Macrophage activation syndrome in MDA5 antibody-positive dermatomyositis and COVID-19 infection

Abstract

Background Macrophage activation syndrome (MAS) is a rare multiorgan system disorder that may present as a fatal complication of underlying rheumatological disease, including dermatomyositis. Case presentation Here, we report the case of a 65-year-old Caucasian female with a history of psoriasis and a recent diagnosis of Coronavirus disease 2019 (COVID-19) who presented with progressive generalized weakness, joint pains, an erythematous rash, shortness of breath, and weight loss. She was ultimately diagnosed with biopsy-confirmed melanoma differentiation-associated protein 5 (MDA5)-positive dermatomyositis complicated by MAS, requiring intravenous immunoglobulin and high-dose methylprednisolone. Conclusions This report serves as a clinical reminder of the rare, yet clinically relevant association between MDA5-positive dermatomyositis and MAS, as well as highlights the potential contribution of other immune system activating diseases, such as COVID-19, associated with a cytokine storm and hyperinflammatory state.

Anti-MDA5 Antibody Linking COVID-19, Type I Interferon, and Autoimmunity: A Case Report and Systematic Literature Review

“…One case of juvenile DM required mechanical ventilation due to respiratory deterioration, but gradual improvement followed thereafter (26). As already stated, two deaths were observed: one following macrophage activation syndrome (23), the other attributable to severe SARS-CoV-2 pneumonia (20); both patients had tested positive for anti-MDA5 autoantibodies.…”

“…Eleven cases of inflammatory myositis temporally related to COVID-19 have been reported (20)(21)(22)(23)(24)(25)(26)(27); the main features are illustrated in Table 1. In nine patients, new-onset inflammatory myositis followed SARS-CoV-2 infection; two cases of disease relapse following COVID-19 have been reported: one at pediatric age (22) (in a child who experienced a skin-only relapse of juvenile DM) and one in the adult setting (20) (in a patient positive for both anti-Mi-2 and anti-PM/Scl antibodies).…”

“…Myopathy was noticed in 10/11 cases, generally in the form of a mild/moderate proximal muscle weakness; cardiomyopathy was only detected in one patient with systemic lupus erythematosus-dermatomyositis overlap ( 21 ). Pulmonary involvement was present or suspected (based on worsening dyspnea) in five cases ( 20 , 21 , 23 , 24 ). There was no report of cancer-related DM.…”

“…In terms of autoimmune profiling, 4/11 cases ( 21 , 22 , 24 ) tested negative for serum autoantibodies, including two pediatric cases ( 22 ) and a lupus/dermatomyositis overlap syndrome ( 21 ). Two patients ( 20 , 23 ) tested positive for anti-MDA5 antibodies: one of them (also positive for anti-Ro52 antibodies) underwent fatal macrophage activation syndrome ( 23 ), the other (also positive for anti-SAE-1 antibodies) died due to pneumonia ( 20 ). Two patients were positive for anti-Mi-2 antibodies: one of them was diagnosed new-onset DM ( 25 ), the other (also positive for anti-PM/Scl antibodies) experienced disease relapse ( 20 ).…”

“…As reported in our systematic review, two out of two patients positive for anti-MDA5 antibodies died. In one case (23) anti-Ro52 antibodies, which are associated with rapidly progressive ILD and worse prognosis (51), were also present; the woman succumbed to macrophage activation syndrome, and there's no reason to attribute her death to COVID-19, since anti-MDA5 syndrome appeared two months after recovery from the infection. Meanwhile, the patient described by Gokhale et al (20) tested positive for anti-SAE1 antibodies, which are associated with ILD and increased cancer risk (52).…”