10. Anti-synthetase syndrome associated with necrotizing myositis – Utility of myositis specific autoantibodies in predicting prognosis and choice of treatment

Abstract

The anti-synthetase syndrome is a rare, autoimmune multi-system disorder of unclear etiology characterized by a variable combination of inflammatory myositis, interstitial lung disease, Raynaud’s phenomenon and arthritis. Serum autoantibodies to aminoacyl-tRNA synthetase (Anti-PL-12) are often present. The prognosis of the disease is largely determined by the pulmonary involvement. Prednisone with or without azathioprine and methotrexate have been used for myositis, while cyclophosphamide should be considered for severe pulmonary involvement. Anti SRP associated necrotizing autoimmune myositis is part of the spectrum of autoimmune inflammatory myopathies. It is characterized by the presence of signal recognizing particle antibodies which may occur in isolation or in some cases, in conjunction with other serum auto-antibodies. We describe a rare and interesting case of a 37 year old female who presented with a progressive proximal muscle weakness involving the upper and lower limbs in association with lethargy. She also displayed Raynaud’s phenomenon and complained of exertional shortness of breath. She had extremely high creatine kinase levels (22,000) U/L and electrophysiological confirmation of an active myositis. She had positive anti SRP antibodies and muscle biopsy findings of a necrotizing autoimmune myositis. In addition, she had anti-PL-12 antibodies and evidence of interstitial lung disease on pulmonary function tests and CT lung imaging. Her constellation of symptoms, signs and investigative findings were consistent with an anti-synthetase syndrome. She was treated initially with methylprednisone, azathioprine and IVIG without significant improvement. Her myositis and ILD partially responded to IV cyclophosphamide therapy. This case demonstrates a unique patient with anti-synthetase syndrome in association with anti-SRP and anti-PL-12 myositis specific antibodies. It highlights the use of myositis-specific antibody testing in assisting the diagnosis and choice of therapy. Further studies are required to determine the occurrence of multiple myositis specific antibodies in necrotizing myopathies and if their presence correlates with prognosis and treatment response.