LAUSR

Dear Editor, Drug-induced aseptic meningitis is suggested by a temporal relationship between onset of aseptic meningitis and drug exposure. We report an 87-year-old woman who presented with aseptic meningitis on a background of two previous similar episodes. Each occasion occurred following trimethoprim use with decreasing interval between dose and symptomatology. On the first occasion she presented with fever, headache and delirium 48 h after taking trimethoprim for a simple urinary tract infection. Computed tomography of her head was unremarkable, but laboratory tests demonstrated leucocytosis in the peripheral blood, and elevated protein (2.89 g/L) and leucocytes (315 x 10/ L) with predominant monocytes (230 x 10/L) in the cerebrospinal fluid (CSF). There were no eosinophils in the CSF or blood. Blood glucose level was normal at 3.6 mmol/L. Microbiological testing for viruses, fungi, bacteria and acid-fast bacilli were all negative. She was managed with 48 h of meropenem and azithromycin, and a 2-week course of acyclovir. The second episode occurred 6 months later with onset of confusion 24 h after ingestion of trimethoprim. CSF, once again, demonstrated an elevated protein (2.46 g/L), leucocytes (717 9 10/L) with predominant monocytes (502 9 10/L) and no eosinophils in the CSF or blood. A third episode occurred with similar symptoms developing within 3 h after a dose. An eosinophilia (4 9 10/L) was noted in CSF but not in blood. On all three occasions neurological recovery occurred within 24 h after drug cessation. The current understanding of pathogenesis is that of a combination of types II and IV hypersensitivity reactions. The initial delay of 48 h is typical of that in type IV hypersensitivity response, in which cell-mediated adaptive immunity is responsible. In type II hypersensitivity reactions, the drug-specific antibody may be formed during earlier exposure of the hapten conjugate to meningeal or CSF protein and can rapidly mediate cytotoxicity when the drug is presented to sensitixed individuals. A literature review of cases from 1996 to 2015 identified 42 cases of aseptic meningitis related to trimethoprim-containing drugs. Eleven were reported to have an underlying autoimmune disease (Table 1), raising the possibility that an alternative etiology to the aseptic meningitis involving immune dysregulation could be considered. As the diagnosis of drug-induced aseptic meningitis is purely clinical, careful follow-up of