Periodic Fever in Children: Etiology and Diagnostic Challenges

Periodic fever in children is an autoinflammatory illness with an unknown cause. Symptoms include frequent episodes of fever that are followed by an increase in inflammatory markers. A genetic background for periodic fever of unknown origin has been hypothesized, based on its family clustering and parallels to other autoinflammatory illnesses such as familial Mediterranean fever. Genome analysis has been used in studies to look for related gene variations in periodic fever of unknown origin in the pediatric population.  Children with periodic fevers might be a diagnostic challenge. After ruling out the most prevalent causes, a wide variety of other possibilities are investigated. Infectious and noninfectious causes of periodic fever in children are discussed in this article. Inflammasomes (intracellular proteins that activate interleukin (IL)-1b and IL-18) and genetic/hereditary variations are thought to be implicated in the pathogenesis of periodic fever. Evaluation and ruling out possible infective or noninfective causes is vital in the diagnosis of periodic fever in children. Investigations demonstrate that there isn't a single gene linked to it, suggesting that it may have a multifactorial or polygenic origin, with an environmental trigger causing inflammasome activation and fever flares. Treatment is usually symptomatic, with drugs such as colchicine and cimetidine having shown promising results in trials. We explored the literature on periodic fever in children for its epidemiology, pathophysiology, the role of various genes and how they influence the disease and associated complications, and its various treatment modalities.