Antisynthetase Syndrome Presenting as Acute Respiratory Distress Syndrome Responsive to Rituximab

Abstract

INTRODUCTION: Antiynthetase syndrome (ASS) is characterized by myositis, interstitial lung disease, Raynaud's phenomenon, fever, mechanics hands and anti-aminoacyl-transfer-RNA synthetases. The most common histopathological diagnosis is nonspecific interstitial pneumonia (NSIP), rarely diffuse alveolar damage (DAD). It is conventionally managed with corticosteroids and other immunosuppressive agents (1). CASE PRESENTATION: A 47 yo man with a history of Raynaud's phenomenon presented with acute respiratory distress syndrome after experiencing cough, shortness of breath, and myalgias for several weeks. His exam revealed mechanics hands. A chest CT demonstrated diffuse bilateral confluent infiltrates. Repeated bronchoalveolar lavages demonstrated no infectious etiology. He was started on high dose steroids, broad spectrum antibiotics and paralyzed as his respiratory status continued to decline. He was transferred to our hospital due to challenging, prolonged (2 weeks) mechanical ventilation. Steroids were held due to lack of significant response. Laboratory tests revealed negative ANA, anti-Jo-1, anti-La, anti-Scl-70, rheumatoid factor. Anti-Ro was positive. Additional anti-synthetase antibody testing was sent. A bedside open lung biopsy of the right upper lung was performed. The biopsy demonstrated acute and organizing (DAD). Due to critically worsening respiratory status (pH 7.37/PaCO2 84 mmHg/PaO2 68 mmHg on 100% FiO2) he was treated with rituximab in addition to high dose steroids. The patient's clinical status improved dramatically with weaning of mechanical ventilation over the next week. Anti-PL-7 antibody returned positive confirming the diagnosis of ASS. DISCUSSION: The prognosis of ASS is poor mainly secondary to mortality associated with respiratory failure from progressive ILD. Those with DAD on histopathology tend to have more rapid progression of disease (1,2). This patient had acute respiratory failure with diffuse alveolar damage that had a marginal response to steroids. A prior retrospective small case series demonstrated efficacy of rituximab in the treatment of less severe steroid refractory ASS (3). CONCLUSIONS: While the majority of patients with ASS have chronic mild/moderate ILD characterized histopathologically by NSIP, this case exhibits that it can present with severe, life-threatening acute respiratory distress syndrome. This patient had a dramatic improvement in his respiratory failure in the context of therapy with rituximab.