Periodic fever, aphthous stomatitis, pharyngitis and adenitis

Lore & Background

PFAPA syndrome was first described in 1987 and named two years later. Its key symptoms are periodic high fever at intervals of about 3–5 weeks, along with aphthous ulcers, pharyngitis, and cervical adenitis. Between episodes, and even during them, affected children appear healthy. At least six months of episodes are required for diagnosis. The cause is unknown, though possible factors include genetic predisposition or an initial infection, and the condition appears to result from a disturbance of innate immunity.

Reader's Guide

PFAPA syndrome is significant as a periodic fever syndrome of unknown cause that primarily affects young children, with episodes recurring every 3–5 weeks. Diagnosis requires recurrent negative throat cultures and exclusion of other causes such as EBV, CMV, and familial Mediterranean fever. Treatment options include corticosteroids at the start of each fever episode, which usually end the fever within hours but may increase episode frequency; interleukin-1 inhibition appears effective; colchicine and cimetidine may reduce flare-up frequency; and surgical removal of the tonsils shows moderate-quality evidence of benefit. The syndrome typically resolves spontaneously in children with no long-term physical effects, but it has been found in adults and may not resolve. Children with PFAPA experience impaired quality of life, including lower physical, emotional, and psychosocial functioning, and substantially impacted school performance.

Did You Know?

• The cause of PFAPA is unknown, but it involves a disturbance of innate immunity with complex immune system changes.
• A single dose of corticosteroid at the start of a fever episode usually ends the fever within hours.
• PFAPA does not lead to other diseases and spontaneously resolves as the child gets older.