Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. In addition to the agents listed below, colchicine, alendronate, and warfarin, among other therapies, have been shown to be potentially beneficial for the treatment of calcinosis.
Prednisone is the first-line therapy for muscle involvement in dermatomyositis. The dose is altered according to the response of the patient’s condition.
Antimalarials, particularly hydroxychloroquine, may be useful for cutaneous disease; however, the majority of patients with cutaneous involvement require additional immunomodulatory medications for adequate control. Patients with dermatomyositis are at increased risk for drug eruptions with hydroxychloroquine.
Immunosuppressive/cytotoxic drugs are used as steroid-sparing agents for the muscle disease of dermatomyositis. Methotrexate has been demonstrated to be useful for skin disease, even in the absence of significant muscle disease, and is considered by many experts in the field to be first-line therapy for patients in whom antimalarials fail. [107, 108, 73, 37] Mycophenolate mofetil may also be useful for cutaneous disease.
Intravenous immunoglobulin (IVIG) is also beneficial for both cutaneous and muscular involvement. In July 2021, Octagam 10% gained FDA approval for dermatomyositis in adults. ProDERM, a prospective double-blind trial that is the first study to assess long-term efficacy and safety of IVIG (Octagam 10%), met its primary efficacy endpoint of at least minimal improvement as defined by the 2016 ACR/EULAR Myositis score without deterioration at 2 consecutive visits up to 16 weeks. [109]
Biologic therapies have been investigated as potential therapeutic options for dermatomyositis. Existing data regarding anti–tumor necrosis factor alpha therapies have been mixed, and raise potential concerns for use in the dermatomyositis population. Therefore, their widespread use is discouraged until adequate, preferably controlled, studies demonstrate their efficacy and safety.
A small, double-blind, placebo-controlled study of etanercept demonstrated a steroid-sparing effect in five of 11 etanercept-treated patients versus treatment failure in all five placebo-treated patients. The effects were mostly on muscle disease, but some positive effects on skin disease were noted, utilizing the Cutaneous Dermatomyositis Area and Severity Index (CDASI) as a measure. However, two patients in the treated group developed rash, and two developed antinuclear antibodies. One patient in the placebo group developed ovarian cancer, but none in the etanercept group developed cancer during the year-long treatment period. [110]
In addition, one retrospective review of eight patients with dermatomyositis or polymyositis treated with etanercept reported improvement in muscle disease in six patients. [111] However, a case series of five patients with dermatomyositis treated with etancercept found exacerbation of myositis and no improvement in skin disease in any patient. [112]
Infliximab has also been investigated in patients with dermatomyositis; however, results have not been promising. In an open study of 13 patients with refractory myositis, no improvement with infliximab was noted. [113] In addition, one study of infliximab combined with methotrexate for patients with myositis was terminated early due to a high drop-out rate and low inclusion rate. [114]
For these reasons, and because there are several reports of dermatomyositis induced by anti-tumor necrosis factor, [115] anti–tumor necrosis factor therapies should be used only rarely and with caution in patients with severe refractory dermatomyositis.
Disease-Modifying Antirheumatic Drugs
Class Summary
Disease-modifying antirheumatic drugs (DMARDs) can retard or prevent disease progression and, thus, joint destruction and subsequent loss of function.
Leflunomide (Arava)
Immunomodulatory agent; inhibits pyrimidine synthesis, which in turn results in antiproliferative and aniti-inflammatory effects.
Corticosteroids
Class Summary
The mainstay of therapy for patients with dermatomyositis and muscle involvement is systemic corticosteroids. Cutaneous disease has a variable response to systemic corticosteroids. Disease with pulmonary or cardiac involvement may respond, whereas disease involving esophageal dysfunction usually does not respond. Glucocorticoids may be used topically for cutaneous disease.
Prednisone (Rayos)
Prednisone is first-line therapy for dermatomyositis. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It may be beneficial to use intravenous (IV) pulses; this may be associated with a lower frequency of calcinosis.
