TNF receptor associated periodic syndrome
A periodic fever syndrome from TNF receptor mutations.
TNF receptor associated periodic syndrome (TRAPS) is a condition marked by recurring episodes of fever, which is passed down in an autosomal dominant pattern. It stems from mutations in a receptor for tumor necrosis factor (TNF). People with TRAPS experience periodic symptoms including high fevers, skin rashes, abdominal pain, joint and muscle aches, and swelling around the eyes.
**Symptoms and signs** The syndrome can involve episodic fever, an elevated erythrocyte sedimentation rate, inflammation of the sac around the heart (pericarditis), an enlarged spleen (splenomegaly), inflammation of the eye (uveitis), vertigo, and a buildup of abnormal protein deposits (AA amyloidosis).
**Cause** TRAPS is autosomal dominant, and around 70 different mutations in the TNFRSF1A gene have been linked to it. The gene’s cytogenetic location is 12p13.31.
**Mechanism** TNF is mainly produced by immune cells called macrophages in response to infection or other triggers. It helps activate other immune cells and is key to starting inflammation. In TRAPS, a mutation occurs in the tumor necrosis factor receptor-1 (TNFR1) gene. Exactly how these mutations cause the condition is not yet understood. One possible defect is impaired shedding of the TNF receptor; most mutations affect the receptor’s extracellular domain, and some affect the cleavage site.
**Diagnosis** Diagnosis may reveal elevated IgD levels in a suspected case. Confirmation typically involves a blood test, genetic testing, and clinical evaluation.
**Treatment** Corticosteroids can help reduce the severity of symptoms, and NSAIDs may be used to manage fever.
**Research** Several medications have been investigated for treating TRAPS, including etanercept, infliximab, and anakinra.
Quick Facts
- Field
- Immunology
- Symptoms
- Vertigo, pericarditis
- Causes
- Mutations in the TNFRSF1A gene
- Diagnosis
- Blood test, Genetic test
- Treatment
- Corticosteroids, NSAIDS
Facts from the source article.
Lore & Background
TNF receptor associated periodic syndrome presents with signs and symptoms including episodic fever, elevated erythrocyte sedimentation rate, pericarditis, splenomegaly, uveitis, vertigo, and AA amyloidosis. The main source of TNF are macrophages, which produce it in response to infection and other stimuli; TNF helps activate other immune cells and plays a major role in initiation of inflammation. Individuals with TRAPS have a mutation in the tumor necrosis factor receptor-1 (TNFR1) gene, though the mechanisms by which mutations lead to the phenotype are still unknown.
Reader's Guide
TNF receptor associated periodic syndrome (TRAPS) is significant as a model of autoinflammatory disease linked to a specific genetic mutation in the TNF receptor pathway. Its autosomal dominant inheritance and the large number of associated mutations (about 70) highlight the genetic heterogeneity underlying periodic fever syndromes. The uncertainty regarding the exact mechanism—whether impaired receptor shedding or other defects cause the phenotype—underscores ongoing research challenges. The condition's episodic symptoms, including fever, rash, abdominal pain, and risk of AA amyloidosis, illustrate the systemic inflammatory burden. Treatment options remain limited to corticosteroids and NSAIDs, with biologic agents like etanercept, infliximab, and anakinra under study, reflecting the need for targeted therapies. TRAPS thus represents a key entry in the compendium of hereditary periodic fever syndromes, bridging genetics, immunology, and clinical management.
Did You Know?
- TRAPS is associated with about 70 mutations of the TNFRSF1A gene.
- The cytogenetic location of the associated gene is 12p13.31.
- Impaired shedding of the TNF receptor is one possible defect, but the mechanisms are still unknown.
- Corticosteroids can be administered to reduce the severity of TRAPS.
More in Autoinflammatory syndromes 1-24
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