PFAPA Syndrome

By Apostolos Kontzias, MD, Assistant Professor of Medicine;Director, Autoinflammatory Clinic, Cleveland Clinic Foundation;Cleveland Clinic Foundation

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Hereditary Periodic Fever Syndromes
Overview of Hereditary Periodic Fever Syndromes
Familial Mediterranean Fever
Hereditary Cryopyrin-Associated Periodic Syndromes (Cryopyrinopathies)
Hyper-IgD Syndrome
PAPA Syndrome
PFAPA Syndrome
TNF Receptor–Associated Periodic Syndrome (TRAPS)

PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome is a periodic fever syndrome that typically manifests between ages 2 yr and 5 yr; 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.

PFAPA syndrome is a relatively common periodic fever among children. Although genetic causes have not been determined, this syndrome tends to be grouped with hereditary fever syndromes. It typically starts in early childhood (between ages 2 yr and 5 yr) and tends to be more common among males.

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.

Diagnosis

Clinical evaluation

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, ESR) 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.