Ankylosing Spondylitis and Reactive
Arthritis
(Harrison’s pp: 1993-1998)
Ankylosing Spondylitis (Marie-Strϋmpell disease
or Bechterew’s disease)
• Inflammatory disorder primarily affecting
the axial skeleton
• May also affect peripheral joints and
extra-articular structures
• Onset: 20-30 y/o
• M(3)=F(1)
Epidemiology
• High incidence with HLA-B27
• 33% of AS pxs have the gene B27
• 65% concordance rate in monozygotic
twins
• High correlation with inflammatory bowel
disease, ulcerative colitis, and Crohn’s
disease
Pathology
• Entheses of the pelvis and spine: main
pathology of AS
o Enthesitis: prominent edema of
adjacent bone marrow with
erosions lesions that undergo
ossification
o Sacroiliitis
o Subchondral granulation tissue
o Infiltrates of lymphocytes and
macrophages in periosteal and
ligamentous zones
o Subchondral marrow edema
o Synovitis  pannus formation
o Erosion of iliac cartilage
followed by the sacral cartilage
o Erosion  sclerosis  fibrosis
 ossicfication  joint
obliteration
o Syndesmophytes: grow by
endochondral ossification
leading to “bridging” of
adjacent vertebrae (ankylosis)
o “Bamboo Spine”
o Diffuse osteoporosis
o “Squaring” of the vertebrae
• Peripheral arthritis
o Synovial proliferation
o Lymphoid infiltration
o Pannus formation
o Central cartilaginous erosions
and subchondral granulation
tissue (rare in RA)
• Extra-articular manifestations
o Acute anterior uveitis (20%)
o Aortic insufficiency
o Microscopic inflammatory
lesions in the colon and
ileocecal valve
Pathogenesis
• Immune-mediated
o Elevated IgA levels, acute
phase reactants
o Inflammatory histology
o HLA-B27
o CD4+, CD8+ T-cells and
macrophages
o TNF-α
o Autoimmunity to: proteoglycan
aggrecan (G1 globulin domain)
Clinical Manifestations
• Initial sxs manifest during adolescence
or early adulthood
• Mean age: 23
• Dull, deep pain in the lumbar or gluteal
region with nocturnal exacerbations
• Low-back morning stiffness
• Bony tenderness: costosternal junctions,
spinous processes, iliac crests, greater
trochanters, ischial tuberosities, tibial
tubercles, and heels
• Hip and shoulder arthritis
• Asymmetric peripheral arthritis
• Neck pain and stiffness (late)
• Older patients: fatigue, anorexia, fever,
weight loss, or night sweats
• Extra-articular manifestations: uveitis, AI
• Limitation of anterior-lateral flexion and
extension of lumbar spine and chest
expansion
• Muscle spasm and pain
• Schober Test: measures flexion of
lumbar spine (Normal mobility: >/=5cm)
• Chest expansion (4th ICS): Normal >/=
5cm
• Severe untreated cases: obliterated
lumbar lordosis, atrophy of buttocks,
accentuated thoracic kyphosis, stooped
neck, flexion contractures of the hip
• Most serious complication of spine
disease: fracture, most commonly the
cervical spine
Laboratory findings:
• No specific lab finding for AS
• Presence of HLA-B27 gene
• Elevated ESR and CRP
• Mild normo-normo anemia
• RF and ANA negative
Radiographic findings
 • Sacroiliitis: blurring of the cortical
margins of the subchondral bone 
erosions and sclerosis
• “Pseudowidening” of joint space
• Joint obliteration due to fibrosis and
ankylosis
• Changes usually symmetric
• Straightening of lumbar spine
• MRI: can detect early intra-articular
changes; POC for dx of sacroiliitis
• Dual energy x-ray bone absorptiometry
of L3 vertebra: reduced mineral bone
density
Diagnosis
• Modified New York Criteria
1. Hx of inflammatory back pain
2. Limitation of motion of lumbar spine
on both sagittal and frontal planes
3. Limited chest expansion
4. Definite radiographic dx of
sacroiliitis
**criteria #4 + any of the three
• The presence of B27 is neither
necessary nor sufficient for the dx but it
is helpful
• Low Back Pain in AS
1. age of onset <40
2. insidious
3. duration >3mos. before consult
4. morning stiffness
5. improved with exercise and activity
• DISH (diffuse idiopathic skeletal
hyperostosis)
o Diarthrodal joints are not
involved
o “Flowing wax”- ligamentous
calcification and ossification
o Vs. spondylosis marginal
osteophytes, there is a
radiolucency between newly
deposited bone and vertebral
body in DISH
o Normal sacroiliac joint
Treatment
• No definitive tx
• Exercise programs
• NSAIDs
• Phenylbutazone (side effects: aplastic
anemia and agranulocytosis)
• Hip joint replacement in some
• Iritis: local glucocorticoid administration
with mydriatic agent
Reactive Arthritis (ReA)
• Acute, nonpurulent arthritis occurs after
infection (i.e. enteric or urogenital
infections)
• HLA-B27
• Reiter’s Syndrome: arthritis, urethritis,
and conjunctivitis; often with
mucocutaneous lesions
• Enteric organisms: Shigella,
Salmonella, Yersinia, and
Campylobacter
• Genital organisms: Chlamydia
Epidemiology
• 60-80% of patients with ReA are HLA-
B27 positive
• Age of onset: 18-40
• Enteric ReA: M=F
• Venereal ReA: M>F
Pathology
• Synovial histology similar to that of
inflammatory arthropathies
• Enthesistis similar to AS
• Keratoderma blenorrhagica in venereal
ReA indistinguishable from psoriatic
lesions
Etiology and Pathogenesis
• Shigella flexneri – 1st to be associated
with ReA
• LPS- attack mucosal surfaces
• Yersinia ReA- LPS and heat shock
proteins
• Chlamydia ReA- DNA and RNA in
synovium  organism present
• CD4+ T-cells (TH1 & TH2): seen in
synovium but not in peripheral blood in
ReA
• CD8+ cytolytic cells: Yersinia and
Chlamydia ReA
Clinical Manifestations
• Appear 1-4 weeks after infection, except
in the venereal type where infection may
not have been obvious
• Fatigue, malaise, fever, weight loss
• Arthritis is usually asymmetric and
additive
• Knee, ankle, subtalar, and toe
interphalangeal joints
• Dactylitis or sausage-finger
• Tenidinitis and fasciitis
• Urethritis or prostatitis in males
• Cervicitis, salphingitis in females
• Ocular symptoms
 • Keratoderma blehnorrhagica:
hyperkeratotic vesicles in the palms and
soles
• Circinate balanitis: lesions of the glans
penis
• Onycholysis or hyperkeratosis
• Rare: cardiac, neuro, pulmo
abnormalities

Laboratory and Radiographic Findings

• Elevated ESR and acute phase
reactants
• Mild anemia
• Synovial fluid: inc. WBC with inc.
neutrophils
• Juxtaarticular osteoporosis
• Marginal erosions with loss of joint
space
• Periostitis with reactive bone formation
• Spurs at plantar fascia insertion
• If sacroiliitis is present, it is usually
asymmetric

Diagnosis
• Suspect in patients presenting with
additive arthritis following an infection
• Differentiate venereal ReA from
gonococcal arthritis and tenosynovitis
where there is equal involvement of UE
and LE (in ReA LE sxs predominate)
• Psoriatic arthritis is usually slowly
progressive vs. ReA

Treatment
• NSAIDs
• Indomethacin: initial DOC
• Sulfasalazine
• In Chlamydia ReA, consider antibiotic
therapy