Prednisolone (Prelone, Flo-Pred, Millipred)
Corticosteroids may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. Shown to improve patients with inflammatory myositis.
Immunosuppressive Agents
Class Summary
Immunosuppressive agents are used early in the treatment course as steroid-sparing agents. They decrease the risk of steroid-related complications.
Methotrexate (Trexall, Rheumatrex)
Methotrexate is used for managing constitutional symptoms. It blocks purine synthesis and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Methotrexate ameliorates symptoms of inflammation.
Azathioprine (Imuran, Azasan)
Azathioprine is a purine analogue that inhibits purine synthesis, resulting in inhibition of DNA, RNA, and protein synthesis. It may decrease proliferation of immune cells, thereby leading to lower autoimmune activity. It has few, if any, effects on the skin.
Mycophenolate (CellCept, Myfortic)
Mycophenolate is useful for both skin and muscle disease. It inhibits purine synthesis and proliferation of human lymphocytes.
Sirolimus (Rapamune)
Sirolimus inhibits lymphocyte proliferation by interfering with signal transduction pathways. It binds to immunophilin FK506 binding protein (FKBP) to block the action of mammalian target of rapamycin (mTOR). It is approved by the US Food and Drug Administration (FDA) for prophylaxis against organ rejection in patients receiving allogeneic renal allografts.
A cyclosporine-sparing regimen has recently been FDA-approved for patients with low-to-moderate rejection risk at 2-4 months after transplantation. This regimen allows cyclosporine to be withdrawn, thus significantly decreasing renal toxicity while maintaining a similar antirejection effect.
Rituximab (Rituxan)
Rituximab is a third-line choice for the treatment of dermatomyositis. It is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. It is an IgG1-kappa immunoglobulin that contains murine light- and heavy-chain variable region sequences and human constant region sequences.
Cyclophosphamide
Cyclophosphamide is used for immunosuppression in cases of autoimmune disorders. This agent is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Cyclosporine (Gengraf, Neoral, Sandimmune)
Cyclosporine (Gengraf, Neoral, Sandimmune)
Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions.
Chlorambucil (Leukeran)
Chlorambucil alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.
Immune Globulins
Class Summary
High-dose IVIG has been reported to be useful in patients with recalcitrant dermatomyositis.
Immune globulin, intravenous (Octagam)
IVIG is useful for patients in whom corticosteroids and immunosuppressants have failed. Octagam 10% has gained FDA approval for this indication in adults.
Calcium Channel Blockers
Class Summary
Calcium channel blockers may be useful for treating calcinosis.
Diltiazem (Cardizem, Cartia XT, Tiazac, Taztia XT)
During depolarization, diltiazem inhibits calcium ions from entering the slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. Treatment of calcinosis is an off-label use (the mechanism of action is unknown). It appears that other calcium channel blockers are not effective in this setting.
Calcium Metabolism Modifiers
Class Summary
Bisphosphonates are used to treat hypercalcemia and to decrease calcium loss from bone.
Pamidronate
Pamidronate inhibits bone resorption via actions on osteoclasts or on osteoclast precursors, without significant effects on renal tubular calcium handling. It is indicated for treatment of hypercalcemia. Intravenous (IV) pamidronate has been demonstrated in several cases to result in resolution of the calcinosis.
Alendronate (Fosamax, Binosto)
Alendronate has been successful in treating the pain of PFD; it may have some benefit in increasing bone mineral density as well. It offers the additional benefit of oral administration. Inhibits bone resorption via actions on osteoclasts or on osteoclast precursors. Has been shown to be potentially beneficial for the treatment of calcinosis
Antimalarials
Class Summary
Antimalarial agents may be used as steroid-sparing agents to treat skin disease. Hydroxychloroquine is preferred; chloroquine and quinacrine (100 mg/day) are second-line agents. Quinacrine may suppress bone marrow and is distributed by the Centers for Disease Control and Prevention (CDC); blood cell counts should be obtained regularly.
