The current report described a case of Kikuchi disease-associated Mollaret meningitis with MEFV gene mutation, which was successfully treated with colchicine. This case of recurrent aseptic meningitis fulfilled the diagnostic criteria reported by Bruyn et al1 and demonstrated the presence of Mollaret cells in the CSF. The lymphadenopathies, which often accompanied the meningitis, was confirmed by biopsy as Kikuchi disease, which was presumed to be the cause of Mollaret meningitis.
We found out two new important clinical issues. First, Mollaret meningitis can be caused by Kikuchi disease. Although Kikuchi disease had been reported to cause recurrent episodes of aseptic meningitis4, there had been no previous reports on Kikuchi disease-associated recurrent meningitis, in which Mollaret cells were identified in the CSF. Clinicians should consider Kikuchi disease as one of the possible causative diseases of Mollaret meningitis and the necessity of excisional lymph node biopsy in a patient with recurrent meningitis and lymphadenopathy.
Second, colchicine may inhibit the recurrence of Kikuchi disease, as well as Mollaret meningitis. In this case, the recurrence of both lymphadenopathy and meningitis was suppressed after starting colchicine. In general, an acute episode of Kikuchi disease is managed with NSAIDs or corticosteroids; to prevent recurrence, corticosteroid is used for a long period5. Some case reports showed that hydroxychloroquine and anakinra were effective for Kikuchi disease6, 7, despite their risk of retinopathy and expensiveness. To our best knowledge, there had been no research that demonstrated the benefits of colchicine for the management of Kikuchi disease. Our case indicated that colchicine can be a safe and inexpensive corticosteroid-sparing agent for the prevention of recurrent Kikuchi disease. The effectiveness of colchicine for the treatment of Kikuchi disease should be further examined in a large-scale study.
The clinical effectiveness of colchicine on Kikuchi disease can be explained by its activity to suppress the inflammasome signaling. Previous reports demonstrated that colchicine inhibits the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which senses pathogen-associated molecular patterns and triggers the secretion of IL1 and IL188. Therefore, colchicine decreases the levels of IL1, IL6, and IL18, which were reported to contribute to the pathogenesis of Kikuchi disease3,7. These reports suggested that colchicine can prevent the recurrence of Kikuchi disease through inactivation of NLRP3 and cytokines.
The presence of MEFV gene mutation may underlie the chronic recurrent inflammation that is observed not only in FMF but also in Kikuchi disease and Mollaret meningitis. This case of recurrent Kikuchi disease and Mollaret meningitis was found to have the P369S/R408Q mutation in the MEFV gene; both of these conditions were successfully treated with colchicine. Previous studies have shown that P369S/R408Q mutation was associated with atypical presentations of FMF and was detected in a patient with Kikuchi disease9, 10. However, the pathological significance of P369S/R408Q mutation in the MEFV gene remains unclear10. Further research is needed to elucidate the association between MEFV gene mutations and Kikuchi disease, as well as the pathological role of P369S/R408Q mutation.
In conclusion, Mollaret meningitis can be caused by Kikuchi disease, and recurrence of both might be suppressed by colchicine.