TRAPS

TNF receptor-associated periodic syndrome

What is TRAPS?

TRAPS is an inflammatory disease characterized by recurrent episodes of spiking fever. The episodes last on average one to three weeks. Symptoms during the fever episodes may include abdominal pain, vomiting, diarrhoea, red aching joints, skin rash, muscle pain, and swelling around the eye socket. In a later stage, the kidneys may also be damaged. Within a family, several people may have the same symptoms.

Cause

TRAPS is caused by a genetic defect in the gene TNFRSF1A.  This gene gives the body instructions to make a protein called tumor necrosis factor receptor I (TNFRI). Patients with a defect in this protein suffer from an increased inflammatory response. This is where the name TRAPS comes from.

Symptoms

The main symptoms are recurrent fever episodes that last from one to three weeks and are accompanied by chills and severe muscle pain. In addition, a painful red rash may occur, caused by an inflammatory response in the skin and muscles. Many patients have severe muscle pain at the beginning of an episode, which increases in intensity. The pain starts locally in an arm or leg and then spreads to other limbs. The rash often starts a little later. Patients may also suffer from diffuse abdominal pain, accompanied by nausea and vomiting. The membrane that protects the eye (conjunctiva) may be inflamed, or the area around the eye may be red and swollen.

Diagnosis

Based on the clinical picture and family history, a specialist may suspect TRAPS. Various blood tests can be performed to find out if there is an inflammatory response during an episode. However, only genetic testing can tell with certainty whether someone has TRAPS.

Treatment

Currently, there are no treatments to prevent or cure the disease. Non-specific anti-inflammatory drugs help relieve symptoms during episodes. High doses of steroids are often effective, but long-term use will lead to serious side effects. This is therefore only recommended for people who don’t suffer from many episodes and who are healthy for months in between.  When the activity of the disease does not subside well with simple means, inhibitors of the inflammatory protein interleukin-1beta appear to be effective.  Canakinumab and anakinra are medicines that block the activity of interleukin-1. Canakinumab is extremely expensive but very effective: in ¾ of the patients, the episodes disappear completely and the remainder patients experience a strong decrease in the number of episodes.  It must be injected under the skin every 4-8 weeks. Anakinra has been studied less well. It is less expensive but must be injected daily.

Side effects of interleukin-1 receptor antagonist.

Interleukin-1 is important for the immune system to fight infections. This is why the main side effect of canakinumab and anakinra is an increased risk of bacterial infections, such as ear infections, pneumonia and impetigo. It is therefore very important that children that are treated with these medicines, are fully vaccinated. Infections should also be treated promptly with antibiotics.

The other important side effect is pain at the injection site. This occurs especially with anakinra.

Prognosis

TRAPS is a life-long disease. Often, the disease seems to decrease in severity as patients get older. The most severe complication of FMF is the development of amyloidosis. Amyloid is an inflammatory protein that deposits in certain organs, such as the intestines, skin, heart, but especially the kidneys. This protein deposition causes the affected internal organ to function less well. In the case of the kidneys, this may eventually lead to kidney failure and require dialysis or a transplant. This dangerous complication is believed to be well-preventable by preventing the inflammation, for example with an interleukin-1 receptor antagonist.

Inheritance

TRAPS is an hereditary disease and is inherited in an autosomal dominant fashion. This means that if one of the two copies of the TNFRSF1A gene is damaged, this is enough to get the disease. Children of a parent with an autosomal dominant disease have a chance of 1 in 2 (50%) to inherit the affected gene and thus of getting the disease. There is also a chance of 1 in 2 (50%) that a child of the affected parent will inherit the good gene. In that case, the child will not get the disease.

Rare disease

Currently, about six families in the Netherlands are known to be affected by TRAPS . In these families, several family members may have the disease. Worldwide, there are about one thousand patients (known cases).