Rheumatology 2002;41:713

Review

Treatment of dermatomyositis and polymyositis

E. H. S. Choy and D. A. Isenberg1
Academic Department of Rheumatology, Division of Medicine, Guys, Kings
and St Thomas Hospitals School of Medicine, Kings College London and
1
The Centre for Rheumatology, Bloomsbury Rheumatology Unit, Department of
Medicine, University College London, London, UK

Abstract
Since idiopathic inflammatory myositis is relatively uncommon, randomized placebo
controlled trials are rare. Although corticosteroids have not been tested in randomized controlled
trials, general clinical consensus among physicians has accepted it as effective therapy. However,
corticosteroid toxicity leads to significant disability in many patients. For patients with refractory
dermatomyositis, intravenous immunoglobulin is an effective short-term treatment but its
long-term effect remains unknown. Immunosuppressants are commonly used in refractory
inflammatory myositis; evidence for their efficacy, with very few exceptions, has been derived
from case reports and open studies with small numbers of patients. Even in randomized trials, the
lack of validated and generally accepted outcome measures makes it difficult to compare the
effect of interventions in different studies. Although the balance of evidence suggests that
immunosuppressants are equally effective in dermatomyositis and polymyositis, there are no
randomized controlled trials to show if any of these drugs, individually or in combination, is best.
For uncommon diseases, such as inflammatory myositis, only multicentre randomized controlled
trials involving rheumatologists and neurologists will define the optimal therapy.

Idiopathic inflammatory myositis is a group of acquired
conditions characterized by inflammation of skeletal
muscles. Bohan and Peter proposed that these condi-
tions be divided into primary idiopathic polymyositis,
primary idiopathic dermatomyositis, dermatomyositisu
polymyositis associated with neoplasia, childhood
dermatomyositisupolymyositis, dermatomyositisupoly-
myositis associated with vasculitis, and polymyositisu
dermatomyositis associated with collagen vascular dis-
ease w1, 2x. Dalakas w3x has more recently proposed that
inclusion body myositis be included in the classification
of inflammatory myopathy, and this is widely accepted,
as is the preferred use of the term autoimmune
rheumatic disease to replace collagen vascular disease.
Although the aetiologies of these six categories are
likely to differ, they share some common features,
notably striking proximal muscle weakness, histological
evidence of endomysial inflammation and activation
of the immune response. Current therapy for inflamma-
tory myositis is broadly similar but patients with
inclusion body myositis are more refractory to therapy.
Furthermore, the inclusion bodies themselves have been
Submitted 24 November 2000; revised version accepted 6 July 2001.
Correspondence to: E. H. S. Choy, Department of Rheumatology,
Kings College Hospital (Dulwich), East Dulwich Grove, London
SE22 8PT, UK.
shown to contain a variety of proteins, including
amyloid and tau, which suggests that this condition
may be more degenerative in nature. Recent reviews of
the treatment of inclusion body myositis have concluded
that corticosteroids give only a modest benefit and that
azathioprine and methotrexate have been shown to be
effective in only eight out of 35 trials w4, 5x. In this review
we will focus on the treatment of dermatomyositis and
polymyositis.
The estimated annual incidence rate of polymyositis
and dermatomyositis varies between 1.9 and 7.7 per
million w615x. In a 20-yr study of inflammatory myositis
in America from 1963 to 1982, the annual incidence
was 5.5 per million w6x. Interestingly, the incidence was
higher (10 per million) in the last decade. A similar study
in Israel showed an annual incidence of 2.2 per million
w7x. In this study, the annual incidence increased from
0.47 per million in the third decade to a peak of 6.32 per
million in the seventh. Disease was more common in
females in both studies, with a female:male ratio of 2 : 1.
However, most of these reports describe retrospective
hospital-based studies with limited searches in which the
true incidence of idiopathic inflammatory myositis
may have been underestimated. Furthermore, different
diagnostic criteria were employed in these studies, so
that comparing their results is problematic. Data on the
prevalence of polymyositis and dermatomyositis are

7 2002 British Society for Rheumatology

8 E. H. S. Choy and D. A. Isenberg
very limited. Estimates from the USA w14x and Japan
w16x range between 50 and 63 per million; however,
these were also retrospective studies and may have
underestimated the true disease prevalence.
The prognosis of dermatomyositis and polymyositis
was poor before the availability of corticosteroids.
In the first literature review in 1903, Steiner w17x
described 28 patients. While noting that patients could
recover from dermatomyositis, he also stressed the grav-
ity of the condition; 17 of these patients had died. The
beneficial effects of steroids have been re-emphasized
by a recent Italian study of 63 patients. The authors
reported that half of their patients were managed
with steroids alone w18x. After the introduction of
corticosteroids in the 1950s, 12 studies examined
the mortality of inflammatory myositis, which ranged
between 11 and 45% w13, 1929x. The variation in
mortality rate in these studies may have been due to the
use of different inclusion criteria, such as the inclusion
of patients with inflammatory myositis associated
with malignancies. Poor prognostic factors common to
many studies include old age, race, bulbar involvement,
delayed treatment and cardiovascular and pulmonary
involvement. Interestingly, the creatine phosphokinase
level, grade of disability and degree of muscle weakness
at presentation do not correlate with prognosis. In one
study in the UK carried out between the 1950s and
1970s, 33% of survivors had significant disability after
3 yr, and in half of these patients the disease remained
active w30x. In a further UK study in the 1980s, of
25 patients followed for up to 10 yr, approximately
one-third returned to normal function but one-third
died or were left severely incapacitated and the
remainder were left with significant weakness w31x.
