Tumor Necrosis Factor Receptor Associated Periodic Syndrome (Juvenile)

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Fast Facts

  • Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a rare genetic disease with episodes of recurrent fever, abdominal, chest and muscle pain and a typical rash lasting for more than one week.
  • The severity of TRAPS varies from patient to patient and often depends on the specific gene defect.
  • Episodes of TRAPS respond to treatment with steroids and other biologic anti-inflammatory medications.
  • TRAPS may result in late kidney failure if not treated.

Formerly known as Familial Hibernian fever, Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a rare, genetic disease that causes recurrent episodes of fever that typically last more than 1 week and are associated with chills and severe muscle pain in the torso and the arms.

Patients develop a red and painful rash that move from the torso to the arms and legs. Abdominal pain with nausea, vomiting and diarrhea are common, as are red, swollen eyes. Other important features include chest pain due to inflammation of the membrane surrounding the lungs or heart.

TRAPS is a rare disease, but since the gene defect was discovered, more patients have been diagnosed. The disease affects both males and females, and usually starts before the age of 10 years, but symptoms may start in late childhood, or even in adulthood. The first cases were reported in patients from Irish-Scottish background; the disease has now been seen in almost all ethnic groups.

What causes TRAPS?

TRAPS is due to a gene defect in a protein called tumor necrosis factor receptor, which leads to an increase of the patient’s normal inflammatory response. Infection, trauma, strenuous exercise or psychological stress may trigger episodes. It is inherited as an autosomal dominant disease – meaning if the abnormal gene is inherited from one parent, you can get the disease. That means that one of the parents may be ill with TRAPS, or that the gene mutation developed in the sick child.

How is TRAPS diagnosed and treated?

A physician will suspect TRAPS based on the clinical features, the physical examination and the family medical history. Blood tests will show signs of inflammation during, and often even between, episodes. Genetic tests are necessary to confirm the diagnosis. The physician will probably also test for other types of periodic fever syndromes.

There is still no proven treatment to prevent or cure the disease. Non-specific anti-inflammatory agents—including steroids—help relieve symptoms, but long-term use of steroids can lead to serious side effects. Etanercept (Enbrel, a medicine used to treat arthritis), which blocks the tumor necrosis factor, has been shown to be an effective treatment in some patients, either when given at the beginning of an attack or as a preventive medicine. However, the effect of etanercept tends to wear off with time. Medications that block interleukin-1, an important protein involved in inflammation, appear to be more effective. These include anakinra (Kineret) and canakinumab (Ilaris). These medications are usually helpful even in those patients who do not respond well to etanercept. In rare cases medications that block interleukin-6, tocilizumab (Actemra) have also been helpful.

Patients with persistent, uncontrolled inflammation may develop a complication called amyloidosis. Amyloid is a protein that deposits in organs in children with chronic inflammatory disease. The most common organ involved is the kidney, but amyloid can deposit in the intestines, skin and heart. Eventually, amyloid causes a loss of function, especially in the kidneys. This is the main reason to continue life-long treatment, even when the child is feeling better. Therefore, it is necessary to regularly exam the urine of TRAPS patients for protein.

Living with TRAPS

Patients with a severe type of TRAPS will suffer from long episodes with severe abdominal and muscle pain as well as side effects of medications, particularly steroids. Many patients will need psychological support or special support to treat the pain during attacks. However, for many, the disease can be controlled with medication, and affected individuals can lead relatively normal lives. New medications that target tumor necrosis factor and particularly interleukin-1 are effective in most patients and decrease the need to treat with steroids.

Updated May 2015. Written by Philip Hashkes, MD, MSc and reviewed by the American College of Rheumatology Committee on Communications and Marketing. This information is provided for general education only.

Individuals should consult a qualified health care provider for professional medical advice, diagnosis and treatment of a medical or health condition.

© 2015 American College of Rheumatology