Pulmonary alveolar proteinosis developing during tofacitinib treatment for anti–MDA5 antibody–positive dermatomyositis–associated interstitial lung disease: a case report and review of the literature

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD) is a rapidly progressive and life-threatening condition that often requires aggressive immunosuppressive therapy, including Janus kinase (JAK) inhibitors, whose safety profile remains incompletely understood. We report an extremely rare case of secondary pulmonary alveolar proteinosis (PAP) that developed during tofacitinib treatment for multidrug-refractory anti-MDA5 antibody-positive DM-associated ILD. A 74-year-old Japanese woman with rapidly progressive DM-associated ILD was treated with high-dose glucocorticoids, intravenous cyclophosphamide, and cyclosporine, followed by tofacitinib due to an insufficient response. Although the ILD initially improved, she later developed progressive elevation of serum KL-6 levels and diffuse ground-glass opacities on chest computed tomography despite only mild respiratory symptoms. Transbronchial lung biopsy revealed periodic acid-Schiff-positive material within the alveolar spaces, and serum anti-granulocyte-macrophage colony-stimulating factor antibodies were negative, leading to a diagnosis of secondary PAP. Discontinuation of tofacitinib alone resulted in rapid clinical and radiological improvement. This case highlights PAP as a rare, potentially reversible complication during JAK inhibitor therapy in anti-MDA5 antibody-positive DM-associated ILD and underscores the importance of considering PAP when elevated KL-6 levels and radiological abnormalities occur despite only mild respiratory symptoms.