Version May 2024
INTRODUCTION — Classic dermatomyositis (DM) is an idiopathic inflammatory myopathy that most commonly presents with progressive, symmetric, proximal muscle weakness and a group of characteristic cutaneous findings. The cutaneous manifestations may also develop in the absence of detectable muscle disease and can persist after the successful treatment of DM-associated myositis.
In addition to pathognomonic findings, such as Gottron's papules and the heliotrope eruption, DM often presents with intensely pruritic areas of confluent, violaceous erythema on the scalp, face, upper trunk, and upper extremities (picture 1A-D). The pruritus can be disabling.
Skin lesions of DM are often resistant to photoprotection and topical therapies alone, necessitating the initiation of antimalarial drugs and/or methotrexate. Patients who fail to respond to these interventions may require more aggressive immunosuppressive or immunomodulatory therapies.
The initial management of the cutaneous manifestations of DM will be discussed here (algorithm 1). The treatment of refractory cutaneous DM, as well as the clinical manifestations, diagnosis, and management of the noncutaneous manifestations of DM and juvenile DM, are reviewed elsewhere.
●(See "Management of refractory cutaneous dermatomyositis in adults".)
●(See "Clinical manifestations of dermatomyositis and polymyositis in adults".)
●(See "Initial treatment of dermatomyositis and polymyositis in adults".)
●(See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults".)
●(See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment".)
●(See "Juvenile dermatomyositis and other idiopathic inflammatory myopathies: Diagnosis".)
●(See "Juvenile dermatomyositis and polymyositis: Treatment, complications, and prognosis".)
OVERVIEW OF CLINICAL FEATURES
Cutaneous findings — Skin changes associated with dermatomyositis (DM) include pathognomonic findings, such as Gottron's papules (pink-violaceous papules overlying interphalangeal and metacarpophalangeal joints), Gottron's sign (macular, pink-violaceous erythema overlying other joints, such as the elbows or knees), and the heliotrope eruption (pink-violaceous erythema, with or without edema, involving the periorbital skin) (picture 2A-D). Pink-violaceous erythema of the scalp, V of the neck, shoulders, extensor surfaces of the upper extremities, upper chest, and upper back are additional characteristic findings (picture 1A-D). Scale may or may not be present but is typically prominent on the scalp, where it may be accompanied by diffuse alopecia (picture 1E).
In patients with darker skin types, cutaneous lesions often exhibit a more violaceous hue and may also exhibit prominent hyperpigmentation (picture 3). In patients with lighter skin types, cutaneous lesions tend to appear pink to red, although some will also demonstrate the characteristic violaceous hue. Additional examples of cutaneous manifestations of DM include poikiloderma, calcinosis cutis, prominent periungual telangiectasias, and cuticular hypertrophy. Panniculitis presenting as erythematous, tender, subcutaneous nodules on the lower or upper extremities is a rare manifestation [1]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Skin findings in dermatomyositis' and "Calcinosis cutis: Etiology and patient evaluation".)
The distribution of cutaneous lesions in DM suggests that photosensitivity may contribute to the development of skin lesions. Similar to findings in lupus erythematosus, significantly reduced minimal erythema doses (MEDs; the minimal irradiation dose required to elicit cutaneous erythema) to ultraviolet B (UVB) light have been detected in patients with DM [2]. In one study in which 19 patients with DM were irradiated with UVB light, 9 (47 percent) exhibited reduced MEDs [2]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Phototesting'.)
Impact on quality of life — Quality-of-life impairment related to skin disease is significant in DM and has been shown to be greater in patients with DM than in patients with psoriasis or atopic dermatitis [3]. Patients frequently experience debilitating symptoms of severe pruritus or burning in affected areas, which can result in emotional distress and loss of sleep. Scalp pruritus may be particularly intense and is the initial presenting symptom in DM in some patients.
Disease course — Cutaneous disease may persist for years. In one systematic review of primarily adult patients with cutaneous DM without myositis, the mean duration of skin disease was 4.5 years [4]. (See "Initial treatment of dermatomyositis and polymyositis in adults".)
CLASSIFICATION OF CUTANEOUS DERMATOMYOSITIS — Most patients with dermatomyositis (DM) exhibit both cutaneous disease and muscle weakness (classic DM). However, a subset of patients develops characteristic skin findings of DM in the absence of muscle symptoms. This group is often referred to as clinically amyopathic dermatomyositis (CADM) and consists of both patients who lack clinical findings of myositis, but have evidence for myositis on laboratory, radiologic, or electrophysiologic studies (hypomyopathic DM), and patients in whom all signs of muscle involvement are absent (amyopathic DM) [5]. It is estimated that 9 to 13 percent of patients with CADM for more than six months eventually develop classic disease [4,5]. Descriptions of the various presentations of cutaneous DM are reviewed below.
