Can Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) be associated with gastrointestinal (GI) symptoms?

PFAPA Syndrome and Gastrointestinal Symptoms

Yes, PFAPA syndrome can be associated with gastrointestinal symptoms, particularly abdominal pain, diarrhea, and vomiting, which may occur during fever episodes. While not part of the classic diagnostic criteria, GI manifestations represent an important clinical feature that should be recognized in patients with PFAPA.

Evidence for GI Symptoms in PFAPA

The 2022 EULAR/American College of Rheumatology guidelines for autoinflammatory diseases provide indirect evidence supporting GI involvement in periodic fever syndromes 1. While these guidelines focus primarily on IL-1 mediated autoinflammatory diseases (CAPS, TRAPS, MKD, and DIRA), they help establish a framework for understanding symptom patterns in periodic fever syndromes like PFAPA.

Key GI manifestations that may occur in PFAPA:

• Abdominal pain - Can be significant during flares
• Diarrhea - May accompany fever episodes
• Vomiting - Particularly early morning nausea and vomiting
• Reduced appetite - Common during attacks

Differentiating PFAPA from Other Periodic Fever Syndromes

When evaluating GI symptoms in suspected PFAPA, it's important to differentiate from other periodic fever syndromes that have more prominent GI involvement:

1. Mevalonate Kinase Deficiency (MKD) - Features severe abdominal pain with vomiting and diarrhea as primary symptoms 1
2. TRAPS - Often presents with abdominal pain
3. CAPS - May include early morning nausea and vomiting 1

Clinical Approach to GI Symptoms in PFAPA

When evaluating GI symptoms in a patient with suspected or confirmed PFAPA:

1. Document pattern and timing:

   • Do GI symptoms coincide with fever episodes?
   • Do they resolve completely between attacks?
   • Are they responsive to treatments that resolve other PFAPA symptoms?

2. Rule out alternative causes:

   • Inflammatory bowel disease
   • Celiac disease
   • Functional GI disorders
   • Infectious gastroenteritis

3. Consider overlapping functional GI disorders:

   • Patients with autoinflammatory conditions may have concurrent functional GI disorders 1
   • Enhanced visceral sensitivity may contribute to pain perception

Management Implications

The presence of GI symptoms in PFAPA may influence treatment decisions:

• Corticosteroids remain first-line therapy for acute attacks and typically resolve both classic PFAPA symptoms and associated GI manifestations 2, 3
• Colchicine has shown efficacy in reducing flare frequency in patients with PFAPA, including those with GI symptoms 2, 3
• IL-1 blockers like anakinra may be considered for severe cases with significant GI involvement 3

Monitoring Considerations

For patients with PFAPA who have prominent GI symptoms:

• Monitor nutritional status, especially in children with frequent episodes
• Assess for signs of dehydration during acute episodes with vomiting/diarrhea
• Consider GI specialist consultation if symptoms are severe or atypical

Prognosis

While PFAPA typically resolves spontaneously in children by age 7-8 years 4, GI symptoms follow the same pattern as other manifestations, with complete resolution between attacks. This cyclical pattern with symptom-free intervals helps distinguish PFAPA-related GI symptoms from other chronic GI conditions.

Clinical Pearls

• GI symptoms may be more prominent in adult-onset PFAPA compared to pediatric cases 2, 5
• The presence of severe or persistent GI symptoms between attacks should prompt investigation for alternative diagnoses
• Continuous pro-inflammatory cytokine activation seen in PFAPA 6 may contribute to GI manifestations even during seemingly asymptomatic periods

Understanding the full spectrum of PFAPA manifestations, including GI symptoms, is essential for accurate diagnosis and appropriate management of this autoinflammatory condition.