Overview

Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis syndrome (PFAPA) is a periodic fever disorder of childhood classically characterized by periodic fevers, pharyngitis, stomatitis, adenitis and leukocytosis. During each 2-5 day fever episode, temperatures often reach 40.5°C. Interestingly, the patients are completely well with normal growth and development between episodes, which occur at nearly fixed intervals every 3-6 weeks. Treatment with antipyretics does not alter the course, and antibiotics have no demonstrable utility in care of the patient with PFAPA. Corticosteroids administered as a single dose at the onset of symptoms have been shown to shorten the course of an individual febrile episode in some patients, with good tolerance of treatment. However, the frequency of episodes has at least anecdotally been shown to increase once corticosteroid use is initiated. PFAPA patients have also been treated successfully with tonsillectomy. Thus far, case reports, retrospective case series, and two clinical trials describing adenotonsillectomy as therapy for PFAPA have been published. While it appears to be a viable option, no data exists in the published literature regarding the mechanism behind its success in resolving the periodic fever symptoms. Evaluation of the extracted tissue in comparison to tonsillar/adenoid tissue removed for recurrent pharyngitis, obstructive sleep apnea and other non-periodic fever-related conditions may provide insight into the mechanisms behind this syndrome.

PFAPA as a clinical entity has only been described since 1986 and many questions exist regarding its etiology. In addition, the cyclic nature of PFAPA is not understood. Resolution of symptoms after tonsillectomy suggests that the syndrome may represent dysymbiosis between the host and colonizing bacteria. More detailed classification of patient symptoms, disease course, and evaluation of immunoregulatory mechanisms may aid in elucidating the natural history of this entity and in identification of best course of treatment, whether medical or surgical.

Funding

University of California, San Diego

Shibu Yooseph

Lori Broderick
UCSD