Classic dermatomyositis — Most patients with DM present with simultaneous cutaneous and muscle involvement, evidenced by proximal muscle weakness and diagnostic testing that reveals the presence of myositis. However, the onset of cutaneous disease can precede the appearance of myositis by up to several months in 30 percent of patients with classic DM and follows shortly after muscle involvement in 10 percent [4]. The term "premyopathic dermatomyositis" is used to describe patients who have no clinical evidence for muscle disease but have had cutaneous manifestations of DM for less than six months.
Amyopathic dermatomyositis — Historically, amyopathic DM was known as "dermatomyositis sine myositis." This variant is considered a distinct form of DM, rather than classic DM in which the onset of muscle involvement is delayed for a prolonged period. Amyopathic DM is diagnosed in patients who lack muscle weakness and have no laboratory or radiologic signs of myositis despite the presence of cutaneous findings consistent with DM for at least six months [5]. Of note, the use of immunosuppressive drugs for cutaneous DM for two consecutive months or longer within the first six months of skin disease may prevent the development of clinically significant myositis [5]. In addition, the presence of drug-induced, DM-like cutaneous changes, such as can occur with hydroxyurea, must be excluded.
Approximately 10 to 20 percent of patients with DM seen in academic health centers have amyopathic disease [6]. The proportion may be higher among patients referred to dermatologists; in one dermatology referral center, approximately 40 percent of patients with DM had the amyopathic variant [7].
Hypomyopathic dermatomyositis — Similar to amyopathic DM, hypomyopathic DM presents with cutaneous findings consistent with DM and the absence of clinically appreciable muscle weakness for at least six months after the appearance of skin lesions [5]. In contrast to amyopathic disease, subclinical evidence for myositis is evident through serologic testing for muscle enzymes, electromyography (EMG), muscle biopsy, or magnetic resonance imaging (MRI).
Hypomyopathic DM is less common than amyopathic DM; among 281 patients with CADM in a systematic review, 37 (13 percent) had hypomyopathic disease and 197 (70 percent) had amyopathic DM.
Postmyopathic dermatomyositis — In classic DM, cutaneous and muscle disease often have a discordant response to therapy. Postmyopathic DM describes the persistence of cutaneous symptoms following the resolution of muscle disease with immunosuppressive therapy [4,5].
PATIENT EVALUATION
Indications for biopsy — A diagnosis of cutaneous dermatomyositis (DM) is suggested by the constellation of characteristic cutaneous findings, muscle weakness, and laboratory evidence of myositis. However, in patients who present with ambiguous cutaneous findings or cutaneous findings that are suggestive of DM in the absence of clinical signs of muscle disease, a skin biopsy should be performed.
The histopathologic findings in DM are variable but typically include an interface dermatitis characterized by vacuolization of basal keratinocytes, a lymphocytic infiltrate in the superficial dermis, and dermal mucin. The biopsy is useful for ruling out other disorders that may resemble DM, including seborrheic dermatitis, contact dermatitis, atopic dermatitis, polymorphous light eruption, and papulosquamous disorders (such as lichen planus or psoriasis). (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Muscle biopsy'.)
The greatest challenge in the diagnosis of DM involves the distinction between amyopathic DM and acute cutaneous lupus erythematosus (ACLE) or subacute cutaneous lupus erythematosus (SCLE), which, like DM, can present with photodistributed erythema and elevated antinuclear antibodies. The histopathologic findings of DM are indistinguishable from those of ACLE and SCLE. Of note, the intense pruritus often associated with DM usually does not occur in patients with ACLE or SCLE. In addition, the malar rash of ACLE traditionally spares the nasolabial folds, while the midfacial erythema of DM often involves these areas. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults" and "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Muscle biopsy'.)
Additional tests — In the patient who presents with cutaneous features that are consistent with DM, investigation for concomitant muscle disease should be performed. Due to the possibility of subsequent development of muscle disease, patients without myositis should be evaluated with a muscle examination and serum creatinine kinase and aldolase levels every two to three months [8]. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Testing for myopathy'.)
