Rapidly progressive fibrinopurulent pleural empyema with systemic juvenile idiopathic arthritis during treatment with tocilizumab

The abrupt discontinuation of anti-IL-6R biologics during infection may lead to IL-6 overactivation. Dear Editor, Interleukin 6 (IL-6) is a pro-inflammatory cytokine with diverse physiological roles [1]. Biologics targeting the IL-6 receptor (IL-6R), including tocilizumab (TCZ), are widely used for the treatment of various inflammatory disorders [2–5]. A 48-year-old man with long-standing systemic juvenile idiopathic arthritis (sJIA) was admitted to our hospital. He had been diagnosed with sJIA accompanied by fever and polyarthritis at the age of two, and had been treated with corticosteroids but self-discontinued because of the absence of symptoms. At the age of 43, he was diagnosed with the relapse of sJIA accompanied by fever, polyarthritis and throat pain with elevated levels of serum ferritin and C-reactive protein (CRP). Restart of immunosuppressive therapy with prednisolone (PSL; 30 mg daily) and methotrexate (16 mg weekly) successfully put him in clinical remission according to the Wallace criteria [6]. One year later, intravenous TCZ (500 mg monthly) was added and then switched to subcutaneous injection (162 mg biweekly). At the age of 46, PSL was tapered off due to maintenance of clinical remission, which had been sustained with subcutaneous TCZ (162 mg biweekly) and oral methotrexate (6 mg weekly). Two weeks prior to admission, he noticed right hypochondoralgia on inspiration, which worsened with the appearance of dyspnea at rest. He was admitted to our hospital because of a right-sided pleural effusion. The last TCZ infusion was conducted on schedule, 7 days prior to admission. On admission, physical examination revealed no abnormalities except for reduced breath sounds in the right lung field. Laboratory investigations showed leucocytosis (14 600/µL) with neutrophilia (85.7%) and mild elevation of CRP (2.05 mg/dl). Analysis of pleural fluid obtained from the right pleural cavity on day 1 of admission was as follows: pH 7.5, lactate dehydrogenase (LDH) 907 U/l, glucose 51 mg/dl, leucocytes 8.4 × 109/l, neutrophils 88% and negative results for smear examinations and cultures for bacteria, including mycobacteria. Cytological examination of the pleural fluid did not show evidence of dysplastic cells. Sulbactam/ampicillin and azithromycin were started on suspicion of infection in addition to a temporary suspension of TCZ and discontinuation of methotrexate. Chest computed tomography (Supplementary Fig. S1A, available at Rheumatology Advances in Practice online) on day 4 showed a marked worsening of pleural effusion, which required tube thoracostomy drainage. A follow-up study of pleural fluid on day 4 revealed an elevation of LDH (1781 U/l) and a decrease in glucose (