ra ve n ou s d ru g u s e rs m a y p re s e n t w it h
• A n e g a t ive g ra m st a in s t e rn ocla vicu la r or s a croilia c join t in volve m e n t . Feve r is t h e m os t com m on ly
a n d cu lt u re d o e s n o t a s s ocia t e d s ym p t om on p re s e n t a t ion a n d is fou n d in 50% of p a t ie n t s , w h ile
e xclu d e a d ia g n o sis o f
b a ct e ria l a rt h rit is.
sw e a t s a n d ch ills a re le s s com m on (4 ).
Clin ica l a cu it y for t h e d ia gn os is of ba ct e ria l a rt h rit is is p a rt icu la rly im p or-
t a n t in a t yp ica l p re s e n t a t ion s , give n t h e ra p id p a ce of join t d e s t ru ct ion ove r a
m a t t er of d ays . Clin ica l s u s p icion s h ou ld re m a in h igh w it h p olya rt icu la r p re s e n -
t a t ion s , w h ich m ay a ccou n t for a q u a rt e r of s ep t ic a rt h rit is ca s es (5 ). Polya rt icu la r
in fe ct ion is m ore like ly in t h e s e t t in g of Staph. aureus in fe ct ion , gon ococca l d is -
ea s e, a n d in p a t ie n t s w it h rh e u m a t oid a rt h rit is a n d ot h e r s ys t e m ic con n e ct ive
t is s u e d is e a s e s . On t h e ot h e r h a n d , p re exis t in g p olya rt icu la r join t d is e a s e m ay
con fou n d t h e d ia gn os is of a m on oa rt icu la r in fe ct ion . In t h e s e p a t ie n t s , ba ct e ria l
a rt h rit is s h ou ld be s u s p e ct e d in t h os e w h o p re s e n t w it h n ew s ym p t om s in on e
join t t h a t a re ou t of p rop ort ion t o t h e ot h e r join t s . Ad d it ion a lly, it is im p ort a n t
n ot t o exclu d e a d ia gn os is of ba ct e ria l a rt h rit is in p a t ie n t s w it h a gra d u a l on s e t
of s ym p t om s , w h ich m ay be fou n d in p a t ie n t s w it h p ros t h e t ic join t s , rh e u m a t ic
d is e a s e, or im m u n ocom p rom is e d s t a t e s .
Give n t h e ris ks a s s ocia t e d w it h a d e la y in d ia gn os is , it is n ot u n re a s on a ble
t o s u gge s t t h a t a bs e n t a cle a rly e s t a blis h e d ot h e r ca u s e, a cu t e m on oa rt icu la r
a rt h rit is is in fe ct iou s u n t il p rove n ot h e rw is e. Likew is e, a h igh d egre e of clin ica l
s u s p icion for ba ct e ria l a rt h rit is s h ou ld be h e ld in p a t ie n t s w it h p re d is p os in g
ris k fa ct ors for s ep t ic a rt h rit is . Th e d iffe re n t ia l d ia gn os is for ba ct e ria l a rt h rit is
is review e d in Ta ble 23.1 . A t h orou gh h is t ory a n d p h ys ica l e xa m in a t ion m a y
h e lp d is t in gu is h be t w e e n a n in fe ct iou s a n d in a m m a t o ry p roce s s . To d is t in -
gu is h p e ria rt icu la r con d it ion s , d ia gn os is w ill be fa cilit a t e d if t h e clin icia n is
con d e n t in h is or h e r p h ys ica l e xa m in a t ion s kills rega rd in g d iffe re n t ia t ion of
a r t h r it is fro m in vo lve m e n t o f s t r u ct u re s s u r ro u n d in g t h e jo in t (e .g., s k in ,
bu rs a s , t e n d on s ).
Studie s
Th e corn e rs t on e of t h e d ia gn os is of ba ct e ria l a rt h rit is is p rom p t a rt h roce n t e s is
a n d s yn ovia l u id a n a lys is (Ta ble 23.2 ). Sa m p le s s h ou ld be s e n t for W BC cou n t
Ch a p te r 23 Ba ct e ria l Art h rit is 243
Table 23.2 Suspect ed Bact erial Art hrit is: Key Point s in
Joint Aspirat ion
WBC, w h it e b lo o d ce ll.
s
i
t
i
a n d d iffe re n t ia l, gra m s t a in , cu lt u re, a n d crys t a l a n a lys is ; t h e s e a re t h e on ly
r
h
t
t e s t s of p rove n d ia gn os t ic va lu e in t h is clin ica l s e t t in g (6 ). In fe ct e d u id is ch a r-
r
A
a ct e ris t ica lly in a m m a t ory (i.e., w it h W BC cou n t 2,500/m m 3 a n d 75% n e u -
s
u
t rop h ils ) in t h e d iffe re n t ia l ( 75%); n ot u n com m on ly, it is p u ru le n t w it h s yn o-
o
i
via l W BC co u n t s o f 30 t o 50,000/m m 3 or h igh e r. Th e like lih o od o f in fe ct io n
t
c
e
f
in cre a s e s w it h ris in g W BC cou n t (4 ). Th e p re d om in a n t d iffe re n t ia l d ia gn os is for
n
I
h igh ly in a m m a t ory s yn ovia l u id is crys t a llin e a rt h rit is (e.g., gou t ). Syn ovia l
5
u id gra m s t a in s give a p os it ive re s u lt in 50% t o 70% of ca s e s of n on gon occoca l
N
O
a rt h rit is a n d s h ou ld be u s e d t o gu id e in it ia l t h e ra py. Pos it ive cu lt u re s in cre a s e
I
T
C
t h e yie ld t o 70% t o 90% of ca s e s of n on gon ococca l a rt h rit is , bu t a n ega t ive gra m
E
NOT TO BE MISSED
S
s t a in or cu lt u re d oe s n ot ru le ou t a n in fe ct e d join t (7 ). For e xa m p le, fa ls e n ega -
• A t h o ro u g h h ist o ry a n d t ive s m a y o ccu r in p a t ie n t s p reviou s ly t re a t e d w it h a n t ibio t ic t h e ra p y o r in
p h ysica l e xa m in a t io n p a t ie n t s w it h gon ococca l in fe ct ion s .
a re crit ica l, a lt h o u g h it Ad d it ion a l t e s t s t h a t s h o u ld be p e rform e d in clu d e blood cu lt u re s , w h ich
m a y st ill b e d if cu lt t o a re p os it ive in u p t o 50% of ca s e s , a n d s h ou ld be obt a in e d t o e xclu d e a ba ct e r-
d ist in g u ish b e t w e e n a n
e m ic origin of t h e in fe ct e d join t . W h e n clin ica lly a p p rop ria t e, u re t h ra l, n a s a l,
in fe ct io u s ca u se a n d a n
in a m m a t o ry a rt h rit is t h roa t , re ct a l, or ce rvica l sw a bs m a y be p e rform e d t o eva lu a t e for gon ococca l
o f o t h e r e t io lo g y (e .g ., in fe ct ion . Ot h e r la bora t ory s t u d ie s s u ch a s p e rip h e ra l W BC cou n t , e ryt h rocyt e
cryst a llin e , a u t o im m u n e ). s e d im e n t a t ion ra t e, a n d C-re a ct ive p rot e in a re u s u a lly e leva t e d a n d m a y h e lp
• Se p t ic a rt h rit is m a y b e in m on it orin g t re a t m e n t .
su p e rim p o se d o n o t h e r Im a gin g s t u d ie s a re of lim it e d d ia gn os t ic va lu e e a rly in t h e d is e a s e cou rs e
jo in t d ise a se s a n d m a y b e of ba ct e ria l a rt h rit is . Pla in ra d iogra p h s m a y on ly reve a l s oft -t is s u e sw e llin g or
m ist a ke n fo r e xa ce rb a t io n join t e ffu s ion (Fig. 23.1 ). De s p it e t h is , t h ey s h ou ld be obt a in e d a s a ba s e lin e a n d
o f t h e p re e xist in g
t o e xclu d e os t e om ye lit is . In la t e r s t a ge s of ba ct e ria l a rt h rit is ( 10 d a ys a ft e r
co n d it io n .
in fe ct io n o n s e t ), ca rt ila ge a n d b o n e d e s t ru ct io n m a y b e vis u a lize d o n p la in
• Ke e p a h ig h in d e x o f ra d iogra p h s , h igh ligh t in g it s ra p id cou rs e . Of n ot e, u n t re a t e d s e p t ic a rt h rit is
su sp icio n in p a t ie n t s
t e n d s t o b e ch a ra ct e riz e d by e ro s io n s w it h re la t ive ly in d is t in ct m a rgin s a s
w h o a re e ld e rly, yo u n g ,
im m u n o co m p ro m ise d , o r op p os e d t o ot h e r join t p a t h ology (e.g., gou t , rh e u m a t oid a rt h rit is [RA]), w h ich
h a ve p re e xist in g jo in t is ch a ra ct e rize d by e ros ion s w it h cle a rly d e n e d e d ge s . Ot h e r m e t h od s of im a g-
d ise a se . in g s u ch a s com p u t e d t om ogra p h y (CT) a n d m a gn e t ic re s on a n ce im a gin g (MRI)
• Pe d ia t ric p a t ie n t s m a y a re m ore s e n s it ive for d is t in gu is h in g os t e om ye lit is , join t e ffu s ion s , a n d p e ri-
p re se n t w it h su b t le a n d a r t icu la r a b s ce s s e s , b u t a re n o t co m m o n ly u s e d fo r t h e eva lu a t io n o f jo in t
n o n sp e ci c n d in g s; in fe ct ion s . Us u a lly t h ey a re re s e rve d for eva lu a t in g t h e s t e rn ocla vicu la r or s a c-
h e ig h t e n e d clin ica l ro ilia c jo in t s , w h ich a re d if cu lt t o vis u a liz e u s in g p la in ra d iogra p h y. La s t ly,
su sp icio n is e sp e cia lly
ra d ion u clid e s ca n s m ay h e lp loca lize a re a s of in a m m a t ion , bu t a re u n a ble t o
crit ica l g ive n t h e p o t e n t ia l
fo r ca t a st ro p h ic o u t co m e s. d e n it ive ly e s t a blis h in fe ct ion . Give n t h e ir low s p e ci cit y, t h ey a re ra re ly u s e d
in t h e d ia gn os is of ba ct e ria l a rt h rit is .
244 Se ctio n 5 In fe ct iou s Art h rit is
Tre a tme nt
All p a t ie n t s w it h s u s p e ct e d ba ct e ria l a rt h rit is s h ou ld be con s id e re d for h os p it a l
a d m is s ion . Ba ct e ria l a rt h rit is is n ot fre q u e n t ly t re a t e d a s a n ou t p a t ie n t a s it
t yp ica lly re q u ire s in t rave n ou s a n t ibiot ics a n d p os s ibly re p e a t e d d ra in a ge of t h e
a ffe ct e d join t d ep e n d in g on t h e clin ica l cou rs e. Con s id e ra t ion s h ou ld be give n
t o rh e u m a t ology or ort h op e d ic s u rge ry con s u lt a t ion , a n d in m ore com p lica t e d
ca s e s , a n in fe ct io u s d is e a s e co n s u lt m a y b e h e lp fu l in gu id in g w o rk -u p a n d
t re a t m e n t .
Ea rly in it ia t ion of a n t ibiot ic t re a t m e n t is crit ica l for im p rovin g p rogn o s is
a n d ou t com e s . If t h e re is a h igh s u s p icion for ba ct e ria l a rt h rit is , e m p iric t h e r-
a py s h ou ld be s t a rt e d im m e d ia t e ly a ft e r cu lt u re s h a ve be e n d ra w n . Cu rre n t ly,
t h e re a re n o ra n d om ize d con t rolle d t r ia ls eva lu a t in g a n t ibiot ic re gim e n s for
ba ct e ria l a rt h rit is (8 ). Th u s , ch oice of in it ia l t h e ra p y s h ou ld be gu id e d by gra m
s t a in , r is k fa ct o r s , a n d clin ica l s e t t in g. Fu r t h e r m o re , re s is t a n ce p a t t e r n s o f
p ot e n t ia l orga n is m s s h ou ld a ls o be t a ke n in t o a ccou n t d u rin g s e le ct ion of in i-
t ia l t h e ra p y. In ge n e ra l, t re a t m e n t d u ra t ion is 3 t o 6 w e e ks , in t ra ve n ou s , a n d
ora l com bin e d .
Join t d ra in a ge a n d lava ge is t h e ot h e r m a in s t ay of t re a t m e n t a n d is im p or-
t a n t in re m ovin g t h e in a m m a t ory ce lls a n d m e d ia t ors t h a t ca u s e p e rm a n e n t
S
E
join t d e s t ru ct ion . W h ile t h e re is con t rove rs y rega rd in g w h e t h e r clos e d n e e d le
C
T
a s p ira t ion s , a rt h ros copy, or op e n a rt h rot om y is be t t e r, in m os t circu m s t a n ce s ,
I
O
re p e a t e d n e e d le a s p ira t ion is u s u a lly s u f cie n t . Se ria l s yn ovia l u id a n a lys e s
N
s h ou ld d e m on s t ra t e a d ow n w a rd t re n d in W BC n u m be rs a n d d e cre a s e in e ffu -
5
I
s ion volu m e w it h re s p on s e t o t re a t m e n t .
n
f
e
c
t
i
o
Clinica l Co urse
u
s
A
r
Lo n g-t e r m p ro gn o s is fo r jo in t p re s e r va t io n co r re la t e s w it h t h e o rga n is m
t
h
r
in volve d , p rom p t n e s s of d ia gn os is , a n d in s t it u t ion of a p p rop ria t e a n t im icrobia l
i
t
i
s
t h e ra p y, a s w e ll a s h os t -re la t e d ch a ra ct e ris t ics . In ge n e ra l, p a t ie n t s w it h gon o-
cocca l a rt h rit is h a ve t h e be s t p rogn os is w it h p rom p t re s olu t ion of s ym p t om s
a n d ra re lon g-t e rm join t m orbid it y from t h is in fe ct ion . Pa t ie n t s w it h s ign i ca n t
com orbid it ie s , e s p e cia lly t h os e w h o a re im m u n os u p p re s s e d , a re m os t vu ln e r-
a ble t o join t d a m a ge be ca u s e of t h e ir in a bilit y t o e ffe ct ive ly cle a r in fe ct ion s in
s p it e of a p p rop ria t e a n t im icrobia l t h e ra py. In fe ct ion s w it h p a rt icu la rly viru le n t
orga n is m s s u ch a s Staph. aureus ca n p rod u ce lo n g-t e rm a rt icu la r d a m a ge in
s p it e of a p p rop ria t e t im in g a n d s e le ct ion of a n t ibiot ic t h e ra py.
Pa t ie n t s w it h p ros t h e t ic d evis e p os e a d if cu lt ch a lle n ge a s s u cce s s fu l join t
re cove ry re q u ire s s u rgica l d e brid e m e n t in con ju n ct ion w it h a n t ibiot ic t h e ra p y;
on occa s ion s , t h is com bin e d fa ils t o cle a r t h e in fe ct ion n e ce s s it a t in g re m ova l
of t h e p ros t h e t ic d evice follow e d by p rolon ge d a n t ibiot ic t h e ra py a n d eve n t u a l
join t re p la ce m e n t .
ca n le a d t o p o t e n t ia lly ca t a s t ro p h ic co n s e q u e n ce s . Ph ys ica l e x a m in a t io n
s h ou ld in clu d e ca re fu l a s s e s s m e n t of t h e h ip , bu t t ocks , a n d groin , a n d w ork-u p
s h ou ld in clu d e u lt ra s ou n d , w h ich h a s a h igh n ega t ive p re d ict ive va lu e for ba c-
t e ria l a rt h rit is in t h e h ip .
s
i
t
i
r
• All p a t ie n t s sh o u ld b e
h
t
r
co n sid e re d fo r h o sp it a l PROSTHETIC JOINT INFECTIONS
A
a d m issio n .
s
As join t rep la ce m e n t p roce d u re s be com e in cre a s in gly com m on , it is im p ort a n t
u
o
• Co n sid e r co n su lt in g rh e u -
i
t o ke e p in m in d t h e u n iq u e ch a ra ct e r is t ics a s s o cia t e d w it h p ros t h e t ic join t
t
c
m a t o lo g y o r o rt h o p e d ics if
e
in fe ct ion s . Th e e t iology, m icrobiology, a n d t re a t m e n t of a n in fe ct ion ca n va ry
f
a se p t ic jo in t is su sp e ct e d
n
I
o r co n rm e d . d e p e n d in g on t h e t im in g of in fe ct ion . Ea rly p os t op e ra t ive in fe ct ion s (w it h in t h e
5
rs t 3 m on t h s ) a re u s u a lly s e con d a ry t o con t a m in a t ion a cq u ire d d u rin g im p la n -
N
• Co n sid e r co n su lt a t io n
O
w ith a n in fe ct io u s d ise a se
t a t ion a n d a re a s s ocia t e d w it h viru le n t orga n is m s s u ch a s Staph. aureus a n d
I
T
gra m -n ega t ive ba cilli. As t im e p a s s e s , t h e like lih ood of h e m a t oge n ou s s e e d in g
C
sp e cia list in t h e im m u n o -
E
com p rom ise d h o st o r w h e n a n d in fe ct ion w it h low -viru le n ce orga n is m s (e.g., Staph. epiderm idis , Diptheroides )
S
u n usu a l o rga n ism s a re in t rod u ce d d u rin g s u rge ry in cre a s e s . It is t h e s e orga n is m s t h a t p rod u ce bio lm s
im p lica t e d in t h e p ro ce ss. a n d a ccou n t for t h e m ore in d ole n t p re s e n t a t ion in p ros t h e t ic join t in fe ct ion s .
• All p a t ie nt s w it h p ro sth e t ic W h ile m a n a ge m e n t for p ros t h e t ic join t in fe ct ion s d ep e n d s on t h e clin ica l s e t -
joint infe ct ions shou ld be t in g, in ge n e ra l, t re a t m e n t for e a rly on s e t in fe ct ion s in volve s s u rgica l d e brid e -
co n sid e re d fo r re fe rra l t o m e n t , a n e xt e n d e d cou rs e of a n t ibiot ics , a n d im p la n t re t e n t ion , w h e re a s fo r
a n o rth o p e d ic su rg e o n fo r
furthe r e va lua t ion a nd p os-
la t e -on s e t in fe ct ion s , it re q u ire s p ros t h e s is re m ova l w it h e it h e r im m e d ia t e or
sible re mova l o f pro sthe sis. d e la ye d re im p la n t a t ion (9 ). In ca s e s of s u s p e ct e d in fe ct ion of join t p ros t h e s e s ,
con s u lt a t ion w it h a n ort h op e d is t s h ou ld be s t ron gly con s id e re d .
Co nclusio ns
Ba ct e ria l a rt h rit is con t in u e s t o be a n im p ort a n t h e a lt h p roble m . Clin ica l s u s p i-
cion , ra p id d ia gn os is , a n d p rom p t t h e ra py a re key t o im p rovin g ou t com e s .
ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
040.89 [711.4] d u e t o o r asso ciat e d w it h b act e rial d ise ase NEC
098.50 g o n o co ccal
727.3 Bursitis NEC
726.79 an k le
726.33 e lb o w
726.8 n g e r
(Co n t in u e d )
246 Se ctio n 5 In fe ct iou s Art h rit is
ICD9 (Co n t in u e d )
726.79 f o o t
726.4 h an d
726.5 h ip
726.60 k n e e
726.33 o le cran o n
726.61 p e s an se rin u s
726.65 p re p at e llar
726.10 sh o u ld e r
726.5 t ro ch an t e ric are a
726.4 w rist
730.2 Oste o mye litis (g e n e ral) (in f e ct ive ) (lo caliz e d ) (n e o n at al)
(p u ru le n t ) (p yo g e n ic) (se p t ic) (st ap h ylo co ccal) (st re p t o co ccal)
(su p p u rat ive ) (w it h p e rio st it is)
730.1 sicca
Re fe re nce s
S
E
1. Sh irt liff ME, Ma d e r JT. Acu t e s ep t ic a rt h rit is . Clin Microbiol Rev 2002 ;15 (2 ):527 –544 .
C
2. Fra n co MP, Mu ld e r M , Gilm a n RH , e t a l. Hu m a n bru ce llos is . Lancet Infect Dis 2007 ;7 (12 ):775 –786.
T
I
O
3. Ros s JJ. Sep t ic a rt h rit is . Infect Dis Clin North A m 2005 ;19 (4 ):853 –861 .
N
4. Ma rga re t t e n ME, Koh lw e s J, Moore D, e t a l. Doe s t h is a d u lt p a t ie n t h a ve s e p t ic a rt h r it is ? JA MA 2007 ;
5
297 (13 ):1478 –1488 .
5. Du bos t JJ, Fis I, De n is P, e t a l. Polya rt icu la r s e p t ic a rt h rit is . Medicine (Baltim ore) 1993 ;72 (5 ):296 –310 .
I
n
f
6. Sch m e rlin g RH , De lba n co ML, Tos t e s o n AN , e t a l. Syn ovia l u id t e s t s : W h a t s h ou ld be ord e re d ? JA MA
e
c
1990 ;264 :1009 –1014 .
t
i
7. Rya n MJ, Ka va n a gh R, Wa ll PG, e t a l. Ba ct e ria l join t in fe ct ion s in En gla n d a n d Wa le s : An a lys is of ba ct e ria l
o
u
is o la t e s ove r a fou r-ye a r p e riod . Br J Rheum atol 1997 ;36 (3 ):370 –373 .
s
8. St e n ga l D, Ba u w e n s K, Se h ou li J, e t a l. Sys t e m a t ic review a n d m e t a -a n ayls is of a n t ibiot ic t h e ra py for bon e
A
r
a n d join t in fe ct io n s . Lancet Infect Dis 2001 ;1 (3 ):175 –188 .
t
h
9. Zim m e rli W, Tra m p u z A, Och s n e r PE. Pros t h e t ic-join t in fe ct ion s . N Engl J Med 2004 ;351 (16 ):1645 –1654 .
r
i
t
i
s
CHAPTER
24 Lyme Disea se
W illiam F. Iobst and Kristin M. Ingraham
s
d is ea s e. W h ile Lym e d ise a s e is t h e
i
t
i
cu rre n t ly d e n ie s o t h e r sig n i can t
r
m os t com m on t ick-born e illn e s s
h
t
r
jo in t p ain , b u t d e scrib e s w h at in t h e Un ite d St a te s , a ccu ra t e d ia g-
A
n os is re q u ire s a n a p p re cia t ion of
s
h e t h o u g h t w as a u -t yp e illn e ss,
u
region a l va ria t ion in d is e a s e p rev-
o
i
ch aract e riz e d b y f at ig u e , h e ad ach e ,
t
c
a le n ce (Fig. 24.1 ). Lym e d is e a s e
e
f
m alaise, and arthralgias 3 to 4 m onths is e n d e m ic in t h e n ort h e a s t e rn ,
n
I
m idw e s t e rn , a n d w e s t e rn region s
5
p rio r t o t h e o n se t o f h is k n e e p ain .
N
o f t h e Un it e d St a t e s . In 2009,
O
He also n o t e s alt e re d se n sat io n in
I
a p p roxim a t ely 30,000 ca s e s of con -
T
C
h is h an d s an d f e e t . He h as n o h ist o ry o f k n e e in ju ry, an d b e lie ve s rm ed a n d s u sp e ct e d d is ea s e w ere
E
S
t h at u se o f o ve r-t h e -co u n t e r ib u p ro f e n h as h e lp e d t ak e t h e e d g e re p ort e d by t h e Ce n t e rs for Dis -
o ff t h e p ain . Th is m e d icat io n h as n o t re d u ce d t h e sw e llin g o r ea s e Con trol a n d Preve n t ion (CDC).
Th e s t a t e s w it h t h e h igh e s t t ot a l
se n sat io n o f w arm t h w h e n h e t o u ch e s t h e k n e e .
n u m b e r o f r e p o r t e d ca s e s a r e
The p at ie n t live s in rural so ut h e ast e rn Pe nn sylvania, an d is an New York, Pe n n s ylva n ia , a n d Ma s -
active hunter. He denies fam ily history of arthritis or arthritis-re lat e d s a ch u s e t t s . Th e h igh e s t in cid e n ce
d ise ase s. He is aw are t h at Lym e d ise ase is a co m m o n illn e ss in t h is of d is e a s e occu rre d in De la w a re
a n d w a s re p o r t e d a t 111.2 p e r
are a an d w o n d e rs if h e in f act h as t h is illn e ss.
