Dermatomyositis: A dermatology-based case series

CLINICAL AND LABORATORY STUDIES Dermatomyositis: A dermatology-based case series Mark A. Dawkins, MD,a Joseph L. Jorizzo, MD,a Francis O. Walker, MD,b David Albertson, MD,c Sara H. Sinal, MD,d and Ann Hinds, MS, PA-Ca Winston-Salem, North Carolina Background: Dermatomyositis is associated with significant morbidity and occasional mortality. Currently there is no consensus on treatment for patients with dermatomyositis. Objective: Our purpose was to review the clinical features and response to therapy of patients with dermatomyositis and compare these data with previous series of patients with dermatomyositis/polymyositis. Methods: Clinical characteristics of 65 patients seen during a 10-year period were reviewed retrospectively. Twenty-one of these patients were enrolled in a prospective, uncontrolled study of treatment with high-dose prednisone followed by slow tapering. Results: Clinical features were similar to those previously described; however, muscle strength at diagnosis was on average greater in patients in this series than in patients previously reported. Malignancy was present in 5 of 43 adult patients (12%), but was not found in patients with juvenile dermatomyositis. Another connective tissue disease was present in 19% of patients. Twelve patients had dermatomyositis sine myositis. Eighteen of 21 patients (85%) in the prednisone study group had resolution of myositis. Conclusion: Patients with dermatomyositis in this series had less active myositis at presentation, but were otherwise similar to patients with dermatomyositis/polymyositis previously reported. Treatment with high-dose daily prednisone followed by slow tapering was effective. (J Am Acad Dermatol 1998;38:397-404.)

Dermatomyositis is an inflammatory myopathy associated with a distinctive cutaneous eruption. The muscle inflammation presents as proximal muscle weakness and an associated elevation of muscle-derived enzymes, especially creatinine phosphokinase (CPK) and aldolase. The cutaneous findings include a periorbital heliotrope eruption and poikilodermatous plaques on extensor surfaces (Gottron’s sign). Dermatomyositis occurs in a biphasic age distribution with an initial peak in children and a second larger peak in middle-aged adults.1,2 The cause of dermatomyositis is unknown, but pathogenic mechanisms are thought to involve immunologically mediated muscle and skin damage.3-5 Dermatomyositis may occur in an From the Departments of Dermatology,a Radiology,b Surgery,c and Pediatrics,d Bowman Gray School of Medicine of Wake Forest University. Supported by the Mark and Catherine Winkler Foundation. Accepted for publication Nov. 18, 1997. Reprint requests: Joseph L. Jorizzo, MD, Department of Dermatology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1071. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/87610

overlap with other collagen vascular diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and scleroderma.6,7 There is an increased frequency of internal malignancy in adults, but not in children, with dermatomyositis. Dermatomyositis may be associated with significant morbidity and with occasional mortality. The mainstay of treatment for dermatomyositis is systemic corticosteroids; however, there is no consensus protocol and debate continues over the use of daily versus alternate-day and low-dose versus high-dose therapy. There are some patients who do not respond adequately to corticosteroids. Other immunosuppressive agents such as methotrexate, intravenous gamma globulin, and azathioprine, have been used in these patients with variable results.8-11 Previous reports of large series of patients have included discussions of treatment and outcome.6,7,12-14 We describe our experience with 53 patients with dermatomyositis and compare outcome and clinical features with previously reported series of patients with dermatomyositis/ 397

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Table I. Clinical features of patients with comparison to previously reported series Dawkins/ Jorizzo* Adult DM

JDM

Bohan and Peter15

Henriksson and Sandstedt12

DeVere and Bradley6

Hoffman et al.13

Baron and Small14

PM/DM

PM/DM

PM/DM

PM/DM

PM/DM

No. of patients 43 11 153 (7% JDM) 107 (20% JDM) 118 (18% JDM) 27 (0 JDM) Mean age (yr) 51.7 7.6 44 44 41.5 59 Malignancy 5 (12%) 0 13 (8.5%) 7 (6.5%) 9 (8%) 2 (7.4%) Overlap 8 (19%) 1 (10%) 32 (21%) 16 (15%) 15%-30% 9 (30%) Sex ratio (F:M) 6.2:1 1:1.75 2:1 1.2:1 1.4:1 2.4:1

