What is it family cold autoinflammatory syndrome?
Familial cold autoinflammatory syndrome (FCAS, MIM 120100) is a genetic Newspaper fever syndrome that occurs with recurrent short episodes of fever, a urticaria-like skin eruption and joint pain, usually after generalized Exposure to cold. It was previously called familial cold urticaria.
Familial cold autoinflammatory syndrome (FCAS) is now grouped along with Muckle-Wells syndrome and NOMID / CINCA as a periodic cryopyrin-associated syndrome (CAPS). FCAS is the least severe of this clinical continuum.
Who gets the family cold autoinflammatory syndrome and why?
Familial cold autoinflammatory syndrome is a autosomal Dominant condition, inherited from one of the affected parents.
Symptoms generally begin at birth (in 60% it occurs within days after birth) or within the first 6 months after birth (95%). However, there is also a late submission. There is generally a delay in diagnosis of, on average, 10 years.
Molecular biology and genetics
Mutations occur in the NLRP3 gene It encodes cryopyrin, a component of protein complexes called inflammasomes that are found inside cells and participate in the innate immune system. Most of the mutations have been identified in exon 3 of this gene. Disease-related mutations result in "gain of function" since abnormal cryopyrin allows continuous stimulation of inflammatory reaction. The mechanism of temperature dependence of this reaction is not yet understood.
What are the clinical features of familial cold autoinflammatory syndrome?
The distinctive clinical features of familial cold autoinflammatory syndrome are acuteShort-term fever attacks with a skin rash and joint pain after widespread exposure to cold.
The clinical features of acute episodes of familial cold autoinflammatory syndrome may include:
- Fever: On the 93%, lasts less than 24 hours, previous chills, associated with profuse sweating, often occur at night, settle in hours
- Skin rash: at 100%, see below
- Muscle pain (myalgia)
- Joint pain (arthralgia) - at 96%, stiffness and swelling of hands and feet
- Be extreme
- Eye - frequent conjunctivitis (at 84%), blurred vision and pain.
What are the characteristics of the familial cold autoinflammatory syndrome rash?
The skin rash is usually the first. sign of this syndrome, which appears shortly after birth or in early childhood. Although it is described as urticarial (like hive), usually comes as light pink or red flat figured patches macules and slightly raised papules (maculopapular skin rash) that disappears within 24 hours after onset.
The patient rarely describes the rash as itching, but uses words like burning, itching, heat, or stiffness. The rash occurs on the trunk and limbs and moves. It is often worse at night. The intensity of the rash varies between patients and the activity of the disease. Petechiae They have also been described.
What triggers attacks in familial cold autoinflammatory syndrome?
The characteristic trigger for an acute attack is general exposure to cold (but not located cold), with symptoms developing 1 to 2 hours (range 30 minutes to 6 hours) after exposure. Symptoms peak at 2-6 hours and resolve within 24 hours. Attacks are most common in winter, on windy, wet days, and can occur with a large drop in temperature or with air conditioning. The severity of an attack varies with the degree of cold, that is, more severe if it is very cold.
Acute episodes generally last less than 24 hours (range 12-48 hours), then settle spontaneously.
How does familial cold autoinflammatory syndrome progress?
Attacks generally begin early in life and tend to worsen with increasing age.
Amyloidosis is a rare complication (<5%) del síndrome familiar autoinflamatorio por frío. La sordera generalmente no se observa. La superposición con el síndrome de Muckle-Wells se ha descrito como el desarrollo de sensorineural Deafness in FCAS, otherwise, typical, or cold-triggering episodes in Muckle-Wells syndrome, otherwise
How is autoinflammatory syndrome of the family cold diagnosed?
A diagnosis of familial cold autoinflammatory syndrome should be considered in patients with acute recurrences. febrile attacks that occur shortly after exposure to cold.
Note that the ice cube challenge test is negative, a useful feature to distinguish from cold urticaria. A typical attack can be triggered by going to a cold room at 4 ° C.
During an acute attack, tests reveal nonspecific characteristics, including:
- Acute phase reactants (blood tests) - elevated erythrocytes sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A (SAA)
- Leukocytosis (a high white blood cell count with a slight increase in peripheral neutrophils)
Skin biopsy of a urticaria injury Show a perivascularand sometimeseccrine, neutrophils infiltrate on top dermis. Since this is different from histology urticaria or urticarial vasculitisIt can be very helpful in suggesting the diagnosis of FCAS.
A commercial genetic test is available to sequence exon 3 of the NLRP3 gene.
What is the treatment for familial cold autoinflammatory syndrome?
Even the biological agents that blocked interleukin-1 were recognized to control Due to the symptoms of the autoinflammatory syndrome of the family cold, many people moved to temperate climates where they could avoid cold winters or hot summers that require air conditioning.
Bed rest, heat, and corticosteroids can be used to treat an acute attack.
Anakinra, an interleukin-1 receiver antagonist, has successfully treated many patients with familial cold autoinflammatory syndrome in large clinical trials. Anakinra is administered daily. subcutaneous injection with a usual dose range of 0.5-1.5 mg / kg / day. All patients respond if given a sufficient dose. Some people use it on and off, such as alternate days, during winter, or when there will be exposure to a recognized trigger. Local reactions at the injection site are the most common adverse effect. Clinical improvement was observed within 12 hours and blood tests returned to normal within one week in the trials. Symptoms reappeared within 26–48 hours after cessation of treatment.
Note: Anakinra is not registered or subsidized in New Zealand (March 2011). In other countries, such as the US and Europe, its registered indication is rheumatoid arthritis.
Rilonacept is used as a weekly subcutaneous injection. In a open pilot study of five patients, after a single dose of 300 mg, maximum clinical improvement was observed on day 6-10 with outbreaks of the disease after 10-28 days. It is approved by the FDA for the treatment of adults and children from the age of 12 who suffer from autoinflammatory syndrome of the family cold.
Canakinumab is approved by the FDA for the treatment of familial cold autoinflammatory syndrome that affects adults and children from 4 years of age. It is given as a subcutaneous injection every 8 weeks. Clinical trials report resolution of urticaria-like rash within 1 day and complete resolution, including joint pain and blood tests within 1 week.
Biological agents that block the effect of interleukin-1.β they have a significant beneficial effect on the quality of life of those with autoinflammatory syndrome of the family cold.