COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report

Abstract

Background Autoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections. Case presentation A 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now). Conclusions We report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.

Rapid Progression of Acute Interstitial Pneumonia in a Patient with Low MDA-5 Antibody Titer

“…In addition to the MDA-5 Abpositive finding, S. pneumoniae, H. influenzae, and parainfluenza virus were detected through PCR by bronchoscopic washing. However, since the radiologic findings of this case were not inconsistent with those of infection and the culture was negative, we considered infection as the trigger factor of ILD rather than main infectious cause, as in previous reports [5,6].…”

A Review of MDA-5 Dermatomyositis and Associated Interstitial Lung Disease

“…Additionally, the imaging findings of ground-glass opacities and predominantly lower lung subpleural consolidations are common between the two diseases [23]. Instances of MDA-5 DM have been reported in case studies following infection or immunization for SARS-CoV-2, further supporting a proposed shared pathogenic mechanism [24,25].…”

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.…”