O39. SUCCESSFUL TREATMENT OF ANTI-ZO ANTI-SYNTHETASE SYNDROME WITH RITUXIMAB

Abstract

Background: Anti-Zo (anti-phenylalanyl tRNA synthetase) antibodies were first described in idiopathic inflammatory myopathy (IIM) in 2007 and are associated with the anti-synthetase syndrome. They remain a relatively rare finding. We describe a patient with anti-Zo positive antisynthetase syndrome who has responded well to rituximab after failing standard second line agents. Methods: The patient was a 51yr old UK born Caucasian male mechanic and part-time football referee with no significant past medical history. Lifelong non-smoker. He was admitted in February 2013 with non-resolving pneumonia despite several courses of antibiotics. He was dyspnoeic on exercise and had a persistent cough and myalgia. Examination showed long cuticles with infarcts and apparent mechanics hands (these persisted even after he had stopped work). Investigations: CK 1303 iu/L (normal 40-320), ALT 84 iu/L (normal 0-50) and CRP 8.4 mg/L (normal 0-10). ANA, ANCA, Ig, C3 and C4 were negative/normal. Local ENA panel including Jo-1 and Scl-70 was negative. Royal Free screening including PL-7, PL-12, Ku, Mi2, PMScl and SRP was also negative. Initial lung function tests: FVC 3.44L (64% predicted), DLCO, 58% predicted. HRCT chest: extensive bilateral organizing pneumonia, particularly affecting the left base. Ba swallow: dysmotility and reflux. Results: He was treated with prednisolone 40mg od and MMF 1g bd with slow normalization of CK over 3 months. Follow up HRCT showed persistent changes. At 5 months he was still steroid dependent (30mg) and was started on the Brompton cyclophosphamide regime for 6 months. As soon as this finished in February 2014 CK rose to 1003 iu/L despite prednisolone 15mg od. DLCO was 55%. At this point serum was sent to Bath for further antibody testing. This showed positive anti-Zo antibodies. IFR funding for rituximab was obtained (partly on the basis of this) and started in July 2014. By July 2015 he was steroid free and DLCO had improved to 64%. In July 2016 after a total of 4 courses of rituximab DLCO has further improved to 70%. CK remains normal and he has resumed football refereeing. He has remained steroid-free on single agent rituximab treatment. Conclusion: NHS England has now approved rituximab for use in patients with active myositis who have auto-antibodies relevant to myositis. This makes a detailed search for related antibodies crucial, even if initial basic screens are negative. It also supports the argument for further research to look for other synthetase syndrome-associated antibodies. The presence of reflux usually makes patients with interstitial lung disease ineligible for lung transplant; this lack of an end game means that aggressive and targeted early treatment is necessary and supports the now mandated use of a national database in this group of patients.