As in classic DM, adults with clinically amyopathic dermatomyositis (CADM) have an increased risk for pulmonary disease and internal malignancy. Thus, patients should be evaluated and followed for the presence of these disorders. In a systematic review that analyzed 291 adult patients with CADM, 36 (13 percent) developed interstitial lung disease, and 41 cases (14 percent) were found to be associated with internal malignancy [5]. Juvenile DM is not associated with pulmonary disease or an increased risk for malignancy. (See "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis", section on 'Evaluation' and "Malignancy in dermatomyositis and polymyositis", section on 'Approach to screening' and "Juvenile dermatomyositis and polymyositis: Treatment, complications, and prognosis", section on 'Risk of malignancy'.)
TREATMENT — Therapy for cutaneous disease is usually indicated due to the presence of severe pruritus and patient distress over the appearance of skin lesions.
Challenges — The management of cutaneous manifestations of dermatomyositis (DM) can be challenging. Cutaneous manifestations are often more resistant to therapy than concomitant muscle involvement.
In addition, the best therapeutic approach for the cutaneous manifestations of DM remains unclear. Data on therapies are limited and primarily restricted to case reports and retrospective studies, although randomized clinical trials are emerging in DM [9-11]. Interpretation of the available literature is difficult because many studies have included patients with different variants of DM (eg, DM, polymyositis, and antisynthetase syndrome; both adult and juvenile DM; or both classic and amyopathic DM) or patients who are also receiving systemic glucocorticoids or other immunosuppressive therapies for muscle disease.
Moreover, the historical lack of standardized measures to assess responses to therapy has compromised the systematic interpretation of published literature. The consistent use of validated, objective measures of response to therapy, such as the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), will be useful for interpreting the results of future studies [12,13].
Treatment overview — A multipronged approach to treatment is often necessary to achieve a satisfactory response in patients with cutaneous DM (algorithm 1).
Our initial approach to patients with cutaneous DM typically consists of four elements:
●Aggressive photoprotection to reduce the exacerbating effects of ultraviolet light
●Antipruritic agents to manage the associated (and often severe) pruritus
●Topical corticosteroids or topical calcineurin inhibitors for local treatment of skin manifestations
●Systemic medications aimed at attaining sustained control of the disease
A small subset of patients with very mild cutaneous DM can achieve satisfactory improvement with the first three interventions. However, most patients with cutaneous manifestations of DM also require systemic treatment with antimalarial drugs, methotrexate, or other medications. (See 'Selection of systemic therapy' below and "Management of refractory cutaneous dermatomyositis in adults".)
Interventions for all patients — Implementation of photoprotection, antipruritic therapies, and topical corticosteroid or topical calcineurin inhibitor therapy is suggested for all patients (algorithm 1).
Photoprotection — Strict photoprotection is considered an integral part of the treatment of cutaneous DM because ultraviolet light exposure may exacerbate cutaneous disease [2,14,15]. Even limited sun exposure can be detrimental [15]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection".)
Year-round daily photoprotection with a broad-spectrum sunscreen with a sun protection factor (SPF) of at least 30 is recommended, and reapplication should occur every three to four hours [16]. Wide-brimmed hats, sun-protective clothing, and avoidance of sun exposure should also be encouraged. Given the degree of photoprotection mandated in this patient population, consideration should be given to vitamin D status and vitamin D supplementation. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection' and "Selection of sunscreen and sun-protective measures" and "Vitamin intake and disease prevention", section on 'Vitamin D'.)
Interventions for pruritus — Pruritus is a prominent feature of DM and can have significant adverse effects on quality of life [3,17]. Pruritus can interfere with sleep patterns and activities of daily living and should be treated aggressively with topical or oral antipruritic agents:
●Topical antipruritic therapies – Topical agents containing pramoxine, menthol, or camphor may provide temporary symptomatic relief. Topical corticosteroid therapy, as described below, may also improve pruritus. (See 'Topical corticosteroids' below.)
●Oral antipruritic therapies – Use of oral sedating antihistamines (eg, hydroxyzine, cyproheptadine, or doxepin) or other agents, such as amitriptyline or gabapentin, is often necessary to improve pruritus. Nonsedating antihistamines are not beneficial. (See "Pruritus: Therapies for generalized pruritus", section on 'General approach'.)
Skin-directed therapy — The relative safety of topical anti-inflammatory agents, including topical corticosteroids and topical calcineurin inhibitors, favors the use of these drugs in DM. However, most patients require combination therapy with a systemic agent. (See 'Selection of systemic therapy' below.)