A more recent national inception cohort study in
Canada examined 257 patients with polymyositis and
dermatomyositis. Disability, as measured by the health
assessment questionnaire, increased with disease dura-
tion and the side-effects of corticosteroids were major
contributors to disability w32x.
Treatment of dermatomyositis and
polymyositis
As dermatomyositis and polymyositis are uncommon,
there have been few randomized controlled trials, and
those that have been completed enrolled small numbers
of patients. Consequently, optimal therapy has not been
defined adequately.
Corticosteroids
Corticosteroids are the standard treatment for idio-
pathic inflammatory myositis, but their efficacy has not
been tested fully in randomized, placebo-controlled
trials w33x and is unlikely ever to be tested in this
way. There is a strong consensus among physicians
that corticosteroids improve disease significantly in
the majority of patients with inflammatory myositis
w30, 3437x. Different treatment regimens have been
advocated, but most suggest using oral high-dose
therapy with prednisolone 60 mguday initially. The
prednisolone dose should then be tapered to either
daily or alternate-day therapy w36x. One retrospective
review suggested that the prognosis of dermatomyositis
and polymyositis had been improved by high-dose
corticosteroid therapy w30x. There was considerable
improvement in average disability with time in the
high-dose corticosteroid therapy group. The maximum
improvement occurring within the first three years.
The degree of improvement in disability was consider-
ably less in those who were treated inadequately. In
contrast, another study has shown that the mortality
and morbidity associated with dermatomyositis and
polymyositis remained high despite treatment with
corticosteroids w20x.
The major drawbacks of long-term corticosteroid
treatment are its side-effects and, in some patients,
insufficient efficacy. Side-effects of corticosteroid
affected 32% w38x to 41% w28x of treated patients with
polymyositis and dermatomyositis. Furthermore, in
long-term studies, disability was associated with cortico-
steroid side-effects, especially osteonecrosis and osteo-
porotic vertebral fractures w32x. In an attempt to
reduce the side-effects of corticosteroids, Nzeusseu
et al. w39x studied the effect of a lower starting dose
than is recommended classically in 25 patients with
polymyositis and dermatomyositis. Fifteen patients were
treated with a high-dose regimen (>0.5 mg prednisoloneu
kguday) and 10 with a low-dose regimen ((0.5 mg
prednisoloneukguday). The functional outcome of the
low-dose regimen group did not differ from that of
patients given higher doses, although the sample size
of the study was small and the lack of a statistically
significant difference may have been the result of a
type II error. Interestingly, vertebral fractures were
less common in patients treated with lower doses of
corticosteroids. With the widespread availability of dual
X-ray absorptiometry and the introduction of effective
prophylactic bisphosphonate therapy, this is one thera-
peutic area in which genuine improvement in outcome
can be expected.
Pulsed intravenous methylprednisolone has also been
advocated for the treatment of refractory inflammatory
myositis w40, 41x without evidence from randomized
control trials. In an open study, the numbers of
macrophages, CD8+ T cells and B lymphocytes in the
inflammatory infiltrate of muscle biopsies decreased
after treatment w42x. There were also reductions in the
expression of intercellular adhesion molecules and
major histocompatibility complex antigens on endo-
thelial cells w42x. However, it is unclear whether these
histological changes correlated with the clinical
response.
Immunosuppressants
Immunosuppressive agents, especially methotrexate
and cyclosporin, are often used in refractory cases of
polymyositis and dermatomyositis, but, once again,
their use is based on clinical experience rather than
 Treatment of dermatomyositis and polymyositis
randomized controlled trials. Based on a literature
search using Medline, a range of immunosuppressants
has been used in polymyositis and dermatomyositis.
These include azathioprine w5, 34, 37, 43 46x, metho-
trexate w5, 43, 44, 4763x, cyclosporin A w3, 33, 35,
36, 6370x, cyclophosphamide w41, 44, 7178x and
chlorambucil w79x.
Azathioprine. Azathioprine is used commonly as a
steroid-sparing agent in chronic inflammatory diseases.
It has been recommended by some as the preferred
immunosuppressant in polymyositis and dermatomyo-
sitis w80x. Its efficacy in idiopathic inflammatory myosi-
tis is supported by a small number of reported cases
w34, 37, 44, 45x. Up to 75% of patients treated
with azathioprine showed a good response in retro-
spective reviews w5, 37, 44x. Disappointingly, a small
randomized placebo controlled trial of azathioprine
(2 mgukg per day) in 16 inflammatory myositis patients
showed no significant difference in muscle strength,
creatine phosphokinase or histopathological features
between the active and placebo groups w46x. However,
the sample size was small and a follow-up period of
3 months may be too short to detect a statistically
significant improvement in muscle function. In con-
trast, a subsequent open study of the same patients
and corticosteroid- and azathioprine-treated patients
had a better long-term outcome after 3 yr than cortico-
steroids alone w45x. A recent trial of azathioprine in
combination with methotrexate showed that combina-
tion therapy was not superior to intravenous metho-
trexate alone in refractory inflammatory myositis,
although there was a trend favouring the combination
therapy w43x. In a retrospective review of 113 consec-
utive patients treated at the National Institutes of
Health, the authors found that methotrexate therapy
may be superior to either azathioprine or further ster-
oid treatment alone in certain patients who do not
respond completely to an initial adequate course of
prednisolone w5x.
