Can Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) present without fever?

TRAPS Can Present Without Fever

Yes, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) can present without fever in some cases, though this is atypical of the classic presentation. 1

Clinical Presentation of TRAPS

TRAPS typically presents with the following features:

• Recurrent episodes of inflammation lasting 1-4 weeks or longer
• Fever (typically high and remittent)
• Migratory myalgias and arthralgias
• Abdominal pain
• Skin rash (often migratory)
• Periorbital edema
• Chest pain

However, atypical presentations can occur:

Non-febrile TRAPS

• Documented cases exist of TRAPS patients who experience inflammatory episodes without fever 1
• Patient case reports have shown individuals with confirmed TNFRSF1A mutations who present with:
  • Recurrent episodes of weakness
  • Migratory myalgias and arthralgias
  • Skin manifestations
  • Chest pain
  • All without fever for extended periods (up to 4 years in one case) 1

Monosymptomatic Presentations

• Some patients with TRAPS mutations may present with isolated manifestations
• Cases have been reported of patients with TNFRSF1A mutations presenting with AA amyloidosis as the only clinical manifestation, without any prior history of inflammatory episodes 1

Diagnostic Considerations

When evaluating a patient with suspected autoinflammatory syndrome without fever:

1. Genetic testing is crucial for diagnosis - look for mutations in the TNFRSF1A gene 2
2. Monitor inflammatory markers - elevated ESR, CRP, CBC with differential (granulocytosis), and S100 proteins may be present even without fever 2
3. Consider other autoinflammatory disorders in the differential diagnosis:
   • Familial Mediterranean Fever (FMF)
   • Cryopyrin-associated periodic syndromes (CAPS)
   • Mevalonate kinase deficiency (MKD/HIDS)
   • Deficiency of IL-1 receptor antagonist (DIRA) 3

Clinical Implications

The absence of fever does not exclude TRAPS, and clinicians should consider:

• TRAPS-associated mutations can induce significant inflammation without fever 1
• Patients may develop serious complications like AA amyloidosis even without classic symptoms 1
• Monitoring for disease-specific symptoms should include not only fever but also:
  • Migratory rash
  • Periorbital edema
  • Abdominal/chest/testicular pain
  • Myalgia 2

Treatment Approach

Treatment for TRAPS should be initiated based on clinical and genetic diagnosis, regardless of fever presence:

• IL-1 receptor antagonists (anakinra) have shown efficacy in controlling disease activity 4, 5
• TNF inhibitors (etanercept) may be effective initially but often show decreased responsiveness over time 5
• Regular monitoring of inflammatory markers and disease-specific symptoms is essential 2

Key Takeaway

While fever is a cardinal feature of TRAPS in most cases, its absence does not rule out the diagnosis. Clinicians should maintain a high index of suspicion for TRAPS in patients with recurrent inflammatory episodes and other characteristic symptoms, even without fever, and proceed with genetic testing when appropriate.