Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) – aka Marshall Syndrome

Acronym:
PFAPA

SAID group:
Idiopathic

Gene:
Currently unknown. No genetic testing available.

Inheritance:
Currently unknown.

Ethnicity:
Affects all races. [40]

Frequency:
Unknown. PFAPA is the most common non-infectious recurrent fever disorder. [40]

Timing of symptoms:
Periodic fevers and symptoms lasting 3-6 days, recurring every 21-28 days. Extremely predictable frequency of days between the onset flares in most cases. Patients are symptom-free between flares. No specific triggers have been identified–flares come at regular intervals, often monthly. [40] If there are any persistent symptoms between flares, evaluation for autoinflammatory periodic fever syndromes is essential.

Age of onset:
Early childhood, usually between 2-5 years of age. A few adult-onset cases are documented. Most teens outgrow it. [40]

Skin cutaneous:
Aphthous ulcers (stomatitis), and pharyngitis with exudate, (but no infection) is a classic finding. [40] [41] Skin rashes are not typical, or a part of the PFAPA diagnostic criteria-if rashes occur with flares, or are persistent between flares, other autoinflammatory diseases should be considered.

Neurologic:
High fevers for 3-6 days, with chills and malaise. Some patients have headaches with flares. Other neurological symptoms are not noted. [41]

Auditory:
Not noted. [40] [41]

Ophthalamic:
Not noted. [40] [41]

Cardiopulmonary:
Flares of fevers, stomatitis and pharyngitis are not associated with respiratory illness. [40] [41]

Abdominal:
Abdominal pain, and diarrhea are often present with flares. [40] [41]

Lymphatic:
Cervical adenopathy or lymphadenopathy during flares. [40] [41]

Joints bones muscles cartilage:
Arthralgias, fatigue and malaise. No permanent joint or bone issues noted, and patients are symptom-free between PFAPA flares. [40] [41]

Vasculitis:
Not noted. [40] [41]

Amyloidosis:
Not noted. [40] [41]

Abnormal labs:
High: ESR, CRP, WBC during flares only. All normal labs when not flaring, or between flares. [40] [41] IgD may be elevated in patients with PFAPA (and these patients were negative for MVK mutations). [126] PFAPA symptoms overlaps with a number of other autoinflammatory periodic fever syndromes, so genetic testing and attention to clinical findings may be helpful.

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