B43-08 Clinically Amyopathic Anti-synthetase Syndrome With Non-specific Interstitial Pneumonia: Diagnostic Challenge in a Jo-1 and Ro52 Positive Patient

Introduction Anti-synthetase syndrome (ASyS) is a heterogeneous autoimmune disorder characterized by the triad of interstitial lung disease (ILD), myositis, and arthritis, associated with anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies such as anti-Jo-1. Co-positivity with anti-Ro52 (SSA) antibodies has been linked to more aggressive or treatment-refractory ILD. Clinically amyopathic or lung-dominant variants may present without muscle involvement, posing a diagnostic challenge when creatine kinase (CK) and aldolase are normal. Case A 46-year-old woman developed progressive shortness of breath that was initially treated as pneumonia. A chest CT scan revealed bilateral ground-glass opacities, and a surgical lung biopsy showed a nonspecific interstitial pneumonia (NSIP) pattern. Infectious and malignant causes were ruled out. Serological evaluation indicated positive results for anti-Jo-1 and anti-Ro52 antibodies, along with elevated levels of C-reactive protein, anticardiolipin IgM, and polyclonal IgM hypergammaglobulinemia. Levels of CK, aldolase, ferritin, RNA polymerase III, RNP, Scl-70, and ANCA antibodies were normal or negative. The patient had no muscle weakness but reported severe dyspnea on exertion, with oxygen saturation dropping below 80%. A six-minute walk test demonstrated poor exercise tolerance, and pulmonary function testing revealed a DLCO of 20% of predicted. She later experienced diffuse muscle and joint pain without any objective weakness. A diagnosis of clinically amyopathic anti-synthetase syndrome was established, and she was treated with mycophenolate mofetil and rituximab, which resulted in stabilization of her symptoms and pulmonary function. Discussion Lung-dominant anti-synthetase syndrome is underrecognized. Patients with normal CK or absent muscle weakness represent a diagnostic pitfall, often misclassified as idiopathic NSIP. Ro52 co-positivity adds clinical value—anti-Ro52 is an emerging poor prognostic marker, associated with more aggressive or refractory ILD even when muscle disease is absent. The coexistence of anti-Jo-1 and anti-Ro52 antibodies defines a subset with higher relapse risk and steroid resistance. Early identification of this serologic profile supports timely immunosuppressive escalation to prevent progressive fibrotic lung disease. Conclusion Anti-synthetase syndrome may present solely with interstitial lung disease despite normal CK and absent myositis. Anti-Ro52 co-positivity should alert clinicians to a potentially aggressive lung-dominant phenotype, warranting early recognition, combination immunosuppression, and close pulmonary follow-up. This abstract is funded by: None