What is the prevalence of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome in adults?

Prevalence of PFAPA Syndrome in Adults

PFAPA syndrome is rare in adults, with prevalence estimated to be less than 1% of unexplained recurrent fever cases, though it is increasingly recognized as not being exclusively a pediatric condition. 1, 2

Epidemiology and Recognition in Adults

PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis) was traditionally considered a childhood-exclusive condition that typically begins before age 5 and resolves spontaneously by age 10. However, recent evidence demonstrates that:

• Adult-onset cases are increasingly being identified and reported 3
• In a study of 359 adults with unexplained recurrent fevers, only 17 (4.7%) were diagnosed with PFAPA syndrome 1
• Another study identified 30 patients with suspected PFAPA among 989 adults (3%) presenting with recurrent fever episodes 4

Clinical Presentation in Adults

Adult PFAPA presents with similar features to pediatric cases but with some differences:

• Mean age of onset in adults ranges from 25.9 to 33.8 years 1, 4
• Episodes occur at regular intervals (typically every 4-8 weeks) 2
• Mean duration of fever episodes is approximately 5.5 days 1
• Key clinical features include:
  • Fever (mean peak temperature 39.5°C) 4
  • Pharyngitis (77% of cases) 4
  • Cervical adenitis (73% of cases) 4
  • Oral aphthosis (50% of cases) 4
  • Complete wellness between episodes 2

Two Patterns of Adult PFAPA

Research has identified two distinct patterns of PFAPA in adults:

1. True adult-onset PFAPA: No history of similar symptoms in childhood
2. Relapsing PFAPA: Patients who had PFAPA in childhood with temporary remission, then recurrence in adulthood (approximately 20% of adult cases) 4

Diagnostic Approach

Diagnosis remains clinical as there are no specific biomarkers for PFAPA syndrome 3, 5. The condition must be distinguished from other periodic fever syndromes including:

• Familial Mediterranean Fever (FMF)
• Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
• Hyperimmunoglobulin D syndrome (HIDS)
• Cryopyrin-associated periodic syndromes (CAPS) 6

Treatment Options

Treatment approaches that have shown efficacy include:

• Single-dose corticosteroids during attacks (most effective for acute episodes) 5
• Tonsillectomy (effective in some adult patients) 5
• Colchicine as prophylaxis to reduce attack frequency 3, 5
• IL-1 blockers in refractory cases 3

Prognosis and Quality of Life Impact

Although PFAPA is considered a benign condition without long-term sequelae, it can significantly impact quality of life due to:

• Frequent febrile episodes (mean 8-12 episodes per year) 1, 4
• Associated symptoms like asthenia (63%), arthralgia (67%), and myalgia (54%) 4
• Disruption of daily activities during episodes

Clinical Implications

The recognition of PFAPA in adults is important because:

• Early diagnosis can prevent unnecessary investigations
• Appropriate treatment can significantly improve quality of life 3
• Distinguishing PFAPA from other autoinflammatory conditions is crucial for proper management

Research Needs

Several aspects of adult PFAPA remain poorly understood:

• Exact etiopathogenesis and genetic background
• Reason for the clock-work regularity of attacks
• Why inflammation is restricted to oropharyngeal lymphoid tissue
• Factors determining self-limited disease course 5

Adult PFAPA represents an important differential diagnosis in patients with unexplained recurrent fevers, and awareness of this condition among clinicians is essential for proper diagnosis and management.