Approach

The ultimate goal of treatment is to achieve disease remission or at least achieve disease control.

Initial treatment goals for patients with muscle weakness and cutaneous involvement, or with skin disease alone (confirmed by skin biopsy) and subclinical muscle disease, is to suppress inflammatory muscle disease, improve muscle strength, and avoid the development of systemic complications (e.g., interstitial lung disease [ILD], cardiac disease).

Of the idiopathic inflammatory myopathies, DM is reputed to be the most responsive to therapy. However, despite good control of muscle disease, skin lesions may be resistant to treatment and the morbidity associated with uncontrolled skin disease should not be overlooked, particularly when cutaneous disease may be the only manifestation.

Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are found in most patients with DM and are associated with clinical subsets that have varying clinical courses and therapeutic responses.[24][88][89]

Severe disease or acute flares

In severe muscle or skin disease or acute flares, short-term use of intravenous corticosteroids may be indicated until other treatments take effect. Patients are subsequently transferred to high-dose oral corticosteroids. To minimise toxicity it is recommended to always use the lowest possible dose and taper dose once response is achieved.[72]

Therapy with intravenous immunoglobulin (IVIG) combined with intravenous corticosteroids is sometimes used initially rather than corticosteroids alone, depending on the physician's experience.[124][125]

Patients diagnosed with anti-synthetase syndrome may be corticosteroid-resistant and concomitant use of immunosuppressive drugs is required.[45]

If anti-signal recognition particle (SRP) antibodies are present in patients with DM, they are associated with acute severe, treatment-resistant necrotising myositis.[46] Immunosuppressive drugs, IVIG, or rituximab are often required at an early disease stage.[93]

The presence of anti-melanoma differentiation-associated gene 5 (MDA5) is specific to clinically amyopathic DM, and is strongly associated with rapidly progressive ILD. Patients often require treatment with immunosuppressive drugs as well as high-dose systemic corticosteroids from an early disease stage.[47]

Muscle disease

In patients with myositis, high doses of oral corticosteroids are recommended as initial treatment.

Second-line therapy with other immunosuppressive agents should be considered primarily in patients who are refractory to corticosteroids or for their corticosteroid-sparing potential.[126][127]

  • Methotrexate has been found to be an effective corticosteroid-sparing agent and may also be effective in myositis refractory to corticosteroids.[128][129][130] Methotrexate is often preferred over azathioprine because it is considered to have a more rapid benefit.[126] Low-dose oral methotrexate is useful for both muscle and cutaneous involvement.[128][129][131][132]

  • Azathioprine is the next choice of therapy. It can be as effective and well tolerated as methotrexate, but seems to take longer to take effect (≥6 months).[133]

All second-line agents may be used alone or in combination with oral corticosteroids.

Third-line treatments are indicated in cases refractory to corticosteroids and second-line agents. These treatments are used as monotherapies or sometimes combined with corticosteroids or other immunosuppressants.

  • Ciclosporin has been shown to be of benefit as a corticosteroid-sparing agent in some patients.[126][134]​​[135][136]

  • Tacrolimus and mycophenolate have both been found to be effective in a few cases.[137] Mycophenolate shows promising results for refractory disease, but controlled trials are lacking.[138][139]

  • Cyclophosphamide is used in patients with refractory disease, particularly when associated with vasculitis, ILD, or respiratory muscle involvement.[140][141][142]

  • Chlorambucil has been used with some success in a few studies of refractory disease.[126][143]

  • In some cases the disease remains active regardless of optimal immunosuppressive therapy, and other alternative options need to be considered. Guidance from the Department of Health in the UK recommends adjunctive IVIG for patients with DM who have significant muscle weakness.[144][145]​​ Small studies and case reports have demonstrated the benefit of adjunctive IVIG.[13][127][146][147][148][149][150][151][152][153]

Skin manifestations

First-line (initial therapy)

Although not all patients report photosensitivity, there is evidence that the skin lesions are exacerbated by sun exposure. All patients should use year-round topical high-protection sunscreens providing protection against both ultraviolet A (3+ star rating) and ultraviolet B (sun protection factor 50 or above).