100,000 in d ivid u a ls (Fig. 24.2 ).
2009
State 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008†
Confirmed Probable Incidence*
Alabama 12 9 11 24 20 6 10 11 8 6 3 11 13 6 3 0 0.1
Alaska 0 0 2 1 0 2 2 3 3 3 4 3 10 6 7 0 1.0
Arizona 1 0 4 1 3 2 3 4 4 13 10 10 2 2 3 4 0.0
Arkansas 11 27 27 8 7 7 4 3 0 0 0 0 1 0 0 0 0.0
Colorado 0 0 0 0 3 0 0 1 0 0 0 0 0 2 0 1 0.0
Connecticut 1548 3104 2297 3434 3215 3773 3597 4631 1403 1348 1810 1788 3058 2738 2751 1405 78.2
Delaware 56 173 109 77 167 167 152 194 212 339 646 482 715 772 984 0 111.2
DC 3 3 10 8 6 11 17 25 14 16 10 62 116 71 53 8 8.8
Florida 17 55 56 71 59 54 43 79 43 46 47 34 30 72 77 33 0.4
Georgia 14 1 9 5 0 0 0 2 10 12 6 8 11 35 40 0 0.4
Hawaii 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0
Idaho 0 2 4 7 3 4 5 4 3 6 2 7 9 5 4 12 0.3
Indiana 19 32 33 39 21 23 26 21 25 32 33 26 55 42 61 22 0.9
Kansas 23 36 4 13 16 17 2 7 4 3 3 4 8 16 18 0 0.6
S
E
Kentucky 16 26 20 27 19 13 23 25 17 15 5 7 6 5 1 0 0.0
C
T
Louisiana 9 9 13 15 9 8 8 5 7 2 3 1 2 3 0 0 0.0
I
O
Maine 45 63 34 78 41 71 108 219 175 225 247 338 529 780 791 179 60.0
N
Maryland 454 447 494 659 899 688 608 738 691 891 1235 1248 2576 1746 1466 558 25.7
5
Massachusetts 189 321 291 699 787 1158 1164 1807 1532 1532 2336 1432 2988 3960 4019 1237 61.0
I
n
f
Michigan 5 28 27 17 11 23 21 26 12 27 62 55 51 76 81 22 0.8
e
c
Minnesota 208 251 256 261 283 465 461 867 474 1023 917 914 1238 1046 1063 480 20.2
t
i
o
Mississippi 17 24 27 17 4 3 8 12 21 0 0 3 1 1 0 0 0.0
u
s
Missouri 53 52 28 12 72 47 37 41 70 25 15 5 10 6 3 0 0.1
A
Montana 0 0 0 0 0 0 0 0 0 0 0 1 4 6 3 0 0.3
r
t
h
Nebraska 6 5 2 4 11 5 4 6 2 2 2 11 7 8 4 1 0.2
r
i
t
i
Nevada 6 2 2 6 2 4 4 2 3 1 3 4 15 9 10 3 0.4
s
New
28 47 39 45 27 84 129 261 190 226 265 617 896 1211 996 419 75.2
Hampshire
New Jersey 1703 2190 2041 1911 1719 2459 2020 2349 2887 2698 3363 2432 3134 3214 4598 375 52.8
New York 4438 5301 3327 4640 4402 4329 4083 5535 5399 5100 5565 4460 4165 5741 4134 1517 21.2
Ohio 30 32 40 47 47 61 44 82 66 50 58 43 33 40 51 7 0.4
Oklahoma 63 42 45 13 8 1 0 0 0 3 0 0 1 1 2 0 0.1
Oregon 20 19 20 21 15 13 15 12 16 11 3 7 6 18 12 26 0.3
Pennsylvania 1562 2814 2188 2760 2781 2343 2806 3989 5730 3985 4287 3242 3994 3818 4950 772 39.3
Rhode Island 345 534 442 789 546 675 510 852 736 249 39 308 177 186 150 85 14.2
Tennessee 28 24 45 47 59 28 31 28 20 20 8 15 31 7 10 27 0.2
Utah 1 1 1 0 2 3 1 5 2 1 2 5 7 3 6 3 0.2
Virginia 55 57 67 73 122 149 156 259 195 216 274 357 959 886 698 210 8.9
Washington 10 18 11 7 14 9 9 11 7 14 13 8 12 22 15 1 0.2
Wisconsin 369 396 480 657 490 631 597 1090 740 1144 1459 1466 1814 1493 1952 637 34.5
Wyoming 4 3 3 1 3 3 1 2 2 4 3 1 3 1 1 2 0.2
U.S. TOTAL 11,700 16,455 12,801 16,801 16,273 17,730 17,029 23,763 21,273 19,804 23,305 19,931 27,444 28,921 29,959 8,509 13.4
†
confirmed cases presented for all years except most recent
*
confirmed cases per 100,000 population
Figure 24 .2 2009 reported Lyme disea se ca ses by sta te, 1995 to 2009. Courtesy of Yehia Mishriki, MD. Centers for Disea se Control
a nd Prevention, a va ila ble a t http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_rptdLymeCa sesbySta te.htm. Accessed Ja nua ry 21, 2011.
Ch a p te r 24 Lym e Dis e a s e 249
s
i
t
ifesta tion s, d iagn osis, a n d trea tm en t of th is illn ess in North Am erica .
i
r
h
t
r
A
s
u
o
i
t
c
e
f
1 inch
n
I
5
Blacklegged Tick (Ixodes scapularis)
N
O
I
T
C
E
S
adult adult
female male nymph larva
Figure 24 .4 Dime ticks tra nsmission a nd size. Ima ge a ccessed Ja nua ry 11, 2011, a t Centers for Disea se
Control a nd Prevention Web site http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_tra nsmission.htm.
250 Se ctio n 5 In fe ct iou s Art h rit is
40,000
Confirmed cases
35,000 Probable cases*
30,000
25,000
s
se
a
20,000
C
15,000
10,000
5,000
0
S
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
E
C
T
*National Surveillance case definition revised in 2008 to include probable cases;
I
O
details at http://www.cdc.gov/ncphi/disss/nndss/casedef/lyme_disease_2008.htm
N
5
Figure 24 .5 Lyme disea se incidence by yea r. Courtesy of Ja mes Ga tha ny. Centers for Disea se Control a nd Prevention, a va ila ble
I
a t http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_UpClimbLymeDis.htm. Accessed Ja nua ry 21, 2011.
n
f
e
c
t
i
o
Clinica l Pre se nta tio n
u
s
A
Th e clin ica l p re s e n t a t ion of Lym e d is e a s e is ge n e ra lly d ivid e d in t o t h re e s t a ge s :
r
t
h
e a r ly lo ca liz e d , e a r ly d is s e m in a t e d , a n d la t e -s t a ge d is e a s e . Tw o a d d it io n a l
r
i
t
i
s
s t a ge s h ave a ls o be e n d e s cribe d , bu t a re n ot u n ive rs a lly a ccep t e d a s p a rt of t h e
n a t u ra l h is t ory of t h e d is e a s e. An u n d e rs t a n d in g of t h e s e s t a ge s is crit -
ica l for e ffe ct ive d ia gn os is a n d t re a t m e n t of Lym e d is e a s e.
s
co m o rb id d ise a se st a t e s. a few ye a rs a n d d o n ot n e ce s s a rily re q u ire a d d it ion a l t re a t m e n t . On goin g s ym p -
i
t
i
r
t om a t ic join t p a in ca n be t re a t e d w it h a n t i-in a m m a t ory m e d ica t ion s .
h
t
r
A
La t e -s t a ge p a t ie n t s ca n a ls o p re s e n t w it h ch ron ic low -gra d e e n cep h a lop a -
s
t h y, e n ce p h a lom ye lit is , a n d /or p e rip h e ra l n e u rop a t h y. Pe rip h e ra l n e u rop a t h y
u
o
t yp ica lly p re s e n t s w it h p a re s t h e s ia s in t h e s e t t in g of u n re m a rka ble s e n s ory
i
t
c
a n d m ot or e xa m in a t ion s . Th e s e s ym p t om s a re s im ila r t o t h os e of e a rly d is -
e
f
n
s e m in a t e d d is e a s e, a n d d iffe re n t ia t in g be t w e e n e a rly d is s e m in a t e d a n d la t e -
I
5
s t a ge d is e a s e ca n be d if cu lt u n le s s t h e re is a cle a r h is t ory of t ick bit e or e a rly
N
s t a ge s ym p t o m s . En ce p h a lo p a t h y a n d e n ce p h a lo m ye lit is ca n p re s e n t ye a r s
O
I
T
a ft e r in fe ct ion a n d ca n be s u bt le a n d d if cu lt t o d ia gn os e.
C
E
In a d d it ion t o t h e t h re e cla s s ica l p h a s e s of Lym e d is e a s e, clin icia n s s h ou ld
S
be aw a re of t w o a d d it ion a l, bu t con t rove rs ia l, s t a ge s ca lle d “p os t –Lym e d is e a s e
s yn d rom e ” a n d “ch ron ic Lym e d is e a s e ” (1 ).
Ch ron ic Lym e d is e a s e d e s cribe s a con d it ion s om e p h ys icia n s a n d p a t ie n t s
be lieve t o be p e rs is t e n t B. bu rgd orfe ri in fe ct ion . Fre q u e n t ly, t h e s e p a t ie n t s h ave
n o re p rod u cible or con vin cin g s cie n t i c evid e n ce lin kin g s ym p t om s t o B. bu rg-
d orfe ri in fe ct ion .
Ch ron ic Lym e d is e a s e ca n be a p p roa ch e d a s h avin g fou r ca t egorie s . In ca t -
egory on e, p a t ie n t s p re s e n t w it h n on s p e ci c s ym p t om s w it h n o obje ct ive clin -
ica l or la bora t ory evid e n ce of in fe ct ion .
In ca t egory t w o, p a t ie n t s p re s e n t w it h a h is t ory of p ot e n t ia l Lym e d is e a s e,
by h a ve evid e n ce of illn e s s ot h e r t h a n Lym e d is e a s e.
Ca t egory t h re e p a t ie n t s h a ve a n t ibod ie s a ga in s t B. bu rgd orfe ri, bu t h ave n o
obje ct ive clin ica l n d in gs .
Fin a lly, ca t e gory fou r p a t ie n t s h a ve s ym p t om s of w h a t h a s b e e n t e rm e d
“p os t -Lym e d is e a s e s yn d rom e ”.
Po s t –Lym e d is e a s e s yn d ro m e is ch a ra ct e r iz e d by s u b je ct ive s ym p t o m s ,
in clu d in g fa t igu e, m a la is e, h e a d a ch e, a n d cogn it ive d ys fu n ct ion . Th e In fe ct iou s
Dis e a s e Socie t y of Am e rica (IDSA) h a s p rop os e d t h e follow in g crit e ria for t h is
s yn d rom e (2 ):
• Sym p t om s m u s t occu r w it h in 6 m on t h s of t h e d ia gn os is of Lym e d is e a s e a n d
m u s t p e rs is t for 6 m on t h s a ft e r re com m e n d e d t re a t m e n t .
• Prior d ia gn os is of Lym e d is e a s e w it h re s olu t ion of obje ct ive s ym p t om s fol-
low in g a p p rop ria t e a n t ibiot ic t h e ra py.
• Exclu s ion of ot h e r com orbid d is e a s e s t a t e s in clu d in g brom ya lgia , a bn orm a l
t h yroid fu n ct ion , lon g-s t a n d in g h is t ory of u n e xp la in e d n e u rologic or m u s cu -
los ke le t a l s ym p t om s cle a rly p re ce d in g t h e d ia gn os is of Lym e d is e a s e, s le ep
252 Se ctio n 5 In fe ct iou s Art h rit is
Co infe ctio n
In a d d it ion t o B. burgdorferi, t h e bla ck-legge d t ick or d e e r t ick ca n a ls o t ra n s m it
t h e p a ra s it e s Theileria m icroti a n d A naplasm a phagocytophilum . Th e s e p a ra s it e s
ca u s e b a b e s io s is a n d h u m a n gra n u lo cyt ic a n a p la s m o s is (HGA), re s p e ct ive ly,
a n d s h ou ld be s u s p e ct e d in t h e s e t t in g of in com p le t e or a t yp ica l re s p on s e t o
a p p rop ria t e a n t ibiot ic t re a t m e n t fo r Lym e d is e a s e . Up t o 40% of e a rly Lym e
d is e a s e ca s e s ca n be coin fe ct e d w it h T. m icroti (ba be s io s is ) a n d 12% w it h A .
phagocytophilum (HGA).
Th e n d in g of a h e m o lyt ic a n e m ia s u gge s t s t h e p os s ibilit y of ba be s io s is
coin fe ct ion .
Th e n d in gs o f t h r o m b o cy t o p e n ia , le u co p e n ia , a n d e le va t e d s e r u m
t ra n s a m in a s e leve ls s h o u ld p ro m p t a n eva lu a t io n fo r HGA. Co in fe ct ion h a s
a ls o be e n rep ort e d w it h Bartonella , Ehrlichia , a n d Rickettsia (5 ).
SKIN
Occa sion a lly, p a tien ts p resen t for exa m in a tion w ith a tick rm ly a tta ch ed to th e
skin . If en gorged , th e tick is feed in g a n d th e likelih ood of d isea se tra n sm ission
in crea ses. Un en gorged ( a t) a n d u n a tta ch ed ticks a re u n likely to tra n sm it d isea se.
Th e likelih ood of d isea se tra n sm ission ca n be estim a ted on th e ba sis of th e d u ra -
tion of feed in g. Given th e m ech a n ism of sp iroch ete tra n sm ission , feed in g p eriod s
of less th a n 48 to 72 h ou rs red u ce th e likelih ood of d isea se tra n sm ission .
In e a rly loca lize d a n d e a rly d is s e m in a t e d d is e a s e, t h e n d in g of a n EM ra s h
ca n p rovid e a n im p ort a n t clu e t o t h e d ia gn os is of t h is d is e a s e. Eryt h e m a m igra n s
d eve lop s d ays t o w e e ks a ft e r t h e in it ia l t ick bit e, a n d is t yp ica lly loca t e d in t h e
a xilla , in gu in a l region , p op lit e a l fos s a , or be lt lin e. At t h e t im e of t h e t ick bit e,
Ch a p te r 24 Lym e Dis e a s e 253
s
i
t
i
Figure 24.7 Solid erythema migrans skin rash. Courtesy of Alison Young, MD.
r
h
Centers for Disea se Control a nd Prevention, a va ila ble a t http:/ / derma tla s. Figure 24 .8 Multiple erythema migra ns skin lesions
t
r
A
med.jhmi.edu/ derm/ indexdispla y.cfm?Ima geID=-323138275. Accessed indica ting ea rly dissemina ted disea se. Courtesy of
s
Ja nua ry 21, 2011. Yehia Mishriki.
u
o
i
t
c
e
f
t h e s p iroch e t e is in ocu la t e d in t o t h e s kin . Aft e r a p e riod of t im e ra n gin g from 3
n
I
t o 30 d ays , t h e s p iroch e t e begin s t o m igra t e ou t w a rd s from t h e in ocu la t ion s it e
5
N
ca u s in g t h e ra s h . Th e ra s h is m in im a lly p a in fu l, bu t is fre q u e n t ly h ot t o t ou ch .
O
I
It e xp a n d s s low ly ove r d ays t o w e e ks a n d is u lt im a t e ly ch a ra ct e rize d by a region
T
C
of ce n t ra l cle a rin g. A fu lly m a t u re ra s h h a s a ch a ra ct e ris t ic a p p e a ra n ce d e s cribe d
E
S
a s a “t a rge t le s ion ” (Fig. 24.6 ). Ea rly le s ion s ca n be a t yp ica l a n d a p p e a r u n iform ly
re d (Fig. 24.7 ). Th e ave ra ge t im e from d is cove ry of a ra s h t o m e d ica l eva lu a t ion
h a s be e n d e m on s t ra t e d t o be a bou t 3 d ays (6 ). Pre s e n t in g ra s h e s in t h e s e p a t ie n t s
w e re u n iform ly re d in a lm os t 60% of ca s e s , w it h on ly 9% of ra s h e s d e m on s t ra t -
in g ce n t ra l cle a rin g. Clin icia n s s h ou ld t h e re fore be w illin g t o d ia gn os e EM eve n
w h e n t h e cla s s ic t a rge t le s ion is a bs e n t . Clin icia n s s h ou ld a ls o re m e m be r t h a t
on ly 80% of p a t ie n t s d eve lop ECM follow in g a t ick bit e.
W h e n m u lt ip le ECM (EM?) les ion s a re id e n t i e d (Fig. 24.8 ), t h e d is e a s e h a s
p rogres se d from e a rly loca lized t o ea rly d is s em in a t ed d is ea s e. Th is n d in g d oe s
n ot rep re s en t m u lt ip le t ick-bite exp os u res .
Pa t ie n t s p re s e n t in g for eva lu a t ion im m e d ia t e ly follow in g t ick re m ova l ca n
a ls o d e m on s t ra t e a n on s p e ci c loca l irrit a t ion a t t h e bit e s it e. Th e s e p a t ie n t s
s h ou ld be re a s s u re d t h a t t h is loca l irrit a t ion is n ot EM a n d d oe s n ot re q u ire s p e -
ci c t re a t m e n t for Lym e d is e a s e.
CARDIAC
Ca rd ia c s ym p t om s a re t yp ica lly s e e n in e a rly d is s e m in a t e d (s t a ge 2) d is e a s e.
On p h ys ica l e x a m in a t io n , ca rd ia c a rrh yt h m ia s ca n in d ica t e t h e p re s e n ce o f
h e a rt blo ck , w h ich ca n ra n ge fro m rs t -d egre e a t riove n t ricu la r (AV) blo ck t o
com p le t e h e a rt block. In a d d it ion , ca rd it is ca n occu r a n d p re s e n t w it h n d in gs
of ve n t ricu la r e ct op y or con ge s t ive h e a rt fa ilu re.
NEUROLOGIC
Neu rologic a bn orm a lities d evelop in both ea rly d issem in a ted (s ta ge 2) a n d la t e -
s t a ge (s t a ge 3) Lym e d is e a s e. Abn orm a l n e u rologic n d in gs in clu d e p e rip h e ra l
n e u rop a t h y, cra n ia l n e u rop a t h y, m e n in git is , a n d ra d icu lon e u rit is .
254 Se ctio n 5 In fe ct iou s Art h rit is
Pe r ip h e ra l n e u ro p a t h ie s w it h o u t o b je ct ive s e n s o ry o r m o t o r a b n o r m a li-
t ie s occu r in bo t h e a r ly d is s e m in a t e d a n d la t e -s t a ge d is e a s e . Cra n ia l n e u ro p a -
t h ie s d eve lo p in u p t o 10% t o 20% o f e a r ly d is s e m in a t e d p re s e n t a t io n s a n d
fre q u e n t ly in clu d e e it h e r u n ila t e ra l o r b ila t e ra l fa cia l n e r ve p a ls ie s . W h e n
fa cia l n e rve p a ls y p re s e n t s w it h h e a d a ch e a n d / o r s ign s o f m é n a ge irr it a b ilit y
(n u ch a l r igid it y), eva lu a t io n fo r p o s s ible m e n in git is is w a r ra n t e d . Lym p h o cyt ic
m e n in git is p re s e n t in g w it h t yp ica l s ign s o f m e n in ge a l ir r it a t io n ca n a ls o
o ccu r w it h o u t cra n ia l n e r ve p a ls y d u rin g e a r ly d is s e m in a t e d d is e a s e . Ra d icu -
lo n e u r it is t yp ica lly p re s e n t s w it h a cu t e o n s e t o f s eve re p a in o r m o t o r w e a k -
n e s s . Eve n w it h o u t t r e a t m e n t , t h e s e s ym p t o m s t yp ica lly r e s o lve w it h in
m on th s of on set.
Ch ro n ic e n ce p h a lo p a t h y a n d e n ce p h a lo m ye lit is ca n a ls o p re s e n t w it h
m e m ory ch a n ge a n d fa t igu e, a n d m ay p re s e n t ye a rs a ft e r t h e on s e t of d is e a s e.
Th e s e n d in gs d o n o t t yp ica lly re m it s p on t a n e ou s ly a n d re q u ire a n t ib io t ic
t re a t m e n t for t re a t m e n t .
MUSCULOSKELETAL
In t e rm it t e n t , m igra t ory a rt h ra lgia s yn d rom e s a re fre q u e n t ly s e e n in t h e rs t
t w o s t a ge s of Lym e d is e a s e. On e xa m in a t ion , p a in fu l join t s ca n be id e n t i e d in
S
t h e a bs e n ce of e ryt h e m a , sw e llin g, or w a rm t h .
E
C
Weeks to yea rs a fter in it ia l in fect ion (sta ge 3), p a tien ts ca n p res en t w it h oligo-
T
I
or m on a rticu la r a rth ritis. Up to 60% of p a tien ts w it h la te-sta ge d isea se rep ort a n
O
N
a sym m et ric rela tively p a in less a rth ritis. W h ile m u ltip le la rge join t ca n be in volved ,
5
th e m ost typ ica l s ite of in volvem en t is th e kn ee. W h ile rela t ively p a in less , kn ee
I
n
a rth ritis ca n be a ssocia ted w ith join t effu sion s a n d Ba ker’s cysts (6 ).
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Studie s
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t
Th e d ia gn osis of Lym e d isea se req u ires kn ow led ge of th e in cid en ce of th e d isea se,
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th e p a tien t’s clin ica l p resen ta tion , a n d w h en a p p rop ria te, serologic con rm a tion
t
i
s
of im m u n e resp on se to th e sp iroch ete. Serologic testin g is n ot recom m en d ed a s
a s cre en in g t e s t for d is e a s e in t h e s e t t in g of p os s ible t ick-bit e exp os u re in t h e
absen ce of su p p ortin g clin ica l p resen ta tion a n d is u sefu l for con rm a tion of d ia g-
n osis in on ly certa in in sta n ces. Gu id elin es for th e a ssessm en t a n d trea tm en t of
su sp ected Lym e d isea se h ave been issu ed by th e IDSA (7 ).
NONSPECIFIC EVALUATION
NOT TO BE MISSED
Eva lu a t io n o f p a t ie n t s p re s e n t in g w it h s ign s o f m e n in git is o r a r t h r it is fre -
• Coinfection with other tick- q u e n t ly re q u ire fu r t h e r eva lu a t io n . W h ile jo in t a n d s p in a l u id a n a lys is m a y
borne illne ss. Inco mp le te n o t co n r m t h e d ia gn o s is o f Lym e d is e a s e , e va lu a t io n o f t h e s e u id s ca n
or a t yp ica l re spo nse to s e r ve t h e im p o r t a n t p u r p o s e o f e x clu d in g o t h e r ca u s e s o f jo in t or m e n in ge a l
sta nda rd a ntibiotic the ra py ir r it a t io n .
or a bn o rma lit ie s o n Th e m e n in git is of Lym e d is e a s e is t yp ica lly a lym p h ocyt ic m e n in git is ch a r-
perip h e ra l b lo o d a n a lysis
should ra ise the possibility a ct e rize d by s p in a l u id ce ll cou n t s ra n gin g from occa s ion a l t o a few h u n d re d
of e it h e r b a b e sio sis o r lym p h ocyt e s . Mild s p in a l u id p rot e in e leva t ion s ca n a ls o occu r, bu t glu cos e
HGA co in fe ct io n . leve ls a re u s u a lly n orm a l. Sp in a l u id a n a lys is for Lym e a n t ibod ie s ca n be p e r-
• Pa t ie n t s p re se n t in g w it h form e d , bu t in t e rp re t a t ion of t e s t re s u lt s ca n be ch a lle n gin g give n t h e la ck of
m u lt ip le ECM le sio n s d o a s s ay s t a n d a rd iza t ion . Be ca u s e n e u rologic s ym p t om s d eve lop in t h e e a rly d is -
n o t h a ve m u lt ip le in it ia l s e m in a t e d s t a ge of d is e a s e, t h e a bs e n ce of s e ru m a n t ibod ie s m a ke s t h e d ia g-
e xp o su re s. Mu lt ip le ECM n os is of Lym e d is e a s e h igh ly u n like ly a n d s h ou ld ca ll in t o q u e s t ion a t t ribu t in g
le sio n s in d ica t e e a rly n e u rologic n d in gs t o B. burgdorferi in fe ct ion .
d isse m in a t e d d ise a se .
