028. When Medication is Not the Culprit: Abnormal Liver Function in a Patient with Polyarticular Juvenile Idiopathic Arthritis

Abstract

Background: Hepatotoxicity is a well-recognised side-effect of diseasemodifying antirheumatic drugs (DMARD). In patients with juvenile idiopathic arthritis (JIA), transient elevation of transaminases is common in those receiving methotrexate and some anti-tumour necrosis factor alpha medications. There is little evidence to guide optimal monitoring, interpretation of results, further investigation or intervention. Aims: We present an 8-year old girl with polyarticular JIA and persistently raised liver enzymes during the first eighteen months of treatment, leading to further investigation and a consequent diagnosis of Wilson's disease. Methods: We produced a retrospective case review. Results: A diagnosis of JIA was made at 6 years. She received steroid injections to multiple joints and was commenced on methotrexate. Alanine aminotransferase (ALT) was marginally elevated at diagnosis (59 U/l, normal range <50), but normalised prior to commencing treatment. ALT levels rose shortly after starting methotrexate and remained elevated. Gamma-glutamyl transferase (GGT) was occasionally marginally raised, but other liver function remained normal. Over subsequent months, elevated ALT often coincided with upper respiratory tract infections. Methotrexate was omitted on a number of occasions due to ALT levels >4x upper limit of normal. The dose was reduced and extended to fortnightly, with improvement but not normalisation of ALT. Infliximab was commenced at eight months due to ongoing active JIA. Liver function remained abnormal (highest ALT 433 U/l) and at twelve months was associated with a new development of worsening abdominal pain and nausea. A decision was made to stop methotrexate and infliximab. Baseline investigations into other causes for continuing hepatitis and abdominal pain were normal. JIA disease control became increasingly difficult and she was commenced on adalimumab. She was discussed with gastroenterology colleagues eighteen months after diagnosis. Further investigations revealed low caeruloplasmin and an alpha-1 antitrypsin (A1AT) carrier phenotype. Repeat ultrasound scan showed mild liver inflammation and fatty infiltration. Serum copper level and urinary penicillamine challenge were highly suggestive of Wilson's disease. Liver biopsy demonstrated an elevated copper content and steatosis. Genetic testing remains outstanding. She was commenced on zinc acetate, with normalisation of liver function within weeks. Abatacept was chosen for ongoing JIA management, with reduced risk of associated liver upset which would interfere with Wilson's disease monitoring. Conclusions: Wilson's disease is rare and transaminase abnormalities vary considerably. Early diagnosis and management, before organ damage has occurred, will optimise outcome. As in this case, however, children are usually asymptomatic and abnormal transaminases noted fortuitously. Interpreting blood results of paediatric patients on methotrexate is challenging, with little evidence to guide intervention. In our case, there was no improvement in liver function with alterations in drug therapy, triggering further investigations for underlying pathology. The case illustrates the importance of consideration of other causes of raised liver transaminases during methotrexate monitoring, and highlights the value of early discussion with gastroenterology.