Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), is one of the autoinflammatory syndromes. In fact, it is a rare autosomal dominant disease where the mutation occurs at the level of TNFRSF1A gene on chromosome 12p13. Actually, this gene encodes for TNFR1 (Tumor necrosis factor receptor 1). Therefore, the mutation affects the receptor structure thus disrupting its binding to the TNF ligand. In other words, if you have TRAPS, leukocytes become hypersensitive to stimulations and they over produce proinflammatory cytokines. TNF protein role is to trigger an inflammatory response upon infection, which can be inhibited by normal the receptor TNFR1. Consequently, the body behaves as if there's an infection eventhough there aren't, and the immune cells thus attack the healthy cells.
Causes of TRAPS:
You may get TRAPS genetic disorder due to a mutation in the TNFRSF1A gene. On the other hand, TRAPS can be inherited as an autosomal dominant mutation from one of the parents. To illustrate, to have the disease it's enough to receive only one copy of the mutated gene. Besides, this disorder affects equally all ethnic groups, but it's very rare.
Symptoms:
Certainly, it's during infancy or childhood when TRAPS multisystemic genetic disorder takes place. As a matter of fact, the symptoms duration isn't specific and can stick for days, weeks, or even months. In addition, keeping in mind that tge symptoms can differ among patients, most patients suffer mostly from repeated fever episodes, aches and inflammation. TRAPS symptoms are:
- Recurrent fever episodes
- Chills
- Abdominal pain
- Diarrhea or constipation
- Nausea and vomiting
- Chest pain
- Muscle pain
- Joint stiffness
- Migratory erythematous (red) rash lasting few days to several weeks
- Swelling around eyes
- Amyloidosis (rare)
Mechanism of TRAPS:
Indeed, the mechanism is not quite known, but it suggests the build-up of the misfolded mutant protein in the intracellular domain. Consequently, this induce a stress in the endoplasmic reticulum (ER) and activates immune pathways of inflammation responses. In the same vein, other suggestions that might cause TRAPS are imperfect receptor shedding, cell death induced by TNF, reactive oxygen species production and finally autophagy impairment.
Diagnosis:
In general, the diagnosis for TRAPS requires gene analysis of the gene TNFRSF1A since the heterozygous variants are responsible for the manifestation of the syndrome.
Furthermore, for more specific prognosis, amyloidosis occurrence after the repeated episodes of fever is an indication of TRAPS.
Besides, dermatologists must distinguish skin complications of TRAPS for they are essential in diagnosis.
Treatment of TRAPS:
Since TRAPS occur due to mutation of TNFRSF1A gene, this propose that the treatment should be blocking TNF. However, the use of tumor necrosis factor (TNF) inhibitor etanercept medicine for treatment results in a reduction in response over time because of some non-specific action of the medicine.
Therefore, switching to anakinra (anti-interleukin (IL)-1β) solves the problem for short- and long-term response.
Also, corticosteroids can be used to reduce the intensity of the symptoms.
References:
-Cudrici C, Deuitch N, Aksentijevich I. Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives. Int J Mol Sci. 2020 May 5;21(9):3263. doi: 10.3390/ijms21093263. PMID: 32380704; PMCID: PMC7246474.
-Aguado-Gil L, Irarrazaval-Armendáriz I, Pretel-Irazabal M. Advances in the diagnosis and treatment of tumor necrosis factor receptor-associated periodic syndrome. Actas Dermosifiliogr. 2013 Sep;104(7):617-22. doi: 10.1016/j.adengl.2012.11.020. Epub 2013 Jul 23. PMID: 23891452.
-Cantarini L, Lucherini OM, Muscari I, Frediani B, Galeazzi M, Brizi MG, Simonini G, Cimaz R. Tumour necrosis factor receptor-associated periodic syndrome (TRAPS): state of the art and future perspectives. Autoimmun Rev. 2012 Nov;12(1):38-43. doi: 10.1016/j.autrev.2012.07.020. Epub 2012 Aug 2. PMID: 22884554.