Join t u id ca n a ls o be a n a lyze d w h e n join t e ffu s ion s a re id e n t i e d on p h ys -
• The d ia g no sis o f Lyme ica l e xa m in a t ion . Kn e e e ffu s ion s ca n ra n ge from m in im a lly t o h igh ly in a m -
disea se d oe s no t re quire a m a t ory e ffu s ion s w it h s yn ovia l u id w h it e blood ce ll cou n t s of p re d om in a n t ly
positive Lym e se ro lo g y in
e a rly d ise a se p re se n ta tio ns. n e u t rop h ils ra n gin g from 500 t o 100,000 ce lls . Syn ovia l u id ca n a ls o be a n a -
lyze d of B. burgdorferi DNA u s in g p olym e ra s e ch a in re a ct ion (PCR) t e s t in g. Th is
Ch a p te r 24 Lym e Dis e a s e 255
SEROLOGIC EVALUATION
Se ro logic s t u d ie s s h ou ld b e ord e re d w h e n t h e h is t ory a n d p h ys ica l e xa m in a -
t io n s t ro n gly s u gge s t Lym e d is e a s e . Mo s t la b o ra t o rie s be gin w it h t h e s e n s it ive
e n zym e -lin ke d im m u n os orbe n t a s s ay (ELISA). If t h is is p os it ive, a re e x We s t e rn
blo t s h o u ld b e p e r fo r m e d a s o t h e r in fe ct io n s a n d co n d it io n s m a y ca u s e a
p o s it ive ELISA. Th e cr it e r ia for a p o s it ive We s t e r n blo t t e s t in clu d e t w o o f t h e
follow in g IgM ba n d s e a r ly in t h e d is e a s e : 24, 39, 41, o r ve o f t h e fo llow in g IgG
b a n d s la t e r in t h e d is e a s e : 18, 23, 28, 30, 39, 41, 45, 58, 66, 93 (9 ). Pa t ie n t s w it h
e a r ly lo ca liz e d d is e a s e p re s e n t in g w it h EM a re o ft e n s e ro n e ga t ive a n d s h o u ld
b e t r e a t e d im m e d ia t e ly o n t h e b a s is o f c lin ic a l gr o u n d s . Th is t w o -s t e p
a p p ro a ch h a s be e n e n d o r s e d by t h e CDC a n d s h o u ld gu id e t h e s e ro logic eva l-
u a t io n of p o t e n t ia l ca s e s o f Lym e d is e a s e . W h ile a d d it io n a l t e s t in g is o ffe re d
s
for t h e d ia gn o s is o f Lym e d is e a s e , t h e a ccu ra cy o f t h e s e t e s t s h a s n o t b e e n
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t
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e s t a blis h e d . Su ch t e s t in g in clu d e s u r in e a n t ige n t e s t in g, im m u n o u o re s ce n t
h
t
r
s t a in in g fo r ce ll-w a ll–d e cie n t fo r m s o f B. bu rgdorferi, a n d lym p h o cyt e t ra n s -
A
fo rm a t ion t e s t in g.
s
u
An t ibod ie s t o Lym e d is e a s e m a y p e rs is t eve n a ft e r a p p rop ria t e t re a t m e n t ;
o
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t
c
t h e re fore, re p e a t e d cou rs e s of a n t ibiot ics a re n ot n e ce s s a ry if t h e clin ica l s ym p -
e
f
t o m s h a ve re s olve d . Pa t ie n t s w h o h a ve re ce ive d t h e va ccin e (LYMErix) m a y
n
I
e xh ibit p os it ive ELISA a n d We s t e rn blot ba n d s . Th e Lym e va ccin e is n o lon ge r
5
N
ava ila ble.
O
I
T
C
E
Tre a tme nt
S
Th e t re a t m e n t of Lym e d is e a s e d ep e n d s on a ge of t h e p a t ie n t a s w e ll a s clin ica l
s t a ge of t h e d is e a s e a t t h e t im e of p re s e n t a t ion . Doxycyclin e is n ot re co m -
m e n d e d in ch ild re n you n ge r t h a n 8 ye a rs or p a t ie n t s w h o a re p regn a n t or la c-
t a t in g. Re la p s e a ft e r t re a t m e n t is p os s ible ; h ow eve r, on ly p a t ie n t s w it h obje ct ive
clin ica l s ign s of d is e a s e s h ou ld be con s id e re d for a s e con d cou rs e of a n t ibiot ics .
Th e follow in g re e ct t h e clin ica l p ra ct ice gu id e lin e s from t h e IDSA (7 ).
Prop h yla xis w it h d oxycyclin e 200 m g on e -t im e d os e is in d ica t e d if t h e t ick
is id e n t i e d a s a d e e r t ick , t h e le n gt h o f e x p o s u re (fe e d in g) w a s a t le a s t
36 h ou rs , p rop h yla xis is begu n w it h in 72 h ou rs of t ick re m ova l, loca l ra t e of
WHEN TO REFER
in fe ct ion of t icks w it h B. burgdorferi is a t le a s t 20%, a n d t h e p a t ie n t is a ble t o
• Pa t ie n t s w h o re q u e st t a ke d oxycyclin e. W h ile p rop h yla xis ca n be give n t o ch ild re n 8 ye a rs a n d old e r
o n g o in g IV a n t ib io t ic (d oxycyclin e 4 m g/kg u p t o a m a xim u m d os e of 200 m g), t h is re com m e n d a t ion
t h e ra p y fo r n o n sp e ci c h a s n ot be e n form a lly eva lu a t e d for e f ca cy or s a fe t y. W h e n d oxycyclin e ca n -
sym p t o m s in clu d in g n ot be p re s cribe d , t h e IDSA d oe s n ot re com m e n d p rop h yla xis .
ch ro n ic fa t ig u e o r
b ro m ya lg ia .
EARLY LOCALIZED DISEASE (ERYTHEMA MIGRANS)
• Pa t ie n t s w h o b e lie ve t h e y
h a ve p o st –Lym e d ise a se Doxycyclin e 100 m g PO BID for 10 t o 21 d a ys
syn d ro m e o r ch ro n ic Lym e Am oxicillin 500 m g PO TID for 14 t o 21 d a ys
d ise a se .
• Pe rsiste n t m on o - or o li-
go a rt icu la r a rt hritis a fte r
Ea rly Disse mina te d Dise a se
a p p ro p ria te a n tib io tic th e r- Is ola t e d fa cia l n e rve p a ls y is t re a t e d t h e s a m e a s e a rly loca lize d ; h ow eve r, it
a p y th a t h a s n o t re sp o n d e d
m a y re q u ire 14 t o 28 d ays of t h e ra p y.
to re com me nde d a nti-
in a m ma tory tre a tme nt. Me n in git is or e n ce p h a lit is is t re a t e d w it h ce ft r ia xon e 2 g in t ra ve n ou s ly (IV)
d a ily for 28 d ays .
256 Se ctio n 5 In fe ct iou s Art h rit is
La te - sta g e Dise a se
Lym e a rt h rit is is t re a t e d w it h t h e s a m e ora l regim e n s a s e a rlie r d is e a s e ; h ow -
eve r, t h e ra p y s h o u ld be con t in u e d for 28 d a ys . If s yn ovia l in a m m a t io n p e r-
s is t s , t re a t m e n t w it h n o n s t e r o id a l a n t i-in a m m a t o ry d r u gs (NSAIDs ) o r
h yd roxych loroq u in e 200 m g BID s h ou ld be con s id e re d (10 ).
A Ja ris ch –He rxh e im e r re a ct ion h a s be e n obs e rve d in u p t o 10% of p a t ie n t s
d u rin g t h e rs t 24 h ou rs of t re a t m e n t (11 ). Th e re a ct ion ca n in clu d e feve r, ra s h
w it h o r w it h ou t p ru rit u s , n on s p e ci c ga s t ro in t e s t in a l com p la in t s , m ya lgia s ,
a n d a rt h ra lgia s .
Clinica l Co urse
Tre a t e d Lym e d is e a s e s h ou ld n ot re s u lt in ch ron ic s ym p t om s . Pa t ie n t s co m -
p la in in g of d iffu s e bod y p a in w it h ou t obje ct ive n d in gs of in a m m a t ion or
S
E
in fe ct ion s h ou ld be eva lu a t e d for brom ya lgia . Coe xis t in g m igra in e h e a d a ch e s ,
C
T
e n d om e t rios is , irrit a ble bow e l s yn d rom e , in t e rs t it ia l cys t it is , a n d u n d e rlyin g
I
O
p s ych ia t ric d is e a s e s h ou ld a ls o p rom p t t h e p h ys icia n t o con s id e r brom ya lgia
N
or ot h e r p os s ible d ia gn os is .
5
I
Lym e d is e a s e ca n p re s e n t a d ia gn os t ic a n d t h e ra p e u t ic ch a lle n ge u n le s s
n
f
e
ca re fu l a t t e n t io n is give n t o co m p le t in g a n a ccu ra t e h is t o ry a n d t h o ro u gh
c
t
i
p h ys ica l e xa m in a t ion . W it h a p p rop ria t e d a t a co lle ct ion , clin icia n s ca n u t ilize
o
u
evid e n ce -ba s e d a p p roa ch e s t o t re a t m e n t a n d p reve n t ion t h a t w ill e n s u re s a fe
s
A
a n d e ffe ct ive ca re for a ll p a t ie n t s d ia gn os e d w it h t h is illn e s s .
r
t
h
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i
t
i
s
ICD9
088.81 Lyme
Re fe re nce s
1. Fe d e r H , Joh n s on BJ, O’Con n e ll S, e t a l. Cu rre n t con ce p t s : A crit ica l a p p ra is a l of “ch ron ic Lym e d is e a s e.”
N Engl J Med 2007 ;357 :1422 .
2. Ce n t e rs fo r Dis e a s e Co n t rol a n d Preve n t ion . Ca s e d e n it io n s for in fe ct iou s con d it ion s u n d e r p u blic
h e a lt h s u rve illa n ce . MMW R Morb Mortal Recom m Rep 1997 ;46 (RR-10 ):1 .
3. Na d e lm a n RB, Worm s e r GP. Re in fe ct ion in p a t ie n t s w it h Lym e d is e a s e . Clin Infect Dis 2007 ;45 :1032 .
4. Silve r HM . Lym e d is e a s e d u rin g p regn a n cy. Infect Dis Clin North A m 1997 ;11 :93 .
5. Worm s e r GP. Clin ica l p ra ct ice. Ea rly Lym e d is e a s e . N Eng J Med 2006;354 (26 ):2794 –801 .
6. Sm it h RP, Sch oen RT, Ra h n DW, e t a l. Clin ica l ch a ra ct erist ics a n d t re a t m en t ou t com e of e a rly Lym e d ise a se
in p a t ie n t s w it h m icrobiologica lly co n rm e d e ryt h e m a m igra n s . A nn Intern Med 2002 ;136 :421 .
7. Worm s e r GP, Da t t w yle r RJ, Sh a p iro ED, e t a l. Th e clin ica l a s s e s s m e n t , t re a t m e n t , a n d p reve n t ion of Lym e
d is e a s e, h u m a n gra n u locyt ic a n a p la s m os is , a n d ba be s ios is : Clin ica l Pra ct ice Gu id e lin e s by t h e In fe ct iou s
Dis e a s e Socie t y of Am e rica . Clin Infect Dis 2006 ;43 :1089 .
8. Noct on JJ, Dre s s le r F, Ru t le d ge BJ, e t a l. De t e ct ion of Borrelia burgdorferi DNA by p olym e ra s e ch a in re a ct ion
in s yn ovia l u id from p a t ie n t s w it h Lym e a rt h rit is . N Engl J Med 1994 ;330 (4 ):229 –234 .
9. Dre s s le r F, W h a le n JA, Re in h a rd t BN , e t a l . We s t e rn blot t in g in t h e s e rod ia gn os is of Lym e d is e a s e . J Infect
Dis 1993 ;167 (2 ):392 –400 .
10. St e e re AC, An ge lis SM . Th e ra py for Lym e a rt h rit is : St ra t egie s for t h e t re a t m e n t of a n t ibiot ic-re fra ct ory
a rt h rit is . A rthritis Rheum 2006 ;54 (10 ):3079 –3086 .
11. St e e re AC, Hu t ch in s on GJ, Ra h n DW, e t a l. Tre a t m e n t of t h e e a rly m a n ife s t a t ion s of Lym e d is e a s e . A nn
Intern Med 1983 ;99 :22 –26.
CHAPTER
25 Vira l Arthritis
Katherine Holm an and Martin Rodriguez
s
d ive rs e . Th e ir a b ilit y t o e it h e r ca u s e a n
i
t
i
w it h a 3-d ay h ist o ry o f jo in t
r
a cu t e illn e s s w it h fu ll re cove ry o r e s t a b-
h
t
r
p ain an d sw e llin g . Sh e st at e s lis h a la t e n t co u r s e —p ro gre s s in g t o a
A
re la p s in g s yn d ro m e o r ch ro n ic p rogre s -
s
t h at t h e sym p t o m s st art e d
u
s ive illn e s s —ca n m a k e t h e ir d ia gn o s e s
o
i
w it h f e ve r u p t o 102 °F an d
t
c
d if cu lt (1 ). Am o n g t h e w id e m a n ife s -
e
f
d iff u se m yalg ias. Th e jo in t t a t ion s o f vira l illn e s s e s , a r t h r it is is a n
n
I
u n co m m o n s ym p t o m ; h ow eve r, in t h e
5
p ain b e g an ab ru p t ly in h e r
N
ca s e o f s p e ci c vir u s e s , a rt h r it is ca n b e
O
k n e e s an d sp re ad t o in vo lve
I
o n e o f t h e m o s t co m m o n s ym p t o m s
T
C
m u lt ip le jo in t s o ve r t h e n e xt f e w d ays. Sh e n o t e s t h at h e r (i.e ., a lp h a vir u s e s ). Th e r e fo r e , va r io u s
E
S
p ain an d st iff n e ss are w o rse in t h e m o rn in g s. He r so cial vira l illn e s s e s s h o u ld be co n s id e re d in
h ist o ry is sig n i can t f o r w o rk in g at an e st ab lish m e n t t h at t h e d iffe re n t ia l d ia gn o s is o f a p a t ie n t
p r e s e n t in g w i t h u n d i ffe r e n t ia t e d
h e ld p art ie s f o r ch ild re n . Ph ysical e xam in at io n is n o t ab le
a r t h r it is .
f o r a t e m p e rat u re o f 102.7 °F, an d t e n d e rn e ss t o p alp at io n
w it h lim it e d ran g e o f m o t io n o ve r k n e e s, w rist s, e lb o w s,
an d p ro xim al in t e rp h alan g e al (PIP) jo in t s sym m e t rically. Pa rvo virus B19
Rash is n o t e d as sh o w n in Fig u re 25.1 . Lab o rat o ry d at a w e re CLINICAL PRESENTATION
sig n i can t f o r w h it e b lo o d ce ll (W BC) 11.3 w it h a n o rm al Pa rvoviru s B19 w a s id e n t i e d in h u m a n
diff e re n t ial, e ryt hro cyt e se dim e nt at io n rat e (ESR) 25 m m /hou r, s e ru m in t h e m id -1970s (2 ). How eve r, it s
d is e a s e m a n ife s t a t ion s h ave be e n re cog-
an d C-re act ive p ro t e in (CRP) 12.2 m g /L; h u m an im m u n o d e -
n ize d s in ce t h e 1800s , w it h t h e in it ia l
cie n cy viru s (HIV) an d h e p at it is B an d C se ro lo g ie s w e re d e s crip t ion of “ ft h d is e a s e ” or e ryt h e m a
n e g at ive . A n t in ucle ar ant ib o die s (A NA ), ant icyclic cit ru llin at e d in fe ct ios u m in ch ild re n (3 ). Th e cla s s ic
p e p t id e an t ib od ie s (an t i-CCP), and rh e u m at o id f act o r (RF) form s of p a rvoviru s B19 in fe ct ion occu r
a t e it h e r t h e vire m ic s t a ge (t ra n s ie n t
w e re n e gat ive . Parvo viru s Ig M an d IgG w e re p o sit ive at 3.4
a p la s t ic cris is a n d p u re re d ce ll a p la s ia )
an d 5.3 re spe ct ive ly. o r t h e p o s t vir e m ic s t a ge (e r yt h e m a
in fe ct ios u m a n d a rt h rop a t h y; 2 ). W h ile
ch ild re n co m m o n ly p re s e n t w it h t h e
cla s s ic “s la p p e d ch e e k” a n d re t icu la r ra s h of e ryt h e m a in fe ct ios u m , ra s h is u s u -
a lly a bs e n t or s u bt le in a d u lt s (1 ). Con ve rs e ly, a rt h ra lgia s or a rt h rit is is fa r m ore
com m on in a d u lt s w it h a cu t e in fe ct ion s (4 ). Th e cla s s ic a rt h rit is begin s p re cip i-
t ou s ly in a few join t s , s p re a d s ra p id ly in 24 t o 48 h ou rs , a n d is ch a ra ct e rize d by
s eve re, p rolon ge d m orn in g s t iffn e s s .
257
258 Se ctio n 5 In fe ct iou s Art h rit is
EXAMINATION
Pa tien ts ten d to p resen t w ith a low tem p era tu re. A la cy
ra sh , m ost com m on ly p resen t in th e extrem ities, ca n be
fou n d . Ten d er, sw ollen join ts a re com m on ly seen , bu t n o
d eform ities a re p resen t. Both sm a ll- a n d m ed iu m -s ize
join ts a re p red om in a n tly a ffected u su a lly in a sym m etri-
ca l fa sh ion (1 ). Axia l join ts a re sp a red .
DIAGNOSIS
Virem ia is evid en t by 5 t o 6 d ays p ostexp osu re, w it h a
p ea k a t 8 to 9 d ays. Th e viru s clea rs q u ickly, a n d IgM is
p resen t by d ays 10 to 12 a n d m ay p ersist for 2 to 3 m on th s
(2 ). Se ru m of in fe ct e d p a t ie n t s ca n s h ow t ra n s ie n t
Figure 25.1 Pa rvovirus infection. Photogra ph demonstra tes the la celike a u t oa n t ibod ies , in clu d in g, bu t n ot lim it e d t o, ANA, RF,
reticula ted ra sh on the a rm of a youngster with fth disea se. From Sweet a n d a n ti-DNAs (4 ). Diagn osis th erefore relies on seru m
RL, Gibbs RS. Atla s of Infectious Disea ses of the Fema le Genita l Tra ct. IgM a n t ibod ies t o p a rvoviru s B19, w ith or w ith ou t IgG
Phila delphia : Lippincott Willia ms & Wilkins; 2005. a n d d em on strable p a rvoviru s DNA.
TREATMENT
Tre a t m e n t is s u p p ort ive, w it h n on s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs )
a s n e e d e d for p a in a n d in a m m a t ion . In t ra ve n ou s im m u n oglobu lin h a s be e n
u s e d in ca s e s of p u re re d ce ll a p la s ia in im m u n ocom p rom is e d p a t ie n t s , bu t it
is n ot re com m e n d e d in a rt h rit is (4 ).
CLINICAL POINTS
• Th e re is n o “ cla ssic” p re s-
e n t a t io n t h a t is t yp ica l o f CLINICAL COURSE
vira lly a sso cia t e d a rt h rit is. Acu t e a rt h rit is re s olve s w it h in w e e ks a lt h ou gh , u n com m on ly, ca s e s h ave p e r-
• Ma n y vira lly a sso cia t e d s is t e d for m on t h s . W h e t h e r p a rvoviru s B19 in fe ct ion ca u s e s a ch ron ic a rt h rit is
a rt h rit id e s ca n b e m ist a ke n re m a in s con t rove rs ia l (4 ), a s d oe s it s p os s ible a s s ocia t ion w it h RA a n d ot h e r
fo r e a rly rh e u m a t o id in a m m a t o ry a r t h ro p a t h ie s . So m e s t u d ie s h a ve fo u n d o n go in g B19 DNA in
a rt h rit is (RA).
s e ru m , bon e m a rrow, a n d s yn oviu m of p a t ie n t s w it h ch ron ic a rt h rit is a n d /or
• Art h rit is m a y o ccu r b e fo re RA, bu t t h ey h ave be e n fou n d in h e a lt h y con t rols a s w e ll, m a kin g a d e t e rm in a -
t h e o n se t o f a t yp ica l t ion of t h e ca u s e d if cu lt (1 , 2, 4 – 6 ).
clin ica l vira l syn d ro m e
(i.e ., HBV, HIV).
He pa titis C
CLINICAL PRESENTATION
He p a t it is C (HCV) is a s in gle -s t ra n d e d RNA Flav iv irus . It is e s t im a t e d t h a t gre a t e r
t h a n 170 m illion p e op le w orld w id e a re in fe ct e d w it h t h e viru s (7 ). Pa re n t e ra l
in fe ct ion occu rs m os t com m on ly, oft e n in t h e s e t t in g of in t ra ve n ou s d ru g u s e.
Tra n s m is s ion in h e a lt h ca re s e t t in gs h a s be com e ra re in d eve lop e d cou n t rie s
s in ce rou t in e t e s t in g of blood p rod u ct s bega n in t h e e a rly 1990s ; h ow eve r, occa -
PATIENT ASSESSMENT s ion a l ca s e s con t in u e t o b e re p ort e d (7 ). Follow in g a cu t e in fe ct ion w it h HCV,
74% t o 86% of p a t ie n t s d eve lop p e rs is t e n t vire m ia a n d 15% t o 20% of t h e s e
• Th o ro u g h h ist o ry, p a t ie n t s w it h ch ron ic in fe ct io n d eve lo p cirr h os is (7 ), w h ich ca n p rogre s s t o
in clu d in g im m u n iza t io n s, h e p a t oce llu la r ca rcin om a a n d e n d -s t a ge live r d is e a s e.
e xp o su re s, o ccu p a t io n ,
t ra ve l, se xu a l, a n d so cia l. Ex t ra h e p a t ic m a n ife s t a t ion s of HCV in fe ct ion a re va r ie d , w it h join t p a in
be in g a com m on on e. St u d ie s e s t im a t e t h a t 9% t o 29% of a ll p a t ie n t s w it h HCV
• Clo se e xa m in a t io n com p la in o f a rt h ra lgia s , w h ile 2% t o 4% o f p a t ie n t s h a ve a rt h rit is (1 , 8 ). Tru e
fo r sig n s o f o t h e r
rh e u m a t o lo g ic co n d it io n s. in a m m a t ory a rt h rit is a p p e a rs t o m a n ife s t in fou r d is t in ct w a ys : (1 ) re la t in g
d ire ct ly t o HCV in fe ct ion (2 ) a s a s ign of m ixe d cryoglobu lin e m ia (3 ) coe xis t in g,
• Sp eci c la b ora to rie s o n bu t s e p a ra t e rh e u m a t ic d is e a s e (4 ) occu rrin g ra re ly s e con d a ry t o t h e ra p y for
the basis of risk assessment
a b ove . HCV (4 ). As t h e ra py-re la t e d a rt h rit is is e xce e d in gly ra re, fu rt h e r d is cu s s ion of
1 t o 3 follow s .
Ch a p te r 25 Vira l Art h rit is 259
Diag no sis
De m on s t ra t ion of HCV a n t ibod y or RNA in s e ru m a n d ru lin g ou t ot h e r ca u s e s
of bot h HCV-re la t e d , s u ch a s m ixe d cryoglobu lin e m ia , a n d n on re la t e d in a m -
m a t ory a rt h rit is .
s
i
t
i
MIXED CRYOGLOBULINEMIA
r
h
t
r
Es s e n t ia l m ixe d cryoglobu lin e m ia is a s s ocia t e d w it h HCV in fe ct ion , a n d s ym p -
A
s
t om s in clu d e p u rp u ra , glom e ru lon e p h rit is , lym p h a d e n op a t h y, s kin u lce rs , a n d
u
o
p e rip h e ra l n e u rop a t h y. Ma n y p a t ie n t s com p la in of a rt h ra lgia s ; h ow eve r, le s s
i
t
c
t h a n 10% d eve lop fra n k a rt h rit is (4 ). Th e cla s s ic t ria d is d e s cribe d a s t h a t of
e
f
n
p u rp u ra , glo m e r u lon e p h rit is , a n d a r t h ra lgia s . Ph ys ica l e x a m in a t ion s e ld o m
I
5
reve a ls evid e n ce of s yn ovit is or d e form it y; s kin e xa m in a t ion s h ow s p a lp a ble
N
p u rp u ra m os t fre q u e n t ly in t h e low e r e xt re m it ie s .