Hydroxychloroquine (Plaquenil)
Hydroxychloroquine may allow partial or complete control of the disease. Anecdotal evidence has suggested that morbilliform drug reactions are more common in patients with dermatomyositis than in those with other collagen vascular diseases. Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.
Chloroquine phosphate (Aralen)
Chloroquine phosphate inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.
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Heliotrope flower, for which characteristic manifestation of dermatomyositis is named.
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Heliotrope rash in a woman with dermatomyositis.
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Gottron papules and nailfold telangiectasia are present in this patient with dermatomyositis.
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These lesions on dorsal hands demonstrate photodistribution of dermatomyositis. Note sparing of interdigital web spaces.
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Diffuse alopecia with scaly scalp dermatosis is common in patients with dermatomyositis.
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Dermatomyositis is often associated with a poikiloderma in a photodistribution.
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Histopathology of dermatomyositis is interface dermatitis.
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Calcinosis caused by dermatomyositis in childhood can be observed in patient who had active dermatomyositis 15 years before time of this photograph.
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Histopathology of dermatomyositis showing inflammatory myopathic changes with a predominantly perivascular chronic inflammatory infiltrate.
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Calcifying panniculitis in patient with dermatomyositis.
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Ulceration over dorsal and lateral fingers in patient with dermatomyositis.
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Hematoxylin and eosin paraffin section shows polymyositis. Longitudinal section shows dense, chronic, endomysial inflammatory infiltrate. Image courtesy of Roberta J Seidman, MD.
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Hematoxylin and eosin frozen section shows polymyositis. Endomysial chronic inflammation is present among intact myofibers that are remarkable only for increased variability of fiber size. Image courtesy of Roberta J Seidman, MD.
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Hematoxylin and eosin paraffin section shows polymyositis. Patient had dense endomysial inflammation that contains abundance of plasma cells, which can be observed in patients with chronic polymyositis. Two necrotic myofibers, characterized by dense eosinophilic staining, are observed. Focal fatty infiltration of muscle is present in lower left quadrant of photomicrograph. Image courtesy of Roberta J Seidman, MD.
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Hematoxylin and eosin paraffin section shows polymyositis. Photomicrograph illustrates attack on nonnecrotic myofiber by autoaggressive T lymphocytes. On left, central myofiber is intact. On right, it is obliterated by segmental inflammatory attack. If immunohistochemistry were performed, expected findings would include admixture of CD8 T lymphocytes and macrophages in inflammatory process. Image courtesy of Roberta J Seidman, MD.
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Hematoxylin and eosin paraffin shows dermatomyositis. In dermatomyositis, inflammation is characteristically perivascular and perimysial. Vessel oriented approximately vertically in center has mild perivascular chronic inflammatory infiltrate. Endothelium is plump; wall is not necrotic. A few lymphocytes in wall of vessel are probably in transit from lumen to external aspect of vessel. Some observers may interpret this finding as vasculitis, but it is certainly neither necrotizing vasculitis nor arteritis. Image courtesy of Roberta J. Seidman, MD.
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Hematoxylin and eosin frozen section shows perifascicular atrophy in dermatomyositis. Fascicles in this sample show atrophy, predominantly at periphery, along connective-tissue border. Ischemia is considered to cause perifascicular atrophy. This finding is characteristic of dermatomyositis, mostly associated with juvenile form but also observed in adult form. Image courtesy of Roberta J Seidman, MD.
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Immunofluorescence for membrane attack complex of complement (MAC) in dermatomyositis. Bright ring of yellow-green fluorescence at center represents MAC in wall of microvessel. Finding was not present after treatment with steroids. Image courtesy of Roberta J Seidman, MD.
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A 47-year-old woman presented with a pruritic, diffuse rash across her upper hands and face that is worsened with sun exposure. ANA testing by outside providers was negative. Her rash was not responsive to topical steroids, and improved with oral prednisone but recurred with tapers beyond 15 mg daily. Diagnosis was dermatomyositis sine myositis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
