A potential partnership between genetics and oral microbiome in children displaying periodic fever/aphthosis/pharyngitis/adenitis syndrome

PFAPA syndrome belongs to the family of autoinflammatory disorders, and its pathophysiology remains mysterious; it is probably related to oligo or polygenic mechanisms and recurs over a variable length of time in combination with clinical signs relating to the oral cavity and cervical lymph nodes. Pharyngitis and cervical adenitis are distinctive manifestations of PFAPA syndrome, which is largely underdiagnosed among the non-hereditary causes of pediatric fevers and is sometimes confused with other hereditary periodic fevers, primary or acquired immunodeficiency disorders, and cyclic neutropenia. Unfortunately, options for successfully managing the disease and stopping the recurrence of fevers are limited. Interventions focused on innate immunity cells might enhance their response and convey possible benefits for these children; how the microbiome interacts with peculiar genotypes to influence PFAPA expression is an open question, and the acquisition of metagenomic data will create opportunities to examine the evolutionary tuning of the microbiome to the host and shed light on the manifold human–microbiome partnership.