Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Ruth Ann Vleugels and Jeffrey P. Callen
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Dermatomyositis (DM) is one of the idiopathic inflammatory myopathies characterized by cutaneous disease, including a heliotrope eruption, Gottron papules, a violaceous erythema on extensor surfaces in a photodistribution pattern, and/or periungual changes. Patients with cutaneous lesions of DM often have weakness of the proximal muscles, elevated enzymes such as creatine kinase or aldolase, or abnormal electromyograms or muscle biopsy findings. Some, however, have cutaneous disease that either precedes the onset of demonstrable muscle disease or occurs in its absence. In addition, many patients have persistent cutaneous manifestations long after their muscle disease is adequately controlled. DM in children and adolescents may be complicated by calcinosis, particularly when treatment is delayed. Adults with DM have a greater risk of having or developing a malignancy, usually within the first 3 years following diagnosis.
Prior to treatment the patient should be thoroughly evaluated to assess the severity of the disease, the presence of systemic involvement such as pulmonary, cardiac, or gastrointestinal involvement, and the presence of malignancy.
The goal of management is to reverse the weakness and allow the patient to return to normal functional status. The prevention of contractures is also a consideration, and the prevention or treatment of calcinosis is usually an issue in the management of children and adolescents, but may occur rarely in adults as well. Patients with cutaneous disease are troubled by intense pruritus and the appearance of their skin, and therefore request management even when the muscle disease has been effectively treated or is absent.
For the myopathy, systemic corticosteroids with or without an immunosuppressive agent are the standard treatment. Most patients respond to these agents, but for those who do not, high-dose intravenous immunoglobulin may be of benefit. Patients with cutaneous disease are photosensitive and are treated with sunscreens and behavior modification, topical corticosteroids, and occasionally topical calcineurin inhibitors, oral antimalarials, and often an oral immunosuppressant. High-dose intravenous immunoglobulin may also be used for recalcitrant cutaneous disease. Ultimately, the therapeutic goal is to provide patient relief from the cutaneous inflammation and associated symptoms utilizing a combination of topical and/or systemic medications selected after considering a patient’s comorbidities.
One of the problems with many of the reports published to date regarding therapeutic options for cutaneous DM is the lack of the use of a validated measure of activity to assess the activity of skin disease and response to therapy. To this end there are three measures that have recently been developed: the Dermatomyositis Skin Severity Index (DSSI) (Br J Dermatol 2008; 158: 345–350), the Cutaneous Dermatomyositis Area and Severity Index (CDASI) (Arch Dermatol Res 2008; 300: 3–9, and Br J Dermatol 2012; 162: 669–673), and a cutaneous assessment tool in juvenile dermatomyositis (Arthritis Rheum 2008; 59: 352–356). Unfortunately, none of these measures is routinely used in studies investigating therapeutic interventions for DM; however, the tools are being utilized more frequently and will ideally become incorporated as standard practice in the future as a means to assess cutaneous disease response.
A thorough evaluation to exclude other causes of myopathy
Malignancy evaluation, including CT scans of chest, abdomen, and pelvis, transvaginal pelvic ultrasound, stool occult blood testing and age-appropriate endoscopy, Papanicolaou smear, mammography, complete blood count, comprehensive metabolic panel, CA-125, CA 19-9, urinalysis, and full physical examination
Serum aldolase or creatine kinase
Electromyogram
Muscle biopsy
Magnetic resonance imaging or ultrasound of muscle
Assessment for the presence of systemic involvement (e.g., pulmonary disease, esophageal dysfunction, cardiac involvement)
Assessment of myositis-specific antibodies
Kasteler JS, Callen JP. JAMA 1994; 272: 1939–41.
Skin lesions in patients with DM, particularly of the scalp, are often confused with psoriasis, seborrheic dermatitis, or lichen planus. Often the lesions simulate cutaneous lupus erythematosus.
Marie I, Hatron PY, Levesque H, Hachulla E, Hellot MF, Michon-Pasturel U, et al. Medicine (Baltimore) 1999; 78: 139–47.
This group compared characteristics of younger versus older adults and found that the incidence of malignancy was much higher in the older population, resulting in a poorer prognosis for this subset of patients.
Lam WW, Chan H, Chan YL, Fung JW, So NM, Metreweli C. Acta Radiol 1999; 40: 69–72.
These authors conducted a prospective study to investigate the role of MRI in 10 patients with amyopathic DM. Three patients demonstrated abnormal signal intensity in muscles on both T2-weighted and fat-suppression sequences. Thus, one-third of patients with DM and clinically normal muscles may have detectable muscle inflammation on MRI, indicating that MRI has a potential role for locating the relevant biopsy site and for longitudinal follow-up.
