Abstract Introduction Antisynthetase syndrome (ASyS) is a rare autoimmune disease caused by antibodies against aminoacyl-tRNA synthetases, most often anti-Jo-1. It commonly affects the lungs, muscles, and joints. Some patients have primarily lung involvement, known as pulmonary-dominant or “amyopathic” disease, which can make diagnosis difficult. We describe a woman with Jo-1-positive ASyS who had interstitial lung disease (ILD) without muscle symptoms and a history of psoriasis, successfully treated with rituximab and mycophenolate. Her course was complicated by an acute pulmonary embolism (PE), a rare event that can mimic ILD progression. Case Report A 65-year-old woman with hypothyroidism and biopsy-confirmed psoriasis developed progressive dyspnea following two COVID-19 infections. Chest CT demonstrated bilateral ground-glass opacities with basal fibrosis. Laboratory testing revealed ANA 1:320 (nucleolar) and anti-Jo-1 antibody 8.0 (high); creatine kinase and aldolase were normal. Bronchoscopy and cytology did not reveal infection or malignancy. She was diagnosed with Jo-1-positive ASyS presenting as ILD without myositis. In February 2025, she was hospitalized with worsening dyspnea and pleuritic chest pain and was found to have an acute right-lower-lobe segmental and subsegmental PE. She was started on intravenous heparin and transitioned to apixaban on discharge. Prednisone was continued for ILD, and plans were made for rituximab initiation. Rituximab (1 g × 2 infusions two weeks apart) began later that month, followed by mycophenolate 1 g twice daily in May 2025. Within three months, dyspnea improved and repeat CT showed decreased ground-glass opacities with stable mild bronchiectasis; diffusion capacity rose to 79% predicted. Over six months of follow-up, lung function and oxygen saturation remained stable, psoriasis activity was minimal, and no new myositis or mechanic’s hands developed. Discussion This case highlights a pulmonary-dominant form of Jo-1-positive ASyS occurring with psoriasis, an uncommon autoimmune overlap. The absence of muscle involvement initially complicated diagnosis, emphasizing the need to integrate antibody testing, imaging, and clinical context when evaluating unexplained ILD. The occurrence of PE during steroid taper illustrates a rare but important complication: new or worsening dyspnea in ASyS-ILD should prompt evaluation for thromboembolism rather than being attributed automatically to ILD flare or infection. When corticosteroids alone provided limited benefit, the addition of rituximab and mycophenolate achieved clinical and radiographic improvement while allowing steroid tapering. Conclusion ASyS can present with isolated lung involvement and may coexist with other autoimmune diseases. Early recognition, combination immunosuppression, and vigilance for complications such as PE can improve outcomes and guide long-term management. This abstract is funded by: None
Harikrishnan et al. (Fri,) studied this question.