G426 A Case report: Copa mutation – a new condition to consider with polyarthritis and interstitial lung disease

Aim We present a case report to illustrate a new condition to consider in a child with clinical features of polyarthritis and interstitial lung disease. Methods Retrospective Case Note Review. Case A 4 year old girl presented to Paediatric Rheumatology with an 18 month history of joint pain. Examination confirmed extensive joint swelling, and investigations revealed she was ANA positive. She was diagnosed with polyarticular juvenile idiopathic arthritis and commenced on steroids and methotrexate, resulting in clinical remission 13 months later. Aged 6, due to persistent cough, decreased exercise tolerance and finger clubbing, she underwent a respiratory workup. Chest xray revealed widespread reticulo-nodular changes; lung function showed a restrictive defect (FEV 1 and FVC both 54% predicted); CT chest showed appearances of interstitial lung disease; bronchoalveolar lavage contained numerous lipid-laden macrophages but no infection was identified; CFTR genetic analysis revealed the genotype F508del/R117H(7T) (sweat chlorides 52 and 38 mmol/L). FEV 1 improved to 64% following antibiotic treatment. Subsequent pH study revealed significant gastro-oesophageal reflux and anti-reflux medications were added. Methotrexate was stopped. A scheduled lung biopsy was postponed when she became unwell with macrophage activation syndrome. She met ACR criteria for SLE and was treated with steroids and cyclophosphamide. When stable, lung biopsy was obtained, which revealed a mixed picture of inflammation and aspiration. She subsequently underwent fundoplication and treatment with Rituximab. Currently (aged 10 years), lung function remains stable (FEV 1 74%, FVC 79% predicted). Medications include mycophenolate mofetil, hydroxychloroquine, prednisolone and antibiotics. In view of new understanding of autoimmune inflammatory lung disease, we undertook genetic analysis, and confirmed she has a COPA mutation (c.727Gu003eA/p.Asp243Asn substitution in exon9). Discussion In 2015, Watkin et al. described COPA mutation, causing hereditary autoimmune-mediated lung disease and arthritis. The COPA gene encodes subunit of the coatomer protein complex, required for retrograde protein trafficking from the Golgi to the endoplasmic reticulum. How this causes inflammatory arthritis and lung disease is unknown. To our knowledge this is the first UK case to be described. This rare condition should be considered in a child with features of polyarthritis and interstitial lung disease. The relevance of the CFTR sequence variants is unclear.