Case report

A 30-year-old man presented with 3 days of headache, nausea, neck pain and photophobia. Two days prior to the onset of symptoms he had taken diclofenac retard for back pain. Examination revealed nuchal rigidity and photophobia, cerebrospinal fluid (CSF) was opaque with an opening pressure of >300 mm, protein concentration was 1.62 g/l and CSF-to-blood glucose ratio was 0.51. Microscopy demonstrated 665 mononuclear cells/mm3 but bacterial and viral culture were negative.

He had six previous documented episodes of aseptic meningitis. Admissions were stereotyped with symptoms improving rapidly following lumbar puncture. Serological tests for herpes viruses, rheumatoid factor and antinuclear antibody were negative. General practitioner records were available for the previous 6 years. All four episodes of aseptic meningitis within this 6-year period had occurred within the month following the prescription of a NSAID (naproxen, piroxicam and diclofenac) for mechanical back pain, suprascapular tendonitis and tennis elbow. In the final three admissions diclofenac was prescribed 6, 5 and 2 days prior to the onset of headache. Over a 3-year period where NSAIDs were not prescribed the patient did not present to his general practitioner with headaches. Following the final admission the patient was advised to avoid all NSAIDs in the future. Re-challenge with a NSAID in hospital was not undertaken following discussion with the patient. In the 2 years since there have been no further episodes of aseptic meningitis.

Discussion

In any patient presenting with fever, headache and meningism with CSF findings consistent with aseptic meningitis, an infective cause should always be sought and treated empirically with antimicrobials. In the rare patient in whom recurrent bouts of aseptic meningitis occur, a chemical trigger should be suspected and a careful drug history, including over-the-counter medications, should be taken. In those in whom a trigger cannot be identified and a predisposing condition, such as autoimmune disease, is not suspected the diagnosis ‘Mollaret’s meningitis' is usually made. The aetiology of this condition is uncertain, although some cases have been associated with recurrent herpes simplex infections (types 1 and 2) demonstrable by amplification of viral DNA in the CSF.4 5

In the patient presented there was a temporal association between the prescription of either diclofenac, piroxicam or naproxen and the development of aseptic meningitis. Most cases of NSAID-induced aseptic meningitis appear to be agent-specific as rechallenge with other agents does not tend to result in aseptic meningitis.3 At least one other patient, however, has had aseptic meningitis related to more than one agent (suldinac and ibuprofen).6 The mechanism for this adverse reaction is unclear. The association is most commonly seen in women with SLE although male patients without underlying pathology have also been described. The most plausible explanation for the association is a hypersensitivity reaction involving the meninges. Evidence for this is mainly circumstantial: the symptoms develop rapidly following the ingestion of the drug, incubation periods become shorter with repeat attacks and recovery is rapid on stopping the drug. A minority of patients also may describe flushing and other symptoms of a hypersensitivity type reaction.1 3 Prostaglandin inhibition as a cause is unlikely in most cases of NSAID-induced aseptic meningitis since rechallenge with an alternate NSAID tends not to reproduce the symptoms although this cause cannot be discounted in our patient. Other central nervous system effects of NSAIDs are well described, particularly in the elderly and these include acute psychosis and cognitive deficits.3 Again the pathophysiology of these adverse effects are not known.

Since NSAIDs are commonly dispensed ‘over-the-counter’, their role in the aetiology of aseptic meningitis may be underestimated.