22 (0 JDM) 58.5 7 (32%) 7 (32%) 1.75:1

DM, Dermatomyositis; JDM, juvenile dermatomyositis; PM, polymyositis. *Current study.

polymyositis. We also discuss 12 patients with dermatomyositis sine myositis (amyopathic dermatomyositis). PATIENTS AND METHODS Patients during a 10-year period (March 1986 to March 1996) who met the clinicopathologic criteria for dermatomyositis, as defined by Bohan and Peter,15 were examined. A total of 53 patients with dermatomyositis, 43 adults and 10 children, were seen. Fortythree patients had definite dermatomyositis, seven had probable dermatomyositis, and three had possible dermatomyositis. In, addition, 11 adults and one child with skin findings consistent with dermatomyositis sine myositis were seen. Patient demographics, laboratory results, muscle strength at presentation, presence of malignancy, and presence of overlap with other collagen vascular diseases were evaluated for both groups. Twenty-one patients with definite dermatomyositis (14 adults, 7 children) were treated with a standard protocol. Adults were given high-dose prednisone, 1 mg/kg/day; this was reduced gradually to half the initial dose during a 6-month period. The prednisone dose was then slowly discontinued during a 20- to 63-month period. If a patient experienced any flare of muscle disease, the prednisone dose was usually doubled. Once control of the myositis was achieved, the prednisone dose was again slowly reduced. Children with dermatomyositis were started on a higher initial prednisone dose (2 mg/kg per day) and were changed to alternate-day prednisone once a daily dose of 10/mg per day was reached. Patients with dermatomyositis sine myositis were, with one exception, not treated with oral corticosteroids. RESULTS

Clinical characteristics The 43 adult patients with dermatomyositis consisted of 6 men and 37 women, with a mean age at diagnosis of 51.7 years (range, 21 to 82 years) (Table I). The 10 patients with juvenile der-

matomyositis included 6 boys and 4 girls; mean age at onset in this group was 7.6 years (range, 1.5 to 17 years). The dermatomyositis sine myositis group consisted of one man and 10 women with a mean age of 48.6 years (range, 26 to 70 years). The male patient with dermatomyositis sine myositis was 17 years old at time of diagnosis. A malignancy was found in 5 of 43 adult patients (12%) with dermatomyositis (Table I). Four patients were diagnosed with cancer after the onset of dermatomyositis. Malignancies in these patients included breast adenocarcinoma, renal cell carcinoma, small cell carcinoma, and adenocarcinoma of unknown primary. The average duration between presentation of dermatomyositis and diagnosis of cancer in these patients was 4 months. The fifth patient had adenocarcinoma of the breast treated 2 years before the onset of dermatomyositis; a recurrence of breast cancer was diagnosed 6 months after the onset of dermatomyositis. Cancer (adenocarcinoma of the breast) was also present in one patient with dermatomyositis sine myositis. No malignancies were present in patients with juvenile dermatomyositis. Overlap with another connective tissue disease was present in 8 of 43 adult patients (19%) (Table I). Overlap diseases included rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Sjögren’s syndrome, and morphea. One patient had both systemic lupus erythematosus and Sjögren’s syndrome. The mean muscle strength of patients at diagnosis was 4.1/5 based on the British Medical Research Council Muscle Strength system,16 where 0 = no muscle contraction and 5 = normal strength. Referring diagnoses were available in 46 of 53 patients with dermatomyositis sent to our institution for consultation. Dermatomyositis was listed

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Table II. Features of patients placed on prednisone protocol Duration of treatment end of review (mo)

Patient No.

Age (yr) at dx

Sex

1 2 3 4 5 6 7 8 9 10 11 12

39 31 59 28 39 32 54 49 46 58 36 50

F F F F F F M F F F M F

43 69 38 43 44 30 3 3 12 19 18 8

13

47

F

4

14

59

F

35

15 16 17 18 19* 20* 21*

8 9.5 11 5 4.5 3 3

F F M M M F F

25 28 56 30 28 18 109

Prednisone dose end of review

0 (off all meds 36 mo) 0 (off all meds 45 mo) 0 (off all meds 13 mo) 0 (off all meds 3 mo) 5 mg/day 5 mg/day 30 mg/day 35 mg/day 15 mg/day 15 mg/day 35 mg/day 15 mg/day MTX 15 mg/wk (added for cutaneous eruption only) 10 mg/day 10 mg/day MTX 5 mg/wk 0 (off all meds 13 mo) 0 (off all meds 66 mo) 0 (off all meds 24 mo) 0 (off all meds 42 mo) 2.5 mg/day 5 mg/qod 6 mg/qod

