Familial hibernian fever or Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS).

What is it?
TRAPS is a dominantly inherited syndrome of recurrent high spiking fevers, usually of two to three weeks duration. The fever is typically accompanied by gastro-intestinal disturbances, painful red skin rashes, muscle pain and periorbital swelling. This disease is very newly recognized and understood.

How common is it?
TRAPS is thought to be a rare disease with less than 100 confirmed cases, however, its true prevalence is currently unknown. It affects males and females equally and the onset seems to be during late childhood, or adulthood.
The first cases were reported in patients from Irish-Scottish ancestry, however the disease has also been identified in other populations: French, Italians, Sephardic and Ashkenazi Jews, Armenians, Arabs and Kabylians from Maghreb.
The seasons and climate have not been demonstrated to influence the course of the disease.

What are the causes of the disease?
TRAPS is due to an inherited anomaly of a protein (Tumor Necrosis F Factor Receptor[TNFR]), which leads to an increase of the patient’s normal acute inflammatory response.
An inflammatory hormone named tumor necrosis factor (TNF) overacts, because it is not controlled by the TNFR that normally binds to it and lowers the magnitude of inflammatory response.
Infection, trauma or psychological stress may induce attacks.

Is it inherited?
TRAPS has a dominant pattern of inheritance meaning that more than one case may be observed in a single family, every generation. The gradual reduction of family’s intermarriages (sibships) has lowered the possibility of this.

Why has my child got the disease? Can it be prevented?
The child has inherited his disease from one of his parents that carries a TNFR gene mutations unless a de novo mutation has occurred.
The person who carries the mutation may, or may not, exhibit the clinical symptoms of TRAPS. The disease cannot currently be prevented.

Is it contagious?
TRAPS is not an infectious disease. Only genetically affected subjects develop the disease.

What are the main symptoms?
The main symptoms are recurrent attacks of fever lasting typically two or three weeks, associated with chills and intense muscle pain involving the trunk and the upper limbs. The typical rash is red and painful, corresponding with underlying inflammation of the skin and muscle area.
Most patients experience a sensation of deep cramping muscle pain at the onset of attacks that gradually increases in intensity and begins to migrate to other parts of the limbs, followed by the appearance of the rash. Diffuse abdominal pain with nausea and vomiting are common. Inflammation of the membrane covering the front of the eye (the conjunctiva), or periorbital swelling, is characteristic of TRAPS, although this symptom can be observed in other diseases.
TRAPS may present somewhat differently with attacks of shorter or longer duration. Chest pain is also reported due to inflammation of the pleural (the membrane surrounding the lungs), or the pericardium (the membrane surrounding a joint) inflammation.
Amyloidosis is the most severe complication of TRAPS, occurring in 14% of patients. It causes large amounts of proteins in the urine and progresses to renal failure.
The relationship between amyloidosis and TRAPS probably relies on both chronic inflammation and genetic factors.

Is the disease the same in every child?
TRAPS presentation varies from one patient to another in terms of the duration of each attack and the duration of symptom-free periods. The combination of the main symptoms is also variable. These differences may be explained, in part, by genetic factors.

How is it diagnosed?
An expert physician will suspect TRAPS on the basis of clinical symptoms identified during a physical examination and from taking a family medical history.
Several blood analyses are useful to detect inflammation during the attacks. The diagnosis is ascertained only by genetic analysis providing evidence of mutations.
Differential diagnoses are other conditions presenting with recurrent fever especially Familial Mediterranean fever and HyperIgD syndrome.

What are the treatments?
To date, no treatment exists to prevent or cure the disease. Non-specific anti-inflammatory agents help to relieve symptoms. High dose steroids are often effective but sustained usage leads to serious side effects. Specific TNF blockade has been shown to be an effective treatment in some patients when given at the beginning of an attack.

How long should treatments last for?
The duration of treatment is limited to relieving acute symptoms, since no drug is effective for the prevention of fever attacks.

How long will the disease last for?
TRAPS will manifests at repeated and irregular occasions throughout the life.

What is the long term prognosis (predicted outcome and course) of TRAPS?
The prognosis is very variable, the worst prognosis affects only the minority of patients and these patients develop secondary amyloidosis. This risk is difficult to determine, because it depends on both genetic and environmental factors. Amyloidosis is a severe complication and frequently leads to renal failure.
At the present time no one knows if this complication can be avoided.

Is it possible to recover completely?
This possibility is currently unknown, but not excluded. Indeed, the genetic TNFR structural modification does not induce a functional defect in the bodies systems, making the discovery of a cure a perceivable possibility. Moreover, the eventual cessation of exposure to a potential triggering agent may induce sustained remission.