Methotrexate. The use of intravenous methotrexate
was first reported in refractory dermatomyositis in
1968 w63x. Subsequently, a few case reports and retro-
spective reviews have suggested that methotrexate is
effective in childhood and adult idiopathic inflammat-
ory myositis w5, 43, 44, 4762x. Oral low-dose metho-
trexate is the commonest second-line treatment for
rheumatoid arthritis. It suppresses inflammation and
improves function. Although it is associated with side-
effects that require regular monitoring by blood
tests, it has one of the best benefiturisk ratios among
second-line drugs in rheumatoid arthritis w81x. Bohan
et al. w29x treated 25 patients with steroid-resistant
inflammatory myositis with oral methotrexate; 88%
had significant disease improvement and 43% were
able to reduce their corticosteroid dose. Miller et al.
w52x reviewed the clinical course of 16 children with
recalcitrant dermatomyositis who were treated with
oral methotrexate in addition to corticosteroids.
Twelve patients who received methotrexate for at
least 8 months regained normal muscle strength.
9
Furthermore, the prednisolone dose in 11 patients
could be reduced to (5 mguday. Complications during
methotrexate treatment required discontinuation of
methotrexate in five patients, and were unrelated
to the cumulative dose of the drug. Active disease
recurred in five patients in whom methotrexate had
been discontinued after apparent clinical remission
had been achieved w52x. In dermatomyositis, two
reviews suggested that cutaneous disease responded
well to methotrexate, with improvement in all
patients, and allowed reduction in the corticosteroid
dose w48, 50x, although methotrexate-induced side-
effects were common w50x. A recent randomized
trial compared the efficacy and tolerability of cyclo-
sporin A with those of methotrexate in 36 patients
with active polymyositis and dermatomyositis w57x.
Clinical improvement and decreased creatine phos-
phokinase were seen in both groups. Patients treated
with methotrexate showed a better response than
patients who received cyclosporin A, although the
difference was not statistically significant.
Cyclosporin A. Cyclosporin A is a T-cell immuno-
suppressant that has been used extensively in the pre-
vention and treatment of transplant rejection. Bendtzen
et al. first reported the use of cyclosporin A in poly-
myositis w83x. Numerous case reports and small open
series have suggested that cyclosporin A, like metho-
trexate, may be efficacious in dermatomyositis and
polymyositis w3, 33, 35, 36, 6370, 8391x. In some
cases, cyclosporin A was effective in patients with
inflammatory myositis who had failed combination
therapy with corticosteroids and other immuno-
suppressants w65, 69x. The dose used was high and
ranged from 3 to 10 mgukguday. In three reviews of
paediatric patients with dermatomyositis and poly-
myositis, cyclosporin A increased muscle strength and
decreased muscle enzyme levels w63, 65, 67x.
Chlorambucil. Clinical experience with chlorambucil
in inflammatory myositis is extremely limited. One
study in five patients with dermatomyositis who had
failed azathioprine and methotrexate suggested that
chlorambucil at a dose of 4 mguday had some benefi-
cial effects w79x. Improvement occurred in all patients
and four patients achieved disease remission after
1330 months of therapy.
Cyclophosphamide. The role of cyclophosphamide
in inflammatory myositis is controversial. There are
reports of success w7275x and failure w71x in open stud-
ies. Cyclophosphamide is toxic and predisposes
patients to malignancies after long-term treatment. Its
use should be restricted to patients who are refractory
to corticosteroids and other immunosuppressants.
Combination therapy. In idiopathic inflammatory
myositis, there are a few reports of combination ther-
apy, such as azathioprine plus methotrexate w43x and
methotrexate plus cyclosporin A w92x. A recent ran-
domized cross-over trial compared the effect of weekly
oral methotrexate and daily azathioprine with that of
intravenous methotrexate with leucovorin rescue given
fortnightly w43x. Thirty patients, most of whom had an
10 E. H. S. Choy and D. A. Isenberg
inadequate response to immunosuppressants, were
studied. Of the 15 patients initially randomized to oral
methotrexate and azathioprine, 12 improved with oral
therapy and four improved with intravenous metho-
trexate. The difference between the two treatments was
not statistically significant. Although the study lacked
the power to compare the two treatments directly,
intention-to-treat analysis showed a trend in favour
of those patients who first received oral combination
therapy.
Cyclosporin A plus methotrexate also appears to be
beneficial in refractory juvenile dermatomyositis and
juvenile rheumatoid arthritis w63x. In five patients with
refractory juvenile dermatomyositis, muscle strength
increased and creatine phosphokinase levels decreased
with combination therapy. Furthermore, combination
treatment permitted the dose of prednisolone to be
reduced.
Immunoglobulin
Intravenous immunoglobulin is used for the treatment
of many autoimmune diseases, including autoimmune
thrombocytopenia and Kawasakis disease. Although its
mechanism of action remains unknown, its efficacy in
autoimmune diseases suggests it is immunomodulatory.
