Familial cold autoinflammatory syndrome

Other Names: FCAS; Familial polymorphous cold eruption; Familial cold urticaria

Familial cold autoinflammatory syndrome is a type of periodic fever syndrome. Management of this condition involves avoiding exposure to cold temperatures and treatment with specific types of medications.

Cause

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.

Inheritance

Familial cold autoinflammatory syndrome is inherited in an autosomal dominant manner.

Autosomal dominant pattern, a 50/50 chance.

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.

Signs and symptoms

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.

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Arthritis(Joint inflammation)
• Dysesthesia
• Erythema
• Fatigue(Tired)
• Fever
• Hyperhidrosis(Excessive sweating)
• Myalgia(Muscle ache)
• Pruritus(Itching)
• Urticaria(Hives)

30%-79% of people have these symptoms

• Headache(Headaches)
• Nausea and vomiting

5%-29% of people have these symptoms

• Abdominal pain(Pain in stomach)
• Arthralgia(Joint pain)
• Conjunctivitis(Pink eye)
• Dehydration
• Polydipsia(Extreme thirst)
• Renal amyloidosis
• Sensorineural hearing impairment

Diagnosis

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. 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. 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.

Treatment

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. 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. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Rilonacept (Brand name: Arcalyst)rilonacept (Arcalyst) was approved for treatment of cryopyrin-assisted periodic syndromes (CAPS).
• Canakinumab (Brand name: Ilaris)

NIH genetic and rare disease info

• NIH info on Familial cold autoinflammatory syndrome

Familial cold autoinflammatory syndrome is a rare disease.

Familial cold autoinflammatory syndrome Resources
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