O
I
T
C
E
Diag no sis
S
Dia gn os is re q u ire s d e m on s t ra t ion of t h e clin ica l s yn d rom e in a d d it ion t o s e ro-
logic, in clu d in g s e ru m cryoglobu lin s , low C4 leve l, a n d p os it ive RF (s e rologic),
w it h h is t o logic n d in gs s u ch a s evid e n ce o f le u ko cyt o cla s t ic va s cu lit is (4 ).
No t a bly, t e s t s for HCV a n t ibo d ie s ca n be fa ls e ly n e ga t ive in t h is con d it io n ,
re q u irin g t e s t s d ire ct e d t ow a rd HCV RNA for d ia gn os is (7 ).
Diag no sis
Clin ica l n d in gs com bin e d w it h ove rla p p in g la bora t ory n d in gs —p os it ive RF,
cyt op e n ia s , ANA, low C4 leve l—m a ke a rm d ia gn os is d if cu lt . To a d d re s s t h is ,
a n t i-CCP a n t ibod y, a fa irly s p e ci c t e s t for RA, h a s be e n eva lu a t e d in p a t ie n t s
w it h HCV. In p a t ie n t s w it h RA, 76.6% h a d p os it ive a n t i-CCP a n t ibod ie s , bu t n o
HCV p a t ie n t s w it h o r w it h o u t jo in t in vo lve m e n t w e re p o s it ive . No t a bly, in
10 p a t ie n t s in it ia lly t h ou gh t t o h a ve HCV-a s s ocia t e d a rt h rit is bu t w h o w e re
u lt im a t e ly fou n d t o h ave RA, 60% of t h e ir in it ia l blood s a m p le s s h ow e d a n t i-CCP
a n t ibod ie s (10 ).
260 Se ctio n 5 In fe ct iou s Art h rit is
He pa titis B
CLINICAL PRESENTATION
He p a t it is B viru s (HBV) is a s m a ll DNA viru s o f t h e fa m ily He p a d n a vir id a e .
Tra n s m is s ion occu rs m os t com m on ly in t h re e w a ys : p e rin a t a lly, s e xu a lly, or
p a re n t e ra lly (11 ). Pe rs is t e n ce of vira l in fe ct ion is la rge ly d e t e rm in e d by a ge a t
in fe ct ion . Pe rin a t a l in fe ct ion oft e n re s u lt s in ch ron ic HBV in fe ct ion , w h e re a s
cle a ra n ce of HBV is m ore com m on w h e n con t ra ct e d in a d u lt h ood , w it h on ly 5%
t o 10% of p e op le in fe ct e d d eve lop in g ch ron ic HBV (1 ). Art h rit is occu rs in t w o
form s . Th e rs t form a p p e a rs d u rin g t h e p re s ym p t om a t ic p h a s e of a cu t e in fe c-
t ion , m os t ly a few d ays a n d u n u s u a lly w e e ks p rior t o t h e on s e t of ja u n d ice or
S
evid e n ce of h e p a t it is . Ch ron ic a rt h rit is , t h e s e con d form , occu rs in t h e s e t t in g
E
C
of HBV-a s s ocia t e d p olya rt e rit is n od os a (PAN; 1 ).
T
I
O
N
5
EXAMINATION
I
n
f
Acu t e HBV-a s s ocia t e d a rt h rit is p re s e n t s a s a s ym m e t ric p olya rt h rit is in volvin g
e
c
t h e PIP join t s , kn e e s , a n d a n kle s (1 , 4 ), w h ich is s im ila r t o RA; h ow eve r, d is t in -
t
i
o
u
gu is h in g fe a t u re s a re a n a bru p t on s e t , a ccom p a n ie d by a con com it a n t ra s h . In
s
HBV-a s s ocia t e d PAN, a rt h ra lgia s a re com m on ly rep ort e d . Fra n k a rt h rit is a ffe ct s
A
r
t
t h e m id -s ize join t s (w ris t , a n kle s , a n d kn e e s ) a n d is m u ch le s s com m on .
h
r
i
t
i
s
DIAGNOSIS
In t h e a cu t e form , t h e d ia gn os is of a rt h rit is is m a d e re t ros p e ct ive ly a ft e r t h e
a p p e a ra n ce of ja u n d ice a n d /or t ra n s a m in it is . Hep a t it is B s u rfa ce a n t ige n (HBs Ag)
is d e t e ct a ble in s e ru m a p p roxim a t e ly 4 t o 10 w e e ks a ft e r in fe ct ion , a ccom p a n ie d
by a s ign i ca n t vire m ia , a n d h e n ce is h e lp fu l t o d ia gn os e on ly t h e ch ron ic form
of t h is d is e a s e. An t ibod ie s t o core a n t ige n (a n t i-Hbc) d eve lop s h ort ly a ft e r (12 ;
Fig. 25.2 ). Sim ila r t o HCV, e ros ive a rt h rit is a n d a n t i-CCP a n t ibod ie s a re n ot u s u -
a lly s e e n a n d s h ou ld p rom p t w ork-u p for a d d it ion a l ca u s e s (4 , 6 ).
Alpha viruse s
EPIDEMIOLOGY AND CLINICAL PRESENTATION
Th e a lp h aviru s e s , a ge n u s of t h e fa m ily Toga virid a e, a re a rt h rop od born e a n d
d ivid e d in t o “Old World ” a n d “New Wor ld ” s p e cie s . Th e form e r ca u s e a s yn -
d rom e of feve r, ra s h , a n d a rt h ra lgia s , w h e re a s t h e ir “New World ” cou n t e rp a rt s
com m on ly ca u s e e n cep h a lit is (13 ). Th e a rt h rit is -in d u cin g a lp h aviru s e s h ave a
w id e ge ogra p h ic d is t ribu t ion a n d ca n ca u s e va s t o u t bre a ks . O’Nyo n g-n yon g
a n d Igbo-Ora occu r m a in ly in Africa , Ba rm a h Fore s t a n d Ros s Rive r m a in ly in
Ch a p te r 25 Vira l Art h rit is 261
l
e
• Increased bilirubin in blood
v
e
l
HBsAg
e
v
i
t
Virus in
a
l
e
blood
R
1 2 3 4 5 6
Exposure Months Years
A Acute hepatitis B with recovery
• Clinical symptoms
• Increased liver enzymes
in blood
• Increased bilirubin in blood Anti-HBs does
l
not appear
e
Antibody in blood
v
HBsAg
e
l
Virus in Anti-HBc
e
v
s
blood
i
i
t
a
t
i
l
r
e
h
R
t
r
A
s
u
1 2 3 4 5 6
o
i
t
Exposure Months Years
c
e
f
B Chronic hepatitis B
n
I
5
N
• Clinical symptoms
O
• Increased liver enzymes Anti-HBs does
I
T
in blood Antibody in blood
C
not appear
• Increased bilirubin in blood
E
S
Anti-HBc
l
e
HBsAg
v
e
Virus in
l
e
blood
v
i
t
a
l
e
R
1 2 3 4 5 6
Exposure Months Years
Figure 25.2 Hepa titis B clinica l pha ses a nd blood ma rkers of infection. A: Acute infection is cha ra cterized by
ra pid a ppea ra nce of the virus in blood before symptoms a ppea r, disa ppea ra nce of the virus from blood, a nd
a ppea ra nce in blood of a ntibodies to hepa titis B surfa ce a ntigen (HBsAg). B: Chronic hepa titis is signa led by
continuing ja undice or clinica l symptoms, or the continued presence of virus in blood (a s is indica ted by the
detection in blood of HBsAg). C: The ca rrier sta te is indica ted by disa ppea ra nce of clinica l symptoms a nd the
persistence of virus in blood (a s is indica ted by the detection in blood of HBsAg).
EXAMINATION
Th e a rt h rop a t h y t yp ica lly a ffe ct s m u lt ip le s m a ll join t s , e s p e cia lly t h os e p revi-
ou s ly in ju re d ; p a t ie n t s oft e n t ry t o lim it m ove m e n t (13 ). Ra s h fre q u e n t ly occu rs ,
262 Se ctio n 5 In fe ct iou s Art h rit is
DIAGNOSIS
Dia gn os is of a s p e ci c a lp h a viru s re m a in s a ch a lle n ge, a s t h ey clin ica lly re s e m -
ble e a ch ot h e r a n d m a n y ot h e r vira l illn e s s e s . In e n d e m ic a re a s , d iffe re n t ia t in g
b e t w e e n t h e m a jo r a lt e r n a t e d ia gn o s e s is k ey: d e n gu e fo r ch ik u n gu n ya o r
Ma ya ro; m a la ria for o’n yon g-n yon g (15 ). Th e Ce n t e rs for Dis e a s e Con t rol a n d
Preve n t ion (CDC) h a s t e s t in g ca p a bilit y for ch iku n gu n ya , o’n yon g-n yon g, Ros s
Rive r, Ba rm a h Fore s t , a n d lim it e d t e s t in g for Sin d bis (16 ). De t a ile d t ra ve l h is t ory
a n d kn ow le d ge of re ce n t a n d on goin g ou t bre a ks a re e s s e n t ia l in t h e eva lu a t ion
of re t u rn in g t ra ve le rs .
TREATMENT
Tre a t m e n t for t h e a lp h a vir u s e s is la rge ly s u p p o rt ive, w it h NSAIDs fo r p a in .
As p irin s h o u ld b e a vo id e d in ca s e s w h e re d e n gu e o r o t h e r h e m o rrh a gic ill-
n e s s e s a re in t h e d iffe re n t ia l a s t h is ca n e xa ce rba t e ble e d in g m a n ife s t a t ion s
S
(15 ). Preve n t ion re m a in s t h e m a in s t a y of t h e ra p y. Th e CDC s p e ci ca lly re com -
E
C
m e n d s t h a t a p e rs on d ia gn os e d w it h ch iku n gu n ya feve r s h ou ld lim it e xp os u re
T
I
O
t o m os q u it oe s t o a void s p re a d of t h e in fe ct ion (17 ).
N
5
I
n
CLINICAL COURSE
f
e
c
As s t u dy of t h e a lp h aviru s e s is lim it e d in m os t ca s e s , clin ica l cou rs e ca n on ly be
t
i
o
u
e s t im a t e d . Ch iku n gu n ya a n d Ros s Rive r a re t h e m os t s t u d ie d of t h e s e a lp h avi-
s
ru s e s . Wit h rega rd t o Ros s Rive r, s ym p t om s ge n e ra lly re s olve w it h in 6 m on t h s
A
r
(15 ). How eve r, rep ort s of ot h e r a lp h aviru s e s h ave d e s cribe d ch ron ic a n d /or re cu r-
t
h
r
re n t a rt h rit is (14 ). Rep ort s from t h e re ce n t ch iku n gu n ya ou t bre a ks h ave d e s cribe d
i
t
i
s
join t s ym p t om s la s t in g fre q u e n t ly for lon ge r t h a n 6 m on t h s (18 ) a n d in s om e
ca s e s for 18 m on t h s follow in g s eve re clin ica l in fe ct ion (19 ). As m ore d a t a be com e
ava ila ble, it is like ly t h a t t h e n a t u ra l p rogre s s ion w ill be fu rt h e r e lu cid a t e d .
Examinatio n
Ha n d s a n d kn e e s a re m os t fre q u e n t ly a ffe ct e d , u s u a lly s ym m e t rica lly; h ow eve r
a m igra t ory p a t t e rn ca n a ls o occu r (1 ). Fra n k a rt h rit is occu rs m ore com m on ly
in a d u lt w om e n com p a re d t o m e n a n d ch ild re n (21 ).
Ch a p te r 25 Vira l Art h rit is 263
Diag no sis
Dia gn os is re s t s on is ola t ion of viru s from t h roa t cu lt u re or d e m on s t ra t ion of
s e ru m a n t ibod ie s t o ru be lla . Pre s e n ce of IgM t o ru be lla in d ica t e s in fe ct ion like ly
in t h e p a s t 1 t o 2 m on t h s ; IgG ca n be u s e d for d ia gn os is on ly if p a ire d a cu t e a n d
con va le s ce n t s e ra a re u s e d (1 ).
Tre a tme nt
SUPPORTIVE AND SYMPTOMATIC
Clinical Co urse
Sym p t o m s ge n e ra lly re s olve w it h in a few w e e ks ; h ow eve r, ca s e s h a ve be e n
re p ort e d in w h ich join t s ym p t om s w e re p e rs is t e n t for m on t h s t o ye a rs (1 , 20 ).
RUBELLA VACCINE
W h ile va ccin a t ion p reve n t s ru be lla in fe ct ion , it ca rrie s a ris k of a rt h rit is a s w e ll,
w it h h igh e s t in cid e n ce s in a d u lt w om e n . Ge n e ra lly, p os t va ccin a t ion a rt h rit is
occu rs 10 t o 28 d ays a ft e r ru be lla va ccin a t ion (22 ). Alt h ou gh it is p os t u la t e d t h a t
t h e in it ia l HPV77/DK12 s t ra in ca rrie d t h e gre a t e s t ris k of p os t im m u n iza t ion
a rt h rit is , rep ort s p os t va ccin a t ion w it h t h e p re s e n t ly u s e d RA 27/3 h ave e m e rge d
s
i
t
(1 , 23 ). Th e In s t it u t e of Me d icin e re le a s e d a rep ort review in g t h e evid e n ce a n d
i
r
h
con clu d e d , it “. . . is con s is t e n t w it h a ca u s a l re la t ion be t w e e n t h e RA 27/3 ru be lla
t
r
A
va ccin e s t ra in a n d ch ron ic a rt h rit is in a d u lt w om e n , a lt h ou gh t h e evid e n ce is
s
u
lim it e d in s cop e ” (23 ). Th u s , d e s p it e w id e s p re a d va ccin a t ion in t h e Un it e d St a t e s ,
o
i
bot h w ild ru be lla a n d it s va ccin e s h ou ld be con s id e re d in t h e d iffe re n t ia l ce r-
t
c
e
t a in ly for a cu t e, a n d p os s ibly ch ron ic, a rt h rit is , p a rt icu la rly in a d u lt w om e n .
f
n
I
5
Huma n Immuno de ficie ncy Virus
N
O
I
T
C
Join t com p la in t s a re d e scribe d a t a ll s t a ge s of HIV in fect ion , eve n d u rin g a cu t e
E
S
in fe ct ion , w h ere a rt h ra lgia s ca n be s e en in 28% t o 54% of ca s e s (24 ). A p a in fu l
a rt icu la r s yn d rom e w a s d es cribe d e a rly in t h e HIV ep id e m ic, m os t com m on ly a s
seve re p a in in volvin g t h e kn ee s (les s fre q u e n tly, s h ou ld ers a n d e lbow s). Typ ica lly,
it la st s 2 t o 24 h ou rs a n d resolves , bu t m ay req u ire NSAIDs or op ia tes (24, 25 ). It is
n ot com m on ly s e en n ow a d ays . Fra n k a rt h rit is a ls o occu rs , e it h er d ire ct ly re la t e d
to HIV or in t h e s e t tin g of a se con d a ry in a m m a tory a rt h rop a t h y. HIV-a ss ocia t e d
a rt h rit is , d e n e d a s a d is a blin g a rt h rit is com m on ly a ffe ct in g t h e kn e e s a n d
a n kle s , h a s a se lf-lim ite d cou rs e. De n it ion of th is d is ord e r in volve s a n on e ros ive
oligoa rth rit is , w it h n ega t ive s tu d ies for RF, ANA, a n d HLA-B27 (24 –26 ).
High ly a ct ive a n t ire t rovira l t h e ra py (HAART) h a s ch a n ge d t h e s p e ct ru m of
join t d is e a s e s in HIV. Hu m a n im m u n od e cie n cy viru s –a s s ocia t e d a rt h rit is a n d
p s oria t ic a rt h rit is occu r m ore com m on ly w it h a d va n ce d s t a ge s of d is e a s e ; t h e
s eve rit y of t h e s e a rt icu la r m a n ife s t a t ion s d e cre a s e s w it h e ffe ct ive a n t ire t rovi-
ra l t h e ra p y. Con ve rs e ly, coe xis t in g in a m m a t ory d is ord e rs s u ch a s RA a n d SLE
t e n d t o im p rove w it h a d va n cin g s t a ge s of HIV d is e a s e (24 , 27 ). Th is obs e rva t ion
p rovid e d bot h a n e loq u e n t p roof of t h e e ffe ct ive n e s s of a n t ire t rovira l t h e ra p y
a n d a clu e t ow a rd t h e p a t h oge n e s is of t h e s e rh e u m a t ic con d it ion s . W h ile t re a t -
NOT TO BE MISSED m e n t of HIV-a s s ocia t e d a rt h rit id e s ge n e ra lly in volve s t re a t in g t h e HIV in fe c-
t ion , m o s t im p ort a n t ly, p a t ie n t s p re s e n t in g w it h a s im ila r a rt h rit is h a ve a n
• Ra sh . in d ica t ion for HIV t e s t in g. It is im p ort a n t t o re m e m be r t h a t t h e CDC re com -
• Ma y in d ica t e p a rvo viru s, m e n d s u n ive rs a l HIV t e s t in g in a d u lt s a ge d 13 t o 64 in t h e Un it e d St a t e s a t le a s t
a cu t e HIV, a cu t e HBV, on ce a n d m ore fre q u e n t ly in t h os e a t ris k (28 ).
ru b e lla , a rb o viru s.
• Jo in t d e fo rm it y.
Othe rs
• Mo re like ly t o b e
n o n vira l. Ot h e r viru s e s h a ve be e n im p lica t e d in t h e s e t t in g o f a rt h rit is . Hu m a n T-ce ll
lym p h ot rop h ic viru s -1 (HTLV-1) ca n ca u s e in a m m a t ory a rt h rop a t h ie s , m os t ly
264 Se ctio n 5 In fe ct iou s Art h rit is
ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
079.99 [711.5] viral d ise ase NEC
S
E
Re fe re nce s
C
T
I
O
1. Ca la bre s e LH , Na id e s SJ. Vira l a rt h rit is . Infect Dis Clin N A m 2005 ;19 :963 –980 .
N
2. You n g NS, Brow n KE. Pa rvoviru s B19 . N Engl J Med 2004 ;350 :586 –597 .
5
3. Brow n KE. Hu m a n p a rvoviru s e s , in clu d in g p a rvoviru s B19 a n d h u m a n bocaviru s . In : Ma n d e ll GL, Be n n e t t
I
JE, Dolin R, e d s . Mandell, Douglas, and Bennett’s: Principles and Practice of Infectious Diseases. Vol. II. 7t h e d .
n
f
Ph ila d e lp h ia , PA: Els evie r ; 2010 :2087 –2095 .
e
c
4. Va s s ilo p o u lo s D, Ca la bre s e LH . Vira lly As s o cia t e d Ar t h r it is 2008: Clin ica l, e p id e m iologic, a n d p a t h o-
t
i
o
p h ys iologic con s id e ra t ion s . A rthritis Res Ther 2008 ;10 :215 .
u
5. Lu n d q vis t A, Is a A, Tolfve n s t a m T. High fre q u e n cy of p a rvoviru s B19 DNA in bon e m a rrow s a m p le s from
s
A
rh e u m a t ic p a t ie n t s . J Clin Virol 2005 ;33 :71 –74 .
r
6. Be cke r J, Win t h ro p KL. Up d a t e on rh e u m a t ic m a n ife s t a t ion s of in fe ct iou s d is e a s e s . Curr Opin Rheum atol
t
h
2010 ;22 :72 –77 .
r
i
t
7. La u e r GM , Wa lke r BD. He p a t it is C viru s in fe ct ion . N Engl J Med 2001 ;345 :41 –52 .
i
s
8. Va s s ilop ou los D, Ca la bre s e LH . Rh e u m a t ic m a n ife s t a t ion s of h ep a t it is C in fe ct ion . Curr Rheum atol Rep
2003 ;5 :200 –204 .
9. Zu ck e r m a n E, Ye s h u r u n D, Ro s n e r I. Ma n a ge m e n t o f h e p a t it is C vir u s -re la t e d a r t h r it is . BioDru gs
2001 ;15 :573 –584 .
10. Bom ba rd ie ri M , Ale s s a n d r i C, La b ba d ia G, e t a l. Role of a n t i-cyclic cit ru llin a t e d p e p t id e a n t ibod ie s in
d iscrim in a tin g p a tien ts w ith rh eu m a toid a rth ritis from p a tien ts w ith ch ron ic h ep a titis C in fection -a ssocia ted
p olya rt icu la r in volve m e n t . A rthritis Res Ther 2004 ;6 :R137-R141 .
11. Kozie l MJ, Th io CL. Hep a t it is B viru s a n d h ep a t it is d e lt a viru s . In : Ma n d e ll GL, Be n n e t t JE, Do lin R, e d s .
Mandell, Douglas, and Bennett’s: Principles and Practice of Infectious Diseases. Vol II. 7t h e d . Ph ila d e lp h ia , PA:
Els evie r ; 2010 :2059 –2086 .
12. Ga n e m D, Prin ce AM . Hep a t it is B viru s in fe ct ion —n a t u ra l h is t ory a n d clin ica l con s e q u e n ce s . N Engl J Med
2004 ;350 :1118 –1129 .
13. Ma rkoff L. Alp h aviru s e s . In : Ma n d e ll GL, Be n n e t t JE, Dolin R, e d s . Mandell, Douglas, and Bennett’s: Principles
and Practice of Infectious Diseases. Vol II. 7t h e d . Ph ila d e lp h ia , PA: Els evie r ; 2010 :2117 –2125 .
14. Toiva n e n A. Alp h aviru s e s : An e m e rgin g ca u s e of a rt h rit is ? Curr Opin Rheum atol 2008 ;20 :486 –490 .
15. Su h rb ie r A, Lin n ML. Clin ica l a n d p a t h o logic a s p e ct s of a r t h r it is d u e t o Ros s Rive r vir u s a n d o t h e r
a lp h aviru s e s . Curr Opin Rheum atol 2004 ;16 :374 –379 .
16. Dia gn os t ic Te s t in g/CDC Ch iku n gu n ya . Ce n t e rs for Dis e a s e Con t rol a n d Preve n t ion We b s it e . h t t p ://w w w.
cd c.gov/n cid od /d vbid /Ch iku n gu n ya /CH_Dia gn os t ic.h t m l. Acce s s e d Oct o be r 29, 2010.
17. Fa ct Sh e e t /CDC Ch iku n gu n ya . Ce n t e rs for Dis e a s e Con t rol a n d Preve n t ion We b s it e . h t t p ://w w w.cd c.gov/
n cid od /d vbid /Ch iku n gu n ya /CH_Fa ct Sh e e t .h t m l. Acce s s e d Oct obe r 5, 2010.
18. Ta u bit z W, Cra m e r JP, Ka p a u n A, e t a l. Ch iku n gu n ya feve r in t rave le rs : Clin ica l p re s e n t a t ion a n d cou rs e .
Clin Infect Dis 2007 ;45 :e 1 –4 .
19. Borgh e rin i G, Pou be a u P, Jos s a u m e A, e t a l. Pe rs is t a n t a rt h ra lgia a s s ocia t e d w it h ch iku n gu n ya viru s : A
s t u d y of 88 a d u lt p a t ie n t s on re u n ion is la n d . Clin Infect Dis 2008 ;47 :469 –475 .
20. Tin gle AJ, Alle n M , Pe t t y RE. Ru be lla -a s s ocia t e d a rt h rit is . I. Com p a ra t ive s t u dy of join t m a n ife s t a t io n s
a s s ocia t e d w it h n a t u ra l ru be lla in fe ct ion a n d RA 27/3 ru be lla im m u n is a t ion . A nn Rheum atic Dis 1986 ;
45 :110 –114 .
21. Yt t e rbe rg SR. Vira l a rt h rit is . Curr Opin Rheum atol 1999 ;11 :275 –280 .
22. Ge ie r DA, Ge ie r MR. Ru be lla va ccin e a n d a rt h rit ic a d ve rs e re a ct io n s : An a n a lys is of t h e va ccin e a d ve rs e
eve n t s rep ort in g s ys t e m (VAERS) d a t a ba s e from 1991 t h rou gh 1998 . Clin Exp Rheum atol 2001 ;19 :724 –726 .
