Sıla Atamyıldız Uçar, Mahmut Seyfeddin Öz, Eray Tunce, Betül Sözeri
Trends in Pediatrics - 2025;6(4):260-267
Objective: To determine whether prolonged colchicine therapy and higher colchicine doses are independently associated with vitamin B12 deficiency in pediatric familial Mediterranean fever (FMF) patients, after adjusting for age as a confounding factor. Methods: This retrospective study included pediatric FMF patients with biallelic exon 10 MEFV mutations, followed between August 2016 and September 2024. Patients receiving colchicine treatment for at least 12 months and with available serum vitamin B12 measurements were included. Vitamin B12 levels were categorized as deficient (<=200 pg/mL) or normal (>200 pg/mL). Demographic data, colchicine treatment duration and dosage, clinical features, and Pras disease severity scores were recorded. Results: Among 339 patients, 193 (56.9%) were female. The median age at FMF diagnosis was 5 years (interquartile range [IQR], 3-9), and at vitamin B12 testing was 13 years (IQR, 9-16). The median of vitamin B12 levels was 317 pg/mL (236.7-447), and 12.1% of patients had vitamin B12 deficiency. Patients with vitamin B12 deficiency had significantly longer colchicine duration (72 months [48-144] vs. 60 months [24-96], p=0.034) and higher daily colchicine doses (1.33+/-0.4 vs. 1.12+/-0.4, p=0.004) compared to those with normal vitamin B12 levels. Patients with a colchicine duration of more than 96 months had the lowest vitamin B12 status (p=0.008) and the highest frequency of vitamin B12 deficiency (p=0.014). Receiver operating characteristic (ROC) system analysis identified an age threshold of 12.2 years as predictive for vitamin B12 deficiency (area under the curve=0.708; sensitivity=85.4%; specificity=53.4%). At the time of vitamin B12 measurement, 28 (8.3%) were colchicine-resistant FMF patients, and vitamin B12 deficiency was significantly more common in colchicine-resistant FMF patients compared to colchicine-responsive FMF patients (n=21, 7%) (p=0.03). No significant association was observed between MEFV mutation subtypes (p=0.35), nor between PRAS severity categories (p=0.71) with vitamin B12 status. Conclusion: Vitamin B12 deficiency appears to be associated with age in pediatric FMF patients. Although prolonged colchicine treatment and higher daily doses were associated with lower B12 levels, these associations were not independent of age. Routine monitoring may be considered in adolescents and with long-standing disease. Further prospective studies are needed to clarify the long-term impact of colchicine on vitamin B12 levels.
