Anti-MDA5 Amyopathic Dermatomyositis—A Diagnostic and Therapeutic Challenge

Abstract

Clinically amyopathic Dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, associated with no muscular manifestations, which is more frequent in Asian women. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a recently discovered type of specific autoantibodies associated with myositis. The anti-MDA5 DM was initially described in Japan and later it was discovered that the target antigen was a protein implicated in the innate immune response against viruses, that is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 DM is characteristically associated with distinguished mucocutaneus and systemic manifestations, including skin ulcerations, palmar papules, arthritis, and interstitial-lung disease. Patients with anti-MDA5 positivity have a high risk of developing rapid progressive interstitial-lung disease (RP-ILD), with a poor outcome. As a result, despite high mortality, diagnosis is often delayed, necessitating increased awareness of this possible condition. Despite a severe course of lung disease and an increased mortality rate, there is currently no standard treatment. Recent insights based on observational studies and case reports support combined therapy with immunosuppressive drugs and corticotherapy, as soon as the symptoms appear. The aim of this paper is to describe anti-MDA5 DM, focusing on the recent literature about the unique clinical manifestations and therapeutic options, starting from a severe clinical case diagnosed in our Rheumatology Department.

MDA5-autoimmunity and interstitial pneumonitis contemporaneous with the COVID-19 pandemic (MIP-C)

“…Several COVID-19 era case reports or series of MDA5+ myositis or ILD have been reported in the UK and internationally either in the setting of infection or post-vaccination. 2 , 3 , 4 , 5 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 Our study is the largest one to document the features and outcomes of this clinical syndrome, especially in 2021. Approximately 42% of our MDA5+ cases have thus far have progressive ILD, with a third of these proving fatal so far, in keeping with the known aggressive course of MDA5 + -ILD.…”

“…This was based on both increased rate of anti-MDA5 related immunology reporting and multiple physicians seeing MDA5 related disease for the first time, combined with emergent literature reporting COVID-19 era anti-MDA5-related disease. 2 , 3 , 4 , 5 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 We collected data on the number of MDA5+ tests per year between January 2018 and December 2022. The clinical notes review focused on patterns of symptomatic MDA5 disease (including degree of ILD); muscle or other organs involvement, therapy, therapy responses and survival data.…”

Comparison of clinical and laboratory features and treatment responses in patients with clinically amyopathic juvenile dermatomyositis and classical juvenile dermatomyositis

“…Similar to our results, Mamyrova et al 9 reported a more frequent rate of anti‐p155/140 (TIF‐1) ab positivity in CAJDM patients. Anti‐MDA‐5 exhibits a relationship with amyopathic dermatomyositis in adults 19 . However, such a relationship was not observed in children with CAJDM 9 .…”

“…Anti-MDA-5 exhibits a relationship with amyopathic dermatomyositis in adults. 19 However, such a relationship was not observed in children with CAJDM. 9 In our cohort, only 1 patient with CAJDM had anti-MDA-5 ab positivity.…”

MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C)

“…We audited the increased anti-MDA5 positivity in relationship to other MSA (Euroimmun immunoblot©) that included MDA5 + cases. This was based on both increased rate of anti-MDA5 related immunology reporting and multiple physicians seeing MDA5 related disease for the first time, combined with emergent literature reporting COVID-19 era anti-MDA5-related disease [1][2][3][4][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] . We collected data on the number of MDA5+ tests per year between January 2018 to December 2022.…”