In a pilot study, Gelfand w93x suggested that it may be
used for the treatment of idiopathic inflammatory
myositis, and reported its efficacy. Patients with
dermatomyositis and polymyositis were treated with
1 gukguday of immunoglobulin for 2 days every
4 weeks. There was increased proximal muscle strength
and reduction in the creatine phosphokinase level.
Subsequently, two open studies in patients with refract-
ory dermatomyositis and polymyositis w94, 95x reported
improvement in cutaneous disease and muscle power.
In 1993, Dalakas et al. w96x reported the result of a
randomized, double-blind, placebo-controlled trial in
15 patients with refractory dermatomyositis. Patients
were randomly assigned to receive either 2 gukg of
immunoglobulin or placebo monthly for 3 months,
with the option of crossing over to the alternative
therapy for 3 more months. Muscle strength was
assessed with a modified Medical Research Council
score. Eight patients assigned to the immunoglobulin
group, but none of the patients in the placebo group,
showed a statistically significant improvement in
muscle strength score. After the cross-over phase,
12 patients in total received immunoglobulin and nine
showed a major improvement. Mean muscle strength
score increased from 74.5 to 84.7, which was statistically
significant. In the placebo-treated group, only three
patients had improvement. Muscle biopsies in the
immunoglobulin-treated patients also showed improve-
ment and there was an increase in muscle fibre diameter,
a decrease in the diameter of capillaries and reduced
complement deposits, especially C3b and the membrane
attack complex on capillaries w96, 97x. Sera from
immunoglobulin-treated patients also inhibited C3
uptake ex vivo w97x, suggesting that immunoglobulin
may act by inhibiting complement activation. Other
open studies of immunoglobulin in inflammatory
myositis, especially dermatomyositis, reported similar
efficacy w66, 98100x. All these studies, except one in
which two patients with juvenile dermatomyositis
were treated for more than 12 months, only assessed
short-term clinical efficacy. More long-term data are
needed to assess the long-term safety and efficacy of
intravenous immunoglobulin in idiopathic inflammatory
myositis.
Plasmapheresis
Plasmapheresis is used in the treatment of refractory
autoimmune diseases to remove circulating autoanti-
bodies and immune complexes. Since idiopathic inflam-
matory myositis is associated with the production
of autoantibodies, plasmapheresis has been tried in
refractory cases. In open studies w101, 102x, the results
appeared promising. Thirty-five patients with inad-
equate clinical responses to corticosteroids anduor
immunosuppressants were treated with plasmapheresis,
chlorambucil and cyclophosphamide w101x. Muscle
strength improved in 32 patients during therapy
and some patients experienced improvement that
approached remission. However, the results of a
subsequent randomized, double-blind controlled trial
in 39 patients with polymyositis or dermatomyositis
were disappointing w103x. Patients were randomized
to receive plasma exchange, leukapheresis or sham
apheresis. Twelve treatments were given over a
1-month period. In each treatment group, three
patients improved, with increased muscle strength
and functional capacity. There was no statistically
significant difference in the clinical response among
the three treatment groups. Given the lack of efficacy,
the cost and the potential for complications, there is
little justification for using plasma exchange in patients
with myositis, with the possible exception of those
patients who have an accompanying monoclonal
gammopathy w104x.
Other therapies
Whole-body irradiation, usually in fractionated doses,
over approximately 1 month has been reported to be
beneficial in a small number of patients with drug-
resistant myositis w105107x. In addition, total lymphoid
irradiation with around 200 rads, delivered over a
period of 56 weeks, has been reported to be beneficial
in some patients with myositis w109x. No double-blind
control trials using sham irradiation have been reported.
Adverse events are common with lymphoid irradiation,
and a long-standing concern about the development of
malignancy remains.
There are also case reports describing thymectomy
and extracorporeal photochemotherapy for refractory
myositis and dermatomyositis, but the number of cases
is small and the efficacies of the treatments remain
uncertain.
In this review, we have focused on the drug treatment
of myositis. However, it is important to recognize
that drug therapy is only one aspect of the management
 Treatment of dermatomyositis and polymyositis
of patients with these diseases. Other aspects of
management, including the use of sun-blocking agents
for the skin in patients with dermatomyositis, the
appropriate use of physiotherapy, occupational therapy
and occasionally surgery, are described elsewhere
w109, 110x.
References
1. Bohan A, Peter JB. Polymyositis and dermatomyositis
(first of two parts). wReviewx. N Engl J Med 1975;292:3447.
2. Bohan A, Peter JB. Polymyositis and dermatomyositis
(second of two parts). wReviewx. N Engl J Med 1975;
292:4037.
3. Dalakas MC. Clinical, immunopathologic and therapeutic
considerations of inflammatory myopathies. wReviewx. Clin
Neuropharmacol 1992;15:32751.
4. Leff RL, Miller FW, Hicks J, Fraser DD, Plotz PH. The
treatment of inclusion body myositis: a retrospective review
and a randomized, prospective trial of immunosuppressive
therapy. Medicine 1993;72:22535.
