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PFAPA Syndrome

By

Apostolos Kontzias

, MD, Stony Brook University School of Medicine

Last full review/revision Jan 2022| Content last modified Jan 2022
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PFAPA (periodic fevers with aphthous stomatitis Recurrent Aphthous Stomatitis Recurrent aphthous stomatitis (RAS) is a common condition in which round or ovoid painful ulcers recur on the oral mucosa. Etiology is unclear. Diagnosis is clinical. Treatment is symptomatic... read more Recurrent 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, cimetidine, and, rarely, tonsillectomy.

Febrile episodes last 3 to 6 days and recur about every 28 days. The syndrome causes fatigue, chills, and occasionally abdominal pain 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

Diagnosis of PFAPA syndrome is based on clinical findings, which include the following:

  • 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 Diagnosis Neutropenia is a reduction in the blood neutrophil count. If it is severe, the risk and severity of bacterial and fungal infections increase. Focal symptoms of infection may be muted, but fever... read more 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

  • Sometimes glucocorticoids, cimetidine, and/or tonsillectomy

Treatment of PFAPA syndrome is optional and depends on the frequency and severity of flare-ups; it can include glucocorticoids, such as a single dose of prednisone (1 to 2 mg/kg orally) or betamethasone (0.1 to 0.2 mg/kg), which, when given at the onset of an episode can dramatically abort fever attacks in a few hours, cimetidine (20 to 40 mg/kg orally once a day), and, rarely, tonsillectomy. Other drugs such as anakinra and canakinumab have been tried with some success in refractory cases. Patients tend to outgrow this syndrome without sequelae.

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