familial cold autoinflammatory syndrome 1

Familial Cold Autoinflammatory Syndrome (FCAS) 1, also known as Familial Cold Urticaria (FCU), is a rare genetic disorder characterized by recurrent episodes of rash, fever, and arthralgias after exposure to cold temperatures.

Symptoms:

• Recurrent attacks of maculopapular rash
• Fever
• Arthralgias (joint pain)
• Myalgias (muscle pain)

These symptoms are typically triggered by exposure to cold temperatures, and can range from mild to severe in intensity. The frequency and severity of the episodes can vary greatly between individuals.

Causes:

FCAS 1 is caused by mutations in the CIAS1/NLRP3 gene, which plays a crucial role in regulating inflammation in the body. This genetic mutation leads to an overactive immune response, resulting in the symptoms associated with FCAS 1.

Prevalence: FCAS 1 is considered a rare condition, with a prevalence of less than 1 per million people [6].

References:

• The disease occurs in large families and is inherited in an autosomal dominant pattern [7].
• It is characterized by episodes of rash, fever, and arthralgia after generalized exposure to cold (see Figure 97-1) [8].

Familial cold autoinflammatory syndrome 1 (FCAS) 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.

Common symptoms of FCAS include:

• Intermittent episodes of rash, which can be urticaria-like in nature [1]
• Fever
• Joint pain (arthralgia)
• Conjunctivitis (inflammation of the eyes) [6]
• Profuse sweating
• Dizziness
• Headaches and nausea are also seen [9]

The symptoms of FCAS typically last less than 24 hours, but can vary in duration.

It's worth noting that FCAS is considered the mildest form of cryopyrin-associated periodic syndrome (CAPS), which includes three conditions with overlapping signs and symptoms: FCAS1, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID) [4][5].

References: [1] - 7 [4] - 4 [5] - 5 [6] - 6 [9] - 9

Diagnostic Tests for Familial Cold Autoinflammatory Syndrome 1 (FCAS1)

Familial cold autoinflammatory syndrome 1 (FCAS1) is a rare autosomal dominant inflammatory disorder that can be challenging to diagnose. However, several diagnostic tests and evaluations can help confirm the condition.

• DNA Gene Analysis: Confirmation of FCAS1 diagnosis is achieved through DNA gene analysis, specifically identifying a mutation in the NLRP3 gene (606416), which encodes cryopyrin [10][13].
• Genetic Testing Registry: The Genetic Testing Registry (GTR) provides information on genetic tests, including those for FCAS1. A comprehensive genetic evaluation is recommended for patients with a personal or family history suggestive of an inherited autoinflammatory disorder [5][6].
• Autoinflammatory Syndrome Panel: An Autoinflammatory Syndrome Panel, such as the one offered by Blueprint Genetics, can be ideal for patients with a clinical suspicion of an autoinflammatory syndrome, including FCAS1 [6].
• Genetic Testing: Genetic testing can help identify the NLRP3 gene mutation associated with FCAS1. This test is typically performed on a blood sample and can provide a definitive diagnosis [10][13].

Other Diagnostic Evaluations

In addition to genetic testing, other diagnostic evaluations may be necessary to rule out other conditions that may present similarly to FCAS1. These include:

• Physical Examination: A thorough physical examination can help identify symptoms such as episodic rash, fever, arthralgias, and fatigue upon exposure to cold [4].
• Medical History: A detailed medical history is essential to understand the patient's symptoms and family history of autoinflammatory disorders [5].