CPK/muscle strength end of review

Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl 262/Nl Nl/Nl Died of pneumonia; CPK normal at time of death Died of complications secondary to cryptogenic cirrhosis; CPK normal at time of death Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl Nl/Nl (4+/5)/Nl

dx, Diagnosis; MTX, methotrexate; Nl, normal; qod, every other day. *These patients each had 3-day courses of IVIG for severe muscle disease. Patients 19 and 20 responded well to one course and continued with the protocol. Patient 21 originally responded, but then flared and could not tolerate multiple treatments with IVIG.

as a possible diagnosis for only 26 of these 46 patients. The most common referring diagnoses were systemic lupus erythematosus (12 of 46), psoriasis (3 of 46), and cutaneous T-cell lymphoma (3 of 46). Response to treatment protocol Adult dermatomyositis Fourteen adults were treated as described. Their clinical data are summarized in Table II. Four had a complete remission and no need for further therapy. The average duration of therapy in these patients was 42.3 months. There were no significant side effects. Two of 14 patients were nearing the end of treatment. The average prednisone dose was 5 mg/day, and the average duration of therapy was 38.7 months. Six of 14 patients began treatment within the last 19 months. Five were responding well. One

patient was taking prednisone 35 mg/day; muscle strength was normal, but the CPK was slightly elevated. One patient died of complications secondary to cryptogenic cirrhosis after 33 months of therapy. Another patient with a history of treated breast cancer died of aspiration pneumonia 4 months after beginning therapy. Neither of these patients had elevations of muscle enzymes at the time of death. Juvenile dermatomyositis Four of seven patients finished treatment with no active myositis or need for immunosuppressive medications. The average duration of therapy was 34.8 months. Three patients did not respond to systemic corticosteroids alone and received additional treatment with intravenous immunoglobulin (IVIG), 2 mg/kg per day for 3 days. Two patients responded with increased muscle strength and a

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Table III. Clinical characteristics and response to therapy of patients with dermatomyositis sine myositis Patient No.

Age (yr) at dx

Sex

Follow-up (yr)

Malignancy or overlap

1

70

F

4

Malignancy (breast cancer)

2 3 4 5

30 26 38 70

F F F F

9 4 2 4.5

6 7

31 63

F F

8 9 10

66 17 57

F M F

11

36

12

48

2 12

— — — —

Therapy

Short-term low-dose prednisone (20 mg/day); topical steroids HQ 200 mg b.i.d. HQ 200 mg b.i.d. Topical steroids (1) Prednisone + HQ 200 mg b.i.d.; (2) HQ 200 mg b.i.d.

— —

HQ 200 mg b.i.d. Low-dose prednisone (≤20 mg)

1.5 6.5 1.5

— — —

F

5

—

F

6

—

HQ 200 mg b.i.d. HQ 200 mg b.i.d. HQ 200 mg b.i.d.; MTX 15 mg/wk HQ, MTX, quinacrine, chloroquine, topical steroids HQ 200 mg b.i.d.; MTX 10 mg/wk; quinacrine 100 mg/day

Response

Cleared while on prednisone; flared when prednisone stopped No improvement No improvement Cleared (1) Cleared, experienced flare; (2) cleared again on HQ alone Cleared 75% improvement; flares when off treatment 75% improvement Cleared No improvement No improvement No improvement

dx, Diagnosis; HQ, hydroxychloroquine; MTX, methotrexate.

