TRAPS: Tumor necrosis factor receptor associated periodic syndrome

What is it?

TRAPS is a very rare autoinflammatory condition usually starts before the age of 4 years.[1–5]

How common is it?

It is estimated that only one in every million people develop TRAPS.[1,6] Europeans are mainly affected but the condition is increasingly occurring within other ethnic groups.[2] Worldwide, only about 1,000 cases have been reported.[7]

What are the symptoms?

TRAPS flares are associated with the following symptoms:[4,5,7]

  • Persistent fever
  • Abdominal and/or chest pain
  • Nausea, vomiting, diarrhoea or constipation
  • Painful, often migrating red rash on the upper body and/or arms/legs
  • Swollen eyes (periorbital oedema) and/or conjunctivitis
  • Joint and muscle pain, often in areas where the rash occurs

TRAPS flares can last a few days to a few months, but typically last about 3 weeks.[7]
They usually occur spontaneously, but can also be triggered by: [7]

  • Minor injury 
  • Infection
  • Stress
  • Exercise
  • Hormonal changes

Possible symptoms of TRAPS (modified according to [2,4,5,7,8])

What typically happens over the course of the illness?

Over time, the fever bouts usually become less intense: some patients may have long periods of time between flares or have less frequent or severe flares in adulthood, but TRAPS is a lifelong condition. However, in about 3 out of 20 people, TRAPS can also lead to amyloidosis.[4] This is a condition in which a protein called amyloid builds up in the kidneys, eventually leading to kidney failure.[9] Recent advances in diagnostic techniques – which have helped to pinpoint a person’s precise type of amyloidosis, together with new medications, have meant that amyloidosis is now much more treatable than it used to be.[10]

How is it caused?

In TRAPS, activation of the innate immune system occurs because of changes in a gene coding for a protein called tumour necrosis factor receptor, which is involved in the inflammatory response.[2,7,11]

The genetic change leading to TRAPS can be inherited from either parent. This means a child will develop the illness even if the genetic change comes from only one parent.[2,7] There are also cases of patients with spontaneous (non-inherited) mutations for TRAPS, who can, however, pass the mutation to their children.[7]

Status: 2016-01-04

[1] Lainka E, Neudorf U, Lohse P et al. Rheumatology. 2009;48:987–91.
[2] Samuels J, Ozen S. Curr Opin Rheumatol. 2006;18:108–17.
[3] Lachmann HJ, Hawkins PN. Arthritis Res Ther. 2009;11:212.
[4] Savic S, Dickie LJ, Battellino M et al. Curr Opin Rheumatol. 2012;24:103–12.
[5] Gattorno M, Federici S, Pelagatti MA et al. J Clin Immunol. 2008;28(suppl 1):S73–83.
[6] Lachmann HJ, Papa R, Gerhold K, et al. Ann Rheum Dis. Published Online First: 21 August 2013 doi:10.1136/annrheumdis-2013-204184.
[7] US National Library of Medicine. Tumor necrosis factor receptor-associated periodic syndrome. Available from: (accessed 2015).
[8] Drenth JPH, van der Meer JWM. NEJM. 2001;345:1748–1757.
[9] Dember LM. J Am Soc Nephrol. 2006;17:3458–3471.
[10] Wechelekar AD. Medicine. 2008;18:391-403.
[11] Ciccarelli F, De Martinis M, Ginaldi L. Curr Med Chem. 2014;21:261–269.

Wondering how your life will change?

If you or your child has a rare disease, your life may look a little different than other people’s, and you may face added challenges or worries.  We’ve gathered some information and articles here that may help address a few of these. 

Life with Periodic Fevers

June 2016 - GLDEIM/ACZ885/0075