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PFAPA syndrome, periodic fever, aphthous stomatitis, pharyngitis, cervical lymphadenitis


PFAPA, the syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical lymphadentitis, is an uncommon disease of episodic immune dysregulation that usually begins in early childhood. Symptoms occur at regular, predictable intervals, with healthy periods in between, and generally include the namesake signs and various other constitutional symptoms such as fever and fatigue. The etiology is unknown and there is no definitive diagnostic test or treatment. Uncertainty during the period of searching for a diagnosis may be disconcerting to the family and the clinician. Single-dose prednisone is effective for resolving the fever of PFAPA episodes within just a few hours, but it does not prevent further episodes. Tonsillectomy is an effective surgical option; however, PFAPA often spontaneously resolves or episodes get less intense and less frequent with age. Febrile PFAPA episodes are an area of active research and may involve environmentally triggered inappropriate interleukin-1 and complement activation leading to chemokine release and trapping of activated T-cells in peripheral tissue.