23. How son CP, Ka tz M, Joh n ston RB, Jr. Ch ron ic a rth ritis a fter ru bella va ccin a tion . Clin Infect Dis 1992 ;15 :307 –312 .
24. Wa lk e r UA, Tyn d a ll A, Da ike le r T. Rh e u m a t ic con d it ion s in h u m a n im m u n od e cie n cy viru s in fe ct ion .
Rheum atology 2008 ;47 :952 –959 .
Ch a p te r 25 Vira l Art h rit is 265
s
i
t
i
r
h
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s
u
o
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e
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5
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O
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E
S
SECTION
6
Chapter 26 Us e of th e Laboratory in
Diagn os in g Rh e u m atic
Dis orde rs
Terry Shaneyfelt and Gustav o R. Heudebert
Chapter 27 Te ch n iqu e s of
Arth roce n te s is
Dennis W. Boulw are
267
CHAPTER
26 Use of the La bora tory
in Dia gnosing
Rheuma tic Disorders
Terry Shaneyfelt and Gustav o R. Heudebert
y
p
As clin icia n s , w e co m b in e clin ica l
a
r
Patient 1: An 80-year-old retire d s kills w it h in form a t ion from d ia gn os -
e
h
T
carpenter presents for e valuation t ic t e s t s t o e s t a blis h a ccu ra t e d ia g-
d
n os e s s o t h a t w e m ay in it ia t e a p p ro-
n
of diffuse joint pain. He re ports
a
p ria t e t re a t m e n t for ou r p a t ie n t s . In
s
gradual onset and progression of
i
t h is ch a p t e r, w e focu s on p roba bilis t ic
s
o
d ia gn os t ic re a s on in g in w h ich p re t e s t
n
pain in the right rst m etacar-
g
p roba bilit y is in form e d by d ia gn os t ic
a
pophalangeal (MCP) joint and
i
D
t e s t in g re s u lt in g in p os t t e s t p roba bili-
bilateral proxim al inte rphalangeal
6
t ie s . We d o n ot focu s on t h e com m on ly
N
(PIP) and distal interphalangeal
O
u s e d d ia gn o s t ic m e t h od of p a t t e rn
I
T
(DIP) joints over the past 5 years. re cogn it ion . We re cogn ize t h a t bot h
C
E
d ia gn os t ic m e t h od s a re a p p rop ria t e
S
He also has pain in both kne es. He has som e stiffness in all the
a n d com p lem en ta ry. Probabilistic d iag-
affected joints, w hich lasts approxim ate ly 15 to 30 m inute s each n os t ic re a s on in g is u s e fu l e s p e cia lly
m orning. Pain is w orse w ith activity. He denies any sw elling, rash- for m ore ch a lle n gin g or le s s fa m ilia r
es, fe vers, or other joint involvem ent. Physical exam in ation of the clin ica l s it u a t ion s w h e re p a t t e rn re c-
hands re veals hard enlarge m e nt of the second through fourth ogn ition fa ils.
Th e ge n e ra t ion of a d iffe re n t ia l
DIP and PIP joints, and painful range of m otion of the right rst d iagn osis relies on u s, h avin g both gen -
MCP joint. No synovitis is detected. Knee e xam ination re veals e ra l m e d ica l kn ow le d ge a n d d is e a s e
cre pitance w ith preserved range of m otion and no joint effusion. p reva le n ce kn ow le d ge. Key fe a t u re s
Pat ie n t 2: A 25-ye ar-o ld f e m ale p re se n t s f o r e valu at io n d e rive d from t h e h is t ory, in con ju n c-
t ion w it h p h ys ica l exa m in a t ion n d -
o f f at ig u e , m yalg ias, an d in t e rm it t e n t h an d p ain . Sh e re p o rt s in gs , s e r ve t o e it h e r in cre a s e o r
t h at t h e p ain t e n d s t o “m o ve aro u n d ” b o t h t h e h an d s an d is d ecrea se th e likelih ood of ea ch d iagn o-
m o d e rat e in se ve rit y an d can re so lve w it h in 24 h o u rs. On sis u n d er con sid era tion in a p rocess of
f u rt h e r q u e st io n in g , sh e re p o rt s an e ryt h e m at o u s rash o n h e r h yp o t h e s is t e s t in g. In e s t a blis h in g
h yp o t h e s e s , it is im p o r t a n t t h a t w e
ch e e k s af t e r w o rk in g o u t in t h e su n a f e w w e e k s e arlie r, b u t it a ccu ra t e ly a s s e s s t h e pretest probabil-
re so lve d an d h as n o t re cu rre d . Sh e also re p o rt s a sh o rt -live d ity of t h e d ia gn os e s w e a re con s id e r-
e p iso d e o f p le u rit ic ch e st p ain a m o n t h e arlie r. Ph ysical e xam i- in g s o t h a t s u b s e q u e n t t e s t in g ca n
n at io n re ve als m ild p ain w it h ran g e o f m o t io n in se ve ral PIP h e lp u s t o r u le in o r ru le o u t t h o s e
p os s ibilit ie s . Pre t e s t p roba bilit y is t h e
jo in t s an d h e r le f t w rist . No e ff u sio n s o r d e f o rm it ie s are se e n . ch a n ce or p roba bilit y t h a t t h e p a t ie n t
No p le u ral o r card iac ru b s are h e ard o n au scu lt at io n an d n o u n d e r co n s id e ra t io n h a s t h e t a rge t
rash e s are n o t e d o n sk in e xam in at io n . d is ord e r be fore a n y t e s t in g is ca rrie d
269
270 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
ou t . It ca n be d e t e rm in e d in s eve ra l w a ys . Va li-
Test threshold Treatment threshold
d a t e d clin ica l p re d ict ion ru le s a re d e cis ion a id s
t h a t com bin e e le m e n t s of h is t ory, p h ys ica l e xa m -
Diagnosis Diagnosis Diagnosis
excluded uncertain established in a t ion , a n d ba s ic d ia gn os t ic or la bora t ory t e s t in g
t o a ccu ra t e ly e s t im a t e p re t e s t p roba bilit y. Dis e a s e
Test further p roba bilit y s t u d ie s , in w h ich rep re s e n t a t ive s a m -
p le s of p a t ie n t s w it h ce rt a in s ym p t om s (e.g., s yn -
0 A B 1.0 cop e ) u n d e rgo e xt e n s ive d ia gn os t ic w ork-u p s a n d
Probability of diagnosis re p ort t h e fre q u e n cy of t h e u n d e rlyin g d is ord e rs
t h a t ca u s e d t h e p a t ie n t s ’ illn e s s e s , ca n p rovid e
ve ry a ccu ra t e e s t im a t e s of p re t e s t p roba bilit y bu t
Disease Present Disease Absent
a re a va ila ble for few d is ord e rs . Mos t com m on ly,
a n d le a s t a ccu ra t e, clin icia n s u s e clin ica l in t u it ion
a n d e xp e rie n ce t o gu e s s a t t h e p re t e s t p roba bilit y.
True Positive False Positive How eve r, t h e re a re few w e ll-va lid a t e d clin ica l p re -
Test Positive d ict ion ru le s in ge n e ra l a s w e ll a s s p e ci ca lly in
(a) (b) t h e a re a of rh e u m a t ologic d is ord e rs ; a s s u ch it is
of cru cia l im p ort a n ce t o u n d e rs t a n d t h e in t e rp lay
be t w e e n re s u lt s of d ia gn os t ic t e s t s a n d t h e clin i-
S
E
False Negative True Negative
cia n in t u it io n o f t h e lik e lih o o d o f t h e d ia gn o s is
C
Test Negative
T
for w h ich t h e t e s t is be in g ord e re d . Sin ce p re t e s t
I
(c) (d)
O
p roba bilit y in form s p os t t e s t p roba bilit y, clin icia n s
N
6
m u s t begin w it h a n a ccu ra t e p re t e s t p roba bilit y.
D
Th e con s e q u e n ce s of in a ccu ra t e p re t e s t p roba bil-
i
a
g
Figure 26.1 Test a nd trea tment thresholds. it y a s s e s s m e n t in clu d e p o o r s e le ct io n o f t e s t s ,
n
p o o r in t e r p re t a t io n o f re s u lt s , a n d u lt im a t e ly
o
s
i
d ia gn os t ic e rror.
s
a
On ce p re t e s t p roba bilit y is d e t e rm in e d , clin icia n s m u s t d e cid e w h e t h e r t o
n
d
in it ia t e t re a t m e n t or t o p e rform fu rt h e r d ia gn os t ic t e s t in g. Th e t re a t m e n t t h re s h -
T
h
old is t h e t h re s h old a bove w h ich t h e p roba bilit y of d is e a s e is s o h igh t h a t fu rt h e r
e
r
t e s t in g is u n n e ce s s a ry a n d t rea t m e n t ca n be in it ia t e d . Th e t e s t in g t h re s h old is
a
p
t h e t h re s h old be low w h ich th e p roba bilit y of d is e a se is s o low t h a t fu rt h e r te s t in g
y
is u n n e ces s a ry a n d t h e d ia gn os is is con s id e re d exclu d e d (Fig. 26.1 ). Dia gn os t ic
t e s t in g is on ly u s e fu l t o in form in t e rm e d ia t e p roba bilit ie s be t w e e n t h e t e s t in g
a n d t re a t m e n t t h re s h old s . Th e s e t h re s h old s va ry on t h e ba s is of t h e d is e a s e
p rogn os is u n d e r con s id e ra t ion , t h e p rop e rt ie s of t h e d ia gn os t ic t e s t s , a n d t h e
n a t u re o f t h e t re a t m e n t . Th e s a fe r t h e t e s t in g s t ra t e gy, t h e m o re s e r iou s
t h e con d it ion if le ft u n d ia gn os e d , a n d t h e m ore e ffe ct ive a n d s a fe t h e ava ila ble
t re a t m e n t , t h e low e r t h e t e s t t h re s h old . For t h e t re a t m e n t t h re s h old , t h e m ore
be n ign t h e p rogn os is of t h e illn e s s a n d t h e h igh e r t h e m orbid it y a s s ocia t e d w it h
t h e ra p y, t h e h igh e r w e w ou ld p la ce t h e t h re s h old . For e xa m p le, ou r t e s t in g
t h re s h old w ou ld be low if a clin icia n s u s p e ct s d e ep ve n ou s t h rom bos is a s t h e
d u p lex u lt ra s on ogra p h y is a t e s t t h a t is bot h s a fe a n d e a s ily ava ila ble ; on t h e
ot h e r h a n d , ou r t re a t m e n t t h res h old w ou ld be re la t ive ly h igh a s a n t icoa gu la t ion ,
e s p e cia lly w h e n con s id e rin g s h ort - a n d lon g-t e rm cou rs e s of t h e ra py, is p ot e n -
t ia lly d a n ge rou s for a p a t ie n t .
Th e rs t p a t ie n t like ly h a s os t e oa rt h rit is . No va lid a t e d clin ica l p re d ict ion
ru le s for t h e d ia gn os is of os t e oa rt h rit is of t h e kn e e or h a n d e xis t , n or a n y d is -
e a s e p roba bilit y s t u d y h a s be e n con d u ct e d . Clin ica l in t u it ion w ou ld p la ce t h e
p re t e s t p roba bilit y of os t e oa rt h rit is a t a rou n d 85% t o 90%. For m os t clin icia n s ,
t h e t re a t m e n t t h re s h old t o in it ia t e a ce t a m in op h e n in t h is p a t ie n t is fa irly low
a n d cou ld be in it ia t e d w it h ou t fu rt h e r t e s t in g (a s w e a re fa irly con d e n t h e h a s
os t e oa rt h rit is a n d t h e con s e q u e n ce s of m od e ra t e d os e s of a ce t a m in op h e n a re
low ). Th e a lt e rn a t ive w ou ld be t o ord e r h a n d lm s , w h ich w e s u s p e ct w ou ld be
d on e t o ru le ou t ot h e r con d it ion s (i.e., rh e u m a t oid a rt h rit is ), a lt h ou gh t h e clin -
ica l s ce n a rio w o u ld m a k e t h is d ia gn os is h igh ly u n like ly ( 5%). Of in t e re s t , a
re la t ive ly n on d ia gn os t ic ra d iologic s t u d y like ly w ou ld n ot s t op m os t clin icia n s
Ch a p te r 26 Us e o f t h e La bora t ory in Dia gn os in g Rh e u m a t ic Dis ord e rs 271
y
p
t o be ce rt a in of or ru le in t h e d ia gn os is of SLE). Th e con s e q u e n ce s of u n d ia g-
a
r
e
n os e d SLE a re gre a t , m a kin g t h e t e s t in g t h re s h old fa irly low. Th u s fu rt h e r t e s t in g
h
T
for SLE is in d ica t e d in p a t ie n t 2 p rior t o in it ia t in g d is e a s e -s p e ci c t h e ra py.
d
n
a
s
i
s
Cho o sing a Dia g no stic Te st
o
n
g
a
Th e m a in d e t e rm in a n t of d ia gn os t ic t e s t ch oice (a s s u m in g m ore t h a n on e t e s t
i
D
is a va ila ble ) is t h e in t e n d e d role of t h e t e s t —w h e t h e r t h e clin icia n w a n t s t o ru le
6
in or ru le ou t a p a rt icu la r d is e a s e. Pre t e s t p roba bilit y in fo rm s t h is d e cis io n .
N
O
W h e n p re t e s t p roba bilit y is low, t h e goa l of d ia gn os t ic t e s t in g s h ou ld be t o ru le
I
T
ou t d is e a s e. Wit h h igh p re t e s t p roba bilit ie s t h e goa l is t o ru le in d is e a s e. On ce
C
E
t h e d e cis ion t o ru le in or ru le ou t d is e a s e is m a d e, clin icia n s t h e n ch oos e a m on g
S
d ia gn os t ic t e s t s on t h e ba s is of t h e ir t e s t p rop e rt ie s (i.e., s e n s it ivit y, s p e ci cit y,
a n d like lih ood ra t ios ).
Sensitiv ity of a d ia gn os t ic t e s t is t h e p rop ort ion of p e op le w it h d is e a s e w h o
t e s t p os it ive. (“PID,” p os it ive in d is e a s e, is a m n e m on ic t o h e lp re m e m be r t h is
a s s ocia t ion .) It re e ct s t h e true positiv e rate of a t e s t (Fig. 26.2 ). Te s t s w it h 100%
s e n s it ivit y d e t e ct eve ry s in gle p e rs on w it h d is e a s e. Te s t s w it h 80% s e n s it ivit y
m is s 20% of p e rs on s w it h d is e a s e, re s u lt in g in a 20% fa ls e n ega t ive ra t e. Se n s i-
t ivit y is ca lcu la t e d by d ivid in g t h e t ru e p os it ive ra t e by t h e t ru e p os it ive p lu s
fa ls e n ega t ive ra t e s . Se n s it ive t e s t s a re m os t u s e fu l t o ru le ou t d is e a s e w h e n
p re t e s t p roba bilit y is low (i.e., u s in g fe ca l occu lt t e s t in g t o s cre e n for colore ct a l
ca n ce r in ave ra ge -ris k in d ivid u a ls ).
Speci city of a d ia gn os t ic t e s t is t h e p rop o rt ion of p e op le w it h ou t d is e a s e
w h o t e s t n ega t ive. (“NIH,” n ega t ive in h e a lt h , is a m n e m on ic t o h e lp re m e m be r
t h is a s s ocia t ion .) It re e ct s t h e true negativ e rate of a t e s t (Fig. 26.2 ). Te s t s w it h
100% s p e ci cit y h ave n o fa ls e p os it ive s a n d a re n ega t ive w h e n d is e a s e is a bs e n t .
Te s t s w it h 80% s p e ci cit y a re fa ls e ly p os it ive 20% of t h e t im e. Sp e ci cit y is
KEY POINT 1 ca lcu la t e d by d ivid in g t h e t ru e n ega t ive ra t e by t h e t ru e n e ga t ive p lu s fa ls e
• Se n sit ive t e st s, w h e n p os it ive ra t e s . Sp e ci c t e s t s a re u s e d t o ru le in d is e a s e. For e xa m p le, colon os -
n e g a t ive , ru le o u t d ise a se co p y h a s a h igh e r s p e ci cit y t h a n fe ca l o ccu lt t e s t in g a n d w o u ld be u s e d t o
(Sn No u t ) w h e n t h e p re t e st follow u p p os it ive fe ca l occu lt t e s t in g.
p ro b a b ilit y is lo w.
Pa t ie n t 1 h a s s u ch a low p re t e s t p roba bilit y of SLE t h a t fu rt h e r t e s t in g for
• Sp e ci c t e st s, w h e n p osit ive , SLE is n ot u s e fu l (i.e., p re t e s t p roba bilit y is be low t h e t e s t t h re s h old ). Pa t ie n t 2,
ru le in d ise a se (Sp Pin ) w h e n on t h e ot h e r h a n d , h a s a fa irly h igh p re t e s t p roba bilit y of h a vin g SLE. In t h is
t h e p re t e st p ro b a b ilit y is
h ig h . ca s e w e w a n t t o r u le in SLE a n d w o u ld ch o o s e t h e t e s t w it h t h e h igh e s t
s p e ci cit y. Ta ble 26.1 s h ow s t h e t e s t p ro p e rt ie s a n d a s s o cia t io n s o f d iffe re n t
272 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
Table 26.1 Sensit ivit y and Speci cit y of Different Ant inuclear Ant ibodies in Syst emic
Lupus Eryt hemat osus
ANTIBODY
RIBONUCLEAR
ds-DNA (%) ss-DNA (%) HISTONE (%) SMITH (%) PROTEIN (%) RO (%) LA (%)
Se nsitivity 70 80 30–80 30 27 25–35 15
Spe ci city 95 50 96 82 87–94
y
ca lcu la t o rs. Th e Ce n t re fo r (lab o rat o ry t e st s)
p
Evidence-Based Medicine also 795.79 an t ib o d y t it e rs, e le vat e d
a
r
h a s se ve ra l EBM ca lcu la t o rs
e
795.79 an t ig e n -an t ib o d y re act io n
h
T
(h t t p ://kt cle a rin g h o u se .ca /
cebm/practise/ca/calculators). 790.95 C-re act ive p ro t e in (CRP)
d
n
791.9 cryst als, u rin e
a
790.1 se d im e n t at io n rat e , e le vat e d
s
i
s
795.79 sk in t e st , p o sit ive
o
n
g
a
i
D
Re fe re nce s
6
N
O
1. Joh n s on AE, Gord o n C, Hobbs FD , e t a l. Un d ia gn os e d s ys t e m ic lu p u s e ryt h e m a t os u s in t h e com m u n it y.
I
T
Lancet 1996 ;347 :367 –369 .
C
2. Law re n ce RC, He lm ick CG, Arn e t t FC, e t a l. Es t im a t e s of t h e p reva le n ce of a rt h rit is a n d s e le ct e d m u s cu -
E
S
los ke le t a l d is ord e rs in t h e Un it e d St a t e s . A rthritis Rheum 1998 ;41 :778 –799 .
3. McGe e S. Sim p lifyin g like lih ood ra t ios . J Gen Intern Med 2002 ;17 :646 –649 .
4. Fa ga n TJ. Le t t e r: Nom ogra m for Baye s t h e o re m . N Engl J Med 1975 ;293 :257
5. Grim e s DA, Sch u lz KF. Re n in g clin ica l d ia gn os is w it h like lih ood ra t ios . Lancet 2005 ;365 :1500 –1505 .
6. Alt m a n DG, Bla n d JM . St a t is t ics n ot e s : Dia gn os t ic t e s t s 2: Pre d ict ive va lu e s . BMJ 1994 ;309 :102 .
CHAPTER
27 Techniques of
Arthrocentesis
Dennis W. Boulw are
274
Ch a p te r 27 Te ch n iq u e s o f Art h roce n t e s is 275
Equipme nt
Ap p ro p ria t e e q u ip m e n t (s e e Ta ble 27.1 ) s h o u ld b e a s s e m ble d a t t h e b e d s id e
y
p rior t o t h e p roce d u re a n d e a s ily a cce s s ible t o t h e op e ra t or d u rin g t h e p roce -
p
a
r
d u re , w it h o u t t h e op e ra t or ch a n gin g p os it io n . An a s s is t a n t is op t ion a l a n d
e
h
d e p e n d e n t on t h e op e ra t or, bu t h e or s h e w ill be h e lp fu l if t h e re is con ce rn of
T
d
p a t ie n t coop e ra t io n or a la rge r e ffu s ion is t o be d ra in e d re q u irin g ch a n gin g
n
s yrin ge s .
a
s
i
s
o
n
Te chnique
g
a
i
D
Aft e r s e le ct in g a n a p p rop ria t e e n t ry s it e, t h e e n t ry s it e ca n be m a rke d u s in g a
6
ba ll-p oin t p e n w it h t h e p e n t ip re t ra ct e d . Th e p e n ’s a p e rt u re ca n be p re s s u re d
N
O
t o t h e s it e t o le ave a n im p re s s ion of t h e s e le ct e d e n t ry s it e be fore cle a n s in g t h e
I
T
C
a re a . Th e s e le ct e d e n t ry p o in t is cle a n s e d a p p ro p r ia t e ly w it h a n a n t is e p t ic
E
s olu t ion follow e d by re m ova l of t h e a n t is e p t ic s olu t ion u s in g t h e a lcoh ol w ip e s .
S
Aft e r cle a n s in g t h e a re a , ca u t ion s h ou ld be e xe rcis e d t o a void con t a m in a t in g
t h e s it e by fu rt h e r p a lp a t ion w it h a n u n s t e rile glove d n ge r. If fu rt h e r p a lp a t ion
is d e s ire d , t h e n a s t e rile glove ca n be u s e d or a s t e rile 4 × 4 ga u ze ca n be p la ce d
ove r t h e a re a a n d p a lp a t ion d on e ove r t h e s t e rile ga u ze t o p re s e rve t h e s it e ’s
a n t is ep t ic con d it ion . Som e t op ica l a n e s t h e s ia is obt a in e d by s p ra yin g t h e s it e
w it h e t h yl ch lorid e u n t il t h e a re a “fros t s .” Alt e rn a t ive ly, a s m a ll a m ou n t of lid o-
ca in e ca n be in je ct e d s u bcu t a n e ou s ly in t o t h e p rop os e d in je ct ion a re a .
W h e n a d va n cin g t h e n e e d le in t o t h e join t cavit y, t h e p a t ie n t e xp e rie n ce s
d is com fort w h e n t h e n e e d le p a s s e s t h rou gh t h e s kin a n d a ga in w h e n it cros s e s
t h e s yn oviu m . Le s s d is com fort is e xp e rie n ce d w h e n t h e s kin a n d s yn oviu m is
cros s e d q u icke r a s op p os e d t o s low ly a n d d e libe ra t e ly. On ce t h e n e e d le is in t ro-
d u ce d in t o t h e join t ca vit y, u id s h ou ld ow e a s ily in t o t h e s yrin ge if u s in g a
n e e d le ga u ge of 20 or la rge r. If n o u id ca n be a s p ira t e d , or u id s t op s ow in g,
t h e m os t com m on ca u s e is t h a t s yn ovia l t is s u e or s olid m a t e ria l (clot , brin ,
ca rt ila ge fra gm e n t s , e t c.) w it h in t h e u id is obs t ru ct in g t h e n e e d le. Rot a t in g t h e
n e e d le o r in je ct in g ba ck a s m a ll a m ou n t o f t h e a s p ira t e d u id in t o t h e join t
ca vit y m ay re m ove t h e obs t ru ct ion . At t h a t p oin t . ge n t le n ega t ive p re s s u re ca n
be p la ce d a n d t h e u id m ay a s p ira t e. As t h e t ot a l e ffu s ion a p p roa ch e s com p le t e
d ra in a ge, t h e s yn ovia l lin in g be com e s clos e r t o t h e n e e d le t ip a n d fu rt h e r d if-
cu lt y is t yp ica lly e x p e rie n ce d o r fre s h blo o d n ow a p p e a r s in t h e a s p ira t e d
u id . Dis com fort by t h e p a t ie n t is com m on a t t h is p oin t , a n d a d e cis ion t o con -
t in u e a s p ira t in g a t t h e p a t ie n t ’s d is com fort s h ou ld be w e igh e d by t h e be n e t of
re m ovin g m ore u id a t t h is t im e. On ce s u f cie n t u id is re m ove d , t h e n e e d le
ca n b e w it h d ra w n a n d a p p ro p ria t e h e m o s t a s is a p p lie d t o t h e in je ct io n s it e .
