Introduction: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever with serositis, synovitis, or skin rash. It is caused by mutations in the MEFV gene, and mutations in exon 10 are associated with typical FMF phenotypes. FMF patients with exon 10 mutations have been reported to show higher serum levels of interleukin (IL)-18 both during attacks and afebrile phases compared to those without exon 10 mutations. However, a longitudinal course of circulating IL-18 after initiation of treatment with colchicine has not been fully characterized.
Methods: We evaluated serum IL-18 in 12 patients with FMF carrying exon 10 mutations, all of whom showed typical FMF attacks.
Results: Significant high concentrations of IL-18 were observed in all patients at diagnosis (5,099±6,084 pg/mL). Serum IL-18 levels declined progressively after colchicine treatment in 7 patients (group A), whereas 5 patients showed continued elevation of circulating IL-18 (more than 1,000 pg/mL; group B). Serum IL-18 levels at last hospital visit in groups A and B were 686±281 and 4,190±2,610 pg/mL, respectively. The mean follow-up time were 4.7±3.2 and 4.8±1.5 years, respectively. No differences in onset age, initial IL-18 levels, and colchicine doses were found in 2 groups. Although FMF attacks almost disappeared in both groups, there were trends towards presenting subtle symptoms such as abdominal discomfort more frequently in group B.
Conclusions: Sustained elevation of serum IL-18 may suggest the presence of persistent subclinical inflammation due to dysregulated inflammasome activation. Longitudinal examination of serum IL-18 may contribute better follow-up of FMF patients with exon 10 mutations.