Recurrent aseptic meningitis in adults: a potential indicator of undetermined autoinflammatory disease

Background: Autoinflammatory diseases (AIDs) are characterized by recurrent episodes of inflammation caused by primary immune system dysregulation. Central nervous manifestations, including aseptic meningitis (AM), are rare in AIDs. In this study, we identified six patients with undetermined AIDs characterized by recurrent aseptic meningitis (RAM). Methods: Patients referred to Centre National de Référence des Maladies Auto-Inflammatoires for AM with an undetermined diagnosis were included. AIDs with RAM were defined by two or more episodes of aseptic meningitis (>10 leukocytes) with a predominance of neutrophils (>50%) and an association with autoinflammatory elements (i.e., fever, C-reactive protein [CRP] elevation) and the absence of an alternative diagnosis. Results: Six patients (four men, two women) were included, all of whom presented with fever and elevated CRP levels (≥30 mg/L), and five patients had clinical meningitis syndrome. The median patient age at disease onset was 41 years (range, 28-49). The frequency of AM was 1-24 episodes/year, and the duration of episodes was ≤8 days. Associated clinical symptoms included cutaneous manifestations (rash [n = 3], Raynaud's syndrome [n = 1]), arthromyalgia (n = 2), and central neurological or ophthalmologic manifestations (n = 2). All patients underwent genetic analysis focusing on AIDs, and variants of undetermined significance within four autoinflammatory genes were noted in three patients. All patients benefited from classical therapeutic regimens of AIDs including corticosteroids, colchicine, and anti-interleukin (IL)-1 receptor or anti-IL6 antibodies. Conclusion: RAM was identified as a potential indicator for undetermined AIDs. Physicians should be aware of this condition and provide adequate analysis and treatment.