PO:25:085 | Anti-MDA5 antibody syndrome, a life-threatening condition for rheumatologist and pulmonologist A case series

Francesca Cozzini^1|2, Cecilia Burattini¹, Elena Bravi¹, Chiara Nani¹, Eugenio Arrigoni¹, Fabia Cavallotti¹, Ilaria Platè¹, Marco Sebastiani^1|3 | ¹Ospedale Guglielmo da Saliceto Piacenza, Italy; ²Università degli studi di Modena e Reggio Emilia, Italy; ³Università degli Studi di Parma, Italy

Introduction. Anti-melanoma differentiation-associated protein 5 (MDA5) antibody positive syndrome is a severe condition classified among the idiopathic inflammatory myopathies, clinically characterized by pulmonary, cutaneous and muscular manifestations. For the high occurrence of rapidly progressive ILD (RP-ILD), anti-MDA5 syndrome is considered as a possible life-threatening condition. However, the clinical features and course of the disease are still poorly understood, and diagnosis is mainly based on the discovery of anti-MDA5 antibodies. Case series: In this case series, we report five patients diagnosed in the last four years with different disease course and prognosis. All patients have been firstly referred to pulmonologist for acute or subacute onset of respiratory symptoms, from dyspnoea and cough to moderate-to-severe acute respiratory failure, requiring intensive care unit referral in two cases. The prevalent radiological pattern on chest CT was fibrosing organizing pneumonia(fOP), in one case overlapping nonspecific interstitial pneumonia (NSIP), while, in another one, a severe OP without fibrosing stigmata was observed. Finally, the last patient presented with fibrosing interstitial pneumonia. Lung function tests of surviving patients are reported in Fig.1. Three subjects presented with a clinically mild inflammatory myopathy; two of whom also exhibited a skin rash typical of dermatomyositis. RP-ILD was observed in three patients; although aggressive therapy with high dose intravenous corticosteroids and immunosuppressants, two patients died few weeks after diagnosis. The third patient suffered from multiple life-threatening complications, including macrophage-activation syndrome and acute exacerbation of ILD triggered by CMV infection. Following recovery, the patient was referred for a lung transplant due to the severe fibrotic progression of the lung. Treatments were tailored to the patients according to the severity of lung involvement. While high-dose steroid therapy effectively resolved both muscular and cutaneous manifestations, the ILD in two cases required several immunosuppressants and the addition of antifibrotics (nintedanib).

Discussion. Anti-MDA5 syndrome is a severe condition characterized by a different degree of lung, skin, and muscle involvement. Our small case series confirmed the heterogeneity of clinical manifestations of the disease, and lung involvement as the most important prognostic factor. The last ACR/CHEST guidelines for the treatment of systemic autoimmune-related ILDs recommend a multidisciplinary approach for the management of this disease, suggesting a combination of corticosteroids and immunosuppressants, mainly rituximab and cyclophosphamide, as treatment of lung involvement. In refractory or severe cases, a triple combination treatment is suggested, adding intravenous immunoglobulins or another immunosuppressant. Due to the frequent occurrence of life-threatening complications, an early referral to expert rheumatologists or pulmonologists would be desirable in anti-MDA5 patients, allowing a correct and prompt diagnosis and the beginning of an effective treatment as soon as possible