Topical corticosteroids are generally the preferred initial topical therapies for involvement on the scalp, trunk, and extremities. Topical calcineurin inhibitors are more expensive than most topical corticosteroids and are typically reserved for patients who do not improve with topical corticosteroids or for long-term topical therapy in areas prone to corticosteroid-induced cutaneous atrophy, such as the face. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)
Topical corticosteroids — Clinical experience supports the use of topical corticosteroids for reducing the erythema and pruritus associated with DM [18]. In general, topical corticosteroids are considered adjunctive as most patients will require systemic therapy to adequately treat their DM skin disease. High-potency (eg, group 1) topical corticosteroids are often used to treat the hands, extensor surfaces, and scalp, where the risk of corticosteroid-induced cutaneous atrophy is low, while lower-potency agents (eg, groups 6 to 7) are used for disease in areas that are more prone to atrophy, such as facial erythema and the heliotrope eruption (table 1).
Application with occlusion (ie, coverage of the site of application by a bandage, gloves, or other dressing) increases the penetration and potency of topical corticosteroids, and the use of high-potency topical corticosteroids under occlusion may be beneficial for refractory, hyperkeratotic lesions, particularly those on the dorsal hands [4]. Topical corticosteroids are generally applied once daily when occlusion is used and twice daily in the absence of occlusion. Foam, spray, gel, oil, shampoo, or solution formulations may facilitate application on hairy areas, such as the scalp. Some experts have found topical clobetasol foam particularly helpful for scalp involvement [4].
Improvement in erythema and pruritus from topical corticosteroid therapy is usually evident within two weeks, but continued treatment is often necessary to maintain the response. Upon achievement of a satisfactory response, the application frequency and potency of the topical corticosteroid can be gradually reduced, as tolerated. The inclusion of treatment-free periods (eg, two weeks on, two weeks off therapy) is suggested to reduce the risk of local and systemic adverse effects. When long-term, continuous use of a topical corticosteroid appears necessary, a topical calcineurin inhibitor can be initiated as a corticosteroid-sparing therapy. (See 'Topical calcineurin inhibitors' below.)
Intralesional corticosteroid therapy is occasionally used for refractory lesions or for scalp disease; however, intralesional therapy is often impractical given the extent of cutaneous disease [18]. (See "Intralesional corticosteroid injection".)
Topical corticosteroids can induce local cutaneous atrophy, particularly in the setting of long-term use of high-potency agents. In addition, systemic absorption can lead to suppression of the hypothalamic-pituitary axis, particularly when used in patients with widespread disease. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)
Topical calcineurin inhibitors — Topical calcineurin inhibitors (most often tacrolimus 0.1% ointment) are typically utilized for patients who do not improve with topical corticosteroids or for long-term topical therapy in areas that are prone to cutaneous atrophy. Topical calcineurin inhibitors are applied to affected skin twice daily. Improvement in erythema and symptoms may be evident within the first month of treatment [19,20].
Several case reports and a small, uncontrolled study have documented successful treatment of cutaneous disease in DM with topical tacrolimus [6,19-22]. All patients were on additional therapeutic agents at the time of treatment. In the uncontrolled study, six patients (five adults and one child) were treated with tacrolimus 0.1% ointment for six to eight weeks [22]. Dramatic (>90 percent) improvement was noted in two patients, and moderate (40 to 90 percent) or minimal (20 to 40 percent) improvement was noted in one and three patients, respectively [22].
In contrast, a prospective study of five patients with cutaneous DM found a lack of benefit with topical tacrolimus [23]. No difference in disease severity was detected between skin treated with tacrolimus 0.1% ointment (twice daily for two months) and contralateral skin that was not treated with tacrolimus.
Additional studies are necessary to determine the efficacy of topical calcineurin inhibitors for cutaneous manifestations of DM. Documentation of a beneficial effect of pimecrolimus for cutaneous DM is limited to case reports documenting improvement after several months of treatment [24]. We personally have noted modest success with this drug.
Pruritus or burning sensations at sites of application are potential adverse effects of topical calcineurin inhibitors. In addition, rare reports of the development of internal malignancies in patients treated with these agents led the US Food and Drug Administration to place a boxed warning on topical tacrolimus and pimecrolimus drug labels. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical calcineurin inhibitors'.)
Selection of systemic therapy — Most patients require systemic therapy to achieve satisfactory suppression of cutaneous disease. The goals of systemic treatment are to achieve resolution of pruritus and skin changes or to achieve a level of improvement in which mild, residual disease can be successfully managed with topical therapy. The clinical presentation influences the approach to treatment (algorithm 1).
