Aseptic meningitis occurring during anti-TNF-alpha therapy in rheumatoid arthritis and ankylosing spondylitis

Objective. Aseptic meningitis is a rare and aggressive complication of rheumatoid arthritis (RA), usually histologically characterised by rheumatoid nodules and lymphocytic aggregates in leptomeninges. The aim of this study was to describe the clinical onset and evolution of aseptic meningitis occurring during anti-TNF-alpha (TNF-alpha) therapy. Methods. we retrospectively analysed the clinical records of patients with RA or ankylosing apondylitis (AS) treated by TNF-alpha drugs in the last 10 years. Results. Four out of 718 patients, treated with TNF-alpha, developed meningitis after a mean of 5 years (SD: 3.7) of TNF-alpha exposure (0.55%). Three subjects were affected by long-standing RA (median: 11 years, IQR:8.5-25), one patient by active AS of 8 years' duration. RA patients were treated with etanercept (2 cases) and infliximab (I case), in association with methotrexate and prednisone. The AS patient was treated with adalimumab. Neurological onset was focal epilepsy (3 cases) and dysarthria (1 case). RM showed leptomeningeal enhancement of basal nuclei (1 case) or fronto-parietal zone (3 cases), associated in one patient with cerebritis. Bacterial, viral or parasitic infections were excluded. One patient underwent cerebral biopsy showing T and B lymphocytes' aggregates. All patients discontinued TNF-alpha drugs and were treated with high dose of steroids, added to methotrexate in two cases. Neurological symptoms resolved without residuals, and meningeal enhancement showed resolution with high latency. Conclusion. Meningeal inflammation is a rare manifestation occurring in long-standing RA and AS in clinical remission. TNF-alpha therapy did not prevent this extra-articular complication.