Anti-MDA5 antibodies-associated amyopathic dermatomyositisis a rare autoimmune disease that involve polyarthritis, cutaneous and pulmonary manifestations. The development of rapidly progressing interstitial lung disease is a life-threatening complication. We report the case of a 45-year-old woman without medical history, who was addressed to the Pulmonary Department for a polyarthritis with dry cough and hypoxemic dyspnea. Initially there was neither cutaneous manifestation nor interstitial lung disease on chest CT scan. After a few days, the patient developed fatal acute respiratory failure with diffuse ground glass opacities. Identification of anti-MDA5 antibodies allowed establishing diagnosis, despite the fact that the first immunological assessment was negative. Corticosteroid bolus of 1 g for three days and immunosuppressive treatment by cyclophosphamide was only initiated at the acute respiratory distress syndrome stage. Given the rapidly unfavorable prognosis of this entity of amyopathic dermatomyositis, the testing for anti-MDA5 antibodies should be recommended in case of progressive pulmonary symptoms associated with joint signs in order to identify this disease at an early stage and to begin rapid and adequate management.