Patients with extracutaneous involvement — Improvement in skin disease may occur during treatment for extracutaneous manifestations of DM, such as during treatment with systemic glucocorticoids or methotrexate, common initial treatments for muscle disease. Thus, in this population, the need for systemic therapy specifically for skin disease usually occurs when there is persistent activity of cutaneous DM despite adequate control of extracutaneous DM (eg, postmyopathic DM) and appropriate use of photoprotection and skin-directed therapies. The approach to the treatment of cutaneous manifestations in this population is similar to the approach for patients without extracutaneous DM. (See "Initial treatment of dermatomyositis and polymyositis in adults" and 'Mild cutaneous dermatomyositis' below and 'Severe cutaneous dermatomyositis' below.)
The type of extracutaneous involvement present may also influence treatment selection. For example, methotrexate is associated with risk for pulmonary toxicity and would be a less favorable choice for skin disease in patients with DM-associated interstitial lung disease. (See "Initial treatment of dermatomyositis and polymyositis in adults" and "Interstitial lung disease in dermatomyositis and polymyositis: Treatment".)
Of note, continuation of systemic glucocorticoid therapy is not advised for the treatment of cutaneous DM when systemic glucocorticoids are no longer required for other manifestations of DM. The potential for serious adverse effects from long-term glucocorticoid treatment and the limited evidence for efficacy of systemic glucocorticoid therapy for cutaneous disease preclude routine use of systemic glucocorticoid therapy [4]. (See "Major adverse effects of systemic glucocorticoids".)
Mild cutaneous dermatomyositis — Mild cutaneous DM is generally considered skin disease that involves a limited body surface area and/or causes minimal pruritus. With the exception of patients with very mild cutaneous DM, photoprotection, antipruritic agents, topical corticosteroids, and topical calcineurin inhibitors alone are generally insufficient for achieving adequate improvement in cutaneous DM; therefore, we typically begin systemic therapy immediately (algorithm 1). The primary systemic agents used for initial management are antimalarial drugs (eg, hydroxychloroquine, quinacrine, chloroquine) and methotrexate.
Preferred initial therapy — Hydroxychloroquine is often used as a first-line therapy for mild cutaneous DM based upon the long history of its use for this indication, the overall well-tolerated nature of this drug, and small, uncontrolled studies that have supported its efficacy (algorithm 1). However, many patients may require additional systemic therapy [25]. (See 'Hydroxychloroquine' below and 'Patients with poor response to hydroxychloroquine' below.)
Of note, antimalarial drugs, such as hydroxychloroquine, do not appear to be useful for other common manifestations of DM, such as muscle or pulmonary disease [26]. This observation suggests that the beneficial effects of antimalarials on the skin may be a result of photoprotective properties of antimalarials rather than systemic immunomodulation. Alternatively, the difference in efficacy may be a result of divergent pathogenic mechanisms for skin and muscle disease [27,28]. (See "Initial treatment of dermatomyositis and polymyositis in adults".)
Hydroxychloroquine — Hydroxychloroquine may improve the cutaneous manifestations of DM:
●Administration and efficacy – The typical total daily dose for cutaneous DM in adults is 300 to 400 mg daily, divided over two doses daily. The total daily dose should be less than or equal to 5 mg/kg (based upon real body weight) to minimize risk for hydroxychloroquine-induced retinopathy [29]. Smoking may decrease the efficacy of antimalarial drugs [30,31], and smoking cessation should be encouraged in patients who receive antimalarial therapy. (See "Antimalarial drugs in the treatment of rheumatic disease".)
Responses to antimalarial medications may not be evident until 6 to 12 weeks after the initiation of therapy [4]. A three-month trial is an appropriate period for the assessment of treatment efficacy.
Evidence for the efficacy of hydroxychloroquine is limited to small, uncontrolled studies. An open study of seven patients in whom cutaneous DM persisted during systemic glucocorticoid therapy or worsened during glucocorticoid tapering found that the addition of hydroxychloroquine to the therapeutic regimen led to complete resolution of skin disease in three patients and partial improvement in the other four [32]. Additional small, retrospective studies also demonstrate favorable results with hydroxychloroquine for cutaneous DM [33-36].
An analysis of a series of 115 patients with amyopathic or hypomyopathic DM managed at tertiary care centers suggests that systemic therapy with hydroxychloroquine alone may not be sufficient for many patients with cutaneous DM; only 10 of 88 patients (11 percent) treated with antimalarial therapy achieved control of skin disease [25]. The severity of disease in patients included in the study was not assessed.
●Adverse effects – Ocular, gastrointestinal, hematologic, and neurologic adverse effects may occur secondary to antimalarial therapy. The risk of irreversible retinopathy is restricted to hydroxychloroquine and chloroquine. Thus, patients treated with either of these drugs should have a baseline ophthalmologic examination prior to, or soon after, the initiation of therapy and require follow-up for the development of retinal abnormalities [29]. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects' and "Antimalarial drugs in the treatment of rheumatic disease", section on 'Monitoring for toxicity'.)