References

[1] Familial Cold Autoinflammatory Syndrome (FCAS) Medically Reviewed by Jabeen Begum, MD on September 20, 2024. Written by Keri Wiginton. [2] The group includes three conditions known as familial cold autoinflammatory syndrome type 1 (FCAS1), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID). [3] Learn about Familial Cold Autoinflammatory Syndrome, including symptoms, causes, and treatments. [4] What is familial cold autoinflammatory syndrome? [5] A comprehensive genetic evaluation is recommended for patients with a personal or family history suggestive of an inherited autoinflammatory disorder. [6] An Autoinflammatory Syndrome Panel can be ideal for patients with a clinical suspicion of an autoinflammatory syndrome, including FCAS1. [10] Familial cold autoinflammatory syndrome is characterized clinically by recurrent attacks of a maculopapular rash associated with arthralgias, myalgias, fever and chills, and swelling of the extremities after exposure to cold. [13] A number sign (#) is used with this entry because familial cold autoinflammatory syndrome-1 (FCAS1) is caused by heterozygous mutation in the NLRP3 gene (606416), encoding cryopyrin, on chromosome 1q44.

Treatment Options for Familial Cold Autoinflammatory Syndrome (FCAS)

Familial cold autoinflammatory syndrome (FCAS) is a rare genetic disorder characterized by recurring episodes of inflammation, typically triggered by exposure to cold temperatures. While there is no cure for FCAS, various treatment options are available to manage symptoms and improve quality of life.

Interleukin-1 (IL-1) Inhibitors

The most effective treatment for FCAS involves blocking the action of interleukin-1 beta (IL-1β), a protein that plays a key role in inflammation. IL-1 inhibitors, such as:

• Canakinumab: A monoclonal antibody that targets and neutralizes IL-1β, reducing inflammation and symptoms.
• Anakinra (Kineret): An interleukin-1 receptor antagonist that blocks the action of IL-1β on its receptor, thereby reducing inflammation.

These treatments have been shown to be highly effective in managing FCAS symptoms, including fever, rash, and joint pain [4][5].

Other Treatment Options

While not as effective as IL-1 inhibitors, other treatment options may also be considered:

• Corticosteroids: May be used to manage acute episodes of inflammation.
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Can help reduce fever and alleviate symptoms.

It's essential to note that each individual with FCAS may respond differently to these treatments, and a personalized treatment plan should be developed in consultation with a healthcare provider [1].

References

[1] DHM Hoffman. Treatment of Familial Cold Autoinflammatory Syndrome. 2001. [4] JB Ross. Anakinra (Kineret) for the treatment of familial cold autoinflammatory syndrome. 2008. [5] FDA-approved medications for CAPS, including Kineret (anakinra), Arcalyst (rilonacept), and Ilaris (canakinumab).

Familial cold autoinflammatory syndrome 1 (FCAS1) is a rare genetic disorder that affects how the body controls inflammation. The differential diagnosis for FCAS1 involves ruling out other conditions that may present with similar symptoms.

Conditions to consider:

• Muckle-Wells syndrome (MWS): A related condition that also presents with fever, rash, and joint pain.
• Familial cold autoinflammatory syndrome type 2 (FCAS2): Another rare genetic disorder that can cause similar symptoms.
• Other autoimmune disorders: Such as rheumatoid arthritis or lupus, which may present with fever, rash, and joint pain.

Key distinguishing features of FCAS1:

• Recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever, chills, and swelling of extremities triggered by exposure to cold temperatures.
• Genetic inheritance pattern: FCAS1 is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is enough to cause the condition.

Diagnostic criteria:

• Recurrent episodes of fever and rash that primarily follow natural or experimental generalized cold exposures.
• Presence of amyloidosis (a condition where abnormal proteins accumulate in organs) later in life.

References:

• [1] Diagnostic criteria/Definition · Recurrent intermittent episodes of fever and rash that primarily follow natural, experimental, or both types of generalized cold exposures.
• [3] Generally, CAPS are characterized by periodic episodes of skin rash, fever, and joint pain.
• [4] FCAS is a rare genetic disorder. It affects how your body controls inflammation. Symptoms are triggered by exposure to the cold.
• [8] Familial cold autoinflammatory syndrome is characterized clinically by recurrent attacks of a maculopapular rash associated with arthralgias, myalgias, ...