5. Joffe MM, Love LA, Leff RL et al. Drug therapy of
the idiopathic inflammatory myopathies: predictors of
response to prednisone, azathioprine and methotrexate
and a comparison of their efficacy. Am J Med
1993;94:37987.
6. Oddis CV, Conte CG, Steen VD, Medsger TA Jr. Incidence
of polymyositisdermatomyositis: a 20-year study of
hospital diagnosed cases in Allegheny County, PA
19631982. J Rheumatol 1990;17:132934.
7. Benbassat J, Geffel D, Zlotnick A. Epidemiology of
polymyositisdermatomyositis in Israel, 196076. Israel J
Med Sci 1980;16:197200.
8. Weitoft T. Occurrence of polymyositis in the
county of Gavleborg, Sweden. Scand J Rheumatol
1997;26:1046.
9. Symmons DP, Sills JA, Davis SM. The incidence of juvenile
dermatomyositis: results from a nation-wide study. Br J
Rheumatol 1995;34:7326.
10. Findlay GH, Whiting DA, Simson IW. Dermatomyositis
in the Transvaal and its occurrence in the Bantu. S Afr
Med J 1969;43:694 7.
11. Medsger TA Jr, Dawson WN Jr, Masi AT. The
epidemiology of polymyositis. Am J Med 1970;48:71523.
12. Hanissian AS, Masi AT, Pitner SE, Cape CC, Medsger TA
Jr. Polymyositis and dermatomyositis in children: an
epidemiologic and clinical comparative analysis. J
Rheumatol 1982;9:3904.
13. Rose AL, Walton JN. Polymyositis: a survey of 89 cases
with particular reference to treatment and prognosis. Brain
1966;89:74768.
14. Kurland LT, Hauser WA, Ferguson RH, Holley KE.
Epidemiologic features of diffuse connective tissue dis-
orders in Rochester, Minn., 1951 through 1967, with
special reference to systemic lupus erythematosus.
Mayo Clin Proc 1969;44:64963.
15. Koh ET, Seow A, Ong B, Ratnagopal P, Tija H,
Chang HH. Adult onset polymyositisudermatomyositis:
clinical and laboratory features and treatment response in
75 patients. Ann Rheum Dis 1993;52:85761.
16. Araki S, Uchino M, Kumamoto T. Prevalence studies of
multiple sclerosis, myasthenia gravis and myopathies in
Kumamoto district, Japan. Neuroepidemiology 1987;
6:1209.
11
17. Steiner WR. Dermatomyositis with a report of case which
presented a rare muscle anomaly but once described in
man. J Exp Med 1903;6:40742.
18. Mosea M, Neri R, Pasero G, Bombardieri S. Treatment of
idiopathic inflammatory myopathies in a retrospective
analysis if 63 Caucasian patients longitudinally followed at
a single centre. Clin Exp Rheumatol 2000;18:4516.
19. Riddoch D, Morgan-Hughes JA. Prognosis in adult
polymyositis. J Neurol Sci 1975;26:7180.
20. Carpenter JR, Bunch TW, Engel AG, OBrien PC.
Survival in polymyositis: corticosteroids and risk factors.
J Rheumatol 1977;4:20714.
21. Hochberg MC, Lopez-Acuna D, Gittelsohn AM.
Mortality from polymyositis and dermatomyositis in
the United States, 19681978. Arthritis Rheum 1983;
26:146571.
22. Lilley H, Dennett X, Byrne E. Biopsy proven polymyositis
in Victoria 19821987: analysis of prognostic factors. J R
Soc Med 1994;87:3236.
23. Maugars YM, Berthelot JM, Abbas AA, Mussini JM,
Nguyen JM, Prost AM. Long-term prognosis of 69
patients with dermatomyositis or polymyositis. Clin Exp
Rheumatol 1996;14:26374.
24. Winkelmann RK, Mulder DW, Lambert EH,
Howard FM Jr, Diessner GR. Course of
dermatomyositispolymyositis: comparison of untreated
and cortisone-treated patients. Mayo Clin Proc 1968;
43:54556.
25. Medsger TA Jr, Robinson H, Masi AT. Factors affecting
survivorship in polymyositis. A life-table study of 124
patients. Arthritis Rheum 1971;14:24958.
26. Benbassat J, Gefel D, Larholt K, Sukenik S,
Morgenstern V, Zlotnick A. Prognostic factors in poly-
myositisudermatomyositis. A computer-assisted analysis of
ninety-two cases. Arthritis Rheum 1985;28:24955.
27. Henriksson KG, Sandstedt P. Polymyositistreatment
and prognosis. A study of 107 patients. Acta Neurol Scand
1982;65:280300.
28. Tymms KE, Webb J. Dermatopolymyositis and other
connective tissue diseases: a review of 105 cases.
J Rheumatol 1985;12:11408.
29. Bohan A, Peter JB, Bowman RL, Pearson CM. Computer-
assisted analysis of 153 patients with polymyositis and
dermatomyositis. Medicine 1977;56:25586.
30. DeVere R, Bradley WG. Polymyositis: its presentation,
morbidity and mortality. Brain 1975;98:63766.
31. Ehrenstein MR, Snaith MI, Isenberg DA. Idiopathic
myositisa rheumatological review. Ann Rheum Dis
1992;51:414.
