TNF receptor associated periodic syndrome
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TNF receptor associated periodic syndrome (also known as TRAPS or familial Hibernian fever) is a periodic fever syndrome associated with mutations in a receptor for the molecule tumor necrosis factor (TNF) that is inheritable in an autosomal dominant manner. Individuals with TRAPS have episodic symptoms such as recurrent high fevers, rash, abdominal pain, and joint/muscle aches.
The main source of TNF is cells in the immune system called macrophages which produce it in response to infection and other stimuli. TNF helps activate other immune cells and plays a major role in initiation of inflammation. Individuals with TRAPS have a mutation in the tumor necrosis factor receptor-1 (TNFR1) gene. The mechanisms by which mutations in TNFR1 lead to the TRAPS phenotype are still under investigation.
Several medications have been studied for the treatment of TRAPS including etanercept, infliximab[1], and tacrolimus[2]. However, no single drug has been shown to treat all cases of TRAPS. TRAPS was first described in 1982 in a boy of Scottish-Irish origin. At that time, it was named familial Hibernian fever.
[edit] Clinical features of TRAPS
The mean age for the first episode of inflammation is 3 years, but this is variable between different patients with initial attacks occurring anywhere from 2 weeks to 53 years of age. Variations between the age of onset can vary widely even within families. Episodes can last from 1-2 days to month long attacks, but average 21 days in length. Like the episode duration, the intervals between attacks can also vary widely. On average, episodes occur every 5-6 weeks, but remission can also occur over a period of months to years. Often there is no known stimulus for attacks, but in some cases they have been associated with physical or emotional stress or local trauma. Attacks are usually heralded by deep muscle pain that can persist throughout the episode, which usually gradually resolves by itself. TRAPS equally affects both males and females, but there are however some gender specific influences on the occurrence of inflammatory outbreaks. It has been noted that inflammatory episodes do not occur during pregnancy and that there may be accentuation of symptoms during menses.
The most common feature of TRAPS attacks is a fever usually greater than 38o C and lasting more that 3 days. Fever accompanies most attacks in pediatric patients but can be absent from attacks in adults. The other most common symptom of a TRAPS episode is a cramp-like myalgia or muscle pain. This pain can vary in severity from uncomfortable in its mildest, to incapacitating at its worst. The myalgia waxes and wanes throughout the course of an attack, affecting primarily the limbs and torso, but also the face and neck. A rash is commonly associated with inflammatory attacks, often occurring over the site of myalgia, with the affected areas being warm and tender. A unique feature of TRAPS is that the rashes can migrate along a limb along with the myalgia. Joint pain (arthralgia)can also occur during these attacks, most often affecting large joints such as the knees, hips and ankles. Arthralgia can accompany the migration of the myalgia or be completely separate from it. Abdominal pain also commonly accompanies a TRAPS attack and is often associated with nausea, vomiting, diarrhea or constipation. Some attacks are characterized by the occurrence of fevers and abdominal pains with no other symptoms. Patients can also experience eye involvement with conjunctivitis, or swelling or pain in the periorbital space. They also may experience chest, testicular or scrotal pain.
The most serious complication associated with TRAPS is kidney amyloidosis (insoluble proteins deposited in the kidney). Proteinuria is a sign for kidney amyloidosis, so this situation can be detected early on, which is important since many of the patients with kidney amyloidosis experience renal failure, a life-threatening complication.
[edit] References
- ^ Church LD, Churchman SM, Hawkins PN, McDermott MF. Hereditary auto-inflammatory disorders and biologics. Springer Semin Immunopathol. 2006 Jun;27(4):494-508. Epub 2006 May 4. PMID 16738958
- ^ Ida H, Aramaki T, Arima K, Origuchi T, Kawakami A, Eguchi K. Successful treatment using tacrolimus (FK506) in a patient with TNF receptor-associated periodic syndrome (TRAPS) complicated by monocytic fasciitis. Rheumatology (Oxford). 2006 Jun 26; PMID 16801330
Mendelian Inheritance in Man (OMIM) 142680
