TNF receptor-associated periodic syndrome
🔥 TRAPS (TNF receptor-associated periodic syndrome) patients show exaggerated innate immune responses.
They present with recurrent prolonged fever, migratory rash, peritonitis, myalgia, and arthralgia, and carry a risk of systemic amyloidosis.
📖 About
- Also known as familial Hibernian fever (FHF).
- Shares features with familial Mediterranean fever (FMF) but FHF is autosomal dominant, whereas FMF is recessive.
🧬 Aetiology
- Caused by mutations in TNFRSF1A gene.
- Autosomal dominant inheritance.
- Encodes TNF receptor 1 (TNFR1), which binds TNF and drives inflammatory responses.
- Defective signalling causes uncontrolled inflammation ± apoptosis dysregulation.
🩺 Clinical Features
- ♨️ Recurrent fevers lasting ~3 weeks.
- ⏳ Variable frequency (weeks to years apart).
- ⚡ Triggers: injury, infection, stress, exercise, hormonal changes.
- 🤕 Abdominal pain, myalgia, spreading erythematous rash.
- 👁️ Periorbital oedema (characteristic).
- 🦴 Arthralgia and stiffness.
- 🔥 Serositis: eyes, heart, joints, throat, mucosa (mouth, gut).
- ⚠️ Secondary amyloidosis → chronic kidney disease / renal failure.
🔬 Investigations
- 📊 FBC, U&E – assess systemic/renal disease.
- ⬆️ ESR / CRP – inflammatory markers elevated.
- 🧬 Genetic testing for TNFRSF1A mutations.
- 🧾 Exclude FMF in differential diagnosis.
- 🧪 High serum IL-6 levels – inflammatory marker.
🧾 Differential
- Familial Mediterranean fever (FMF).
- Systemic vasculitis.
💊 Management
- 🌡️ Symptomatic relief: NSAIDs or corticosteroids for acute flares.
🧪 Antibody / Biologic Therapy
- 🛑 TNF inhibitors: Etanercept (useful but may lose efficacy).
- 🧩 IL-1 inhibitors: Anakinra, Canakinumab (Ilaris) – highly effective, even in TNF-resistant cases.
- 🧪 IL-6 inhibitors: Tocilizumab – benefits some patients.
💡 UK Clinical Pearls
- 👁️ Periorbital oedema + recurrent fever is a diagnostic clue for TRAPS.
- 🧬 Think of TRAPS when there is a dominant inheritance pattern (FMF is recessive).
- ⚠️ Always assess for amyloidosis and renal function in long-standing cases.
- 📚 In exams, TRAPS is often contrasted with FMF: note longer fever duration (weeks vs. days) and dominant inheritance.
- 💉 IL-1 blockade (e.g. canakinumab) is now standard therapy in resistant disease in UK/EU practice.
🔗 Links
