Makindo Medical Notes

TRAPS patients demonstrate exaggerated innate immune responsiveness and are characterized clinically by recurrent prolonged episodes of fever, migratory rash, peritonitis, myalgia, and arthralgia, with systemic amyloidosis.

About

• TNF receptor-associated periodic syndrome, also called familial Hibernian fever (FHF).
• FHF resembles familial Mediterranean fever (FMF) in several clinical features, but the mode of inheritance of FHF is dominant, whereas FMF is recessive.

Aetiology

• Mutations in the TNFRSF1A gene.
• Autosomal dominant pattern of inheritance.
• This gene codes for tumour necrosis factor receptor 1 (TNFR1).
• TNFR1 binds to tumour necrosis factor (TNF), a protein involved in systemic inflammation.
• Binding results in inflammatory responses or induces cell apoptosis (self-destruction).

Clinical

• Recurrent episodes of fever lasting approximately 3 weeks.
• Variable frequency: episodes can occur from weeks to years apart.
• Triggers: minor injury, infection, stress, exercise, or hormonal changes.
• Abdominal and muscle pain accompanied by a spreading skin rash.
• Puffiness or swelling in the skin around the eyes (periorbital oedema).
• Joint pain and stiffness.
• Inflammation affecting eyes, heart muscle, certain joints, throat, or mucous membranes (e.g., the lining of the mouth and digestive tract).
• Secondary amyloidosis leading to potential renal failure.

Investigations

• Full Blood Count (FBC) and Urea & Electrolytes (U&E): To check for renal disease.
• Elevated ESR (Erythrocyte Sedimentation Rate), indicating inflammation.
• Genetic testing for mutations in TNFRSF1A.
• Exclusion of familial Mediterranean fever (FMF) through differential diagnosis.
• High serum IL-6 levels, a marker of inflammation.

Differential

• Familial Mediterranean fever (FMF).
• Systemic vasculitis.

Management

• Consider nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids to manage acute symptoms.

Antibody Therapy

• TNF inhibitors: Using etanercept. This is effective in some patients but may become less effective over time.
• Interleukin-1 inhibitors: Using anakinra and canakinumab (Ilaris). These medications are usually effective, even in patients who do not respond well to etanercept.
• Interleukin-6 inhibitors: Using tocilizumab, which has also been helpful in reducing symptoms in some patients.

Links

• Review article