Methotrexate/naproxen - Associated severe hepatitis in a child with juvenile idiopathic arthritis

Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). Although associated with many mild adverse effects, the short and long-term safety of MTX in JIA has been excellent. While many JIA children treated with MTX develop liver enzyme abnormalities, no cases of irreversible liver damage or of severe non-infectious hepatitis with Reye-like features have been reported in non-systemic JIA. We report a 2-year-old girl with oligoarthritis whose liver enzyme increased to greater than 45 times the upper limit of normal, and developed hypoglycemia and hyperammonemia after 10 months of MTX and naproxen therapy. An infectious and metabolic work-up for other causes was unremarkable. She recovered completely after folinic acid therapy; AM and naproxen was not restarted. While very rare in JIA, MTX in synergism with naproxen can induce severe liver toxicity and it is important to screen children for liver enzyme abnormalities.