What is the definition of 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.

What are the alternative names for Familial Cold Autoinflammatory Syndrome?

  • FCAS
  • Familial polymorphous cold eruption
  • Familial cold urticaria

What are the causes for 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.

What are the symptoms for 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.

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.

What are the current treatments for Familial Cold Autoinflammatory Syndrome?

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. These agents reportedly have a significant beneficial effect on quality of life for individuals with FCAS.

What is the outlook (prognosis) for Familial Cold Autoinflammatory Syndrome?

Symptoms of familial cold autoinflammatory syndrome continue throughout one's lifetime, but may improve with treatment. Rare complications that have been reported in individuals with this disorder include amyloidosis and kidney failure.  

Is Familial Cold Autoinflammatory Syndrome an inherited disorder?

Familial cold autoinflammatory syndrome is inherited in an autosomal dominant manner. 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.
  • Condition: Cryopyrin-Associated Periodic Syndrome (CAPS), Hyperimmunoglobulin D Syndrome (HIDS), and Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
  • Journal: RMD open
  • Treatment Used: Current Therapies
  • Number of Patients: 0
  • Published —
This review of the literature examined the treatment outcomes of current therapies for rare auto-inflammatory conditions, such as cryopyrin-associated periodic fever syndromes (CAPS), hyperimmunoglobulin Dsyndrome (HIDS)/mevalonate kinase deficiency (MKD) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS).
  • Condition: Monogenic Autoinflammatory Diseases and PFAPA Syndrome
  • Journal: Frontiers in immunology
  • Treatment Used: anti-IL-1 agents and other biologic drugs
  • Number of Patients: 0
  • Published —
This review analyzed the treatment of the most frequent monogenic autoinflammatory diseases.