Cutaneous adverse effects related to hydroxychloroquine treatment have also been reported in patients with DM. Retrospective studies suggest cutaneous drug eruptions secondary to hydroxychloroquine occur in approximately 30 percent of patients with DM [25,37]. The eruption is most often a morbilliform eruption, but the development of bullae or drug reaction with eosinophilia and systemic symptoms (DRESS) is possible. In addition, worsening of cutaneous disease has been reported in two children with DM after the initiation of hydroxychloroquine [38]. The autoantibody phenotype may influence risk for cutaneous adverse reactions [39].
Patients with poor response to hydroxychloroquine — When the response to hydroxychloroquine is inadequate, we typically add quinacrine or methotrexate to hydroxychloroquine therapy in an attempt to augment the response (algorithm 1). Methotrexate may be used alone for patients who cannot tolerate antimalarial therapy.
The efficacy of hydroxychloroquine plus quinacrine versus hydroxychloroquine plus methotrexate for cutaneous DM has not been directly compared, leaving uncertainty regarding relative efficacy. Our selection of quinacrine versus methotrexate is often influenced by patient comorbidities and disease severity. Although quinacrine offers the advantage of a more benign adverse effect profile, in our experience, the combination of hydroxychloroquine and methotrexate often provides a more substantial response than the combination of hydroxychloroquine and quinacrine. Thus, for patients who are likely to tolerate either agent, we tend to favor the addition of methotrexate as disease severity increases. (See 'Severe cutaneous dermatomyositis' below.)
Substitution of hydroxychloroquine with chloroquine is an alternative for patients with insufficient responses to hydroxychloroquine that we use less frequently because of greater concern for ocular toxicity. (See 'Chloroquine' below.)
Therapeutic options for patients who fail to respond to antimalarials and methotrexate are reviewed separately. (See "Management of refractory cutaneous dermatomyositis in adults".)
Quinacrine — The addition of quinacrine (100 mg per day) to hydroxychloroquine or chloroquine therapy may improve the response to treatment. In the United States, quinacrine can only be obtained at compounding pharmacies. In addition, it is not approved for human use in the United States. Limited availability and increased cost has made obtaining quinacrine difficult in the United States:
●Administration and efficacy – Similar to hydroxychloroquine, responses to quinacrine may not be evident before six to eight weeks. At least three months of treatment is suggested prior to assessing the response to treatment.
In a retrospective case series in which 7 out of 17 patients (41 percent) with DM experienced at least near clearance of cutaneous disease with antimalarial therapy alone, 4 of the responders required the addition of quinacrine to hydroxychloroquine or chloroquine therapy to achieve this level of improvement [40]. This observation suggests that a subset of patients may benefit from combination antimalarial therapy after failure to respond sufficiently to monotherapy.
●Adverse effects – Reversible yellow discoloration of the skin is a common adverse effect of quinacrine. Quinacrine does not cause retinopathy, which enables use of the drug in patients taking hydroxychloroquine or chloroquine. In contrast, hydroxychloroquine and chloroquine, both of which can induce ocular damage, should not be taken simultaneously. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects'.)
Methotrexate — Methotrexate can be effective for cutaneous disease in DM; however, the drug has a broader side effect profile than hydroxychloroquine, supporting the use of hydroxychloroquine as the initial choice of therapy in patients with mild disease (algorithm 1):
●Administration and efficacy – Methotrexate is taken on a weekly basis and can be given orally, intramuscularly, or subcutaneously. Methotrexate is not given daily.
Treatment with methotrexate requires monitoring of complete blood counts, liver function, and renal function. Prior to administering methotrexate, we obtain baseline laboratory tests (complete blood count, renal function tests, and liver function tests). In addition, we assess patients for hepatitis B and C because chronic liver disease is a risk factor for methotrexate-induced hepatotoxicity.
We usually begin at a dose of 5 to 10 mg per week, depending upon the patient's age and health status (eg, healthy people under 65 years of age may begin at 7.5 or 10 mg weekly, whereas those with renal insufficiency or other comorbidities that may make tolerating methotrexate more challenging may be started at 5 mg/week).
Laboratory tests (complete blood count with differential, hepatic function panel, and renal function) are checked after two weeks, and if normal and the patient is not experiencing any clinical side effects, the weekly dose is increased. Various methods are utilized in terms of dose escalation. Some experts increase the weekly dose by 2 to 5 mg per week (depending on the patient's age and health status) every one to two weeks until the target dose is reached, checking laboratory tests every two weeks. Others choose to increase the dose directly to 25 mg after the first two-week laboratory check in healthy patients.
