Growth outcomes in children with familial Mediterranean fever: a question beyond chronic or relapsing inflammation

Background/Objective: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by missense MEFV mutations, leading to recurrent episodes of interleukin (IL)-1β mediated inflammation, and represents a model of cytokine-induced growth hormone (GH) resistance. Chronic or relapsing inflammatory bouts may impair growth in FMF children through functional alterations of the GH-insulin-like growth factor 1 (IGF-1) axis; however, the impact and reversibility of growth deficit remain unclear. The aim of this review is to assess data related to linear growth in young patients with FMF. Methods: This scoping review was conducted following PRISMA guidelines, searching for studies evaluating growth outcomes in FMF via the PubMed database. Fourteen studies, including 1144 children, were analyzed, evaluating height, growth velocity, IGF-1 levels, and treatment effects of colchicine or IL-1–targeted biologics. Results: Growth was generally preserved in a con siderable number of children with FMF. Longitudinal analyses showed improvement in height standard deviation scores (HSDS) along with earlier and higher cumulative doses of colchicine. FMF attack frequency and overall disease severity modestly seemed to influence growth, whereas inflammatory markers were inconsistently correlated with growth parameters. Biologic therapies targeting IL-1 (canakinumab and anakinra) also showed positive effects on HSDS. Children with specific MEFV variants (such as M694V) or higher disease activity scores were at risk of developing a subtle growth impairment. Conclusions: Data on final height, though limited, suggest the preservation of growth in most pediatric patients with FMF. The maintenance of a normal linear growth is related to regular treatment with colchicine, though IL-1 blockers also appear to be beneficial in refractory FMF cases. These data highlight the importance of periodic, proactive check-ups and regular growth monitoring in children with FMF.