Callen JP. J Am Acad Dermatol 1982; 6: 253–9.
DM has been linked to internal malignancy in adults, but the value of an extensive malignancy evaluation in patients with DM is controversial. Fifty-seven patients who had DM with malignancies for whom data were available regarding the discovery of malignancy have been analyzed: 53 of these were reported previously. There were 67 malignancies in the 57 patients. The malignancy preceded (26 cases), followed (23 cases), or occurred with the DM (18 cases). A ‘blind’ (non-directed) malignancy search was not of value in any of the cases analyzed. Rather, the tumors were discovered in 40 cases by history (preceding tumor or abnormal symptoms), in 14 cases by physical examination, and in 12 cases by abnormal laboratory findings (e.g., chest radiograph, urinalysis, stool guaiac). One case was not discovered until autopsy (adenocarcinoma of the broad ligament). Analysis of tumor sites further negates the value of a malignancy work-up because most tumors (>90%) occur in areas not amenable to a ‘routine malignancy search.’ In several instances patients had an extensive search without having a complete physical examination.
Malignancy evaluations should be directed by abnormalities found on history, physical findings, or routine laboratory testing. However, since this paper was published, new, less invasive methods of malignancy search have been developed, and therefore the initial search should include CT scans of the chest, abdomen, and pelvis in most patients, and these scans should be repeated annually for at least 3 years. Malignancy screening should also include annual physical examinations.
Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, et al. Lancet 2001; 357: 96–100.
This study combined prior studies from Sweden, Finland, and Denmark and demonstrated that patients with dermatomyositis were at increased risk of an accompanying malignancy, whereas those with polymyositis had a less clear risk of associated malignancy. The malignancy risk decreased with each passing year after diagnosis, and approached background levels at 3 years. Malignancies of the ovaries, pancreas, stomach, colon and rectum, and non-Hodgkin’s lymphoma were over-represented in patients with DM.
Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, et al. Medicine (Baltimore) 1991; 70: 360–74.
This study compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-signal recognition particle [anti-SRP], anti-Mi-2, and anti-MAS) to the standard clinical categories (polymyositis, DM, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms and prognosis in 212 adult patients. Compared to those without these antibodies, patients with anti-aminoacyl-tRNA synthetase autoantibodies (n = 47) had significantly more frequent arthritis, fever, interstitial lung disease, and ‘mechanic’s hands’; higher mean prednisone dose at survey; higher proportion of patients receiving cytotoxic drugs; and higher death rates. Those with anti-SRP antibodies (n = 7) had more frequent palpitations, myalgias, severe refractory disease, and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased ‘V-sign’ and ‘shawl-sign’ rashes and cuticular overgrowth, as well as a good response to therapy. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis.
These antibodies are less common in patients with DM than in patients with polymyositis, and currently only the anti-amino-acyl-tRNA synthetase autoantibodies are frequently incorporated into clinical practice.
Hamaguchi Y, Kuwana M, Hoshino K, Hasegawa M, Kaji K, Matsushita T, et al. Arch Dermatol 2011; 147: 391–8.
In this study of 376 adult Japanese patients with DM, anti-CADM-140 autoantibodies were associated with clinically amyopathic DM and rapidly progressive interstitial lung disease, whereas anti-155/140 autoantibodies were associated with malignancy. Anti-Mi-2 autoantibodies were associated with classical DM without either malignancy or pulmonary disease. The authors note that these autoantibodies define distinct clinical subsets and therefore are useful in predicting patient outcomes in DM.
The anti-CADM-140 and anti-155/140 autoantibodies are considered investigational at present and are not routinely available in commercial laboratories. They may, however, alter the screening practices for patients with DM in the future.
Morganroth PA, Kreider ME, Okawa J, Taylor L, Werth VP. Arch Dermatol 2010; 146: 729–38.
In this retrospective cohort study, 23% of patients had interstitial lung disease (ILD) based on CT findings, and all of these had a reduced diffusion capacity (DLCO) on pulmonary function tests as well. Prevalence of ILD was not statistically different between patients with and without muscle disease. The authors conclude that serial DLCO testing is reasonable in all patients with DM to screen for pulmonary involvement.
Bendewald MJ, Wetter DA, Li X, Davis MD. Arch Dermatol 2010; 146: 26–30.
This retrospective population-based study found an overall age- and sex-adjusted incidence of dermatomyositis including all subtypes to be 9.63 (95% CI: 6.09–13.17) per one million persons. The incidence of clinically amyopathic dermatomyositis was 2.08 (95% CI: 0.39–3.77) per 1 million persons. Twenty percent of the dermatomyositis cases were amyopathic in this population.
