Periodic fever, aphthous stomatitis, pharyngitis and adenitis

Overview

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome is a non-hereditary autoinflammatory disorder that typically affects children under the age of five. It is characterized by regularly recurring episodes of high fever accompanied by at least one of the following symptoms: mouth ulcers (aphthous stomatitis), sore throat (pharyngitis), and swollen lymph nodes in the neck (cervical adenitis). Each episode lasts several days and recurs at predictable intervals—often every 3 to 6 weeks. Despite the dramatic nature of the symptoms, children are generally well between episodes and show normal growth and development. PFAPA is considered a benign condition with no long-term complications and often resolves spontaneously as the child grows older.

Causes

The exact cause of PFAPA syndrome is unknown, but it is thought to involve dysfunction of the innate immune system. Unlike genetic periodic fever syndromes, PFAPA is not linked to a specific gene mutation and is considered non-hereditary in most cases. It is categorized as an autoinflammatory condition, meaning it results from unregulated inflammation rather than autoimmunity or infection. Immune dysregulation, possibly involving cytokine imbalances (especially interleukin-1), is believed to drive the inflammatory episodes. There are no known infectious triggers or environmental factors definitively associated with the onset of PFAPA.

Symptoms

PFAPA is defined by its classic symptom triad that occurs alongside periodic fever. Each episode typically follows a consistent pattern and resolves spontaneously within 3 to 7 days. The key symptoms include:

• High fever: Rapid onset, often rising above 39°C (102°F), and lasting 3–5 days

• Aphthous stomatitis: Painful mouth ulcers on the lips, tongue, or inside the cheeks

• Pharyngitis: Red, inflamed sore throat that may resemble a strep throat but without bacterial cause

• Cervical adenitis: Swollen and tender lymph nodes in the neck

Additional symptoms that may occur include:

• Fatigue or malaise during episodes

• Headache or abdominal discomfort

• Irritability or decreased appetite in younger children

Between episodes, children appear completely healthy, with normal growth and development.

Diagnosis

PFAPA is a clinical diagnosis based on characteristic symptoms and the exclusion of other causes of recurrent fever. There is no specific laboratory test for PFAPA, making careful history-taking and observation critical.

Diagnostic Criteria for PFAPA:

• Regularly recurring fever starting before age 5

• Fever episodes accompanied by at least one of the following: aphthous ulcers, pharyngitis, or cervical adenitis

• Normal growth and development between episodes

• No evidence of infection, autoimmune disease, or hereditary periodic fever syndromes

Diagnostic Workup May Include:

• Blood tests during episodes: Elevated inflammatory markers such as CRP and ESR

• Throat cultures: To rule out streptococcal infections (usually negative)

• Genetic testing: Considered if symptoms overlap with hereditary periodic fever syndromes like FMF or TRAPS

The regularity of fever episodes and rapid return to normal health between episodes are key clues to diagnosis.

Treatment

Management of PFAPA is aimed at shortening or preventing episodes and reducing discomfort. Because the condition is self-limiting and non-progressive, treatment is often conservative.

Common Treatment Approaches:

• Single-dose corticosteroids: A one-time dose of prednisone or prednisolone at the onset of fever can rapidly abort an episode, often within a few hours. However, frequent use may shorten the interval between episodes in some cases.

• Tonsillectomy: Surgical removal of the tonsils (with or without adenoids) may lead to complete remission in many children, especially those with prominent pharyngitis or adenitis.

• Antipyretics and analgesics: Ibuprofen or acetaminophen can be used to manage fever and discomfort during episodes.

Other Considerations:

• Daily or prophylactic medications are generally not necessary

• Immunomodulatory drugs and biologics are rarely used unless PFAPA overlaps with other syndromes

Prognosis

The long-term outlook for children with PFAPA syndrome is excellent. Most cases resolve spontaneously within a few years, often by the age of 10. Children continue to grow and develop normally, and there are no known long-term complications associated with the condition. Even without treatment, the syndrome is benign, though episodes may cause temporary disruption to daily activities and school attendance.

Parents and caregivers benefit from reassurance and guidance on recognizing and managing episodes. Tonsillectomy may offer a curative option in select cases, especially when symptoms are severe or frequent. Overall, with supportive care and minimal intervention, most children with PFAPA lead healthy, active lives.