TRAPS Syndrome

TNF receptor associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disease from TNFRSF1A mutations, causing prolonged recurrent fevers.

• Prevalence about 1 per million; onset in childhood to adulthood (median 3 years in children, adults later).

• Mutations (often cysteine substitutions) cause protein misfolding, ER stress and NF-kB activation; low penetrance variants R92Q and P46L are mild.

• Attacks last 1 to 3 weeks (up to 6 weeks) and recur every few weeks to months.

• Complications: AA amyloidosis in 10 to 14% (higher with cysteine variants and positive family history).

• Prolonged fever, migratory centrifugal erythematous rash with underlying myalgia, periorbital oedema, conjunctivitis, abdominal pain, chest pain, arthralgia, pericarditis, testicular pain.

• Systemic inflammation with raised CRP during attacks.

• Fatigue, weight loss.

• Clinical suspicion with family history and attack pattern; elevated CRP, SAA, ESR, ferritin during attacks.

• Genetic testing of TNFRSF1A (structural variants more often disease causing).

• Low serum soluble TNFRSF1A (below 1 ng/mL) in some, not specific.

• Exclude infection, Still disease, FMF, mevalonate kinase deficiency, CAPS, malignancy.

• Urinalysis, proteinuria monitoring for amyloidosis.

• Mild attacks: NSAIDs, short prednisolone 0.5 to 1 mg/kg (taper over days), which often need dose escalation over time.

• First line prophylaxis: IL-1 blockade with anakinra 1 to 2 mg/kg (100 mg) SC daily or canakinumab 150 mg (2 to 4 mg/kg) every 4 weeks (best evidence, complete response in over 70%); rilonacept 160 mg weekly.

• Etanercept 25 mg twice weekly or 50 mg weekly offers partial benefit; infliximab and adalimumab can paradoxically worsen disease.

• Colchicine has limited benefit.

• Amyloidosis prevention: control inflammation to normalise SAA; treat established amyloidosis with anti-IL-1 and supportive care.

• Genetic counselling; periodic measurement of CRP, SAA and proteinuria.