Medical and Surgical Management of PFAPA Syndrome: An Updated Review of Therapeutic Evidence From 2016 Onward

Abstract

Introduction: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent periodic fever disorder of childhood. Although its long-term prognosis is usually favorable, recurrent attacks can substantially disrupt family life, school attendance, healthcare use, and routine preventive care.

Objective: To reassess therapeutic evidence published from 2016 onward and to describe how newer data modify or extend the treatment framework summarized by Vanoni, Theodoropoulou, and Hofer in 2016.Results: Corticosteroids continued to provide the most rapid control of individual attacks, although shorter intervals between episodes were reported in a proportion of patients. Colchicine was the most extensively studied preventive agent, but response varied across cohorts; a randomized comparison of prednisolone plus colchicine and prednisolone plus cimetidine showed improvement in both groups without a clear difference between them. Controlled or prospective studies also suggested potential benefit from pidotimod and ketotifen. Tonsillotomy and tonsillectomy were associated with high short-term remission rates, while long-term observational findings were more heterogeneous. No eligible study of targeted biologic treatment met the review criteria.

Conclusions: The evidence published from 2016 onward favors an individualized treatment sequence based on disease burden and response: corticosteroids for attack termination, selected pharmacological prophylaxis for frequent or disruptive disease, and surgery for appropriately chosen patients. More robust randomized and long-term comparative studies remain necessary.