Alt e rn a t ively, if s t e roid s or m ed ica t ion a re p la n n e d t o be in je cte d a fte r a s p ira t ion ,
276 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
Figure 27.1 Medial entry point of knee beneath the superior medial Figure 27.2 Entry point of the a nkle joint, a t the sa me pla ne of the media l
pole of the patella. Needle is positioned parallel to the inferior surface ma lleolus a nd media l to the a nterior tibia lis tendon.
y
p
of the patella.
a
r
e
h
T
s u rfa ce of t h e p a t e lla , t yp ica lly a bou t 30 t o 45 d egre e s from h orizon t a l. Ad -
d
va n ce t h e n e e d le q u ickly t h rou gh t h e s kin a n d t h e n a d va n ce fu rt h e r u n t il t h e
n
a
s yn oviu m is cros s e d .
s
i
s
o
n
g
ANKLE (TIBIOTALAR) JOINT
a
i
D
• Patient position: Pa t ie n t s u p in e a n d a n kle re la xe d .
6
• Entry site: An t e rom e d ia l.
N
O
• Technique: Id en tify t h e p a tien t’s m e d ia l m a lleolu s a n d a n t erior t ibia lis t en d on .
I
T
Th e en t ry p oin t w ill be in th e s a gitt a l, or h orizon ta l, p la n e of t h e m ed ia l m a lleo-
C
E
lu s a n d im m ed ia t ely m ed ia l to t h e a n te rior tibia lis t en d on (Fig. 27.2 ). Th e n ee d le
S
sh ou ld be d irect ed t ow a rd th e cen t er of th e con cave d is ta l en d of t h e t ibia . Th is
tra ject ory w ill p os it ion th e n ee d le betw een th e ta lu s a n d t h e d ist a l tibia .
METATARSOPHALANGEAL,
METACARPOPHALANGEAL, AND
INTERPHALANGEAL JOINTS
• Patient position: Pa t ie n t s u p in e a n d join t re la xe d .
• Entry site: Dors a l, m e d ia l, or la t e ra l t o t h e e xt e n s or
t e n d on .
• Technique: Id e n t ify t h e ba s e of t h e d is t a l p h a la n x a n d
t h e e xt e n s or t e n d on a s it cros s e s t h e join t s p a ce. Se -
le ct t h e a re a m e d ia l or la t e ra l t o t h e e xt e n s or t e n d on
t h a t a void s a n y vis ible s u bcu t a n e ou s ve in s . Us e t h is
a s you r e n t ry p oin t a n d d ire ct t h e n e e d le t ow a rd t h e
ce n t e r of t h e con ca ve p roxim a l e n d of t h e d is t a l p h a -
la n x (Figs . 27.3 a n d 27.4 ). Th is t ra je ct ory w ill p os it ion
t h e n e e d le be t w e e n t h e con ve x h e a d of t h e p roxim a l
bon e a n d t h e d is t a l p h a la n x.
SHOULDER
• Patient position: Pa t ie n t s e a t e d , e lbow e xe d t o 90 d e -
gre e s , fore a rm re s t in g on t h e la p , a n d join t re la xe d .
Figure 27.3 Entry point of the ha nd—meta ca rpopha la ngea l joint. • Entry site: Pos t e rior.
278 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
Figure 27.4 Entry point of the foot—meta ta rsopha la ngea l joint. Figure 27.5 Posterior entry point into the shoulder benea th the sca pula r
spine’s a cromia n with the needle directed towa rd the cora coid process.
S
E
C
• Technique: St a n d in g be h in d t h e p a t ie n t , id e n t ify t h e s ca p u la r s p in e a n d d is t a l
T
I
O
a crom ia n on t h e ba ck of t h e p a t ie n t , a n d t h e cora coid p roce s s on t h e a n t e rior
N
ch e s t of t h e p a t ie n t . Pla ce t h e h a n d n ot h old in g t h e n e e d le on t h e s h ou ld e r
6
a n d id e n t ify or p a lp a t e t h e cora coid p roce s s . Th e e n t ry p oin t w ill be im m e -
D
i
d ia t e ly in fe rior t o t h e d is t a l a crom ia n a n d t h e n e e d le t ip d ire ct e d t ow a rd t h e
a
g
p a lp a ble cora coid s p roce s s (Fig. 27.5 ).
n
o
s
i
s
a
SUBACROMIAL BURSA
n
d
• Patient position: Pa t ie n t s e a t e d , e lbow e xe d t o 90 d egre e s , fore a rm re s t in g on
T
h
t h e la p , a n d join t re la xe d .
e
r
a
• Entry site: La t e ra l.
p
y
• Technique: St a n d in g on t h e s id e of t h e p a t ie n t , id e n t ify t h e a crom ia n p roce s s .
Th e e n t ry p oin t w ill be in fe rior t o t h e la t e ra l m os t p oin t of t h e a crom ia n
p roce s s a n d t h e n e e d le d ire ct e d s u p e riorly rou gh ly 30 d egre e s be low t h e h ori-
zon t a l leve l. Th is w ill p la ce t h e n e e d le a bove t h e h u m e ra l h e a d a n d be low t h e
a crom ia n p roce s s (Fig. 27.6 ).
ELBOW
• Patient position: Pa t ie n t lyin g, e lbow e xe d t o 90 d e -
gre e s , fore a rm re s t in g on t h e a bd om e n , a n d join t
re la xe d .
• Entry site: La t e ra l.
• Technique: Id e n t ify t h e la t e ra l e p icon d yle, ra d ia l
h e a d , a n d ole cra n on p roce s s , a n d e s t a blis h t h e ce n -
t e r of t h is t ria n gle (Fig. 27.7 ). Th e n e e d le w ill e n t e r
in t h e ce n t e r of t h e t ria n gle, d ire ct e d p e rp e n d icu la r
t o t h e s kin ’s e n t ry p oin t , a n d e n d u p in t h e e lbow ’s
la t e ra l p a ra ole cra n on groove.
WRIST
• Patient position: Pa t ie n t s e a t e d or lyin g, w ris t in m ild
p a s s ive e xion of 10 d egre e s w it h a s u p p ort be n e a t h
t h e w ris t for com fort , a n d re la xe d .
Figure 27.6 Entry point of the suba cromia l bursa . • Entry site: Dors a l.
Ch a p te r 27 Te ch n iq u e s o f Art h roce n t e s is 279
Figure 27.7 Entry point of the elbow between la tera l epicondyle, ra dia l Figure 27.8 Entry point between the dista l ra dius a nd sca phoid bone in
hea d, a nd olecra non process. the wrist dista l to the ra dia l tubercle.
y
p
a
• Technique: Id en tify t h e ra d ia l tu bercle on t h e d ist a l ra d iu s a n d a n in d en t a tion
r
e
WHEN TO REFER
h
bet w een th e d ist a l ra d iu s a n d th e sca p h oid bon e in th e w rist. En try p oin t w ill
T
be d is ta l t o th e ra d ia l tu bercle in th e in d en t a tion a n d d irectin g th e n eed le p er-
d
• Wh e n in d o u b t a b o u t
n
p en d icu la r to t h e skin (Fig. 27.8 ).
a
p e rfo rm in g t h e p ro ce d u re .
s
i
s
• Jo in t s in a cce ssib le w it h o u t
o
n
im a g in g g u id a n ce .
g
ICD9
a
i
D
81.91 Arthro ce nte sis
6
Jo in t asp irat io n
N
O
I
T
C
E
Additio na l Re a ding
S
1. Moo re GF. Te ch n iq u e s of a rt h roce n t e s is a n d in je ct ion t h e ra p y. In : Koop m a n W J, Bou lw a re DW, He u d e be rt
GR, e d s . Clinical Prim er of Rheum atology . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d W ilkin s ; 2003:354 –367 .
2. Lo t k e PA. In je ct ion t e ch n iq u e s for jo in t s a n d bu rs a . In : Lot ke PA, Ab bou d JA, En d e J, e d s . Lippincott’s
Prim ary Care Orthopaedics . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s ; 2008:389 –394 .
3. Moo re GF. Art h ro ce n t e s is t e ch n iq u e a n d in t ra -a rt icu la r t h e ra p y. In : Ko o p m a n W J, More la n d LW, e d s .
A rthritis and A llied Conditions . 15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s ; 2005:755 –774.
CHAPTER
28 Monitoring of Pa tients
on Antirheuma tic
Thera py
W. W inn Chatham
S
Th e ch ron icit y of t h e m a jorit y of rh e u m a t ic d is e a s e s oft e n in volve s t h e lon g-
E
C
t e r m u s e of a n t ir h e u m a t ic t h e ra p ie s . Mu lt ip le in a m m a t ory m e d ia t o r s a n d
T
I
O
m e ch a n is m s of t is s u e in ju ry op e ra t ive in bot h a cu t e a n d ch ron ic in a m m a t ion
N
fre q u e n t ly re q u ire t h e con cu rre n t u s e of s eve ra l re a ge n t s t o a d e q u a t e ly s u p -
6
p re s s d is e a s e a ct ivit y. More ove r, t h e in cre a s e d p reva le n ce of rh e u m a t ic d is e a s e
D
i
a
w it h a ge d ict a t e s t h a t u s e of a n t irh e u m a t ic a n d im m u n om od u la t in g t h e ra p ie s
g
n
m u s t oft e n be p re s cribe d in t h e con t e xt of com orbid it ie s . As s u ch , it is im p or-
o
s
t a n t for clin icia n s in volve d in t h e ca re of p a t ie n t s w it h rh e u m a t ic d is e a s e t o be
i
s
m in d fu l of t h e s h ort -t e rm a s w e ll a s lon g-t e rm con s e q u e n ce s of a n t irh e u m a t ic
a
n
t h e ra p ie s , n ot on ly on orga n s ys t e m s a ffe ct e d by t h e ra py, bu t a ls o on t h e cou rs e
d
T
or t re a t m e n t of coe xis t in g d is e a s e.
h
e
r
a
p
Co rtico ste ro ids
y
Glu cocort icoid s h ave broa d in h ibit ory e ffe ct s on s p e ci c im m u n e re s p on s e s
m ed ia t ed by T- a n d B-cell lym p h ocyt es a s w ell a s p oten t su p p re ss ive effe cts on
t h e effe ctor fu n ct ion s of m on ocyt es a n d n eu trop h ils. Alt h ou gh th ese a t tribu tes
cou p le d w it h t h e ir ra p id on s e t of a ct ion re n d e r s t e roid s ext re m e ly va lu a ble in
s u p p re s s in g u n d e s ire d in a m m a t ory p roce s s e s , cort icos t e roid s h a ve s im ila r
COMMON PITFALLS TO broa d e ffects on th e fu n ction of cells com p risin g ot h er orga n syst em s. Th e im m u -
AVOID WHEN USING
GLUCOCORTICOSTEROIDS n ocom p rom ised st a t u s a n d ca t a bolic con s eq u en ces a ss ocia t ed w it h u se of corti-
cos teroid s lim it t h eir lon g-term u se in h igh d os es a n d d ict a t e t h e n eed for ca refu l
1. Infection with mycobacteria, s u rve illa n ce a n d p reven t ive in t erven t ion s to avoid u n d es ired com p lica tion s.
list e ria , cryp t o co cci, a n d
n o ca rd ia Us e of h igh d os e s of cort icos t e roid s rs t a n d fore m os t re q u ire s vigila n ce
for t h e d eve lop m e n t of in t e rcu rre n t in fe ct ion s . Pa t ie n t s w it h e it h e r rh e u m a t oid
2. Sa lt a n d w a t e r re t e n t io n a rt h rit is or s ys t e m ic lu p u s e ryt h e m a t os u s (SLE) h a ve a n in t rin s ic s u s cep t ibilit y
3. Glu co se in t o le ra n ce t o in fe ct ion , a n d t h e a d m in is t ra t ion o f glu coco rt icoid s e n h a n ce s t h e ris k of
4. Mu scle a n d skin w a st in g in fe ct ion . In a d d it ion t o t yp ica l ba ct e ria l orga n is m s , in fe ct ion s w it h m ycoba c-
t e ria , cryp t ococci, lis t e ria , a n d n oca rd ia h ave be e n a s s ocia t e d w it h cort icos t e r-
5. Ost e o p o ro sis oid t h e ra p y. Th e co m b in a t io n of s t e ro id u s e w it h cyt ot oxic a ge n t s , s u ch a s
6. Ost e o n e cro sis cyclop h os p h a m id e, h a s be e n a s s ocia t e d w it h h igh e r ris k of in fe ct ion w it h Pneu-
m ocystis jirov ecii p n e u m on ia , m os t n ot a bly a m on g p a t ie n t s w it h lym p h op e n ia .
Un le s s life - or orga n -t h re a t e n in g d is e a s e com p lica t ion s d ict a t e ot h e rw is e, in
t h e s e t t in g of s e riou s in t e rcu rre n t in fe ct ion , d os e s of cort icos t e roid s s h ou ld be
a t t e n u a t e d t o t h a t re q u ire d t o avoid a d re n a l cris is .
Give n t h e s ign i ca n t ca t a bolic e ffe ct s of glu cocort icoid s on m u s cle, s kin ,
a n d bon e , p a t ie n t s t a kin g m od e ra t e o r h igh d o s e s of s t e roid s for p rolon ge d
in t e rva ls re q u ire p e riod ic a s s e s s m e n t for t h e evolu t ion of s t e roid m yop a t h y or
280
Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 281
y
p
cocort icoid -in d u ce d os t e op oros is (1 ). Pe riod ic a s s e s s m e n t of bon e d e n s it y a t 1-
a
r
e
t o 2-ye a r in t e rva ls is re com m e n d e d t o a s s e s s t h e e f ca cy of t h e s e in t e rve n t ion s
h
T
in p a t ie n t s on ch ron ic s t e roid t h e ra py.
d
Th e p re d ict a ble m e t a bolic con s e q u e n ce s of s t e roid s in clu d e s a lt a n d w a t e r
n
a
re t e n t ion a s w e ll a s va ria ble d egre e s of in s u lin re s is t a n ce w it h h yp e rglyce m ia .
s
i
s
Th e m in e ra locort icoid e ffe ct s of s t e roid s w a rra n t e xp e ct a n t obs e rva t ion for t h e
o
n
d eve lop m e n t of h yp e rt e n s ion or h e a rt fa ilu re e xa ce rba t ion s in p a t ie n t s w h o
g
a
h a ve or a re a t ris k for t h e s e ca rd iova s cu la r d is ord e rs . Lon g-t e rm m e t a bolic con -
i
D
s e q u e n ce s of cort icos t e roid u s e in p a t ie n t s w it h rh e u m a t ic d is e a s e m ay in clu d e
6
a cce le ra t e d a t h e roge n e s is . At t e n t ion t o ot h e r ca rd iova s cu la r ris k fa ct ors in clu d -
N
O
in g a s s e s s m e n t for a n d t re a t m e n t of h yp e rch ole s t e role m ia m ay s low t h e p ro-
I
T
gre s s ion of a t h e roge n e s is a n d low e r t h e ris k for va s cu la r eve n t s in p a t ie n t s
C
E
w h o re q u ire lon g-t e rm s t e roid u s e for m a n a ge m e n t of rh e u m a t ic d is e a s e m a n -
S
ife s t a t ion s .
Ot h e r co m p lica t io n s o f co r t ico s t e ro id t h e ra p y a re le s s p re d ict a ble b u t
n on e t h e le s s re q u ire vigila n ce for t h e ir occu rre n ce s o a s t o a void u n fa vora ble
COMMON PITFALLS TO
AVOID WHEN USING NSAIDs ou t com e s . Cort icos t e roid s m ay h a ve u n t ow a rd e ffe ct s on t h e ce n t ra l n e rvou s
s ys t e m , in clu d in g e m ot ion a l irrit a bilit y, d if cu lt y in con ce n t ra t ion , d e p re s s ion ,
1. De clin e in g lo m e ru la r con fu s ion , or p s ych os is . High -d os e cort icos t e roid s t h e ra py h a s be e n im p lica t e d
lt ra t io n ra t e
a s a p os s ible in d u ce r of p a n cre a t it is . Sin ce p a n cre a t it is m a y be a m a n ife s t a t ion
2. Ga st ro p a t h y in clu d in g of lu p u s , t h e occu rre n ce of p a n cre a t it is in p a t ie n t s w it h lu p u s re ce ivin g glu co-
u lce ra t io n a n d b le e d in g cort icoid t h e ra py m ay re s u lt in a t h e ra p e u t ic d ile m m a . Os t e on e cros is is a re c-
3. Pla t e le t d ysfu n ct io n a n d ogn ize d co m p lica t io n o f h igh -d os e s t e ro id u s e. In p a t ie n t s w it h lu p u s , o t h e r
b le e d in g d is e a s e -re la t e d fa ct ors m ay a ccou n t for t h e d eve lop m e n t of os t e on e cros is , bu t
4. Sa lt a n d w a t e r re t e n t io n t h e in cid e n ce a p p e a rs t o corre la t e w it h t h e cu m u la t ive s t e roid d os e. Sin ce rou -
t in e ra d iogra p h s t yp ica lly fa il t o reve a l t h e p re s e n ce of os t e on e cros is d u rin g it s
NSAIDs, n o n st e ro id a l a n t i-
in a m m a t o ry d ru g s. e a rly s t a ge s , p a t ie n t s on h igh d os e s of s t e roid s w h o d eve lop ot h e rw is e u n e x-
p la in e d p a in in t h e s h ou ld e rs , h ip s , kn e e s , or a n kle s s h ou ld be eva lu a t e d w it h
m a gn e t ic re s on a n ce im a gin g t o ru le ou t t h e p re s e n ce of os t e on e cros is .
NSAID, n o n st e ro id a l a n t i-in a m m a t o ry d ru g s.
Risk fa ct o rs co m p ile d fro m t h e ARAMIS d a t a b a se a n d o u t co m e s in t h e MUCOSA t ria l (2,3).
Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 283
y
2. Myo p a t h y w it h ch ro n ic u se
p
d a m a ge from d ru g-in d u ce d in t e rs t it ia l n e p h rit is .
a
r
e
h
T
COLCHICINE
d
n
a
Colch icin e is m os t com m on ly u s e d in t h e t re a t m e n t of a cu t e gou t or p s eu d ogou t ;
s
i
t h e d ru g m ay be u s e d for ext e n d e d p e riod s of t im e t o p reve n t rep e a t e d a res of
s
o
a cu t e crys t a llin e -in d u ce d a rt h rit is . Th e a n t i-in a m m a t ory e ffe ct s of colch icin e
n
g
a re a t t ribu t e d t o t h e d ru g’s in t e rfe ren ce w it h t h e fu n ct ion of t u bu la r m icro la -
a
i
D
m en t s re q u ired for ch e m ot a xis , m igra t ion , a n d re lea s e of gra n u le con s t it u e n t s by
6
n e u t rop h ils . Th e t oxicit y of colch icin e w h e n u s e d a cu t e ly is p rim a rily re la t e d t o
N
O
effe ct s on t h e in t e s t in a l m u cos a w h e n a d m in is t e re d exces s ive ly. W h e n u s e d in
I
T
t h e a p p rop ria t e s e t t in g of a n a cu t e a t t a ck of crys t a llin e -in d u ce d a rt h rit is of
C
E
s h ort e r t h a n 24 h ou rs ’ d u ra t ion , it is s e ld om n ece s s a ry t o a d m in is t e r ora l d os in g
S
of colch icin e t h a t in d u ce s d ia rrh e a . Tw o ora l d os e s of 0.6 m g a d m in is t e red 1 h ou r
a p a rt follow ed by a t h ird d os e 6 h ou rs la t er is u s u a lly s u f cien t t o m a n a ge a n
a cu t e a t t a ck of gou t or p s e u d ogou t . At t a cks of crys t a llin e -in d u ce d a rt h rit is of
lon ge r t h a n 24 h ou rs ’ d u ra t ion a re le s s likely t o re s olve w it h a d m in is t ra t ion of
colch icin e a n d a lt e rn a t ive t h era p ies , s u ch a s NSAIDs , or cort icos t e roid s s h ou ld
be con s id e re d in t h is s et t in g.
A va cu ola r m yop a t h y m a y evolve in t h e s e t t in g of ch ron ic colch icin e u s e,
p a rt icu la r ly a m on g p a t ie n t s w it h re n a l s u f cie n cy. For p a t ie n t s t re a t e d w it h
colch icin e ove r e xt e n d e d p e riod s , m on it orin g for t h e d eve lop m e n t of m yop a t h y
w it h p e riod ic a s s e s s m e n t for s e ru m e leva t ion s in cre a t in e kin a s e is p ru d e n t .
Pa t ie n t s w it h re n a l in s u f cie n cy m ay a ls o be a t gre a t e r ris k for m a rrow t oxicit y
a n d s h o u ld a ls o be m o n it ore d p e riod ica lly for evid e n ce of cyt op e n ia s w h e n
t a kin g colch icin e ove r e xt e n d e d p e riod s .
METHOTREXATE
An a n a logu e of folic a cid , m eth otrexa te in h ibits folic a cid –d ep en d en t p a th w ays
t h rou gh n u m e rou s m e ch a n is m s . At h igh d os e s , m e t h ot rexa t e is a n e ffe ct ive
ch em oth era p eu tic a gen t for th e trea tm en t of lym p h oid n eop la sm s a n d som e solid
tu m ors . At low e r d os es , m et h otrexa t e h a s im m u n osu p p re ss ive a n d s ign i ca n t
a n ti-in a m m a tory effects, m ost likely m ed ia ted by effects of its p olyglu ta m a ted
m e t a bolit e s on AICAR t ra n s form yla s e. In h ibit ion of AICAR t ra n s form yla s e by
p olyglu t a m a t e d m e t h o t re x a t e re s u lt s in im p a ire d s yn t h e s is of p u r in e s a n d
p yrim id in e s , a s w e ll a s a ccu m u la t ion of AICAR, a p ot e n t in d u ce r of a d e n os in e
re le a s e. Th e la t t e r m ay a ccou n t for m e t h ot re xa t e ’s a n t i-in a m m a t ory e ffe ct s ,
a s e n ga ge m e n t of a d e n os in e re cep t ors on le u kocyt e s a t t e n u a t e s t h e ir a d h e r-
e n ce t o e n d ot h e lia l ce lls .
Alt h ou gh u n com m on in t h e d os e s u s u a lly e m p loye d for m a n a ge m e n t of
rh e u m a t oid a rt h rit is , m u cos it is , bon e m a rrow s u p p re s s ion , a n d h ep a t oce llu la r
S
E
in ju ry con s t it u t e t h e p rim a ry t oxicit ie s a s s ocia t e d w it h t h e u s e of m e t h ot re xa t e.
C
T
Le s s com m on com p lica t ion s in clu d e a cu t e in t e rs t it ia l p n e u m on it is , in t e rs t it ia l
I
O
N
n e p h rit is , a n d t ra n s ie n t p os t d os e s yn d rom e s t h a t m ay in clu d e feve r, n e u rocog-
6
n it ive im p a irm e n t , a rt h ra lgia , a n d /or m ya lgia . Th e occu rre n ce of m u cos it is or
D
cyt op e n ia s m ay d ep e n d in p a rt on fola t e s t ore s , a s t h e s e com p lica t ion s ca n be
i
a
g
p reve n t e d or s ign i ca n t ly re d u ce d w it h folic a cid s u p p le m e n t a t ion (4 ). Folic
n
o
a cid d oes n ot im p a ir th e form a t ion of p olyglu ta m a ted m et h ot rexa te m eta bolites ,
s
i
a n d u s e of folic a cid su p p lem e n ts h a s been sh ow n n ot to a lter th e a n tirh eu m a t ic
s
a
ef ca cy of m e th otrexa te.
n
d
Effe ct s o f m e t h o t re xa t e o n h e m a t op o ie s is a re t yp ica lly d os e d e p e n d e n t ,
T
h
bu t t h e re is con s id e ra ble in d ivid u a l va ria bilit y in t h e d os e t h re s h old for d eve l-
e
r
op m e n t of m e t h ot re xa t e -in d u ce d cyt op e n ia s . Ra re, s eve re id ios yn cra t ic cyt op e -
a
p
n ia s m ay d eve lop eve n in t h e s e t t in g of low w e e kly d os e s a n d a d e q u a t e fola t e
y
s t ore s . Re n a l in s u f cie n cy gre a t ly e n h a n ce s t h e like lih ood of m a rrow t oxicit y,
d u e in la rge p a rt t o t h e p rom in e n t role of re n a l e xcre t ion in e lim in a t ion of t h e
d ru g. Us e of m e t h ot re xa t e in p a t ie n t s w it h e n d -s t a ge re n a l d is e a s e, eve n w h ile
on regu la r h e m od ia lys is , m ay h a ve d e le t e riou s a n d irreve rs ible con s e q u e n ce s .
