Anti-MDA5 Antibody Dermatomyositis Overlap with Systemic Lupus Erythematosus: A Case Report and Review of the Literature

Abstract

Background:Dermatomyositis (DM) is an autoimmune connective tissue disease that primarily targets the muscle, skin, and lungs. Many patients have autoantibodies that correspond to distinct clinical phenotypes. Melanoma differentiation-associated gene 5 (anti-MDA5) antibody, a specific antibody that targets the melanoma differentiation-associated gene 5 (MDA5), has been reported in DM cases and is significant for a distinct cutaneous presentation and rapidly progressive interstitial lung disease.Objective:Herein, we describe a patient with DM with a positive anti-MDA5 antibody and characteristic clinical phenotype, who subsequently developed coexisting systemic lupus erythematosus (SLE). A diagnosis of SLE was supported by his clinical phenotype, positive serologies, hypocomplementemia, and progression to glomerulonephritis and lupus cerebritis, features of which fulfilled the American College of Rheumatology criteria for SLE.Conclusion:DM is known to overlap with other autoimmune diseases, including SLE, and coexistence can lead to a wide variety of clinical presentations. SLE overlapping with anti-MDA5 positive DM may present with distinct clinical features.

Hsa_circ_0012919 regulates expression of MDA5 by miR-125a-3p in CD4+ T cells of systemic lupus erythematous

“…As the hypomethylation of SLE-related genes promoters had unique effects on the activation of the dysfunction of immune systems in SLE, so we suggested hypomethylation level of MDA5 promoter might also activate the abnormal immune responses in SLE. It has been shown that MDA5 could be induced in human mesangial cells, and it was detectable in patients with severe lupus nephritis, 16 our results confirmed that MDA5 expression in patients with lupus nephritis was significant higher. As dsDNA antibody reflects the activity of SLE and the involvement of lupus nephritis, and our results demonstrated patients with dsDNA(+) had higher level of MDA5.…”

“…Milam once reported a patient with a positive anti-MDA5 antibody, who subsequently developed coexisting SLE. 16 More importantly, DM is known to overlap with other connective tissue diseases (CTD), such as SLE, so we supposed MDA5 might be involved in the development of SLE.…”

Clinical Images: A not so common overlap presentation in systemic lupus erythematosus

“…On retesting, all antiphospholipid antibodies were negative. Therefore, consistent with previous reports, a skin biopsy lacking evidence of vasculitis or thrombotic vasculopathy, and a great response to IVIG, we report a not so common overlap presentation of necrotic skin lesions driven by MDA‐5 in lupus (2).…”

“…Melanoma differentiation–associated gene 5 (MDA‐5) is associated with dermatomyositis and often presents with a distinct cutaneous presentation and progressive interstitial lung disease (ILD) (1–3). MDA‐5 signaling often leads to increased interferon signaling, which contributes to atypical vasculopathy, leading to atypical, and at times ulcerative or necrotic, cutaneous manifestations, which are challenging to diagnose and treat (2). Rarely, patients with lupus present with necrotic skin lesions as an overlapping presentation from MDA‐5 dermatomyositis.…”

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies

“…Interestingly, MDA5 showed the highest prevalence in the control population, including two SLE patients and one individual with infectious disease. Overlap cases of MDA5 associated CADM and SLE have been previously described [ 40 ]. Whether the reactivity in the ID patient represents a pathogenic mechanism as discussed previously deserved further research [ 41 , 42 ].…”