decrease in CPK. These patients were again treated with prednisone with good results. The third patient treated with IVIG showed improvement early but later began to have flares of myositis as well as side effects from IVIG, necessitating its discontinuation. This patient was taking prednisone 6 mg every other day and was in her ninth year of therapy. Response of cutaneous manifestations to therapy The response of cutaneous lesions to therapy was assessed in 35 patients. Fifteen of 35 patients had resistant cutaneous lesions despite a reduction in muscle disease. In these patients cutaneous lesions were difficult to control even when oral corticosteroids and antimalarials (oral hydroxychloroquine 200 mg twice daily with or without oral quinacrine 100 mg once daily) followed by weekly oral methotrexate (5 to 20 mg per week), and topical corticosteroids were used alone or in combination. Cutaneous lesions eventually cleared in 7 of these 15 patients. The average time from muscle response to cutaneous clearing was 23 months. Calcinosis cutis was present in three

patients with juvenile dermatomyositis. In one, contractures of the feet and elbows occurred. Dermatomyositis sine myositis Twelve patients were diagnosed with dermatomyositis sine myositis (11 adults, one child). Characteristics of these patients are shown in Table III. These patients had the typical cutaneous features of dermatomyositis, but no myositis as evidenced by normal findings from muscle enzyme levels, muscle biopsy specimens, electromyography, and, in some patients, magnetic resonance imaging (MRI) and ultrasound. Patients with normal muscle strength and normal muscle enzymes but with evidence of myositis on biopsy or electromyography were classified as having dermatomyositis and not dermatomyositis sine myositis. The time from the initial cutaneous eruption to the most recent patient visit ranged from 18 months to 12 years. Adenocarcinoma of the breast was found in one patient. No overlap was present in these patients. Five patients responded well to therapy. Four had complete clearing of cutaneous lesions (patients 4, 5, 6, and 9; Table III), and the fifth had

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Fig. 1. Characteristic Gottron’s papules present over dorsal interphalangeal and metacarpal joints.

75% improvement (patient 8; Table III). The average time to improvement was 16 months. However, cutaneous involvement was recalcitrant to therapy in the remaining seven patients. Therapy in these patients included antimalarials (oral hydroxychloroquine 200 mg twice daily with or without oral quinacrine 100 mg once daily), weekly pulse oral methotrexate (5 to 20 mg per week), and topical corticosteroids alone or in combination. One patient (patient 5; Table III) received systemic corticosteroids concomitantly with hydroxychloroquine for severe cutaneous involvement. This patient’s disease cleared, but recurred 43 months after cessation of therapy. The patient was restarted on a regimen of hydroxychloroquine alone and had total resolution after 11 months. Two patients (patients 1 and 7) were treated by other physicians with short courses of oral prednisone that led to transient improvement of cutaneous lesions. However, we did not use oral corticosteroids because the cutaneous involvement was not deemed sufficiently severe to warrant the use of systemic corticosteroids with their associated side effects.

Fig. 2. Periungual telangiectases, erythema, and cuticular dystrophy in patient with dermatomyositis.

Fig. 3. Photomicrograph of dermatomyositis reveals vacuolar interface changes and scant perivascular superficial lymphohistiocytic infiltrate.

DISCUSSION

The clinical features of our patients, including age at onset, frequency of malignancy, and association with other connective tissue diseases, were similar to those described in previous series.6,7,12,17-22 There was a higher than expected ratio of female to male patients (6.2:1). This difference may be the consequence of a relatively small study group or selection bias related to early consultation for a cutaneous eruption.

Another exception was less active myositis at diagnosis, as evidenced by higher mean muscle strength (Table IV). A possible reason for this difference may be earlier diagnosis. The cutaneous manifestations of dermatomyositis (Figs. 1 and 2) can occur with, or precede, muscular inflammation.7,23 Recognition of the skin findings may lead to early intervention before extensive myositis has evolved. Histopathologic evidence of interface

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Table IV. Strength at diagnosis and response to therapy of patients with dermatomyositis/polymyositis reported in current and previous series Dawkins/Jorizzo*,‡

Bohan and Peter15,§

Baron and Small14,§

Strength at diagnosis||

4.1/5

3.0/5

3.4/5

Muscle and clinical response to therapy

Mean strength (5/5); 35% off all therapy

Mean strength (3.9/5); 9% off all therapy

Mean strength (4.5/5); 27% off all therapy

* Current study. ‡Dermatomyositis patients placed on treatment protocol. §Dermatomyositis and polymyositis patients. ||British Medical Research Muscle Strength grading system.