Alt h ou gh s e ru m leve ls of m e t h ot re xa t e ca n be e f cie n t ly low e re d by h e m od i-
a lys is u s in g h igh - u x d ia lyze rs , p e rit on e a l d ia lys is is in e ffe ct ive a t low e rin g
s e ru m leve ls of m e t h ot re xa t e, a n d d ia lys is of a n y t yp e like ly h a s lit t le e ffe ct on
re m ova l of t h e a ct ive p olyglu t a m a t e d m e t a bolit e s w it h in ce lls .
Gu id e lin e s for m on it orin g of p a t ie n t s w it h rh e u m a t oid a rt h rit is re ce ivin g
m e t h ot re xa t e h ave be e n e s t a blis h e d (Ta ble 28.2 ) (5,6 ). Prior t o s t a rt in g m e t h -
ot re xa t e, a com p le t e blood cou n t (CBC) w it h s e ru m leve ls of live r t ra n s a m in a s e s
(ALT, AST), a lbu m in , a n d cre a t in in e s h ou ld be ch e cke d . Scre e n in g for h ep a t it is
B a n d C in fe ct ion is a ls o a d vo ca t e d . Tra n s a m in a s e leve ls a n d CBC s h ou ld be
ch e cke d w it h in 4 w e e ks of in s t it u t in g t h e ra py a n d w it h in 4 w e e ks of a n y d os e
in cre m e n t . More fre q u e n t a s s e s s m e n t of blood cou n t s m a y be in d ica t e d for
p a t ie n t s w it h re n a l in s u f cie n cy. Alt e rn a t ive ly, t h e in t e rva l be t w e e n a s s e s s -
m en t of blood cou n t s a n d liver fu n ct ion t es t s m ay be exte n d e d to 3 m on th s for
p a t ie n t s w h o h ave be e n on a s t a ble d os e of m e t h ot re xa t e in e xce s s of 6 m on t h s .
Cre a t in in e leve ls s h ou ld be ch e cke d a t le a s t eve ry 6 m on t h s .
Fo r p a t ie n t s w h o d e ve lo p cyt o p e n ia s (W BC 3,000; h e m a t o cr it 30;
p la t e le t s 130,000), m e t h ot re xa t e s h ou ld be w it h h e ld u n t il t h e ca u s e o f t h e
cyt op e n ia is e lu cid a t e d or t h e leve l of t h e d ep re s s e d blood e le m e n t re cove rs .
A s im ila r s t ra t egy s h ou ld be e m p loye d for p a t ie n t s w h o d eve lop e leva t ion in
live r t ra n s a m in a s e s in e xce s s of t w ice t h e u p p e r lim it of n orm a l. In e it h e r ca s e,
if it is d e e m e d t h e a b n o r m a lit y w a s d u e t o m e t h o t re x a t e , t re a t m e n t w it h
Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 285
Ba se lin e e va lu a t io n :
Co m p le t e b lo o d co u n t
Live r fu n ct io n t e st s—AST, ALT, b iliru b in , a lka lin e p h o sp h a t a se , a lb u m in
He p a t it is B su rfa ce a n t ig e n , h e p a t it is C a n t ib o d y
Pre t re a t m e n t live r b io p sy fo r p a t ie n t s w it h :
Prio r h ist o ry o f e xce ssive a lco h o l co n su m p t io n
Pe rsist e n t a b n o rm a l e le va t io n s in t ra n sa m in a se s (AST, ALT) le ve ls
Evid e n ce o f p e rsist e n t in fe ct io n w it h h e p a t it is B o r C
Mo n it o r CBC, AST, ALT, a n d a lb u m in a t 4- t o 12-w e e k in t e rva ls
Mo n it o r cre a t in in e a t 3- t o 6-m o n t h in t e rva ls
In se t t in g o f cyt o p e n ia o r e le va t io n in AST, ALT t w ice u p p e r ra n g e o f n o rm a l:
Ho ld m e t h o t re xa t e a n d re su m e a t lo w e r d o se o n ce la b o ra t o ry
a b n o rm a lit y re so lve s
Pe rfo rm live r b io p sy b e fo re co n t in u in g t re a t m e n t if:
Five o f n in e o r six o f t w e lve AST d e t e rm in a t io n s in a 1-ye a r t im e fra m e a re
y
a b n o rm a l, o r
p
a
Alb u m in d e cre a se s b e lo w n o rm a l ra n g e d e sp it e a d e q u a t e co n t ro l o f syn o vit is
r
e
h
T
d
n
a
m e t h ot re xa t e a t a low e r d os e ca n oft e n be e m p loye d w it h s u cce s s . Eleva t ion s
s
i
s
of cre a t in in e w h ile on m e t h ot re xa t e w a rra n t e xclu s ion of in t e rs t it ia l n ep h rit is
o
n
a n d a t t e n t ion t o t h e n e e d for d os e a d ju s t m e n t t o avoid m a rrow t oxicit y. Th e
g
a
occu rre n ce of cou gh , d ys p n e a , a n d feve r s h ou ld p rom p t w it h h old in g of m e t h -
i
D
ot re xa t e u n t il it ca n be e s t a blis h e d t h a t t h e s yn d rom e is n ot like ly a t t ribu t a ble
6
t o m e t h ot re xa t e p n e u m on it is .
N
O
Th e rep ort ed occu rren ce of cirrh os is a m on g p a t ien ts w ith p s oria s is t re a t ed
I
T
C
w it h lon g-t e rm w e e kly m e t h ot rexa t e in it ia lly p rom p t e d re com m e n d a t ion s for
E
rou t in e live r biop s y in p a t ie n t s w it h rh e u m a t oid a rt h rit is t re a t e d w it h m e t h -
S
ot rexa t e on ce t h e cu m u la t ive d ose a p p roa ch e d 2 g. How eve r, given t h e in freq u en t
occu rre n ce of s e riou s live r d is e a s e obs e rve d a m on g p a t ie n t s w it h rh e u m a t oid
a rt h rit is t rea t ed w it h m et h ot rexa t e (es t im a t ed ris k a t 5 yea rs 1 in 1,000), cu rren t
gu id e lin e s d o n ot a d voca t e rou t in e live r biop s y for p a t ie n t s t re a t e d w it h lon g-
t e rm m e t h ot re xa t e w h o h ave n orm a l live r fu n ct ion . Live r biop s y is a d voca t e d
p re t re a t m e n t for p a t ie n t s w it h kn ow n h is t ory of p reviou s h e avy a lcoh ol u s e,
a ctive h ep a t it is B, or h ep a t it is C in fection , a n d for p a t ie n t s on m e th ot rexa te w h o
d eve lop p ers is t e n t e leva t ion in liver t ra n s a m in a s e s or a fa ll in s e ru m a lbu m in
d es p ite w e ll-con trolled rh eu m a toid a rt h rit is .
ANTIMALARIALS—HYDROXYCHLOROQUINE,
CHLOROQUINE, AND QUINACRINE
Mos t com m on ly e m p loye d in t h e m a n a ge m e n t of lu p u s or rh e u m a t oid a rt h rit is ,
a n t im a la ria ls h ave m u lt ip le e ffe ct s on im m u n ologic fu n ct ion a n d h ave a ve ry
favora ble t oxicit y/be n e t p ro le. Hyd roxych loroq u in e a n d ch loroq u in e d o n ot
s u p p re s s bon e m a rrow fu n ct ion a n d live r t oxicit y is u n com m on . Sid e e ffe ct s
con s is t p rim a rily of cu t a n e ou s re a ct ion s , GI in t ole ra n ce, a n d m ild CNS s ym p -
t om s . Wit h t h e e xcep t ion of s eve re s kin e ru p t ion s , m a n y of t h e GI a n d n e u ro-
logic s id e e ffe ct s m ay a ba t e w it h re d u ct ion in t h e d os e of a n t im a la ria ls . Alt h ou gh
ra re, ca rd ia c con d u ct ion a bn orm a lit ie s , ca rd iom yop a t h y, a n d n e u rom yop a t h y
h ave be e n rep ort e d a s m ore s e riou s com p lica t ion s . As is re com m e n d e d follow -
in g in it ia t ion of t h e ra py w it h m os t a n t irh e u m a t ic d ru gs , a s s e s s m e n t of live r
t ra n s a m in a s e s s h ou ld be p e rform e d w it h in t h e rs t 2 or 3 m on t h s of t re a t m e n t
t o e n s u re t h e a bs e n ce of id ios yn cra t ic live r t oxicit y.
286 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
SULFASALAZINE
Su lfa s a la zin e con s ist s of a sa licyla te (5-a m in os a licylic a cid ) a n d a su lfa pyrid in e
m ole cu le a d join ed by a n a zo bon d t h a t is cle ave d by ba cte ria l orga n is m s in t h e
S
E
gu t. In a d d it ion t o th e a n ti-in a m m a t ory effe ct s a fford e d by t h e libera t ed s a li-
C
T
cyla t e, su lfa pyrid in e a n d /or its m e ta bolite s a p p e a r to h ave im m u n om od u la t ory
I
O
N
effects t h a t a re of ben e t in th e m a n a ge m e n t of p a t ie n t s w it h rh eu m a t oid a rt h ri-
6
tis, a n kylos in g s p on dylit is , or on e of t h e ot h e r s p on dyloa rt h rop a t h ies . Ga s t roin -
D
tes t in a l s ym p t om s a re u s u a lly t h e m os t com m on s id e e ffect s rep ort ed w ith u s e
i
a
g
of s u lfa sa la zin e, bu t t h e se oft en res olve w it h d os e a tt en u a t ion . Th e le ss com m on ,
n
o
bu t p ot e n t ia lly m ore s e riou s , h e m a t ologic con s e q u e n ce s of s u lfa s a la zin e u s e
s
i
in clu d e a p la s t ic a n e m ia , a gra n u locyt os is , or h e m olyt ic a n e m ia , w it h t h e la t t e r
s
a
occu rrin g p re d om in a n t ly in p a t ie n t s w it h glu cos e -6-p h os p h a t e d e h yd roge n a s e
n
d
d e cie n cy. Le u kop en ia m os t oft en occu rs d u rin g t h e rs t s eve ra l m on th s of t re a t -
T
h
m e n t , bu t m ay occu r a t a n y tim e. In d e cre a sin g ord er of fre q u en cy, cu ta n eou s ,
e
r
h ep a t ic, p u lm on a ry, a n d ren a l h yp ers en s it ivit y rea ct ion s m ay a lso occu r.
a
p
W h e n in it ia t in g t h e ra py w it h s u lfa s a la zin e, it is a d vis a ble t o ch e ck ba s e lin e
y
blo o d co u n t s a n d live r fu n ct io n t e s t s , a n d s cre e n fo r glu co s e -6-p h o s p h a t e
d e h yd roge n a s e d e cie n cy. Th e d ru g is be s t in t rod u ce d in cre m e n t a lly, s t a rt in g
w it h a 500 m g d a ily d os e a n d t h en in cre a s in g by 500 m g w e e kly u n t il t h e t h e ra -
p e u t ic t a rge t d os e of 1 t o 2 g t w ice d a ily is re a ch e d . Blood cou n t s a n d live r fu n c-
t ion t e s t s h ou ld be a s s e s s e d a t 2-w ee k in t e rva ls u n t il t h e p a t ie n t h a s be e n on t h e
t a rge t m a in t e n a n ce d os e for a t le a s t 1 m on t h . Blood cou n t s a n d liver t ra n s a m i-
n a s e leve ls ca n t h e n be m on it ore d le s s fre q u e n t ly, bu t s h ou ld be a s s e s s e d a t
le a s t eve ry 3 m on t h s . As le u kop e n ia m ay occu r p recip it ou s ly, p a t ie n t s s h ou ld be
in s t ru ct e d t o p rom p t ly rep ort t h e occu rre n ce of feve r, m a la is e, m ou t h u lce rs , or
s ore t h roa t .
LEFLUNOMIDE
Le u n om id e is a n in h ibit or of d ih yd ro-orot a t e d e h yd roge n a s e, a n e n zym e m e d i-
a t in g s yn t h e s is of pyrim id in e s . Le u n om id e h a s s ign i ca n t in h ibit ory e ffe ct s on
p rolife ra t ion of lym p h ocyt e s a n d h a s d e m on s t ra t e d e f ca cy in t h e m a n a ge m e n t
of rh e u m a t oid a rt h rit is . Ad ve rs e e ffe ct s of le u n om id e a re re la t ive ly m ild a n d
in fre q u e n t , a n d in clu d e reve rs ible a lop e cia , s kin ra s h , d ia rrh e a , a n d e leva t ion in
live r e n zym e s . Le u n om id e is t e ra t oge n ic in a n im a ls a n d con t ra in d ica t e d in
w om e n w h o a re or w is h t o be com e p regn a n t .
Live r fu n ct ion t e s t s s h ou ld be a s s e s s e d a t ba s e lin e a n d a t m on t h ly in t e r-
va ls fo llow in g in it ia t io n o f t h e ra p y. Fre q u e n cy o f t e s t in g ca n b e e xt e n d e d t o
eve ry 3 m on t h s for p a t ie n t s w h o h ave be e n on t h e ra p y in e xce s s of 6 m on t h s
w it h ou t s ign s of live r t oxicit y. Le u n om id e s h ou ld be p rom p t ly d is con t in u e d if
s ign i ca n t e leva t ion s in live r t ra n s a m in a s e s occu r. Th e s e ru m h a lf-life of t h e
Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 287
y
p
Th e m o s t co m m o n a d ve r s e eve n t s lim it in g u s e of gold co m p o u n d s a re
a
r
e
m u cocu t a n e o u s re a ct io n s in clu d in g s t om a t it is , p r u r it is , a n d a n y n u m b e r of
h
T
va rio u s fo rm s o f d e rm a t it is . Alt h ou gh ra re ly re p o rt e d w it h u s e of a u ra n o n ,
d
p rot e in u ria m a y be a com p lica t ion of p a re n t e ra l gold s a lt t h e ra p y t h a t m a y
n
a
re q u ire e it h e r d os e a t t e n u a t ion or ce s s a t ion of t h e ra p y. Le u kop e n ia , t h rom bo-
s
i
s
cyt op e n ia , a n d a p la s t ic a n e m ia a re ra re , bu t p ot e n t ia lly, fa t a l co n s e q u e n ce s
o
n
t h a t m a y occu r a t a n y t im e d u rin g t h e cou rs e of gold t h e ra py.
g
a
For p a tien ts on p a ren tera l gold th era py, blood cou n ts a n d a u rin a lysis sh ou ld
i
D
be ch ecked p rior to ea ch in jection d u rin g th e rst yea r of trea tm en t. On ce a p a tien t
6
is on a stable regim en beyon d th e in itia l yea r, th e m on itorin g in terva l for p rotein u -
N
O
ria a n d cytop en ia s ca n be exten d ed to every oth er in jection . Th e d evelop m en t of
I
T
sign i ca n t leu kop en ia ( 3,500/m m 3), th rom bocytop en ia ( 100,000/m m 3), or a p er-
C
E
sisten t d ow n w a rd tren d in th e p la telet cou n t or h em a tocrit sh ou ld p rom p t cessa -
S
t ion of ch rysoth e ra py. In th e a bs en ce of oth er id en ti a ble ca u ses for observed
cytop en ia (s), trea tm en t w ith gold com p ou n d s sh ou ld n ot be rein stitu ted . Protein u -
ria d u rin g trea tm en t w ith gold com p ou n d s is often tra n sien t, resp on d in g to tem -
p ora ry w ith h old in g of gold ; m ost p a tien ts ca n resu m e trea tm en t a t low er d oses
w ith ou t recu rren ce of th e p rotein u ria . Gold sh ou ld n ot be rein stitu ted in p a tien ts
w h o d evelop n ep h rotic-ra n ge p rotein u ria ( 1 g p rotein excreted /24 h ou rs).
Mon it orin g of p a t ie n t s on gold t h e ra py a ls o re q u ire s a t t e n t ion t o t h e occu r-
re n ce of s kin ra s h , p ru rit is , or m ou t h u lce rs . Prior t o e a ch in je ct ion of p a re n t e ra l
go ld , p a t ie n t s s h o u ld b e q u e s t io n e d a s t o t h e o ccu rre n ce of m u co cu t a n e o u s
s ym p t om s ; p a t ie n t s on ora l gold s h ou ld be a d vis e d t o rep ort t h e occu rre n ce of
s kin ra s h o r s ym p t o m s o f s t o m a t it is t h a t m a y a ris e b e t w e e n m o n t h ly bloo d
ch e cks . Th e m a jorit y of m u cocu t a n e ou s s id e e ffe ct s a re be s t m a n a ge d by in t e r-
ru p t ion of t h e ra p y a n d t h e n re s u m in g t re a t m e n t a t a low e r d os e on ce t h e d e r-
m a t it is or s t om a t it is h a s re s olve d .
Nit rit oid re a ct ion s a re va s om ot or re s p on s e s t o in je ct ion of gold m a n ife s t by
s ym p t om s of u s h in g, n a u s e a , vom it in g, sw e a t in g, or d izzin e s s . Su ch re a ct ion s
a re ra re ly s e e n follow in g a d m in is t ra t ion of a u rot h ioglu cos e, bu t h a ve be e n
rep ort e d w it h u s e of a u ra n o n . Th e p e rip h e ra l va s od ila t a t ion a s s ocia t e d w it h
n it rit oid re a ct ion s is u s u a lly w e ll t ole ra t e d , bu t in e ld e rly p a t ie n t s w it h a rt e rio-
s cle rot ic va s cu la r d is e a s e m ay, it re s u lt in s t roke or m yoca rd ia l in fa rct ion .
y
p
cys t it is , s m okin g, d u ra t ion of t h e ra py of m ore t h a n 2 ye a rs , a n d a cu m u la t ive
a
r
e
d os e in e xce s s of 100 g (9 ). For p a t ie n t s w h o h ave e xp e rie n ce d a n ep is od e of
h
T
cyclop h os p h a m id e -in d u ce d cys t it is , life -lon g s u rve illa n ce for bla d d e r ca n ce r is
d
re com m e n d e d w it h ye a rly u rin a lys is a n d u rin e cyt ologic eva lu a t ion .
n
a
Rega rd le s s of t h e rou t e of a d m in is t ra t ion , t h e re is a 45% t o 71% p e rce n t ris k
s
i
s
of ova ria n fa ilu re follow in g t re a t m e n t w it h cyclop h os p h a m id e, w it h h igh e s t
o
n
ra t e s o bs e rve d a m o n g w om e n w h o a re o ld e r a n d w h o h a ve re ce ive d h igh e r
g
a
cu m u la t ive d os e s . Sim ila r ra t e s of a zoos p e rm ia a re rep ort e d for m a le s re ce ivin g
i
D
a lkyla t in g a ge n t s , s u ch a s cyclop h os p h a m id e. To p re s e rve fu t u re fe rt ilit y, s p e rm
6
or ova ca n be ba n ke d be fore t re a t m e n t w it h cyclop h os p h a m id e is in it ia t e d .
N
O
Th e re is n o evid e n ce t h a t p rior t re a t m e n t of e it h e r p a re n t w it h cyclop h os p h a -
I
T
m id e is a s s ocia t e d w it h ge n e t ic a bn orm a lit ie s in s u bs e q u e n t offs p rin g.
C
E
Tre a t m e n t w it h ora l cyclop h os p h a m id e is a s s ocia t e d w it h a t w o- t o fou rfold
S
in cre a s e d ris k of m a lign a n cy. Bla d d e r, s kin , m ye lop rolife ra t ive, a n d orop h a ryn -
ge a l ca n ce r s h a ve be e n re p ort e d m ore com m o n ly a m on g p a t ie n t s w it h RA
t re a t e d w it h d a ily cyclop h os p h a m id e t h a n p a t ie n t s w it h RA n ot t re a t e d w it h
cyclop h os p h a m id e. Alt h ou gh t h e re a re in s u f cie n t d a t a t o re n d e r a q u a n t i a ble
ris k for m a lign a n cy follow in g t re a t m e n t w it h p u ls e in t rave n ou s cyclop h os p h a -
m id e, few m a lign a n cie s h ave be e n rep ort e d in t h is s e t t in g.
CHLORAMBUCIL
Ch lora m bu cil a n d it s p rim a ry m e t a bolit e, p h e n yla ce t ic a cid m u s t a rd , a re p ot e n t
a lkyla t in g a ge n t s . Th e clin ica l e ffe ct s a re com p a ra ble t o cyclo p h os p h a m id e ,
a lt h ou gh s low e r in on s e t . Ch lora m bu cil d oe s n ot in d u ce bla d d e r t oxicit y a n d is
m os t oft e n u s e d a s a n a lt e rn a t ive t o cyclop h os p h a m id e w h e n cyt ot oxic t h e r-
a p y is in d ica t e d . It is o ft e n t h e d ru g of ch oice t o s u p p re s s clon e s of im m u -
n oglobu lin ligh t ch a in s e cre t in g ce lls in p a t ie n t s w it h p rim a ry (AL) a m yloid os is .
Th e p rim a ry t oxicit y of ch lora m bu cil is t h a t of m ye los u p p re s s ion , w h ich m a y
occu r a bru p t ly a t a n yt im e d u rin g t h e cou rs e of t re a t m e n t . Alt h ou gh reve rs ible,
ch lora m bu cil-in d u ce d le u kop e n ia m ay p e rs is t for m on t h s follow in g d is con t in -
u a t ion of t h e d ru g.
Be ca u s e of t h e o ccu r re n ce of p re cip it o u s le u ko p e n ia in p a t ie n t s t a k in g
ch lora m bu cil, fre q u e n t s u rve illa n ce for cyt op e n ia is im p e ra t ive. Follow in g t h e
in it ia t ion of t re a t m e n t , CBCs s h ou ld be a s s e s s e d a m in im u m of eve ry 2 w e e ks .
On ce t h e d os e a n d le u kocyt e cou n t a re s t a ble, t h e m on it orin g in t e rva l ca n be
e xt e n d e d t o eve ry 4 w e e ks . Th e ris k of m ye loid le u ke m ia s a s w e ll a s lym p h o-
m a s is in cre a s e d a m on g p a t ie n t s w h o h a ve be e n t re a t e d w it h ch lora m b u cil;
290 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
MYCOPHENOLATE MOFETIL
Mycop h e n ola t e m ofe t il is a n e s t a blis h e d t h e ra p y for t h e s u p p re s s ion of gra ft
re je ct ion in orga n t ra n s p la n t re cip ie n t s t h a t is a cq u irin g a n exp a n d e d role a s a n
im m u n os u p p re s s a n t in t h e m a n a gem e n t of p a t ie n t s w it h a u t oim m u n e d is ea s e.
Follow in g in ge s t ion t h e d ru g is h yd rolyzed t o it s a ct ive m e t a bolit e, m ycop h e n olic
a cid , a n in h ibit or of in os in e m on op h os p h a t e d e h yd roge n a s e. As lym p h ocyt e s a re
p a rt icu la rly d ep e n d e n t on t h is e n zym e for d e n ovo s yn t h e s is of p u rin e s , m yco-
p h e n ola t e s e lect ive ly t a rge t s p rolife ra t ion of T- a n d B-ce ll lym p h ocyt es w it h ou t
a s ign i ca n t im p a ct on gra n u lop oie s is , e ryt h rop oies is , or t h rom bop oies is .