We typically titrate methotrexate up to a dose of 25 mg/week, although occasionally, doses of up to 30 mg weekly are used [41]. We hold at that dose for at least 12 weeks, as the onset of action of methotrexate is frequently not seen until two to three months of therapy at the "full" "target" dose. Because absorption of oral methotrexate may be reduced at higher doses [42], when doses exceed 15 mg/week, we split the total dose of methotrexate into a morning and an evening dose or instruct the patient to take the second half of the dose on the following day.
Once the dose of methotrexate is stable, laboratory tests are repeated every two to three months. Improvement in cutaneous manifestations usually occurs within eight to twelve weeks.
Administration of folic acid (1 mg per day) or leucovorin (5 mg per week, 8 to 12 hours after methotrexate administration in patients who do not respond sufficiently to folic acid) may decrease the incidence of some methotrexate-induced adverse effects.
The efficacy of methotrexate for the cutaneous manifestations of DM has not been studied in randomized trials, and evidence for the support of this therapy is primarily limited to retrospective analyses [43-46]. In one retrospective study of 13 patients with cutaneous DM who were treated with methotrexate (2.5 to 30 mg/week), eight achieved complete or almost complete clearance of skin lesions [45]. All patients who were simultaneously treated with systemic glucocorticoids were able to reduce or discontinue glucocorticoid therapy.
The presence of an abundant lymphocytic infiltrate on skin biopsy seemed to portend an increased likelihood for a response to methotrexate (7.5 to 20 mg/week) in a separate retrospective study in which 8 of 11 patients who failed to improve adequately with systemic glucocorticoids improved during methotrexate therapy [46]. However, further investigations are necessary to confirm this finding.
●Adverse effects – Gastrointestinal upset, stomatitis, and leukopenia can occur during treatment with methotrexate but may be minimized by folic acid or leucovorin supplementation. Hepatotoxicity and pulmonary fibrosis are additional adverse effects associated with this drug [43]. (See "Major side effects of low-dose methotrexate".)
Due to the risk of liver toxicity, pre-existing liver disease and alcohol abuse are relative contraindications for methotrexate. In addition, the risk of methotrexate toxicity is increased in patients with renal insufficiency; doses must be adjusted in this population.
Teratogenicity is another potential adverse effect of methotrexate; the drug should not be given to pregnant women. Methotrexate should also be avoided in women for one to three menstrual cycles prior to pregnancy and in men for one month prior to an attempt to conceive.
Chloroquine — An alternative intervention for patients who fail to respond adequately to hydroxychloroquine is to discontinue hydroxychloroquine and switch to chloroquine (250 mg per day). This concept is based upon the perception that some patients who do not respond to hydroxychloroquine can respond to chloroquine, although the response to a switch appears variable and data to confirm greater efficacy of chloroquine in cutaneous DM are lacking [40]. Similar to hydroxychloroquine, responses may not be evident until six to eight weeks after treatment initiation. A reasonable trial period for assessment of effect is three months.
The greater risk for drug-induced retinopathy from chloroquine compared with hydroxychloroquine contributes to our preference for hydroxychloroquine for first-line therapy [47]. To minimize the risk for retinopathy, the dose of chloroquine should not exceed more than 3 mg/kg per day based upon the patient's ideal body weight. (See "Antimalarial drugs in the treatment of rheumatic disease".)
Severe cutaneous dermatomyositis — Often, despite its broader side effect profile, we utilize methotrexate alone or in combination with hydroxychloroquine rather than hydroxychloroquine alone as the initial systemic treatment for severe cutaneous DM (algorithm 1). Severe cutaneous DM is generally considered disease that is associated with intolerable pruritus, impacts a substantial body surface area, or is otherwise disabling. The regimen for methotrexate is similar to the regimen used for milder disease.
The preference for methotrexate for severe disease is based upon clinical experience that suggests methotrexate may be more effective than hydroxychloroquine for cutaneous DM. In one series of 115 patients with amyopathic or hypomyopathic DM managed at four tertiary care centers, only 10 of 88 patients (11 percent) treated with antimalarial drugs achieved control of skin disease [25].
Clinicians vary on the approach to methotrexate therapy. While some clinicians, including the author, prefer to start methotrexate and hydroxychloroquine simultaneously, others assess the response to methotrexate and subsequently add hydroxychloroquine if there is an insufficient response to therapy.
