Understanding PFAPA Syndrome: Causes, Symptoms, and Diagnosis
What is PFAPA Syndrome?
PFAPA is an acronym that describes the central clinical manifestations of this disorder: Periodic Fever , Recurrent Aphthous Stomatitis Aphthous Stomatitis, Pharyngitis, and Adenitis. This syndrome represents the most frequent cause of recurrent febrile syndromes areas), as well as the hands, feet, and genitals. It can also involve the tongue, uvula, soft palate, and observed in the pediatric population.
Condition Profile: Who Develops PFAPA Syndrome and Why?
PFAPA syndrome predominantly affects children, typically manifesting within the first five years of life, although cases have been reported since the first month (with an average It is crucial to keep in mind that a notable proportion of patients (between 10% and 15%) who initially present with SCLE may progress to full Systemic Lupus Erythematosus (SLE). This progression carries the potential risk of developing serious involvement, including of presentation at 18 months of age).
There is no established correlation with race, sex or geographic area; however, most reports come from Europe and America.
To date, no specific genetic defect has been identified genetic that causes PFAPA syndrome. Nevertheless, since 14% of cases report a positive family history, the possible existence of an as-yet-undiscovered genetic basis for a subset of patients is suggested.
This syndrome is a more common cause of recurrent fever in children than monogenic periodic fevers, monogenic, and the age of onset is usually older compared to genetically positive patients presenting with symptoms similar to PFAPA.
Distinct Clinical Manifestations of PFAPA Syndrome
Children affected by PFAPA syndrome experience recurrent febrile episodes, occurring every 2 to 6 weeks; in 60% of cases, they exhibit almost mechanical regularity. Each episode lasts 3 to 6 days, followed by asymptomatic intervals of 3 to 5 weeks. During these intercritical periods, the child generally enjoys good health and maintains normal growth and development normal development.
The defining characteristic of each episode is high fever, with peaks ranging between 101.3°F and 105.8°F (38.5 and 41ºC).
| Aphthous Stomatitis |
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| Skin Involvement |
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| Pharyngitis |
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| Adenitis |
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| Other Associated Features |
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Approximately 30% of patients with PFAPA syndrome experience spontaneous remission remission after 4 to 8 years from onset.
How is PFAPA Syndrome Diagnosed?
The diagnosis of PFAPA syndrome is fundamentally clinical and is established by excluding other possible conditions. The diagnostic process is based on the presence of early-onset recurrent fever and the appearance of several of the cardinal symptoms described above.
under 5 years old) and meet at least one of the following additional conditions:
- Presence of aphthous stomatitis.
- Tender and enlarged lymph nodes in the neck area.
- Previous diagnosis of pharyngitis.
The diagnosis is established in the absence of:
- Respiratory tract infections.
- Cyclic neutropenia.
- Monogenic periodic fever.
Although there are no definitive specific tests for PFAPA syndrome, during a febrile episode, the following blood test may show abnormalities: abnormalities:
- Slight increase in total white blood cell count.
- Elevation of ESR and other acute phase reactants. acute.
- Slight elevation of IgA, IgD, IgM in certain cases.
The white blood cell count and acute phase reactants are generally normal when the child is asymptomatic.
A study conducted in Italy with 210 children diagnosed with PFAPA syndrome revealed that 43 of them presented mutations associated with the febrile syndrome fever: mevalonate kinase deficiency (33 cases), familial Mediterranean fever (7 cases), and TRAPS (3 cases). The Gaslini score is a useful tool for identifying patients who meet the criteria for PFAPA syndrome and present a low risk of carrying a , originating from a linked to monogenic periodic fevers.
The Gaslini score is calculated considering the following factors:
- Early age of symptom onset.
- Positive family history of periodic fever.
- Presence of chest pain or abdominal pain.
- Diarrhea.
- Aphthous ulcers.
Patients classified with a low-risk Gaslini score may receive a diagnosis of PFAPA syndrome without requiring genetic testing. However, those with a high-risk score should be genetically evaluated, based on clinical and laboratory findings. The diagnosis of PFAPA syndrome is only confirmed if the genetic test is negative.
Treatment and Management of PFAPA Syndrome
Therapeutic options available for the management of PFAPA syndrome include several alternatives:
- Systemic Corticosteroids: For example, prednisolone administered at a dose of 1-2 mg/kg/day at the onset of fever. This intervention shortens the duration of the febrile episode but may also reduce the latency period between episodes.
- Cimetidine: This medication has been associated with fever resolution in certain patients. Approximately 30% experience a reduction in attack frequency when taking it for months, although the exact mechanism of its action remains uncertain.
- Tonsillectomy/Adenoidectomy: The role of this intervention is controversial, given that a significant proportion of cases resolve spontaneously over time.
It is essential to address the differential diagnosis and evaluate the need for genetic testing in high-risk cases to differentiate PFAPA from other monogenic periodic fevers.
