TNF receptor associated periodic syndrome (TRAPS)

TRAPS is the second commonest of the inherited fever syndromes. It was originally thought to be commonest in North Western Europe, and was first called familial Hibernian fever, reflecting the Irish/Scottish ancestry of patients in early reports. It is now known to affect people from all around the world.

TRAPS is caused by mutations in a gene called TNFRSF1A, which lead to production of an abnormal white cell protein called a tumour necrosis factor (TNF) receptor. This abnormal protein leads to overactive inflammation by methods that are not yet fully understood.

Inheritance of TRAPS is autosomal dominant. But some mutations have incomplete penetrance. This means that some people who inherit a mutated copy of the gene do not develop disease. About half of all patients with TRAPS do not have a family history of disease. These patients may have a parent with the mutation but without disease. It is not known why the presence of a mutation causes disease in some people but not in others.

The symptoms in TRAPS can be very variable and can mimic FMF and MKD (see below). In general, attacks start in childhood, before age 4.

Symptoms during attacks usually include:

Typical rash in TRAPS, affecting the arm

  • Fever lasting around 1 to 4 weeks
  • abdominal pain
  • joint or muscle aches and swelling
  • rash

more rarely there may also be:

  • headache
  • chest pain
  • enlarged glands in the neck
  • painful, red eyes.

There have also been reports of nervous system abnormalities and appearances on imaging studies that are similar to multiple sclerosis.

As in all the inherited fever syndromes there are raised levels of inflammatory markers.

Typical rash in TRAPS, affecting the abdomen

For 1 in 3 patients, symptoms are nearly continuous.

Diagnosis rests on suspicious symptoms and the finding of a mutation in the TNFRSF1A gene. This is the gene which encodes a protein receptor for an inflammatory messenger called tumour necrosis factor alpha. The exact way abnormal TNFα receptors cause spontaneous attacks of inflammation and fever are not fully understood.

Colchicine is not usually effective in TRAPS.

Steroid therapy can be beneficial during attacks. Injected drugs which block messengers of inflammation (cytokines) are very effective in more severe disease. These drugs all have to be injected either under the skin or into a vein. The one used most at present is called anakinra. This drug blocks a molecule called IL-1 which is involved in the overactive auto-inflammatory pathway.

Anakinra has to be given at home every day. Other, similar drugs may be injected every week. In the future it may be possible to give drugs only every one or two months.

The side effects of these drugs include:

  • stinging
  • skin redness at the injection site, in some people
  • increased risk of infection.

In general the infections reported have been mild all patients are screened for tuberculosis and asked about a history of other infections before starting such drugs.