This epidemiologic study supports other data demonstrating that 20% to 30% of adult DM patients lack muscle involvement.
Paller AS. Pediatr Dermatol 1996; 13: 347–8.
This report notes that pulse administration of systemic corticosteroids might result in less toxicity, and further that this therapy aids in the prevention of calcinosis.
Dourmishev L, Meffert H, Piazena H. Photodermatol Photoimmunol Photomed 2004; 20: 230–4.
About half of the patients with DM were found to have a reduced minimal erythema dose to UVB radiation. The action spectrum of DM remains unknown.
Woo TY, Callen JP, Voorhees JJ, Bickers D, Hanno R. J Am Acad Dermatol 1984; 10: 592–600.
Seven patients with cutaneous lesions of DM that had not responded to therapy with corticosteroids and/or immunosuppressants were treated with hydroxychloroquine 200 mg once or twice daily in an open study. The response to the addition of hydroxychloroquine was good in all patients, and three had total resolution of their skin lesions. In two patients the corticosteroid dosage could be tapered. Therapy with hydroxychloroquine did not appear to have any beneficial effect on the myositis.
Ang GC, Werth VP. Arch Dermatol 2005; 141: 855–9.
In this retrospective analysis, seven of 17 patients experienced at least near clearance of cutaneous symptoms with the use of antimalarial therapy alone: four of them required combination therapy (hydroxychloroquine sulfate 200 mg once or twice daily + quinacrine hydrochloride 100 mg daily; or chloroquine phosphate 250 mg daily + quinacrine 100 mg daily), and three of them responded well to antimalarial monotherapy. The median time required to efficacy was 3 months.
When considering combination antimalarial agents as a therapeutic option, it is critical to use quinacrine in addition to either hydroxychloroquine or chloroquine given that quinacrine lacks ocular toxicity. Hydroxychloroquine and chloroquine both have ocular toxicity and should not be given concurrently.
Hollar, CB, Jorizzo, JL. J Dermatol Treat 2004; 15, 35–39.
This open-label study of six patients with cutaneous DM treated with topical tacrolimus noted a very good to excellent response in two patients, a moderate response in one, and essentially no response in three.
This agent is worthy of a trial, but does not seem to be highly effective.
Kasteler JS, Callen JP. J Am Acad Dermatol 1997; 36: 67–71.
The records of 13 patients who received oral methotrexate in doses ranging from 2.5 to 30 mg weekly were reviewed. Their skin lesions had not been completely responsive to sunscreens, topical corticosteroids, oral prednisone, oral antimalarial therapy, or, in one patient each, chlorambucil and azathioprine. Four of these 13 patients had complete clearance of cutaneous manifestations, and another four had almost complete clearance. In the remaining five patients, methotrexate induced moderate clearing of their cutaneous lesions. In all patients, the addition of methotrexate allowed a reduction in or discontinuation of other therapies, including prednisone.
Edge JC, Outland JD, Dempsey JR, Callen JP. Arch Dermatol 2006; 142: 65–9.
Rowin J, Amato AA, Deisher N, Cursio J, Meriggioli MN. Neurology 2006; 66: 1245–7.
These two open-label studies suggest that in 60–75% of patients with myositis, mycophenolate mofetil 1–1.5 g twice daily is an effective steroid-sparing agent for skin and muscle disease. The first report dealt only with patients with DM, whereas the latter included some with polymyositis. There was toxicity noted in these relatively small case series, including an Epstein–Barr virus-associated lymphoma of the central nervous system in the former study, which resolved upon cessation of therapy, and opportunistic infections in the latter study, one of which was fatal.
This agent, albeit seemingly useful, needs careful monitoring for the development of neoplasia and infection.
Dalakas MC, Illa I, Dambrosia JM. N Engl J Med 1993; 329: 1993–2000.
These authors conducted a double-blind, placebo-controlled trial of intravenous immunoglobulin in 15 patients with biopsy-proven treatment-resistant DM. The patients continued to receive prednisone (mean daily dose 25 mg) and were randomly assigned to receive one infusion of immunoglobulin (2 g/kg body weight) or placebo monthly for 3 months, with the option of crossing over to the alternative therapy for 3 more months. The eight patients assigned to immunoglobulin showed a significant improvement in scores of muscle strength (p < 0.018) and neuromuscular symptoms (p < 0.035), whereas the seven patients assigned to placebo did not. With crossovers, a total of 12 patients received immunoglobulin. Of these, nine with severe disabilities showed a major improvement to near normal function. Of 11 placebo-treated patients, none had a major improvement, three had a mild improvement, three had no change in their condition, and the condition of five worsened. Skin disease also responded in the treated patients with eight of 12 demonstrating ‘marked clearance’ of cutaneous disease as assessed through clinical photographs.