32. Clarke AE, Bloch DA, Medsger TA Jr, Oddis CV.
A longitudinal study of functional disability in a national
cohort of patients with polymyositisudermatomyositis.
Arthritis Rheum 1995;38:121824.
33. Dalakas MC. Current treatment of the inflammatory
myopathies. wReviewx. Curr Opin Rheumatol 1994;
6:595601.
34. Ansell BM. Management of polymyositis and dermato-
myositis. Clin Rheum Dis 1984;10:20513.
35. Mastaglia FL, Phillips BA, Zilko P. Treatment of
inflammatory myopathies. wReviewx. Muscle Nerve
1997;20:65164.
36. Oddis CV. Therapy for myositis. Curr Opin Rheumatol
1993;5:7428.
37. Ng YT, Ouvrier RA, Wu T. Drug therapy in juvenile
dermatomyositis: follow-up study. J Child Neurol
1998;13:10912.
12 E. H. S. Choy and D. A. Isenberg
38. Baron M, Small P. Polymyositisudermatomyositis: clinical
features and outcome in 22 patients. J Rheumatol
1985;12:2836.
39. Nzeusseu A, Brion F, Lefebvre C, Knoops P,
Devogelaer JP, Houssiau FA. Functional outcome of
myositis patients: can a low-dose glucocorticoid regimen
achieve good functional results? Clin Exp Rheumatol
1999;17:4416.
40. Villalba L, Adams EM. Update on therapy for refract-
ory dermatomyositis and polymyositis. Curr Opin
Rheumatol 1996;8:54451.
41. Hirano F, Tanaka H, Nomura Y et al. Successful
treatment of refractory polymyositis with pulse intra-
venous cyclophosphamide and low-dose weekly oral
methotrexate therapy. Intern Med 1993;32:74952.
42. Matsubara S, Hirai S, Sawa Y. Pulsed intravenous
methylprednisolone therapy for inflammatory myopathies:
evaluation of the effect by comparing two consecutive
biopsies from the same muscle. J Neuroimmunol 1997;
76:7580.
43. Villalba L, Hicks JE, Adams EM et al. Treatment of
refractory myositis: a randomized crossover study of two
new cytotoxic regimens. Arthritis Rheum 1998;41:3929.
44. Ramirez G, Asherson RA, Khamashta MA, Cervera R,
DCruz D, Hughes GR. Adult-onset polymyositis
dermatomyositis: description of 25 patients with
emphasis on treatment. Semin Arthritis Rheum
1990;20:114 20.
45. Bunch TW. Prednisone and azathioprine for polymyositis:
long-term followup. Arthritis Rheum 1981;24:458.
46. Bunch TW, Worthington JW, Combs JJ, Ilstrup DM,
Engel AG. Azathioprine with prednisone for polymyositis.
A controlled, clinical trial. Ann Intern Med 1980;92:3659.
47. Zieglschmid-Adams ME, Pandya A, Cohen SB,
Sontheimer RD. The value of methotrexate in dermato-
myositis. J Am Acad Dermatol 1998;38:1302.
48. Kasteler JS, Callen JP. Low-dose methotrexate adminis-
tered weekly is an effective corticosteroid-sparing agent
for the treatment of the cutaneous manifestations of
dermatomyositis wsee commentsx. J Am Acad Dermatol
1997;36:6771.
49. Blanche P, Dreyfus F, Sicard D. Polymyositis and chronic
graft-versus-host disease: efficacy of intravenous gamma-
globulin and methotrexate. Clin Exp Rheumatol
1995;13:3779.
50. Zieglschmid-Adams ME, Pandya AG, Cohen SB,
Sontheimer RD. Treatment of dermatomyositis with
methotrexate. J Am Acad Dermatol 1995;32:754 7.
51. Blanche P, Sicard D. Methotrexate for polymyositis
associated with primary biliary cirrhosis. Clin Exp
Rheumatol 1999;12:694.
52. Miller LC, Sisson BA, Tucker LB, DeNardo BA,
Schaller JG. Methotrexate treatment of recalcitrant child-
hood dermatomyositis. Arthritis Rheum 1992;35:11439.
53. Samuels AJ, Berney SN, Tourtellotte CD, Artymyshyn R.
Coexistence of adult onset Stills disease and polymyositis
with rhabdomyolysis successfully treated with metho-
trexate and corticosteroids. wReviewx. J Rheumatol 1989;
16:685 7.
54. Fischer TJ, Rachelefsky GS, Klein RB, Paulus HE,
Stiehm ER. Childhood dermatomyositis and polymyositis.
Treatment with methotrexate and prednisone. Am J Dis
Child 1979;133:386 9.
55. Sarova-Pinhas I, Siegal T, Turgman J, Braham J.
Methotrexate treatment in dermatomyositis. Eur Neurol
1977;16:14954.
56. Mitsunaka H, Tokuda M, Hiraishi T, Dobashi H,
Takahara J. Combined use of cyclosporine A and
methotrexate in refractory polymyositis. Scand J
Rheumatol 2000;29:192 4.
57. Vencovsky J, Jarosova K, Machacek S et al. Cyclosporine
A versus methotrexate in the treatment of poly-
myositis and dermatomyositis. Scand J Rheumatol
2000;29:95102.
58. Sokoloff MC, Goldberg LS, Pearson CM. Treatment of
corticosteroid-resistant polymyositis with methotrexate.
