Review
Anti-melanoma differentiation–associated gene 5 (MDA5) dermatomyositis: A concise review with an emphasis on distinctive clinical features

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Melanoma differentiation–associated gene 5 (MDA5) is a recently described autoantigen target in a subset of patients with dermatomyositis. Anti-MDA5 dermatomyositis is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, importantly, an elevated risk of interstitial lung disease with a potentially fatal course. Because the clinical features can differ substantially from those typically observed in cutaneous dermatomyositis, the diagnosis is often overlooked, which might negatively affect patient outcomes. This review aims to familiarize the clinician with the distinctive clinical features of anti-MDA5 dermatomyositis in order to enhance its recognition and to facilitate an appropriate screening and management strategy.

Section snippets

History and putative function of MDA5

Anti-MDA5 dermatomyositis was first described in a Japanese cohort by Sato et al in 2005.1 Among the 42 patients studied, sera from 8 (19%) had antibodies directed against an unknown 140-kd protein. Because each patient had clinically amyopathic dermatomyositis (CADM), the antibody was originally designated anti–CADM-140.1 Subsequent studies demonstrated that the autoantigen target for CADM-140 antibodies was MDA5 (also known as interferon-induced helicase C domain–containing protein 1), a

Methods of detecting MDA5 antibodies

MDA5 antibodies were first discovered by using immunoprecipitation.1 Enzyme-linked immunosorbent assays (ELISAs) that included a recombinant MDA5 antigen were subsequently developed,2, 10, 11 and, recently, line blot immunoassays have been partially validated for detecting MDA5 antibodies.12 Testing for MDA5 antibodies by ELISA has 2 advantages over immunoprecipitation: faster detection times and the provision of a quantitative measure of antibody titers, which has prognostic implications.13

Unique mucocutaneous features of anti-MDA5 dermatomyositis

Individuals with anti-MDA5 dermatomyositis have a distinctive mucocutaneous phenotype, which might reflect a severe underlying vasculopathy. A seminal retrospective study delineating these unique features was first reported by Fiorentino et al in 2011,24 and their findings were validated by several subsequent studies.17, 25, 26, 27, 28, 29, 30, 31 Although typical cutaneous dermatomyositis features often accompany the distinctive anti-MDA5 phenotype, the anti-MDA5 phenotype might dominate the

Systemic features of anti-MDA5 dermatomyositis

Systemic disease is common in anti-MDA5 dermatomyositis (Table II). Despite the morbidity associated with the typical mucocutaneous phenotype, systemic involvement represents a critical consideration for this population, as it constitutes the major cause of mortality.

ILD is the most important systemic complication in anti-MDA5 dermatomyositis because it may have a rapidly progressive and fatal course. ILD develops as a result of inflammation and fibrosis of the lung parenchyma and is defined by

Laboratory evaluation in anti-MDA5 dermatomyositis

The diagnosis of anti-MDA5 dermatomyositis is contingent upon the detection of MDA5 antibodies by immunoprecipitation or ELISA in the appropriate clinical setting. In the United States, a reliable immunoprecipitation assay from the Oklahoma Medical Research Foundation is commercially available.16

Apart from directly testing for MDA5 antibodies, other laboratory investigations might provide useful clinical and prognostic information in suspected cases of anti-MDA5 dermatomyositis, particularly in

Management of anti-MDA5 dermatomyositis

While a complete discussion of the management of dermatomyositis and the anti-MDA5 subtype is beyond the scope of this review, there are several important points to consider when evaluating and treating the patient with anti-MDA5 dermatomyositis. First, screening for pulmonary disease is mandatory for each suspected or confirmed case. While high-resolution CT of the chest is the gold standard for diagnosing ILD, its use might be limited by high cumulative radiation exposure. Therefore, PFT with

Conclusion

Anti-MDA5 dermatomyositis is a unique subtype of dermatomyositis that exhibits distinctive mucocutaneous and systemic features. The disorder carries a significant risk for ILD and RP-ILD with a potentially fatal course. For this reason, it is imperative that the clinician recognizes its unique clinical presentation in order to appropriately screen for and manage the complications of this condition.

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    Funding sources: No funding was obtained for the preparation, synthesis, or submission of this manuscript. Dr Vleugel is supported by a Medical Dermatology Career Development Award from the Dermatology Foundation.

    Conflicts of interest: None disclosed.

    Reprints not available from the authors.

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