Case Presentation:

A 37‐year‐old nonsmoking female with a history of Raynaud symptoms presented to our hospital with 3 months of fatigue, progressive shortness of breath, and a painful, pruritic rash over her trunk and proximal extremities. An outside facility diagnosed mononucleosis (monospot + and transaminitis), but her symptoms persisted, with 2 weeks of recent fever, arthralgias, and difficulty walking. Physical exam was significant for tachycardia, O2 desaturation, fine bibasilar rales, 4/5 proximal muscle strength, and diffuse rash. Lab abnormalities included AST 221, ALT 77, CK 237, CRP 13.9, low C3, but normal C4. All cultures, HIV test, and RPR titer were negative. Chest x‐ray revealed nodular interstitial disease. Chest computed tomography showed patchy ground‐glass opacities with scattered consolidation. Broad autoimmune panel including anti‐Jo antibodies was negative. Skin biopsy revealed epidermal vacuolar interface alteration, increased interstitial dermal mucin, and a lymphocytic inflammatory infiltrate. Treatment with methylprednisolone 60 mg q6h IV for suspected antisynthetase syndrome was initiated. The patient's myalgias, arthralgias, and rash markedly improved, and oxygen requirements improved slowly. She was discharged home on 4 L/min nasal cannula oxygen, prednisone 60 mg daily, and azathioprine 100 mg daily.


Antisynthetase syndrome (AS) is an extremely rare (2.5 per million) autoimmune disease characterized by myositis, arthritis, Raynaud's phenomenon, cutaneous involvement, fever, and interstitial lung disease (ILD). Clinical diagnosis can be challenging, as patients often do not manifest all symptoms simultaneously and may not test positive for typical autoantibodies. Histological findings from skin biopsy or lung biopsy are helpful in the diagnosis. AS has been associated with antibodies to aminoacyl‐transfer RNA synthetases that catalyze the binding of amino acids to their target tRNA during protein synthesis. Some studies suggest a viral illness may incite the formation of the autoantibodies, but definitive etiology is unknown. The most common anti‐tRS antibody is anti‐Jo‐1, found in 30% of patients, but other serotypes can be found in 1%‐4% of patients. Treatment often begins with high‐dose steroids and immunosuppressive agents, although progression of disease seems to be inevitable. Antibody‐negative AS syndrome is associated with an increased risk of malignancy, and age‐appropriate cancer screenings should be performed. Treatment of cancer, when found, can lead to resolution of AS syndrome. Prognosis in antisynthetase syndrome varies based on organ involvement. ILD with myositis confers higher mortality.


Antisynthetase syndrome is a rare disease entity that should be considered for patients presenting with ILD and myositis with a negative autoantibody panel and without other disease manifestations initially, as early initiation of therapy is imperative.

Author Disclosure:

C. Jones, none; K. Valiani, none; D. Dressier, none.