Lancet 1971;1:146.
59. Arnett FC, Whelton JC, Zizic TM, Stevens MB.
Methotrexate therapy in polymyositis. Ann Rheum Dis
1973;32:53646.
60. Metzger AL, Bohan A, Goldberg LS, Bluestone R,
Pearson CM. Polymyositis and dermatomyositis: com-
bined methotrexate and corticosteroid therapy. Ann Intern
Med 1974;81:1829.
61. Giannini M, Callen JP. Treatment of dermatomyositis
with methotrexate and prednisone. Arch Dermatol
1979;115:12512.
62. Malaviya AN, Many A, Schwartz RS. Treatment of
dermatomyositis with methotrexate. Lancet 1968;2:4858.
63. Reiff A, Rawlings DJ, Shaham B et al. Preliminary
evidence for cyclosporin A as an alternative in the treat-
ment of recalcitrant juvenile rheumatoid arthritis and
juvenile dermatomyositis. J Rheumatol 1997;24:2436 43.
64. Maeda K, Kimura R, Komuta K, Igarashi T.
Cyclosporine treatment for polymyositisudermato-
myositis: is it possible to rescue the deteriorating cases
with interstitial pneumonitis? Scand J Rheumatol 1997;
26:24 9.
65. Zeller V, Cohen P, Prieur AM, Guillevin L. Cyclosporin A
therapy in refractory juvenile dermatomyositis. Experience
and longterm followup of 6 cases. J Rheumatol
1996;23:1424 7.
66. Saadeh C, Bridges W, Burwick F. Dermatomyositis:
remission induced with combined oral cyclosporine and
high-dose intravenous immune globulin. South Med J
1995;88:86670.
67. Pistoia V, Buoncompagni A, Scribanis R et al.
Cyclosporin A in the treatment of juvenile chronic arthritis
and childhood polymyositisdermatomyositis. Results of a
preliminary study wsee commentsx. Clin Exp Rheumatol
1993;11:203 8.
68. Tindall RS. Immunointervention with cyclosporin A
in autoimmune neurological disorders wReviewx. J
Autoimmun 1992;5(Suppl. A):30113.
69. Lueck CJ, Trend P, Swash M. Cyclosporin in the
management of polymyositis and dermatomyositis. J
Neurol Neurosurg Psychiatry 1991;54:10078.
70. Casato M, Bonomo L, Caccavo D, Giorgi A. Clinical
effects of cyclosporin in dermatomyositis. Clin Exp
Dermatol 1990;15:1213.
71. Cronin ME, Miller FW, Hicks JE, Dalakas MC, Plotz PH.
The failure of intravenous cyclophosphamide therapy in
refractory idiopathic inflammatory myopathy. J
Rheumatol 1989;16:12258.
72. De Vita S, Fossaluzza V. Treatment of idiopathic
inflammatory myopathies with cyclophosphamide pulses:
clinical experience and a review of the literature. wReviewx.
Acta Neurol Belg 1992;92:21527.
73. Chwalinska-Sadowska H, Maldykowa H. Polymyositis
dermatomyositis: 25 years of follow-up of 50 patients
disease course, treatment, prognostic factors. wReviewx.
Mater Med Pol 1990;22:2138.
 Treatment of dermatomyositis and polymyositis
74. Kono DH, Klashman DJ, Gilbert RC. Successful IV
pulse cyclophosphamide in refractory PM in 3 patients
with SLE wletterx. J Rheumatol 1990;17:9823.
75. Al-Janadi M, Smith CD, Karsh J. Cyclophosphamide
treatment of interstitial pulmonary fibrosis in
polymyositisudermatomyositis wsee commentsx. J trial of high-dose intravenous immune globulin infusions
Rheumatol 1989;16:15926.
76. Bombardieri S, Hughes GR, Neri R, Del Bravo P,
Del Bono L. Cyclophosphamide in severe polymyositis
wletterx. Lancet 1989;1:11389.
77. Fries JF, Sharp GC, McDevitt HO, Holman HR.
Cyclophosphamide therapy in systemic lupus erythema-
tosus and polymyositis. Arthritis Rheum 1973;16:15462.
78. Yoshioka M, Okuno T, Mikawa H. Prognosis and
treatment of polymyositis with particular reference to
steroid resistant patients. Arch Dis Child 1985;60:23644.
79. Sinoway PA, Callen JP. Chlorambucil. An effective
corticosteroid-sparing agent for patients with recalcitrant
dermatomyositis wsee commentsx. Arthritis Rheum
1993;36:31924.
80. Dalakas M. Treatment of polymyositis and dermato-
myositis. wReviewx. Curr Opin Rheumatol 1989;1:4439.
81. Felson DT, Anderson JJ, Meenan RF. The comparative
efficacy and toxicity of second-line drugs in rheumatoid
arthritis. Results of two metaanalyses wsee commentsx.
Arthritis Rheum 1990;33:144961.
82. Bendtzen K, Tvede N, Andersen V, Bendixen G. Cyclo-
sporin for polymyositis wletterx. Lancet 1984;1:7923.
83. Keen RW, Gumpel JM. Cyclosporin A in adult
dermatomyositis wletterx. Br J Rheumatol 1993;32:439.
