Case Presentation: A 35-year-old female with tobacco use disorder presented to the emergency department with three months of recurrent fevers, non-productive cough, and dyspnea on exertion. She was initially seen by her primary care physician for these symptoms in the context of multiple sick contacts and was treated empirically for streptococcal pharyngitis with amoxicillin. Due to persistent symptoms with recurrent hospital presentations and multifocal opacities on chest radiograph, the patient was treated for presumed COVID-19 pneumonia under full respiratory isolation, despite two negative COVID-19 PCR tests and lack of respiratory improvement. Upon her current admission the patient was febrile (38.1 C), tachycardic (106 BPM), and requiring 2L of oxygen via nasal cannula to maintain resting oxygen saturation above 90%, and her exam was notable for bilateral pulmonary rales. The patient denied arthralgias, proximal muscle weakness, and vision changes. CT angiography of the chest was negative for pulmonary embolism and showed extensive mixed reticular and airspace opacities with peribronchial predilection and peripheral sparing, suggestive of organizing pneumonia and fibrotic interstitial lung changes (figure 1). Laboratory studies were notable for negative COVID-19 PCR, mildly elevated CRP (10 mg/dL), weakly positive anti–Sjögren’s Syndrome related antigen A (SSA) antibody (50 AU/ml), undetectable anti-Jo-1 antibody (< 0.2 AI) and positive anti-PL-12 antibody. Infectious disease workup, including bronchoscopy with invasive bronchoalveolar lavage sample, was negative for bacterial, viral, and fungal infection. Pulmonary function tests showed reduced total lung volumes (40%) and DLCO (28%). The patient was diagnosed with anti-synthetase interstitial lung disease and started on an immunosuppressive regimen comprising oral prednisone and mycophenolate mofetil. Patient was followed in rheumatology clinic and noted to have symptomatic improvement and stable hypoxia requiring 2L of oxygen without clinical signs of disease progression.

Discussion: Anti-synthetase syndrome is characterized by interstitial lung disease, arthritis, myositis, fever, or Raynaud’s phenomenon in the presence of an anti-synthetase autoantibody. (1) The most well-characterized subtype is the anti-histidyl antibody (anti-Jo-1), which was negative in this patient. At least 70% of patients with anti-synthetase syndrome develop ILD, and it represents the major cause of mortality in these patients with a 10-year survival rate of 73% according to data from the Norwegian CTD and vasculitis registry (NOSVAR). (2) As it pertains to this case, the anti-PL-12 antibody is directed against alanyl-transfer RNA synthetase. This subtype is associated with ILD rather than musculoskeletal disease, with 90% of patients presenting with lung disease according to one cohort study. (3)

Conclusions: The learning point here is the importance of avoiding anchoring bias, which is complicated with respiratory diseases during the COVID-19 pandemic. The clinical and radiographic presentation of interstitial lung can resemble COVID-19 pneumonia, and without a high level of suspicion for other etiologies, there will be a delay in diagnosis and treatment. Additionally, anti-synthetase syndrome should be considered in the differential diagnosis of ILD even in the absence of arthritis and myositis. Thus, in a patient with a positive anti-PL-12 antibody and respiratory symptoms, it is prudent to look for interstitial lung disease.

IMAGE 1: Figure 1: extensive mixed reticular and airspace opacities