What is the definition of TNF Receptor-Associated Periodic Syndrome?

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an inherited condition characterized by recurrent episodes of fever. Episodes can begin at any age but most often begin in early childhood. Fevers typically last about 3 weeks but can last from a few days to a few months. The amount of time between episodes may vary from weeks to years. Episodes usually occur spontaneously, but are sometimes brought on by a variety of triggers (such as injury, infection, or stress). Symptoms during fever episodes may include abdominal, muscle or joint pains; skin rashes (usually on the limbs); puffiness around the eyes; and inflammation in various areas of the body. Some people develop amyloidosis. TRAPS is caused by mutations in the TNFRSF1A gene and is inherited in an autosomal dominant manner. Treatment may include systemic corticosteroids at the beginning of an episode to reduce its severity and duration.

What are the alternative names for TNF Receptor-Associated Periodic Syndrome?

  • FPF
  • Familial Hibernian fever
  • FHF
  • Hibernian fever, familial
  • TNF receptor-associated periodic syndrome
  • Periodic fever, familial, autosomal dominant
  • TNF receptor-associated periodic fever syndrome

What are the causes for TNF Receptor-Associated Periodic Syndrome?

TRAPS is a genetic condition caused by mutations in a gene called TNFRSF1A. This gene gives the body instructions to make a protein called tumor necrosis factor receptor 1 (TNFR1). This protein exists in cell membranes where it binds to another protein called tumor necrosis factor (TNF). The binding sends signals that tell the cells to trigger inflammation (producing immune system proteins) or self-destruct.

Most TNFRSF1A gene mutations that cause TRAPS result in incorrectly-shaped TNFR1 proteins, which become trapped in cells and cannot reach the surface to bind with TNF. The trapped proteins then clump together and are thought to trigger other pathways involved in causing inflammation. Affected people typically have a mutation in only one of their 2 copies of the TNFRSF1A gene, so some normal TNFR1 proteins are still produced, leading to even more inflammation. This is what leads to excess inflammation in people with TRAPS. It is unclear if abnormalities in the cells' ability to self-destruct also plays a role in causing the features of TRAPS.

What are the symptoms for TNF Receptor-Associated Periodic Syndrome?

The characteristic feature of TRAPS is recurrent episodes of fever. Episodes may begin at any age, but most often begin in early childhood. Fevers usually last around 3 weeks but can last from days to months. The time between episodes can vary considerably from weeks to years. Fevers are often associated with other symptoms, which may include muscle, joint, and/or abdominal pain; a spreading rash; puffiness and/or swelling around the eyes; and/or inflammation in various other areas of the body including the heart muscle, joints, throat, or mucous membranes. About 25% of people with TRAPS develop amyloidosis, which can lead to kidney or liver failure.

What are the current treatments for TNF Receptor-Associated Periodic Syndrome?

While there is no proven treatment for TRAPS, non steroidal anti-inflammatory drugs (NSAIDS) may be used to relieve symptoms of fever, and corticosteroids may be used to reduce severity of symptoms in most people. However, these medications typically don't decrease the frequency of attacks. Etanercept, a TNF inhibitor, has been shown to be effective but its efficacy tends to wane over time. Standard doses of etanercept twice a week have been shown to decrease the frequency, duration, and severity of attacks in some people and it may also reverse or slow the progression of amyloidosis. More studies are needed to evaluate this medication for TRAPS.

Additional information about the treatment of TRAPS can be viewed on Medscape's Web site.

What is the outlook (prognosis) for TNF Receptor-Associated Periodic Syndrome?

The long-term outlook (prognosis) for people with TRAPS depends largely on the development of amyloidosis, which happens in a minority of affected people. The risk to develop amyloidosis depends on the specific mutation an affected person has, as well as possible environmental factors. Without amyloidosis, life expectancy is normal. In general, people with TRAPS continue to have episodes of fevers and symptoms throughout life. However, with age, fever attacks may decrease in intensity and a more chronic and fluctuating course may continue.

Is TNF Receptor-Associated Periodic Syndrome an inherited disorder?

TRAPS is inherited in an autosomal dominant manner. This means that having a mutation in only one of the 2 copies of the responsible gene is enough to cause signs and symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated copy of the gene. In many cases, a person with TRAPS inherits the condition from an affected parent. In other cases, the mutation occurs for the first time in the affected person and is not inherited from a parent. For unknown reasons, some people who inherit the mutated gene never develop features of TRAPS. When this occurs, a condition is said to have reduced penetrance.

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