Sinoway PA, Callen JP. Arthritis Rheum 1993; 36: 319–24.
Five patients with recalcitrant DM were treated with oral chlorambucil, 4 mg daily, after discontinuation of another immunosuppressive agent (azathioprine or methotrexate). Three patients were treated with a combination of prednisone and chlorambucil, and two with chlorambucil alone. Beneficial effects were noted within 4–6 weeks in all five patients, and corticosteroids were eventually discontinued in four. The chlorambucil was stopped after 13–30 months of treatment in four patients, and their disease remained in remission. Minimal chlorambucil toxicity was noted, consisting of leukopenia in two patients.
Although chlorambucil was effective, its potential for subsequent malignancy makes it a less desirable choice.
Danieli MG, Malcangi G, Palmieri C, Logullo F, Salvi A, Piani M, et al. Ann Rheum Dis 2002; 61: 37–41.
This is a retrospective review of 20 patients, including 12 with DM. It suggests that combining prednisone, cyclosporine, and intravenous immunoglobulin was the most useful regimen.
Vencovský J, Jarosová K, Machácek S, Studýnková J, Kafková J, Bartünková J, et al. Scand J Rheumatol 2000; 29: 95–102.
Patients were randomly assigned to receive either methotrexate or cyclosporine in addition to prednisone. The methotrexate dosage was 7.5–15 mg/week and that of cyclosporine was 3.0–3.5 mg/kg daily. Both groups improved. This is a small study of a heterogeneous group of patients treated with adequate doses of corticosteroid, but relatively low doses of the second agent.
Levine TD. Arthritis Rheum 2005; 52: 601–7.
This is an open-label study of seven patients given four weekly infusions at either 100 or 375 mg/m2. In the six evaluable patients there was an improvement in muscle disease as well as the skin disease although no validated score to assess cutaneous disease was utilized.
Chung L, Genovese MC, Fiorentino DF. Arch Dermatol 2007; 143: 763–7.
In this open-label pilot study with seven evaluable patients who received 1 g infusions administered 2 weeks apart, only three had partial response of their muscle disease. Skin disease using the validated DSSI did not demonstrate notable improvement over the study period, with the mean change in DSSI not reaching statistical significance.
Oddis CV, Reed AM, Aggarwal R, Ascherman DP, Barohn RJ, Feldman BM, et al. Arthritis Rheum 2013; 65; 314.
An NIH-sponsored multicenter randomized controlled trial of 200 participants, including 76 with DM, 48 with juvenile DM, and 76 with polymyositis. Patients were randomized to either a ‘rituximab early’ arm, receiving drug at weeks 0 and 1 and placebo at weeks 8 and 9, or a ‘rituximab late’ arm, receiving placebo at weeks 0 and 1 and rituximab at weeks 8 and 9. The primary endpoint, time to achieve improvement based on specifically defined muscle parameters, was not met, nor were the secondary endpoints, which were also based on muscle involvement. Despite this, 83% of patients met the definition of improvement (DOI) by week 44. In addition, a steroid-sparing effect of rituximab was noted in both groups. The authors propose that the trial design, particularly the short placebo-phase of 8 weeks, may have reduced the ability to detect differences between the groups given the median time to DOI from rituximab. Of note, neither of the 2 validated indices for cutaneous dermatomyositis were utilized in the RIM Study.
The two pilot studies, along with other case reports, suggest that there might be a place for this agent in the treatment of dermatomyositis. Study design concerns with the RIM Study make recommendations regarding the use of rituximab in inflammatory myopathy, inlcuding DM, challenging. At this time, however, there is little data to support the use of rituximab for cutaneous dermatomyositis specifically.
Oliveri MB, Palermo R, Mautalen C, Hubscher O. J Rheumatol 1996; 23: 2152–5.
This report describes a case of juvenile DM associated with severe corticosteroid-induced bone loss (osteoporosis) and calcinosis in an exoskeleton-like pattern. The patient was treated with diltiazem 5 mg/kg/day and pamidronate 4 mg/kg/day. After 21 months, clinical and radiological examination revealed dramatic regression of the calcinosis, and bone mass reached normal levels.
Balin SJ, Wetter DA, Andersen LK, Davis MD. Arch Dermatol 2012; 148: 455–62.
