Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome: Evaluation of Patients in San Diego, California

Abstract

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood. Little is known about the true incidence, natural course, pathogenesis, and most appropriate therapy. Patient data was collected for over 150 children with recurrent fevers including 70 patients with PFAPA to create a prospective cohort to delineate the natural history of recurrent fever syndromes, with a specific focus on patients with PFAPA, over a 4-year period. In our cohort, the average age of onset is 2.9 years, but diagnosis delayed until 4.9 years. Febrile episodes last 3.3-4.5 days and occur every 23-38 days, with 66% experiencing stomatitis, 84% pharyngitis, and 69% adenitis. The diverse ethnic background of San Diego was reflected in this group, without predilection more common to the hereditary fever syndromes. Family histories revealed 33% of patients with a first degree relative with recurrent fevers or tonsillitis and 50% with a history of tonsillectomy in childhood. For a subset of patients electing to undergo tonsillectomy, symptoms are equivalent to those of entire cohort. Post-operatively, tonsils from patients with PFAPA are notably smaller and grossly friable, although no granulomas or abscesses are noted on histological examination. With an average of 18 months of follow-up, 90% of the patients have not experienced any additional fever episodes. Our cohort demonstrates clinical characteristics consistent with PFAPA. The presence of atopic diseases and family history of fevers, recurrent tonsillitis and tonsillectomy suggests that patients with recurrent fever syndromes including PFAPA may have a general propensity toward immunodysregulation.