changes (Fig. 3) is important in these cases. The comparable groups6,7,12-14 included patients with both polymyositis and dermatomyositis; thus more significant muscle disease may have been present because of a later diagnosis of myositis. Another possibility for the greater muscle strength in our patients may be selection bias. Patients in this series were referred for evaluation of cutaneous findings. Patients with more severe muscle weakness may have been more likely to be referred to neurologists or rheumatologists. A better response to treatment was also seen in our group. Patients treated with a protocol of highdose prednisone with slow taper had greater muscle strength at follow-up than did patients in previously reported series (Table IV). Eighteen of 21 patients (85%) responded with normalization of muscle strength within 4 months of therapy. Sustained response was also excellent; 18 of 19 patients had normal muscle strength at the end of review (Table II). Eight patients had completely stopped therapy, five patients were taking lowdose prednisone and nearing end of treatment, and six patients who had been receiving therapy 19 months or less were taking prednisone at doses of 15 to 35 mg/day. We believe that there are several possible reasons why our patients responded better than previously reported patients. First, patients treated with the protocol regimen were diagnosed early (all within 12 months of onset of the cutaneous eruption). Fafalak, Peterson, and Kagen24 found that patients with dermatomyositis or polymyositis treated early, within 12 months of onset of signs and symptoms, had less muscle weakness than those treated late. Second, patients in this study in general had less active myositis at presentation. It is logical to assume that these patients would

respond better to therapy. Of note, five patients on the treatment protocol (Table II) had extensive muscle inflammation with CPK values greater than 4000 U/L (patients 11, 13, 16, 19, and 20). Two of these patients did not respond to the protocol (patients 19 and 20), and a third (patient 11) responded more slowly than other patients to treatment. Finally, prednisone was tapered in a slow, controlled manner with a target treatment period of 24 to 36 months. Thus prednisone was continued over an extended period after parameters of myositis (muscle strength, muscle enzymes) were normal. If a patient experienced a flare during the steroid taper, the prednisone dose was increased to control the myositis, and then again gradually tapered. In several patients (patients 1, 2, 4, 5, 17, and 21; Table II) who experienced flares, treatment extended beyond 36 months. By tapering in a controlled manner, sustained suppression of the inflammatory process is obtained and flares of myositis are minimized. In our experience, early low-dose therapy or rapid tapering can lead to short-term contol in a small group of patients; however, in most patients, this therapy allows the disease to smolder, leading to recrudescence, much in the same way that tapering steroids too rapidly in other inflammatory conditions such as pyoderma gangrenosum can lead to flares. Side effects of steroid therapy in our adult patients included the development of cushingoid appearance, elevated serum glucose levels, and hypertension in several patients. Cataracts developed in three patients with juvenile dermatomyositis, and one patient had gastritis. No cases of steroid-induced myopathy or bone fractures occurred. Adjuvant therapy in patients who are unrespon-

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Hoffman et al.13,§

3.9/5

Mean strength (4.6/5); 41% off all therapy

Dawkins et al. 403

DeVere and Bradley6,§

Henrikkson and Sandstedt12,§

“Disability grade of 4.8 where 4 = unable to run, but able to climb stairs; 5 = unable to climb stairs w/o support 66% of survivors at follow-up had no “functional disability”

sive to corticosteroids is important and should not be delayed. However, an adequate trial of systemic corticosteroids with emphasis on controlled lowering of prednisone dose should be considered first-line therapy. We reserve use of other immunosuppressive agents for those patients who do not adequately respond to corticosteroids, that is, slow return of enzymes and strength to normal, or persistently high corticosteroid requirement (e.g., > 30 mg prednisone daily at 6 months). Although response of muscle disease to therapy was excellent, cutaneous lesions were more resistant to therapy. The discordance of muscle and skin response with resistant skin lesions has been well described; although cutaneous disease may be of minor importance in patients with active myositis, it can often cause considerable distress to patients. The effective use of antimalarials for treatment of cutaneous lesions has been reported.25,26 More recently, Kasteler and Callen27 described the effective use of low-dose weekly methotrexate for treatment of resistant cutaneous lesions. Oral hydroxychloroquine at 200 mg twice daily and low-potency topical corticosteroids were our first treatment choice for resistant lesions. If this was not effective, oral quinacrine at 100 mg/day was added. For patients with fulminant cutaneous disease unresponsive to antimalarials, low-dose weekly pulse methotrexate therapy was used, either alone or in combination with antimalarials. Despite this aggressive treatment regimen, 15 of 35 patients had resistant cutaneous lesions despite excellent response of muscle disease. Cutaneous lesions eventually cleared spontaneously in 7 of these 15 patients, although the average time from muscle response to cutaneous response was 23 months. Our findings again emphasize the difficulty in treating the

