Case Presentation: A 36-year-old female with a history of morbid obesity and hypertension presented with three weeks of progressive dyspnea and productive cough. She was previously diagnosed with community-acquired pneumonia and completed two five-day courses of azithromycin, without improvement in her symptoms. She denied smoking but reported increased smoke inhalation due to local forest fires. She endorsed a family history of rheumatoid arthritis. Initial vital signs were blood pressure 104/78 mmHg, heart rate 96 beats/minute, respiratory rate 29 breaths/minute, oxygen saturation 85% on room air, and temperature 37.2C. Physical exam was notable for fine rales at bilateral lung bases. Her musculoskeletal and skin examination was normal. Laboratory studies revealed neutrophil-predominant leukocytosis to 13.3 x 10^9. The patient was placed on high-flow nasal cannula (HFNC) and admitted to the intensive care unit.
An initial computed tomography of the chest revealed peribronchovascular and subpleural multifocal consolidations, ground glass opacities, and discrete pulmonary nodules concerning for multifocal infection versus cryptogenic organizing pneumonia. Sputum cultures, blood cultures, respiratory viral panel, beta-D-glucan and serologies for Coccidioides, Histoplasma and Cryptococcus were negative. Despite receiving broad spectrum antibiotics and pulse-dose steroids, the patient remained on 15-20 liters HFNC with frequent desaturations. Given her strong family history of autoimmune disease and lack of response to treatment, further serologic work-up was sent. Anti-nuclear antibody returned with a 1:40 titer in a speckled pattern. Creatine kinase was 496 U/L, aldolase was 16.7 U/L, and anti-Jo-1 antibody was positive, confirming a diagnosis of anti-synthetase syndrome. The patient was treated with rituximab and intravenous immunoglobulin with rapid improvement in oxygen requirement, and was discharged home on prednisone and mycophenolate, with close follow-up with Rheumatology.

Discussion: Anti-synthetase syndrome (ASS) is a rare autoimmune multisystem disease characterized by interstitial lung disease (ILD), inflammatory myopathy/dermatomyopathy, polyarthropathy, mechnanic’s hand, and Raynaud’s phenomenon, with antibodies against amino acyl-transfer RNA synthetase, the most common being anti-Jo-1 antibody. Although ILD is more commonly associated with other manifestations of ASS such as polymyositis and dermatomyositis, it can also present without any other clinical manifestation, as in this case.

Conclusions: Presence of ILD in ASS is associated with increase morbidity/mortality, due to progressive lung involvement in the setting of delayed treatment. Given ASS-associated ILD can occur without other clinical manifestation and is considered a treatable cause of ILD, clinicians should consider ASS in the differential for unexplained ILD, especially in patients with risk factors for autoimmune disease, to achieve early diagnosis for appropriate therapy.