In most cases, PFAPA syndrome presents during childhood, with up to 90% of cases presenting before the age of 5 years. Less commonly, it can have a delayed onset in adulthood.
The typical presentation consists of fever lasting 3-6 days and recurring every 4-8 weeks. Febrile episodes are accompanied by aphthous stomatitis, adenitis, or pharyngitis in the absence of concomitant upper respiratory infection or other periodic fever syndrome. Individuals are otherwise healthy between episodes and have normal growth and development. In adults, febrile episodes are more likely to be associated with additional symptoms of fatigue, chest pain, arthralgias, arthritis, myalgias, conjunctivitis, and rash.
The pathogenesis is not fully understood. Recent studies suggest that PFAPA syndrome is likely due to dysregulation of both the innate and adaptive immune systems. Dysregulation of the innate immune system leads to T-cell recruitment and activation, leading to increased T-helper 1 cytokines such as tumor necrosis factor (TNF)-alpha, interferon-gamma, IL-6, and IL-10.
Predisposing factors are not well known, but a few small studies have found a significant correlation between PFAPA syndrome and vitamin D deficiency. Mutations in the Mediterranean fever gene (MEFV), which is implicated in familial Mediterranean fever (FMF), have been found in selected cohorts. The significance of this finding is unclear.
PFAPA syndrome is considered a self-limited disease. In most pediatric cases, it resolves during late childhood, typically by age 10. There are no known long-term complications of this condition. In adults, no long-term outcome data are available, so it is not known whether adults undergo spontaneous clinical remission.
R50.81 – Fever presenting with conditions classified elsewhere
398870000 – Recurrent aphthous ulcer
717231003 – PFAPA syndrome