12% slight disability; 63% moderate disability (unable to climb stairs); 20% severe disability (wheelchair required) 50% responded; 50% did not respond to therapy

cutaneous lesions of dermatomyositis in patients whose muscle disease responds to systemic corticosteroids, but whose cutaneous disease does not. The designation dermatomyositis sine myositis (amyopathic dermatomyositis) has been used to refer to patients who have the typical cutaneous findings of dermatomyositis, but no myopathy. There remains debate as to whether these patients actually represent a distinct class of dermatomyositis. Several groups of investigators have suggested that the interval between skin manifestations and myositis is usually less than 2 years and often less than 6 months.23,28 Some authors believe that myositis will develop in all patients with cutaneous changes of dermatomyositis if they are followed up long enough.29,30 However, several recent reports have been published of patients with cutaneous changes consistent with dermatomyositis and no evidence of myopathy with long-term follow-up.31,32 Muscle strength, muscle enzymes, electromyography, and muscle biopsy findings were normal in the 12 patients with dermatomyositis sine myositis. Three of these patients (patients 2, 9, and 11; Table III) were previously described by us33 and had additional testing with ultrasound and MRI with no evidence of myositis. The time from initial cutaneous eruption to most recent follow-up ranged from 18 months to 12 years. Given the long-term follow-up periods and lack of objective myositis by all universally accepted diagnostic tests, we are convinced that dermatomyositis sine myositis is indeed a distinct entity. Because of the lack of myositis and the side effects of systemic corticosteroids, prednisone was not used by our group to treat the cutaneous manifestations in patients with dermatomyositis sine myositis except for one patient with exten-

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404 Dawkins et al. sive, severe skin involvement. However, patients with normal muscle enzymes who have myositis demonstrated by two of the following modalities (electromyography, muscle biopsy, ultrasound, and/or MRI) were treated with prednisone. As with patients with dermatomyositis, cutaneous disease was often resistant to treatment. Five of 12 patients had at least 75% clearing with hydroxychloroquine 200 mg twice daily. However, the remaining seven patients had lesions that were recalcitrant to therapy with antimalarials, weekly pulse methotrexate, topical corticosteroids, and, in one patient, systemic corticosteroids, when these medications were used alone or in combination. Also of note, one patient with dermatomyositis sine myositis had a malignancy. Because of this association, we believe that patients without evidence of myositis should be evaluated for occult malignancy in a manner similar to those with dermatomyositis. REFERENCES 1. Stonecipher MR, Callen JP, Jorizzo JL. The red face: dermatomyositis. Clin Dermatol 1993;11:261-73. 2. Callen JP. Dermatomyositis and polymyositis. Dis Month 1987;33:239-305. 3. Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME. Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. Ann Intern Med 1989;111:143-57. 4. Kissel JT, Halterman RK, Rammohan KW, Mendell JR. The relationship of complement-mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis. Arch Neurol 1991;48:26-30. 5. Mascaro JM, Hausmann G, Herrero C, Grau JM, Cid MC, Palou J, et al. Membrane attack complex deposits in cutaneous lesions of dermatomyositis. Arch Dermatol 1995;131:1386-92. 6. DeVere R, Bradley WC. Polymyositis: Its presentation, morbidity, and mortality. Brain 1975;98:637-66. 7. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;56:255-86. 8. Metzger AL, Bohan A, Goldberg LS, Bluestone R, Pearson CM. Polymyositis and dermatomyositis: combined methotrexate and corticosteroid therapy. Ann Intern Med 1974;81:182-9. 9. Bunch TW, Worthington JW, Combs JJ, Ilstrup DM, Engel AG. Azathioprine with prednisone for polymyositis. Ann Intern Med 1980;92:365-9. 10. Bunch TW. Prednisone and azathioprine for polymyositis: long-term follow up. Arthritis Rheum 1981;24:45-8. 11. Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993-2000. 12. Henriksson KG, Sandstedt P. Polymyositis: treatment and prognosis. Acta Neurol Scand 1982;65:280-305. 13. Hoffman GS, Franck WA, Raddatz DA, Stallones L.

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