Anti-synthetase syndrome presenting primarily as interstitial lung disease in a young adult: a diagnostic challenge in acute medicine

Abstract

Anti-synthetase syndrome (ASyS) is a rare autoimmune connective tissue disorder (CTD) characterized by the presence of autoantibodies targeting tRNA synthetase, most notably the anti-Jo1 antibody. Clinically, it typically manifests with interstitial lung disease (ILD), inflammatory myopathy, arthritis, Raynaud's phenomenon, and the so-called mechanic's hands. Diagnosis can be challenging due to clinical overlap with other pulmonary and rheumatological disorders. We report a case of a young woman in her early 20s who presented at our same day emergency care (SDEC) with a four-week history of exertional dyspnea, low-grade fever, and productive cough, initially managed as a lower respiratory tract infection in the community. Persistent symptoms prompted further evaluation, and CT imaging of the chest, abdomen, and pelvis revealed bilateral ground-glass opacities suggestive of ILD. Five days later, she re-presented with hemoptysis, worsening breathlessness, new-onset myalgia, arthralgia, facial erythema, and hyperkeratosis of the fingertips. Autoimmune screening revealed strongly positive anti-Jo-1 and anti-Ro52 antibodies, confirming the diagnosis of anti-synthetase syndrome. She was treated with intravenous (IV) pulse methylprednisolone, mycophenolate mofetil, and rituximab, with partial clinical improvement and ongoing follow-up for advanced ILD management in a tertiary center. This case highlights how an initial diagnosis of lower respiratory tract infection (LRTI) may mask an underlying autoimmune syndrome (anti-synthetase syndrome), which later manifests as progressive respiratory failure requiring lung transplant. Therefore, as acute medicine physicians, it is imperative to maintain a broad differential diagnosis, particularly in young females newly diagnosed with possible ILD. There may be underlying conditions that require careful examination by acute care physicians, especially in the presence of systemic symptoms, notably rheumatological symptoms. This vigilance is crucial to avoid delayed diagnosis of anti-synthetase syndrome, which necessitates early multidisciplinary involvement to achieve better outcomes.