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Familial cold autoinflammatory syndrome


Other Names for this Disease

  • Familial cold urticaria
  • Familial polymorphous cold eruption
  • FCAS
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My daughter was recently diagnosed with familial cold autoinflammatory syndrome. I have many questions and concerns. Can you refer me to valid useful information?

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What is familial cold autoinflammatory syndrome?

Familial cold autoinflammatory syndrome is a type of periodic fever syndrome. Signs and symptoms may include include an itchy or burning rash; fever; and joint pain which are triggered by exposure to cold temperatures. It is inherited in an autosomal dominant manner and can be caused by mutations in the NLRP3 or NLRP12 genes. Management of this condition involves avoiding exposure to cold temperatures and treatment with specific types of medications.[1][2]
Last updated: 10/30/2013

What are the signs and symptoms of familial cold autoinflammatory syndrome?

Signs and symptoms of familial cold autoinflammatory syndrome may include rash, fever, and joint pain triggered by exposure to cold temperatures. The rash often begins on exposed arms and legs and extends to the remainder of the body. The rash may consist of red macules and plaques, hives (urticaria), and petechiae. The skin rash can cause burning or itching. Conjuctivitis during a fever episode is also common. Other symptoms can include swelling, muscle pain, profuse sweating, drowsiness, headache, extreme thirst, and nausea.[1]

Symptoms may begin anywhere between 10 minutes to 8 hours after cold exposure. Fever attacks may last a few hours up to three days. Most people with familial cold autoinflammatory syndrome experience their first fever attack within the first year of life, many within the first day of life. Episodes continue to occur throughout life.[1]

Last updated: 11/1/2013

What causes familial cold autoinflammatory syndrome?

Familial cold autoinflammatory syndrome is caused by changes (mutations) in either one of two genes: NLRP3 or NLRP12. These genes normally provide instructions for making proteins involved in the immune system, helping to regulate the process of inflammation. Changes in these genes impair the body's mechanisms for controlling inflammation, resulting in the signs and symptoms of this condition. It remains unclear why episodes are triggered by cold exposure.[2]
Last updated: 11/1/2013

How is familial cold autoinflammatory syndrome inherited?

Familial cold autoinflammatory syndrome is inherited in an autosomal dominant manner.[2] This means that a mutation in only one of the two copies of the responsible gene is sufficient to cause signs and symptoms of the condition. When an individual with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the mutated copy of the gene. This also means that each child has a 50% risk to not inherit the mutated copy of the gene and therefore be unaffected.

There have been reported cases of this condition occurring in individuals with no history of the condition in the family; in these cases, the condition was not inherited from a parent, but occurred for the first time in the affected individual.[1]
Last updated: 11/1/2013

How is familial cold autoinflammatory syndrome diagnosed?

Familial cold autoinflammatory syndrome (FCAS) is primarily a clinical diagnosis, meaning that it is mostly based on the presence or absence of specific of signs and symptoms as well as family history.[3] Diagnostic criteria have been proposed in order to distinguish FCAS from acquired cold urticaria and other periodic fever disorders. The criteria include: recurring episodes of fever and rash that primarily follow cold exposures; autosomal dominant pattern of disease inheritance in a family; age of onset younger than 6 months; duration of most attacks less than 24 hours; conjunctivitis in association with attacks; and absence of deafness, swelling around the eyes, enlarged lymph nodes, and serositis.[1][3] Having four of six of the criteria strongly suggests a diagnosis of FCAS. A diagnosis of FCAS may also be confirmed in some affected individuals by genetic testing.[3]
Last updated: 11/1/2013

How might familial cold autoinflammatory syndrome be treated?

Individuals with familial cold autoinflammatory syndrome (FCAS) are generally advised to avoid exposure to cold temperatures. Bed rest, warmth and corticosteroids can be used to treat an acute attack.[4] Treatment may include the use of biologic agents (drugs derived from living material) which can control the symptoms of FCAS by blocking interleukin-1; they are called selective recombinant interleukin-1 receptor agonists. Examples of these agents are rilonacept, anakinra, and canakinumab.[5][4] These agents reportedly have a significant beneficial effect on quality of life for individuals with FCAS.[4]
Last updated: 11/14/2013

What is the prognosis for people with familial cold autoinflammatory syndrome?

Symptoms of familial cold autoinflammatory syndrome tend to become less severe as a person ages. Complications that have been reported in three families with this syndrome include type AA amyloidosis and renal insufficiency.[1]  The identification of the mutations in the CIAS1 gene and subsequent understanding of the molecular mechanisms underlying the symptoms of familial cold autoinflammatory syndrome and other cryopyrin-associated periodic syndromes (CAPS) accompanied with the development of IL-1 targeting biologics has been a major therapeutic advance for patients suffering with CAPS. For the medical community, the availability of anakinra, rilonacept and ACZ885 (in clinical trials)  has transformed the prognosis and treatment of patients from one of limited success to one of muted confidence. [6]
Last updated: 9/10/2009

References
Other Names for this Disease
  • Familial cold urticaria
  • Familial polymorphous cold eruption
  • FCAS
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.