PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome is a periodic fever syndrome that typically manifests between ages 2 years and 5 years; it is characterized by febrile episodes lasting 3 to 6 days, pharyngitis, aphthous ulcers, and adenopathy. Etiology and pathophysiology are undefined. Diagnosis is clinical. Treatment can include glucocorticoids, colchicine, cimetidine, and, rarely, tonsillectomy.
PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome is the most common periodic fever syndrome among children. Although genetic causes have not been determined, this syndrome tends to be grouped with hereditary fever syndromes. PFAPA syndrome typically starts in early childhood (between ages 2 years and 5 years) and tends to be more common among males. It has been recognized in adults as well (1).
Febrile episodes typically last 3 to 6 days and recur about every 21 to 28 days. The syndrome causes fatigue, chills, and occasionally abdominal pain, arthralgia, and headache, as well as fever, pharyngitis, aphthous ulcers, and lymphadenopathy. Patients are healthy between episodes, and growth is normal.
General reference
1. Rigante D, Vitale A, Natale MF, et al: A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome. Clin Rheumatol 36(2):463–468, 2017. doi: 10.1007/s10067-016-3317-7
Diagnosis of PFAPA Syndrome
Clinical evaluation
Diagnosis of PFAPA syndrome is based on clinical findings, which include the following (1):
≥ 3 febrile episodes, lasting up to 5 days and occurring at regular intervals
Pharyngitis plus adenopathy or aphthous ulcers
Good health between episodes and normal growth
Acute-phase reactants (eg, C-reactive protein, erythrocyte sedimentation rate) are elevated during a febrile episode but not between episodes. Neutropenia or other symptoms (eg, diarrhea, rash, cough) are not present; their presence suggests a different disorder. Specifically, cyclic neutropenia needs to be ruled out.
Diagnosis reference
1. Cantarini L, Vitale A, Sicignano LL, et al: Diagnostic criteria for adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Front Immunol 8:1018, 2017. doi: 10.3389/fimmu.2017.01018
Treatment of PFAPA Syndrome
Sometimes glucocorticoids, colchicine, cimetidine, and/or tonsillectomy
Treatment of PFAPA syndrome is optional and depends on the frequency and severity of flare-ups.
1).
Patients tend to outgrow this syndrome without sequelae.
Treatment reference
1. Amarilyo G, Rothman D, Manthiram K, et al: Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group. Pediatr Rheumatol Online J 18(1):31, 2020. doi: 10.1186/s12969-020-00424-x
