Subclinical inflammation in pediatric familial Mediterranean fever: predictors and follow-up results of a retrospective single-center cohort study

Abstract Introduction/objectives Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease in childhood. Subclinical inflammation is defined as persistently elevated acute phase reactants despite the absence of clinical attacks. The aim of this study was to determine the frequency of subclinical inflammation and its clinical predictors in pediatric FMF patients, and to assess treatment responses following therapeutic adjustments. Methods Medical records of FMF patients followed between January 2011 and February 2024 were retrospectively reviewed. Patients were grouped based on the presence of subclinical inflammation, and clinical features, genetics, and treatment responses were compared to identify risk factors for subclinical inflammation. Results A total of 572 pediatric FMF patients were included, of whom 89 (15.6%) exhibited subclinical inflammation. Patients with subclinical inflammation had significantly earlier disease onset, longer disease duration, numerically more frequent comorbid conditions, and more biallelic exon 10 mutations ( p < 0.05). In addition, arthritis and higher disease severity scores were detected as independent predictors of subclinical inflammation. Regarding treatment, 45% of patients with subclinical inflammation achieved resolution after colchicine dose adjustments. However, 55% required biologic therapies. Among biologic-treated patients, 87.7% showed normalization of inflammatory markers, whereas 12.3% continued to exhibit persistent inflammation; all of these patients had comorbid conditions. Conclusion Subclinical inflammation is common in pediatric FMF patients. Our findings suggest that earlier disease onset, biallelic exon 10 mutations, arthritis, and higher disease severity scores are associated with persistent inflammation. Colchicine dose optimization effectively controls inflammation in nearly half of these patients, while biologic therapies, particularly IL-1 inhibitors, are effective for the remaining cases. Key points • Subclinical inflammation is common in pediatric FMF patients. • Early disease onset, biallelic exon 10 mutations, arthritis, and higher disease severity scores are associated with subclinical inflammation. • Colchicine dose adjustments are effective for nearly half of patients, while biologic therapies, particularly IL-1 inhibitors, are needed for the rest.