Is recurrent aseptic meningitis a manifestation of familial Mediterranean fever? A systematic review

Objectives. Familial Mediterranean fever (FMF) causes recurrent episodes of fever and painful serositis. It has been suggested that FMF can cause recurrent aseptic meningitis (RAM). Due to the rarity of both diseases, this claim cannot be assessed with epidemiological methods. We therefore decided to perform a systematic review of the literature to assess the number and validity of published case reports. Methods. Medline, Embase, Pascal, Web of Science and the proceedings of relevant conferences were searched. Two independent investigators selected reports asserting RAM in FMF patients, abstracted data and rated the strength of evidence with a custom tool designed to assess: (a) the diagnosis of FMF; (b) the diagnosis of RAM; and (c) the link between FMF and RAM. A causal link was supported by (i) evidence of inflammation and/or clinical FMF features during episodes of RAM; (ii) effectiveness of colchicine to prevent further bouts of meningitis; and (iii) the exclusion of other causes of RAM. Results. Among 944 retrieved references, 917 were rejected by title and abstract screening and 15 after full text review. The strength of evidence of 12 alleged cases of RAM due to FMF was assessed. FMF was unsupported in 4 cases and RAM in 3 further cases. Four of the 5 remaining cases did not provide adequate evidence to support a. causal relationship between FMF and RAM. Conclusion. The possibility of RAM due to FMF is poorly supported by a single fairly documented case report that does not, however, meet current diagnostic standards.