84. Pugh MT, Collins NA, Rai A, Hollinrake K, Coppock JS.
A case of adult dermatomyositis treated with cyclosporin
A wletterx. Br J Rheumatol 1992;31:855.
85. Stedeford J, Wordsworth BP. Cyclosporin A treatment
of dermatomyositis wletterx. Arthritis Rheum 1991;34:933.
86. Kavanagh GM, Ross JS, Black MM. Dermatomyositis
treated with cyclosporin. J R Soc Med 1991;84:306.
87. Alijotas J, Barquinero J, Ordi J, Vilardell M. Poly-
myositis and cyclosporin A wletterx. Ann Rheum Dis
1990;49:66.
88. Levi S, Hodgson HJ. Cyclosporin for dermatomyositis
wletterx. Ann Rheum Dis 1989;48:856.
89. Ejstrup L. Severe dermatomyositis treated with cyclos-
porin A wletterx. Ann Rheum Dis 1986;45:6123.
90. van der Meer S, Imhof JW, Borleffs JC. Cyclosporin for
polymyositis wletterx. Ann Rheum Dis 1986;45:612.
91. Zabel P, Leimenstoll G, Gross WL. Cyclosporin for acute
dermatomyositis wletterx. Lancet 1984;1:343.
92. Wallace DJ, Metzger AL, White KK. Combination
immunosuppressive treatment of steroid-resistant derma-
tomyositisupolymyositis. Arthritis Rheum 1985;28:5902.
93. Gelfand EW. The use of intravenous immune globulin
in collagen vascular disorders: a potentially new modality
of therapy. J Allergy Clin Immunol 1989;84:6135;
discussion 6156.
94. Cherin P, Herson S, Wechsler B et al. Efficacy
of intravenous gammaglobulin therapy in chronic refrac-
tory polymyositis and dermatomyositis: an open study
with 20 adult patients wsee commentsx. Am J Med
1991;91:1628.
13
95. Lang BA, Laxer RM, Murphy G, Silverman ED,
Roifman CM. Treatment of dermatomyositis with
intravenous gammaglobulin wsee commentsx. Am J Med
1991;91:16972.
96. Dalakas MC, Illa I, Dambrosia JM et al. A controlled
as treatment for dermatomyositis wsee commentsx. N Engl
J Med 1993;329:19932000.
97. Basta M, Dalakas MC. High-dose intravenous immuno-
globulin exerts its beneficial effect in patients with
dermatomyositis by blocking endomysial deposition of
activated complement fragments. J Clin Invest
1994;94:172935.
98. Cherin P, Piette JC, Wechsler B et al. Intravenous gamma
globulin as first line therapy in polymyositis and
dermatomyositis: an open study in 11 adult patients wsee
commentsx. J Rheumatol 1994;21:10927.
99. Sansome A, Dubowitz V. Intravenous immunoglobulin
in juvenile dermatomyositisfour year review of nine
cases. Arch Dis Child 1995;72:258.
100. Vedanarayanan V, Subramony SH, Ray LI, Evans OB.
Treatment of childhood dermatomyositis with high
dose intravenous immunoglobulin. Pediatr Neurol
1995;13:3369.
101. Dau PC. Plasmapheresis in idiopathic inflammatory
myopathy. Experience with 35 patients. Arch Neurol
1981;38:54452.
102. Clarke CR, Dyall-Smith DJ, Mackay IR, Emery P,
Jennens ID, Becker G. Plasma exchange in dermato-
myositisupolymyositis: beneficial effects in three cases. J
Clin Lab Immunol 1988;27:14952.
103. Miller FW, Leitman SF, Cronin ME, Hicks JE, Leff RL,
Wesley R. Controlled trial of plasma exchange and
leukapheresis in polymyositis and dermatomyositis. N
Engl J Med 1992;326:13804.
104. Alexanderson H, Stenstrom CH, Jenner G, Lundberg I.
The safety of a resistive home exercise program in
patients with recent onset active polymyositis or
dermatomyositis. Scand J Rheumatol 2000;29:295301.
105. Engel WK, Lighter AS, Galdi AP. Polymyositis,
remarkable response to total body irradiation. Lancet
1981;1:658.
106. Kelly JJ, Madoc-Jones H, Adelman LS, Andres PL,
Munsatz TL. Response to total body irradiation
dermatomyositis. Muscle Nerve 1988;11:1203.
107. Morgan SH, Bernstein RM, Coppen J, Halnan KE,
Hughes GR. Total body irradiation and the cause of
polymyositis. Arthritis Rheum 1985;28:8315.
108. Rosenberg NL, Ringel SP. Adult polymyositis and
dermatomyositis. In: Mastaglia FL, ed. Inflammatory
diseases in muscles. Oxford: Blackwell Scientific
Publications, 1988:87106.
109. Wiesinger GF, Quittan M, Aringer M et al. Improve-
ment of physical fitness and muscle strength in poly-
myositisudermatomyositis patients by a training
programme. Br J Rheumatol 1998;37:196200.
110. Targoff IN. Polymyositis and dermatomyositis. In:
Maddison P, Isenberg DA, Woo P, Glass DN, eds.
Oxford textbook of rheumatology, 2nd edn. Oxford:
Oxford University Press, 1998:124986.