  • Topical corticosteroids are indicated in patients with cutaneous disease and are usually beneficial even in patients who are already being treated with systemic corticosteroids for myositis. They help control erythema and pruritus, and can provide adequate relief when used alone in some patients.[154][155] Topical corticosteroids of different potencies may be used in combination depending on the patient's symptoms. Potent and very potent corticosteroids are often used to treat the trunk and limbs including the hands, as well as the scalp. Mild to moderate potency corticosteroids are used in areas more prone to atrophy such as the face (including eyelids) and neck. Scalp involvement may be treated with foam or lotion formulations.[72][155]

  • Topical antipruritic treatments can be used as adjuncts to topical corticosteroid therapy. They include simple moisturisers, emollients, topical antipruritic formulas (with menthol, phenol, or camphor), and topical antihistamines (e.g., doxepin).[155]

  • For patients with severe pruritus unresponsive to topical treatments, a trial of oral antihistamines can be considered. Pruritus is often a nocturnal symptom; therefore, long-acting sedating antihistamines are useful. Non-sedating antihistamines are preferred for daytime use.[155]

Second-line (unresponsive to topical therapy)

For patients with DM with skin manifestations unresponsive to topical treatments, antimalarials can be used.

  • Hydroxychloroquine has been shown to improve skin lesions and scalp pruritus with no effect on myositis.[156][157][158]

  • Chloroquine is also of benefit, although the risk of retinopathy is greater than with hydroxychloroquine, and therefore hydroxychloroquine is the preferred antimalarial.[159]

  • There are anecdotal reports of improvement of pruritus, eczematous components, and poikiloderma, with topical tacrolimus used as adjunctive treatment in resistant cutaneous DM.[160][161] Controlled trials are required, but an excellent safety profile makes it an attractive option for both adult and juvenile DM.[162]

  • Cutaneous disease often responds to short-term use of oral corticosteroids but flares when the corticosteroid dose is tapered. Other treatments should be added to control cutaneous disease in this setting rather than increasing corticosteroid dose. Systemic corticosteroids are rarely indicated in amyopathic DM.[72]

Third-line (unresponsive to topical treatments and antimalarials)

  • Methotrexate is indicated in patients with ongoing disease despite topical treatments and antimalarials, and may be used in combination with these treatments. Low-dose oral methotrexate is useful for both muscle and cutaneous involvement.[128][129][131][132] Response has been reported in resistant disease.[163] Haematological, hepatic, and pulmonary toxicity may occur, but risks are reduced by following monitoring guidelines.[164]

  • There is anecdotal evidence of benefit of using corticosteroid-sparing immunosuppressants such as azathioprine in patients with skin disease resistant to methotrexate.[165] Dose-related toxicity (haematological, hepatic, and gastrointestinal) is a common cause of drug withdrawal.[166] Mycophenolate has been shown to be beneficial in patients with recalcitrant skin disease, and ciclosporin in patients with recalcitrant skin disease and early ILD.[134][137][138][167][168][169][170][171] Most common adverse effects of treatment with mycophenolate are gastrointestinal, although opportunistic infection may occur.[167] Ciclosporin is contraindicated in patients with renal impairment and hypertension.

  • Anti-inflammatory agents such as thalidomide and dapsone are an alternative treatment to immunosuppressants. Case reports of rapid response of refractory cutaneous DM following treatment with dapsone have been published.[172][173] There is anecdotal evidence of benefit following treatment with thalidomide.[72] Thalidomide is highly teratogenic.[174] Serial monitoring for peripheral neuropathy is recommended.[175] The haematological toxicity of dapsone is increased in glucose-6-phosphate-dehydrogenase-deficient patients.[176]

  • Guidance from the Department of Health in the UK recommends adjunctive IVIG for patients with DM with refractory skin involvement.[144][145]​​ Small studies and case reports have demonstrated benefit of adjunctive IVIG in resistant skin and muscle disease.[146][147][148][149]

Patients with underlying malignancy

When malignancy is present, treatment of underlying malignancy is essential if the disorder is to be controlled. Improvement or complete resolution of DM has been reported in some cases after successful treatment of underlying malignancy.[177]

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