Mycop h e n ola t e h a s be e n s t u d ie d a s a n a lt e rn a t ive t o cyclop h os p h a m id e in
t h e m a n a ge m e n t o f lu p u s n e p h r it is a n d is ge n e ra lly w e ll t o le ra t e d . Mo s t
a d ve rs e eve n t s re la t e t o GI in t ole ra n ce in clu d in g n a u s e a , vom it in g, d ia rrh e a ,
a n d a bd om in a l p a in . For p a t ie n t s e xp e rie n cin g s ign i ca n t GI in t ole ra n ce, u s e of
m ycop h e n olic a cid p rep a ra t ion s m ay be be t t e r t ole ra t e d . Live r e n zym e a bn or-
m a lit ie s m ay occu r, a n d p a t ie n t s t a kin g m ycop h e n ola t e s h ou ld h ave live r fu n c-
t ion t e s t p e rfor m e d a t ba s e lin e, 1 m on t h follow in g in it ia t ion of t h e ra p y a n d
eve ry 3 t o 4 m on t h s t h e re a ft e r.
y
p
Othe r Immuno mo dula ting Drug s
a
r
e
h
CYCLOSPORINE A AND TACROLIMUS
T
d
Origin a lly d eve lop e d a n d e m p loye d t o s u p p re s s gra ft re je ct ion in re cip ie n t s of
n
a
orga n t ra n s p la n t s , cyclos p orin e a n d t a crolim u s a re u s e d a s a d is e a s e -m od ifyin g
s
i
s
d r u gs in t h e m a n a ge m e n t o f r h e u m a t o id a r t h r it is a n d o t h e r a u t o im m u n e
o
n
d is ord e rs , in clu d in g ch ron ic re cu rre n t a n t e rior u ve it is , p s oria t ic a rt h rit is , a n d
g
a
Be h ce t ’s s yn d rom e. Th e s e d ru gs in h ibit t h e a ct iva t ion of T ce lls a n d s e cre t ion
i
D
of IL-2 (a m a jor T-ce ll grow t h fa ct or) by form in g a cyt op la s m ic com p le x w it h
6
cyclo p h ilin . Th e re s u lt in g co m p le x in a ct iva t e s a p h o s p h a t a s e (ca lcin e u r in )
N
O
re q u ire d for t h e t ra n s loca t ion of a fa ct or t o t h e n u cle u s t h a t a ct iva t e s t ra n -
I
T
C
s crip t ion of IL-2 a n d ot h e r ge n e s a s s ocia t e d w it h a ct iva t ion of T ce lls .
E
Alt h ou gh cyclos p orin e a n d t a crolim u s a re ge n e ra lly w e ll t ole ra t e d , m e a s u r-
S
a ble bu t reve rs ible d e cre a s e s in re n a l fu n ct ion occu r in t h e m a jorit y of p a t ie n t s
t re a t e d . A s m a ll ris e in s e ru m cre a t in in e w it h in t h e rs t 3 m on t h s of t re a t m e n t
is fa irly p re d ict a ble, bu t oft e n re m a in s s t a ble t h e re a ft e r. How eve r, a n in cre a s e
in s e ru m cre a t in in e t h a t e xce e d s 30% of t h e ba s e lin e va lu e p ort e n d s p os s ible
irreve rs ible n e p h rot oxicit y. In s u ch in s t a n ce s t h e a d m in is t e re d d os e s h ou ld be
a t t e n u a t e d by 1 m g/kg/d ay a n d t e m p ora rily d is con t in u e d if t h e s e ru m cre a t i-
n in e re m a in s e leva t e d . Provid e d t h e s e ru m cre a t in in e leve l re t u rn s t o w it h in
15% of t h e e s t a blis h e d ba s e lin e leve l, cyclos p orin e ca n be s a fe ly re s t a rt e d a t t h e
a t t e n u a t e d d os e (11 ). Hyp e rt e n s ion is re p ort e d t o occu r in a p p roxim a t e ly 20%
p e rce n t of p a t ie n t s bu t ca n be m a n a ge d w it h e it h e r a t t e n u a t ion in t h e d os e of
cyclos p orin e or a d d it ion of a n t ih yp e rt e n s ive d ru g t h e ra py.
Ot h e r com m o n s id e e ffe ct s of cyclo s p o rin e in clu d e t re m or, p a re s t h e s ia ,
h yp e r t r ich o s is , h yp e r k a le m ia , h yp o m a gn e s e m ia , a n d h yp e r u r ice m ia . Live r
e n zym e a bn orm a lit ie s , p a rt icu la rly a ris e in s e ru m a lka lin e p h os p h a t a s e, occu r
n o t u n com m on ly, bu t a re s e ld om of clin ica l s ign i ca n ce. W h ile cyclo s p o rin e
u s e in re cip ie n t s of orga n t ra n s p la n t s h a s be e n a s s ocia t e d w it h a n in cre a s e d
ris k of s kin ca n ce r a n d lym p h om a , t h is a s s ocia t ion h a s n ot be e n con rm e d
a m on g s m a lle r coh ort s of p a t ie n t s w it h RA t re a t e d w it h cyclos p orin e.
DAPSONE
Origin a lly e m p loye d in t h e t re a t m e n t of lep ros y, d a p s on e is a s u lfon e w it h s ig-
n i ca n t in h ibit ory e ffe ct s on t h e fu n ct ion of n e u t rop h ils . Alt h ou gh t h e re a re few
con t rolle d t ria ls e xa m in in g it s e f ca cy, it is m os t com m on ly u s e d in t h e m a n -
a ge m e n t of cu t a n e ou s le u kocyt ocla s t ic va s cu lit is , u rt ica ria l va s cu lit is , bu llou s
292 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
y
p
In ixim a b is u s u a lly w e ll t ole ra t e d a n d rou t in e la bora t ory m on it orin g for t oxic-
a
r
e
it y is n ot re q u ire d . Hu m a n a n t ich im e ric a n t ibod y re s p on s e s t o m u rin e com p o-
h
T
n e n t s of t h e a n t ibody d eve lop in u p t o 40% of p a t ie n t s give n in ixim a b. In fu s ion
d
re a ct ion s w it h p ru rit is , u rt ica ria , a n d / or ch ills occu r in a s m a ll m in orit y of
n
a
p a t ie n t s a n d re s p on d favora bly t o h a lt in g of t h e in fu s ion a n d a d m in is t ra t ion of
s
i
s
a n t ih is t a m in e s . Re t re a t m e n t of p a t ie n t s w h o h a ve e xp e rie n ce d a n in fu s ion
o
n
re a ct ion is n ot re com m e n d e d . Alt h ou gh n ot re q u ire d for in it ia l e f ca cy, cot re a t -
g
a
m e n t w it h low -d os e w e e kly m e t h ot re xa t e h a s be e n s h ow n t o d e cre a s e (bu t n ot
i
D
a broga t e ) h u m a n a n t ich im e ric a n t ibody re s p on s e s a n d m ay ext e n d t h e d u ra t ion
6
of in ixim a b e f ca cy.
N
O
Fu lly h u m a n ized a n tibod ies to TNF- a re a d m in istered a s su bcu ta n eou s in jec-
I
T
tion s a t 1- to 2-w eek (adalim um ab ) or 4-w eek (golim um ab ) in terva ls. Th e d evelop -
C
E
m en t of n eu tra lizin g a n tibod ies is ra re, a n d a lth ou gh in jection site rea ction s m ay
S
occu r, th ey a re often tra n sien t a n d u su a lly d o n ot req u ire cessa tion of th era py.
CERTOLIZUMAB
Ce rt olizu m a b is a p egyla t e d con s t ru ct of F(a b’) com p on e n t s of m on oclon a l re a -
ge n t s h avin g s p e ci cit y for TNF- cova le n t ly bou n d t o p olye t h yle n e glycol. It s
e f ca cy in n e u t ra lizin g TNF- is com p a ra ble t o t h a t of a n t i-TNF- a n t ibod ie s ,
bu t t h e a bs e n ce of t h e Fc-a s s ocia t e d com p le m e n t xin g d om a in s m a y re n d e r
it le s s like ly t o e n ge n d e r in je ct ion s it e re a ct ion s occa s ion a lly s e e n w it h e t a n e r-
ce p t , a d a lim u m a b, or golim u m a b.
In p a t ie n t s w it h a ct ive h ep a t it is C, t re a t m e n t w it h a n t i-TNF- re a ge n t s h a s
n ot in cre a s e d vira l loa d s , u n favora bly a lt e re d t h e cou rs e of d is e a s e, or im p a ire d
re s p on s e s t o a n t ivira l t h e ra py. How eve r, exa ce rba t ion of h ep a t it is B vira l (HBV)
in fe ct ion h a s be e n rep ort e d in t h e con t ext of t h e ra py w it h a n t i-TNF- re a ge n t s ,
a n d t h is cla s s of biologic t h e ra py is be s t avoid e d in t h e con t e xt of a ct ive HBV
d is ea s e ; a s s u ch , s cre e n in g for HBV is re com m e n d e d be fore s t a rt in g a n t i-TNF-
re a ge n t s . Pa t ie n t s w it h h u m a n im m u n od e cie n cy viru s (HIV) d is e a s e w h o
d eve lop s eve re p s oria s is m ay be t re a t e d w it h a n t i-TNF- re a ge n t s ; a lt h ou gh
d oin g s o d oe s n ot a p p e a r t o a d ve rs e ly a ffe ct re s p on s e s t o a n t ire t rovira l t h e ra py,
ext ra vigila n ce for ba ct e ria l, fu n ga l, a n d m ycoba ct e ria l in fe ct ion is re q u ire d in
p a t ien t s re ce ivin g a n t i-TNF- t h e ra py w h o a re im m u n ocom p rom is e d from HIV.
Em e rge n ce of lym p h om a s h a s be e n rep ort e d in p a t ie n t s re ce ivin g a n t i-TNF-
t h e ra p y; h ow eve r, t h e p reva le n ce of lym p h oid m a lign a n cie s h a s n ot be e n
s h ow n t o be h igh e r in coh ort s of p a t ie n t s w it h RA w h o h ave re ce ive d a n t i-TNF-
re a ge n t s re la t ive t o t h os e w h o h ave n ot . Give n t h e role of TNF- in h os t d e fe n s e
a ga in s t m a lign a n cy, d is con t in u a t ion of t re a t m e n t is n on e t h e le s s a d vis e d in t h e
con t e xt of t h e d eve lop m e n t of lym p h om a a n d ot h e r m a lign a n t n e op la s m s .
Ad m in is t ra t ion of a n t i-TNF- m on oclon a l re a ge n t s is a s s ocia t e d w it h t h e
d eve lop m e n t of a n t in u cle a r a n t ibod ie s in a m in orit y of p a t ie n t s . Clin ica l m a n -
S
E
ife s t a t ion s of lu p u s h a ve be e n re p ort e d t o occu r follow in g a d m in is t ra t ion of
C
T
in ixim a b, a n d a n t i-TNF- a n t ibod ie s a re n ot re com m e n d e d for u s e in p a t ie n t s
I
O
N
w it h s ys t e m ic lu p u s e ryt h e m a t os u s . Up t o 15% of p a t ie n t s t a kin g e t a n e rce p t
6
a re rep ort e d t o d eve lop n ew p os it ive a n t in u cle a r a n t ibod ie s , a n t ibod ie s t o d ou -
D
ble -s t ra n d e d DNA, or bot h . Alt h ou gh n o p a t ie n t s in p re m a rke t con t rolle d clin i-
i
a
g
ca l t ria ls w h o d eve lop e d s u ch a n t ibod ie s d eve lop e d clin ica l m a n ife s t a t ion s of
n
o
s ys t e m ic lu p u s e ryt h e m a t os u s , a n u m be r of p os t m a rke t ca s e re p ort s h a ve d oc-
s
i
u m e n t e d t h e occu rre n ce of d e m ye lin a t in g s yn d rom e s follow in g in it ia t ion of
s
a
t re a t m e n t w it h e t a n e rcep t . Alt h ou gh la bora t ory m on it orin g for e m e rge n ce of
n
d
a u t oa n t ibod ie s is n ot n e ce s s a ry, a n t i-TNF- t h e ra p y s h o u ld be d is con t in u e d
T
h
s h o u ld a u t o im m u n e d is e a s e m a n ife s t a t io n s n o t n o r m a lly a s s o cia t e d w it h
e
r
rh e u m a t oid a rt h rit is or s p on d yloa rt h rop a t h ie s e m e rge.
a
p
y
IL- 1 Anta g o nists
Biologics t a rge t in g IL-1 in clu d e an akin ra (re com bin a n t h u m a n IL-1 re cep t or
a n t a gon is t ), can akin u m ab (a n a n t i-IL-1 m on oclon a l a n t ibod y), a n d rilon oce pt
(a n IL-1 re ce p t o r/ a cce s s o ry p rot e in con s t ru ct fu s e d t o im m u n oglobu lin Fc).
An a k in ra is a p p rove d fo r t h e t re a t m e n t o f rh e u m a t o id a rt h rit is a n d is co m -
m on ly u s e d in t h e m a n a ge m e n t of s ys t e m ic-on s e t ju ve n ile id iop a t h ic a rt h rit is
a n d a d u lt St ill’s d is e a s e. Ca n a kin u m a b a n d rilon ocep t a re a p p rove d for u s e in
m a n a gin g p a t ie n t s w it h cryop yrin -a s s o cia t e d a u t oin a m m a t ory s yn d ro m e s ;
IL-1 a n t a gon is t s a re a ls o be in g s t u d ie d for p ot e n t ia l u s e in m a n a gin g a n d s u p -
p re s s in g a re s of gou t .
IL-1 a n t a gon is t s a re ge n e ra lly ve ry w e ll t ole ra t e d , a n d t h e ir u s e d oe s n ot
re q u ire la bora t ory m on it orin g ot h e r t h a n p e riod ic m on it orin g of blood cou n t s
t o m on it or for le u cop e n ia t h a t m ay d eve lop in a ve ry s m a ll m in orit y of p a t ie n t s .
In je ct ion s it e re a ct ion s w it h a n a kin ra a re com m on , p a rt icu la rly d u rin g t h e in i-
t ia l w e e ks o f t h e ra p y, bu t d o n o t re q u ire ce s s a t io n o f t re a t m e n t a n d oft e n
d im in is h in t h e ir fre q u e n cy a n d s eve rit y w it h con t in u e d t re a t m e n t .
s e r u m ch o le s t e ro l co m m o n ly o ccu r fo llow in g in it ia t io n o f t re a t m e n t w it h
t ocilizu m a b, a n d m on it orin g of s e ru m ch ole s t e rol is re com m e n d e d d u rin g t h e
in it ia l m on t h s of t re a t m e n t . Dos e -lim it in g e leva t ion s in live r t ra n s a m in a s e s
m ay a ls o occu r in t h e con t e xt of t re a t m e n t w it h t ocilizu m a b, a n d m on it orin g
of AST a n d ALT leve ls a t 3- t o 4-m on t h in t e rva ls is re com m e n d e d . Sin ce IL-6
p ro m ot e s t h ro m b op oie s is a s w e ll a s gra n u lo p o ie s is , p e r io d ic m on it or in g a t
3-m on t h in t e rva ls for le u cop e n ia a n d t h rom bocyt op e n ia is a ls o re com m e n d e d
for p a t ie n t s re ce ivin g t ocilizu m a b.
y
ra t e s a re n ot re p ort e d t o be h igh e r in p a t ie n t s w it h rh e u m a t oid a rt h rit is re ce iv-
p
a
in g a ba t a ce p t . How eve r, vigila n ce for in fe ct ion s w it h p a t h oge n s in w h ich in t a ct
r
e
h
T-ce ll fu n ct ion m ay be re q u ire d for re s olu t ion is a p p rop ria t e. Tit e rs of a n t ibod -
T
ie s in re s p on s e t o p rim a ry im m u n iza t ion a re a t t e n u a t e d in p a t ie n t s re ce ivin g
d
n
a ba t a cep t re la t ive t o t h os e n ot re ce ivin g a ba t a ce p t . Alt h ou gh t h e clin ica l s ig-
a
s
n i ca n ce of t h is a t t e n u a t ion is u n cle a r, it is re co m m e n d e d t h a t p a t ie n t s in
i
s
o
n e e d of p rim a ry im m u n iza t ion re ce ive s u ch im m u n iza t ion s p rior t o in it ia t in g
n
g
t re a t m e n t w it h a ba t a cep t .
a
i
D
Us te kin u m ab is a h u m a n ge n om e –d e rive d m on oclon a l re a ge n t w it h s p e -
6
ci cit y for t h e p 40 s u bu n it s h a re d by IL-12 a n d IL-23. Blockin g IL-12 a t t e n u a t e s
N
t h e m a t u ra t ion a n d a ct iva t ion of t h e Th 1 lin e a ge of T ce lls , w h ile blockin g IL-23
O
I
T
a t t e n u a t e s t h e m a t u ra t ion a n d s u rviva l of T17 ce lls , a s u bs e t of T ce lls im p li-
C
E
ca t e d in t h e p a t h oge n e s is o f a n u m b e r o f a u t o im m u n e d is o rd e rs , in clu d in g
S
in a m m a t ory bow e l d is e a s e, p s oria s is or p s oria t ic a rt h rit is , a n d RA. High e r-
t h a n -e xp e ct e d ra t e s of in fe ct ion or m a lign a n cy h a ve n ot be e n obs e rve d in con -
t rolle d s t u d ie s of u s t e kin u m a b; h ow eve r, give n t h e in h ibit ory e ffe ct s on T-ce ll
m a t u ra t ion a n d a ct iva t ion , vigila n ce for t u be rcu los is a n d fu n ga l in fe ct ion s is
n on e t h e le s s re com m e n d e d .
Re fe re nce s
1. Sa a g KG, Em key R, Sch n it ze r TJ, e t a l . Ale n d ron a t e for t h e p reve n t ion a n d t re a t m e n t of glu cocort icoid -
in d u ce d os t e o p oros is . N Engl J Med 1998 ;339 (5 ):292 –299 .
2. Fr ie s JF. Th e e p id e m io logy o f NSAID ga s t ro p a t h y: Th e ARAMIS e x p e r ie n ce . J Clin Rheu m atol 1998 ;
4 (Su p p l ):S11 .
S
E
3. Silve rs t e in FE, Gra h a m DY, Se n ior JR, e t a l. Mis op ros t ol re d u ce s s e riou s ga s t ro in t e s t in a l com p lica t io n s
C
in p a t ie n t s w it h rh e u m a t oid a rt h rit is re ce ivin g n on s t e roid a l a n t i-in a m m a t ory d ru gs . A nn Int Med 1995 ;
T
I
123 :241 .
O
N
4. Morga n SL, Ba ggot t JE, Va u gh n W H , e t a l. Th e e ffe ct of folic a cid s u p p le m e n t a t ion on t h e t oxicit y of low -
d os e m e t h ot re xa t e in p a t ie n t s w it h rh e u m a t oid a rt h rit is . A rthritis Rheum 1990 ;33 :9 .
6
5. Kre m e r JM , Ala rcon GS, Ligh t foot RW, Jr , e t a l. Me t h ot re xa t e for rh e u m a t oid a rt h rit is : Su gge s t e d gu id e -
D
i
lin e s fo r m on it orin g live r t oxicit y. A rthritis Rheum 1994 ;37 :316 .
a
g
6. Pa vy S , Con s t a n t in A, Ph a m T, e t a l. Me t h o t re xa t e t h e ra p y fo r rh e u m a t o id a rt h r it is : Clin ica l p ra ct ice
n
gu id e lin e s ba s e d on p u blis h e d evid e n ce a n d e xp e rt op in ion . Joint Bone Spine 2006 ;73 (4 ):388 –395 .
o
s
7. Ea s t e r b ro o k M . De t e ct io n a n d p reve n t ion o f m a cu lop a t h y a s s ocia t e d w it h a n t im a la r ia l a ge n t s . Int
i
s
Ophthalm ol Clin 1999 ;39 (2 ):49 –57 .
a
8. Blyt h C, La n e C. Hyd roxych loroq u in e re t in op a t h y: Is s cre e n in g n e ce s s a ry ? BMJ 1998 ;316 (7133 ):716 –717 .
n
d
9. Ta la r-Willia m s C, Hija zi YM , Wa lt h e r MM e t a l. Cyclo p h os p h a m id e -in d u ce d cys t it is a n d bla d d e r ca n ce r
T
in p a t ie n t s w it h Wege n e r’s gra n u lom a t os is . A nn Intern Med 1996 ;124 :477 .
h
10. McLe od HL, Lin JS, Scot t EP, e t a l. Th iop u rin e m e t h ylt ra n s fe ra s e a ct ivit y in Am e rica n w h it e s u bje ct s a n d
e
r
bla ck s u bje ct s . Clin Pharm acol Ther 1994 ;55 :15 .
a
p
11. Pa n ayi GS, Tu gw e ll P. Th e u s e of cyclos p orin A m icroe m u ls ion in rh e u m a t oid a rt h rit is . Con clu s ion s of
y
a n in t e rn a t ion a l review . Br J Rheum atol 1997 ;36 :808 .
12. Tu be rcu los is a s s ocia t e d w it h blockin g a ge n t s a ga in s t t u m or n e cros is fa ct or-a lp h a —Ca liforn ia , 2002–2003 .
MMW R Morb Mortal W kly Rep 2004 ;53 (30 ):683 .
Index
297
298 In d e x
s t u d ie s , 52 Ma le os t e op oros is , 215–216
t re a t m e n t , 52–53 Ma lign a n cie s w it h a rt h rop a t h ie s . See under
Kyp h op la s t y, 212 Art h rop a t h ie s
Ma rfa n s yn d rom e, 57
La ch m a n t e s t , 51 McMu rra y t e s t , 50, 50f
La rge -ve s s e l va s cu lit is . See under Va s cu lit is Me ch a n ic’s h a n d s , 120f, 123, 153
Le u n om id e, 107, 286–287 Me d ia l re t in a cu la r la xit y, 52
Legg-Ca lve -Pe rt h e s ’ d is e a s e, Me d iu m -ve s s e l va s cu lit is , 134
55, 56f Me n in git is t re a t m e n t , 255
Liga m e n t la xit y, 45 Me n is ca l t e a rs , 52
Lim it e d s cle rod e rm a , 113 ch ron ic, 49
Lin e a r e xt e n s or e ryt h e m a , 120f 6-m e rca p t op u rin e, 290
Lin e a r s cle rod e rm a , 113 Me t a ca rp a l p h a la n ge a l join t (MCP), 80, 277,
Live r fu n ct ion t e s t s , 286 277f
Lofgre n s yn d rom e, 6 Me t a ca rp op h a la n ge a l join t , 82, 82f
Low ba ck p a in Me t a t a rs a lgia , 39
clin ica l cou rs e, 27 Me t a t a rs a l s t re s s fra ct u re, 39, 40f
clin ica l p re s e n t a t ion , 23–25, 24f Me t a t a rs op h a la n ge a l join t , 277, 278f
e xa m in a t ion , 25 Me t h ot re xa t e, 90, 107, 284–285, 285t
s t u d ie s , 25–26 ora l, 130
t re a t m e n t , 26–27 Me t h yls u lfon ylm e t h a n e (MSM), 180
Lu m be r s t e n os is . See Low ba ck p a in Mid foot d is e a s e, 84
Lu p u s n e p h rit is , 104 Migra t ory a rt h rit is , 3
Lym e d is e a s e, 247–250, 247f, 248f, Milw a u ke e s h ou ld e r, 197f
249f, 250f Min ocyclin e, 287
clin ica l cou rs e, 256 Mixe d con n e ct ive t is s u e d is e a s e (MCTD),
coin fe ct ion , 252 154–155, 154t
e a rly d is s e m in a t e d d is e a s e, 250–251, 255–256 Mon oa rt icu la r in volve m e n t , 5
e a rly loca lize d d is e a s e, 250, 250f Mon os od iu m u ra t e (MSU), 183
la t e -s t a ge d is e a s e, 251, 256 Morn in g s t iffn e s s , 15, 95, 158
p h ys ica l e xa m in a t ion Mort on n e u rom a , 42
ca rd ia c s ym p t om s , 253 MRI. See Ma gn e t ic re s on a n ce im a gin g (MRI)
m u s cu los ke le t a l, 254 Mu cos a l u lce rs , 96
n e u rologic a bn orm a lit ie s , 253–254 Mu lt ice n t e r Art h ros copy of t h e Hip Ou t com e s
s kin , 252–253, 253f Re s e a rch Ne t w ork, 59
in p regn a n cy, 252 Mu lt ice n t ric re t icu loh is t iocyt os is (MR), 229, 229f
re in fe ct ion w it h B. burgdorferi, 252 Mu s cle d is ord e rs , 7–8, 8t
s t u d ie s , 254 Mu s cle in a m m a t ion , 153
t re a t m e n t , 255 Mu s cu los ke le t a l lu p u s , 104
Lym p h om a s , 294 Mycop h e n ola t e m ofe t il, 108, 291
Myop a t h y, 7
Ma gn e t ic re s on a n ce im a gin g (MRI), 12, 40, 52,
61, 62f, 67, 221f, 231, 233f Na il-fold m icros copy, 111, 111f
Ma gn e t ic re s on a n ce im a gin g a n giogra p h y Na rcot ic a n a lge s ics , 34
(MRA), 144 Na s a l u lce rs , 105
304 In d e x