Tuberculosis in a nine year old girl treated with Infliximab for systemic juvenile idiopathic arthritis

A five year old girl presented in 1998 with typical features of systemic juvenile idiopathic arthritis (S-JIA). Remission was difficult to accomplish despite the use of steroids and indomethacin, later followed by high dose methotrexate (MTX), ciclosporin, methyl prednisone pulses and etanercept (0,4mg/kg twice a week). Then, high-dose infliximab (20mg/kg/month) was added in January 2002. Since 2001 she had a severe lymphopenia and decreased in vitro cellular responses to mitogens, antigens and PPD. In April 2002, fever changed from a spiking to a more continuous pattern and arthritis persisted. Infliximab was stopped. A broncho-alveolar lavage was negative for pathogens including M. tuberculosis. Two months later she developed a cystic swelling at the left wrist. MRI showed a cystic process without signs of osteomyelitis. PCR on the fluid of the cyst was positive for M. tuberculosis. Culture was negative. Cultures and PCR of cerebrospinal fluid, fasting stomach contents, bone marrow aspirate and blood for M. tuberculosis remained negative. Tuberculostatic therapy with 4 different drugs was started. Four months later she died unexpectedly due acute respiratory insufficiency and cardiac arrest. Lung microscopy revealed a lipid pneumonia with fulminant alveolar damage with an infiltrate of neutrophils and macrophages. A chronic (opportunistic) infection on the basis of these findings was strongly suspected but could not be proven by cultures. Apart from one case of an adolescent developing osteoarticular tuberculosis shortly after commencing etanercept, an increased incidence of tuberculosis has not been proven during etanercept treatment in contrast to infliximab. The diagnosis of tuberculosis in immune-compromised patients on anti-TNF-α therapy may be difficult. Because of the absence of granulomas due to anti-TNF-α therapy, radiological screening and histopathology are mostly not conclusive. Skintest is often negative due to impaired cellular immunity.