What is the incidence of Naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID))-induced aseptic meningitis?

Incidence of Naproxen-induced Aseptic Meningitis

Naproxen-induced aseptic meningitis is a rare adverse effect, occurring in less than 1% of patients taking this medication, with higher risk in those with underlying autoimmune conditions such as systemic lupus erythematosus. 1, 2

Definition and Clinical Context

Aseptic meningitis is characterized by:

• Symptoms of meningism (neck stiffness, headache, photophobia) 3
• Raised numbers of cells in the cerebrospinal fluid (CSF) 3
• Sterile bacterial culture 3

Epidemiology and Risk Factors

Incidence

• Drug-induced aseptic meningitis is rare, with NSAIDs being one of the causative agents 3
• Among NSAIDs that cause aseptic meningitis:
  • Ibuprofen is most frequently implicated 2
  • Naproxen is another common NSAID associated with this condition, but less frequently than ibuprofen 2

Risk Factors

• Underlying autoimmune diseases, particularly systemic lupus erythematosus (SLE), significantly increase the risk 2, 4
• Women may be at higher risk than men 4, 5
• Previous episodes of drug-induced aseptic meningitis increase risk of recurrence 4, 6

Clinical Presentation

Typical symptoms include:

• Headache (severe) 5
• Fever 5
• Neck stiffness (nuchal rigidity) 5
• Nausea and vomiting 5
• Photophobia 3

Laboratory findings typically show:

• CSF pleocytosis (often polymorphonuclear) 5
• Elevated CSF protein 5
• Normal CSF glucose 7
• No evidence of bacterial, fungal, or viral infection 5

Diagnosis

Diagnosis is primarily by exclusion:

• CSF analysis showing aseptic inflammation 5
• Negative microbiological studies 5
• Temporal relationship between naproxen administration and symptom onset 4
• Resolution of symptoms after drug discontinuation 4, 5
• Recurrence with rechallenge (though intentional rechallenge is not recommended) 4

Management

The primary management approach is:

• Immediate discontinuation of naproxen 4, 5
• Supportive care for symptoms 8
• Avoidance of all NSAIDs in the same chemical class in severe cases 3
• Consider alternative pain management options from different drug classes 3

Prognosis

• Most cases resolve without long-term sequelae after drug discontinuation 2
• Symptoms typically improve within 24-48 hours of stopping the medication 5
• Potential complications may include sensorineural hearing loss and tinnitus, which typically resolve after discontinuation 9

Special Considerations

Cross-reactivity

• Cross-reactivity between NSAIDs has been reported, though it is not universal 3
• Patients with naproxen-induced aseptic meningitis may also react to other NSAIDs 6, 7

Recurrence

• Recurrent episodes can occur with repeated exposure to the causative NSAID 4, 6
• Multiple episodes of aseptic meningitis should prompt investigation of NSAID use, including over-the-counter medications 6

Clinical Pitfalls to Avoid

• Failing to obtain a complete medication history, including over-the-counter NSAIDs 6
• Misdiagnosis as infectious meningitis, leading to unnecessary antimicrobial treatment 7
• Failure to recognize the association between naproxen and aseptic meningitis, particularly in patients with autoimmune conditions 4
• Not considering drug-induced aseptic meningitis in the differential diagnosis of recurrent meningitis 6