Familial Cold Auto-inflammatory Syndrome (FCAS): Fact Sheet
TOPICS:
What It Is
Causes and Symptoms
FCAS Characteristics
Incidence and Prevalence
Living with FCAS
Diagnosis & Treatment
References
What It Is
Familial cold auto-inflammatory syndrome (FCAS), also known as familial cold urticaria, is a rare, inherited inflammatory disorder characterized by intermittent episodes of rash, fever, joint pain and other signs/symptoms of systemic inflammation triggered by exposure to cold.(1) Onset of FCAS occurs during infancy and early childhood and persists throughout the patient's life.
FCAS is one of the cryopyrin associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 gene. These syndromes are characterized by intermittent attacks of fever associated with rash and joint pain.(2)
FCAS shares symptoms, and should not be confused, with acquired cold urticaria, a more common condition mediated by different mechanisms that usually develops later in life and is rarely inherited.
Causes and Symptoms
FCAS is caused by a mutation in a gene identified as the cold-induced auto-inflammatory syndrome 1 (CIAS1) gene. The mutation in the CIAS1 gene causes increased activity of cryopyrin, a protein that regulates inflammation in the body. The increased activity of cryopyrin results in an overproduction of a protein known as interleukin 1ß, which leads to symptoms of inflammation such as fever and joint pain.(3,4)
FCAS Characteristics
Patients with FCAS experience debilitating symptoms such as rash, fatigue, recurrent fever and chills, recurrent joint pain, and recurrent conjunctivitis (inflammation of the outer most layer of the eye causing redness, discomfort and discharge from the eye).
Other symptoms include profuse sweating, drowsiness, headache, extreme thirst, red eyes, blurred vision, eye pain, watering eyes and nausea.
Symptoms occur within hours after exposure to cold. In most cases, a rash will occur within the first 1-2 hours, followed by a fever and joint pain.(5) Episodes usually last for less than 24 hours.(6)
Incidence and Prevalence
Since FCAS is a newly discovered condition, the actual incidence and prevalence of the disease is difficult to determine at this time.
Living with FCAS
The joint pain associated with FCAS can cause many patients to become incapacitated. A lack of effective treatments causes patients to utilize any remedies that alleviate symptoms, including additional sleep, warming treatments and, in some cases, moving to warmer climates to reduce the frequency of attacks. FCAS can continue to be a problem, even in warm climates, because signs and symptoms can be triggered even by minor exposure to cold such as air conditioning or a cool breeze.
Diagnosis & Treatment
Diagnosis of FCAS is determined through an evaluation of a patient's symptoms. Confirmation of the diagnosis is achieved through DNA gene analysis and the identification of a CIAS1 mutation.(6)
Some of the common criteria that distinguish FCAS from other hereditary periodic fevers include:(2)
- Recurrent, intermittent episodes of fever and rash that primarily follow exposure to cold
- Family history of the disease
- Age of onset of less than 6 months of age
- Duration of most attacks less than 24 hours
- Presence of conjunctivitis associated with attacks
- Absence of swelling of the eyes, swelling of one of more lymph nodes, and serositis (the inflammation of the serous membrane which lines and encloses several body cavities including the abdomen and the heart).
While there are no medications currently indicated for the treatment of FCAS, non-steroidal anti-inflammatory drugs are often used to alleviate joint pain. High doses of corticosteroids have shown to be somewhat effective, but may cause short- and long-term side effects. In recent clinical studies, investigational interleukin-1 inhibitors had encouraging preliminary results in addressing the inflammatory features of the conditions in study patients, but these product candidates have not been approved by the FDA for the treatment of FCAS.(8)