title: Aseptic meningitis occurring during anti-TNF-alpha therapy in rheumatoid arthritis and ankylosing spondylitis.
abstract: 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-α) therapy.
  
  
  METHODS
  we retrospectively analysed the clinical records of patients with RA or ankylosing apondylitis (AS) treated by TNF-α drugs in the last 10 years.
  
  
  RESULTS
  Four out of 718 patients, treated with TNF-α, developed meningitis after a mean of 5 years (SD: 3.7) of TNF-α 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 (1 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-α 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.
  
  
  CONCLUSIONS
  Meningeal inflammation is a rare manifestation occurring in long-standing RA and AS in clinical remission. TNF-α therapy did not prevent this extra-articular complication.
authors.affiliation: Rheumatology and Clinical Immunology Unit, Spedali Civili di Brescia, Brescia, Italy. ilariacava@virgilio.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavazzana
authors.forename: Mara
authors.initials: M
authors.lastname: Taraborelli
authors.forename: Micaela
authors.initials: M
authors.lastname: Fredi
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.forename: Franco
authors.initials: F
authors.lastname: Franceschini
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008582:Meningitis, Aseptic / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha