TRAPS: Causes, Clinical Features, Diagnosis, and Treatment

What Is TRAPS?

TRAPS or Tumor necrosis factor receptor-associated periodic syndrome is a rare genetic condition that usually begins in childhood. A distinguishing character is the recurrent episodes of fever that can last more than a week or longer and are associated with chills and severe muscle pain in the abdomen and arms. The frequency of fever may vary greatly among affected individuals and the fever can occur anywhere between every six weeks to a few years. However, in some cases, they may go many years without having an episode of fever and the episodes can occur due to some triggering factors such as minor injury, infection, exercise, stress, or hormonal changes.

What Is the Frequency of TRAPS?

1. The first cases of this condition were first reported in patients from Irish-Scottish backgrounds.

2. TRAPS is a very rare genetic condition with an estimated incidence rate of one in every million individuals. It is the second most common inherited recurrent fever syndrome.

3. More than 1000 people worldwide have been found to have this condition.

4. TRAPS affects both males and females and usually starts before the age of ten, but in some cases, the symptoms may appear in late childhood or even adulthood.

What Causes TRAPS?

1. TRAPS is a genetic condition caused due to mutation in the TNFRSF1A gene. This gene is responsible for providing instructions for making a protein called tumor necrosis factor receptor 1 (TNFR1).

2. This protein is usually found in the cell membrane, where it attaches to another protein called tumor necrosis factor (TNF).

3. When this binding occurs, it can trigger inflammation or self-instruct the cell.

4. This process of self-destruction is also called apoptosis and occurs due to the binding of the TNFR1 protein to the TNF protein.

These gene mutations lead to a build-up of these proteins and can trigger alternate pathways that initiate inflammation. As multiple alternative inflammatory pathways are created, it leads to excess inflammation in people with TRAPS. However, it is still very clearly understood if apoptosis pathway is solely responsible for producing signs and symptoms of TRAPS.

What Is the Genetic Inheritance of TRAPS?

1. This condition is a genetic disorder and is inherited in an autosomal dominant pattern, which means that one copy of the defective gene in each cell is enough to cause the disorder. However, in some cases, people who inherit the defective gene may not develop features of TRAPS and it is unclear why some individuals with mutated genes develop the disease and while others do not.

2. In majority of the cases, the affected person usually inherits the mutation from the affected parent, and in other cases, it results from new mutations in the gene in individuals with no history of this condition in the family.

What Are the Clinical Features of TRAPS?

These clinical features of TRAPS that differentiate it from other syndromes include:

1. Prolonged fever episodes lasting three to four weeks.

2. Conjunctivitis with or without swelling.

3. Muscle pain with skin redness.

Some of the additional features of TRAPS are mentioned below -

1. Fever

• Usually affects all but can also be absent in some cases.

• Usually 40 degrees Celsius.

• Can last from two days to more than one month, most commonly one to three weeks.

• Can recur two to six times per year.

• Does not respond to Aspirin or Paracetamol.

2. Abdominal Pain

• Seen in 90 percent of the cases.

• Pain is usually abdominal and is associated with loss of appetite, vomiting, constipation, and bowel obstruction.

3. Muscle Pain (Myalgia)

• Seen in 80 percent of cases.

• Pain is migratory and begins on the proximal limb and moves distally (from the hip or shoulder area towards the ankle or wrist).

• Deep cramping pain can be disabling in nature.

4. Skin Rash

• Affects 80 percent of patients.

5. Eye

• Affects 44 percent of patients.

• Conjunctivitis along with swelling around the eye.

• Uveitis or middle layer of the eye inflammation, and episcleritis, or inflammation of the clear layer on top of the white part of the eye, called the sclera may also be present.

6. Joint Pain

• Affects 50 patients.

• Usually affects a single large joint (hips, knees, or ankles).

7. Headache

• Affects 70 percent of patients.

8. Chest Pain

• Affects 40 of patients and occurs due to pleuritis (inflammation of the tissues that line the lungs and chest cavity) or pericarditis (swelling and irritation of the membrane surrounding the heart).

9. Testicular Pain

• Occasional.

10. Lymph Node Swelling

• May or may not be seen.

What Are the Triggering Factors for TRAPS?

Some of the triggering factors for recurrent febrile tracks include:

• Physical trauma.

• Physical and emotional stress.

The frequency of attacks may range from every few weeks up to years. The frequency may decrease with age.

How Is TRAPS Diagnosed?

TRAPS is diagnosed by a physician after a clinical examination of the patient. The physician will consider the acute recurrent febrile attacks with the characteristic muscle pain and skin changes, with the absence of any infection or autoimmune disorder.

1. Blood test may also be advised which will show the following results as

• Increased neutrophil count (neutrophilia).

• Increase in acute phase reactants such as ESR (erythrocyte sedimentation rate) or CRP (c-reactive protein test) which helps in detecting infections.

• Detecting anemia.

• An increased level of immunoglobulin IgA means the presence of chronic infections or inflammation.

2. Skin biopsy can also help detect this condition as it will show increased levels of cells like T-lymphocytes and monocytes, indicating the presence of inflammation or infection.

3. Presence of muscle pain may reveal a normal level of muscle enzymes in the blood test, but in muscle biopsy inflammation of deep fascia can be seen.

4. Genetic testing is the best way of diagnosing TRAPS.

How Is TRAPS Treated?

Generally, there is no cure for tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, some medications can be prescribed to relieve the symptoms such as non-steroidal anti-inflammatory (NSAIDs) drugs and even steroids, but long-term usage of steroids can cause serious side effects.

Other than that medications that block the effect of interleukin-1 which is one of the important proteins involved in the process of inflammation can also be used for treating this condition. The medications include:

• Anakinra.

• Canakinumab.

• Etanercept.

• Tocilizumab.

These medicines are successful in blocking the tumor necrosis factor (TNF) which has shown effective results in some patients, and they can also be used in cases where other medicines may not be used because of their adverse effects.

Conclusion:

TRAPS is a rare condition and can also cause serious complications, such as kidney failure, without any treatment. This syndrome can be managed by taking proper medications, which help with symptoms and improve the quality of life. Tumor necrosis factor receptor-associated periodic syndrome does not shorten life expectancy for most people and the episodes of fever may also get shortened with age. But still, patients with this condition have to go for regular check-ups to avoid any complications.