This retrospective study found that DM and systemic sclerosis were the most common autoimmune connective tissue diseases associated with calcinosis cutis. Therapy with diltiazem resulted in partial benefit in nine of 17 patients. Of 28 patients who had surgical excision of one or more lesions, 22 noted complete response, five had partial response, and one patient did not respond.
A wide variety of agents have been used in the treatment of DM-associated calcinosis although none are uniformly effective.
Kelly JJ, Madoc-Jones H, Adelman LS, Andres PL, Munsat TL. Muscle Nerve 1988; 11: 120–3.
Two patients with severe DM refractory to immunosuppressive therapy were treated with 15 Gy of total body irradiation over a period of 5 weeks. Both patients responded promptly, with minimal side effects, and remained in partial remission 42 and 18 months after completion of the treatment.
This observation offers another therapy to consider for patients with DM; however, no additional reports on this approach exist.
Hengstman GJ, De Bleecker JL, Feist E, Vissing J, Denton CP, Manoussakis MN, et al. Eur Neurol 2008; 59: 159–63.
Although case series and reports have suggested that anti-TNF-α agents may be useful agents in DM, this open-label trial found differing results. The trial was terminated prematurely due to low rate of patient acquisition, as well as poor responses in many patients. The authors conclude that TNF antagonists do not have a place in the therapeutic armamentarium of dermatomyositis.
Amato A. Ann Neurol 2011; 70: 427–36.
In this randomized double-blind placebo-controlled trial of 16 participants with DM on prednisone (11 randomized to etanercept arm 50 mg subcutaneously weekly for 52 weeks and five to placebo arm), a steroid-sparing effect was demonstrated in five patients in the treatment arm. There was no statistically significant difference in skin disease response assessed by CDASI between the groups. In addition, cutaneous disease worsened in five etanercept-treated patients, and two of these also developed a positive anti-nuclear antibody during the study period.
In addition to the potential worsening of muscle disease in patients with DM treated with anti-TNF-α therapy, reports of TNF inhibitor-associated DM have also recently been reported (Tumor necrosis factor inhibitor-associated dermatomyositis. Klein R, Rosenbach M, Kim EJ, Werth VP, Dunham J. Arch Dermatol 2010; 146:780–784). For these reasons, anti-TNF therapy is utilized with caution in patients with DM.
Sereda D, Werth VP. Arch Dermatol 2006; 142: 70–2.
In this report, two women experienced improvement in their DM-associated skin eruptions while taking anti-estrogen medication, either tamoxifen 10 mg twice daily, a selective estrogen receptor modulator, or anastrozole (dosage not specified), an aromatase inhibitor. When tamoxifen therapy was discontinued after 4 years of use in the first patient, her cutaneous DM worsened and remained difficult to control with conventional immunosuppressant medication.
This observation offers a novel approach to consider for women with DM; however, no further reports of either medication have appeared in the literature.
Nadiminti U, Arbiser JL. J Am Acad Dermatol 2005; 52: 17–19.
A single case of dermatomyositis that was recalcitrant to prior therapies responded to this anti-rejection agent 5 mg/day for 2 weeks, then 2 mg/day. Both muscle disease and skin manifestations were noted to improve.
Wang D, Zhang H, Cao M, Tang Y, Liang J, Feng X. J Ann Rheum Dis 2011; 70: 1285–8.
An open study of 10 patients with refractory DM (n = 4) or polymyositis who underwent stem cell transplantation (SCT) noted recurrence of disease in three patients and death in two patients. The remaining patients had improvement in muscle disease, pulmonary disease, and chronic cutaneous ulcers.
Other reports of patients with adult and juvenile DM have noted improvement in both skin disease and calcinosis following SCT in severe cases. Given infection risks, SCT is considered only in highly refractory cases at this time.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Sunscreens
Topical corticosteroids
Antimalarials – hydroxychloroquine or chloroquine
Combination antimalarial therapy
Systemic corticosteroids
Immunosuppressive agents – methotrexate, azathioprine
Topical calcineurin inhibitors (tacrolimus or pimecrolimus)
Methotrexate
Mycophenolate mofetil
Intravenous immunoglobulin
Other immunosuppressive agents – cyclophosphamide, chlorambucil, mycophenolate mofetil, cyclosporine, tacrolimus
Intravenous immunoglobulin
Rituximab
Dapsone for cutaneous disease
Thalidomide for cutaneous disease
Anti-estrogen medication for cutaneous disease
Diltiazem for calcinosis
Etanercept
Infliximab
Total body irradiation
Rituximab for cutaneous disease
Leflunomide
Sirolimus
Stem cell transplantation