Tapering of systemic therapy — Once a patient achieves satisfactory improvement with antimalarial and/or methotrexate therapy and maintains the response for several months, slow tapering of the treatment should be attempted to reach the lowest dose necessary to maintain the response. For patients who respond to combination therapy with hydroxychloroquine and quinacrine or hydroxychloroquine and methotrexate, we typically attempt to discontinue quinacrine or methotrexate prior to tapering hydroxychloroquine. Quinacrine can be stopped acutely without tapering. We generally taper the weekly dose of methotrexate by 2.5 to 5 mg every two to three months, provided relapse has not occurred.
Cutaneous DM is usually a chronic condition. In our experience, many patients require continuation of some level of systemic therapy for years. (See 'Disease course' above.)
Recurrent and resistant disease — Some patients with DM may relapse after an initial response to the above therapies or may fail to respond to these treatments [48]. The management of patients with recalcitrant or recurrent DM is reviewed separately (algorithm 1). (See "Management of refractory cutaneous dermatomyositis in adults".)
Other therapies — Treatment with topical brimonidine, an alpha-2 adrenergic agonist used to improve facial erythema in patients with rosacea, appeared effective for temporarily improving DM-associated facial erythema in a single patient with amyopathic DM [49]. Further study is necessary prior to a recommendation for the use of this therapy for cutaneous DM.
CALCINOSIS CUTIS — The treatment of calcinosis cutis in patients with dermatomyositis (DM) is reviewed elsewhere. (See "Management of refractory cutaneous dermatomyositis in adults", section on 'Calcinosis cutis' and "Calcinosis cutis: Etiology and patient evaluation" and "Calcinosis cutis: Management".).
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dermatomyositis and polymyositis".)
SUMMARY AND RECOMMENDATIONS
●General principles – Dermatomyositis (DM) is an idiopathic inflammatory disorder for which cutaneous findings are a prominent feature. Inflammatory myopathy also frequently occurs in DM but may precede, follow, or remain absent in patients with cutaneous manifestations of the disease. In some patients, cutaneous findings may persist after the successful treatment of myositis. (See 'Overview of clinical features' above and 'Classification of cutaneous dermatomyositis' above.)
●Clinical features – Patients with DM often present with a pruritic, pink-violaceous, macular, and papular eruption that primarily affects the upper body (picture 1D-E). Pruritus can be intense and may have significant effects on patient quality of life. (See 'Overview of clinical features' above.)
●Management – Data on treatment options for the cutaneous manifestations of DM are limited. Photoprotection, management of pruritus, and topical therapy are important components of management for all patients. Most patients also require systemic therapy to achieve control of cutaneous DM (algorithm 1) (see 'Treatment overview' above and 'Interventions for all patients' above):
•Skin-directed therapy – For patients with cutaneous manifestations of DM, we suggest topical corticosteroids for initial topical therapy (Grade 2C). Topical calcineurin inhibitors are an additional option that may be useful for long-term treatment in skin areas at greatest risk for corticosteroid-induced skin atrophy. (See 'Skin-directed therapy' above.)
•Systemic therapy:
-Associated extracutaneous involvement – Cutaneous DM may improve during treatment of other manifestations of DM, such as myositis. The need for systemic treatment specifically for cutaneous disease typically arises when active skin disease persists despite adequate control of other manifestations. (See 'Patients with extracutaneous involvement' above.)
-Mild cutaneous dermatomyositis – For patients with mild cutaneous DM (eg, less than 10 percent body surface area involvement, tolerable pruritus, and nondisabling), we suggest hydroxychloroquine rather than methotrexate as the initial systemic therapy (Grade 2C). For patients who do not improve sufficiently with hydroxychloroquine, we suggest the addition of quinacrine or methotrexate (Grade 2C). (See 'Mild cutaneous dermatomyositis' above.)
-Severe cutaneous dermatomyositis – For patients with severe cutaneous DM (eg, at least 10 percent body surface area involvement, intolerable pruritus, or otherwise disabling disease), we suggest methotrexate rather than hydroxychloroquine as the initial systemic therapy (Grade 2C). Methotrexate and hydroxychloroquine may be started simultaneously or hydroxychloroquine may subsequently be added if there is an insufficient response to methotrexate. (See 'Severe cutaneous dermatomyositis' above.)
•Role of systemic glucocorticoids – Systemic glucocorticoids are not indicated for the initial management of cutaneous DM. The response to systemic glucocorticoids is unpredictable, and the adverse effects associated with long-term therapy limit the use of these drugs for cutaneous DM. (See 'Patients with extracutaneous involvement' above.)
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