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Familial Cold Autoinflammatory Syndrome (FCAS)

Medically Reviewed by Brunilda Nazario, MD on October 02, 2020

What Is Familial Cold Autoinflammatory Syndrome (FCAS)?

FCAS is a rare genetic disorder. It affects how your body controls inflammation. Symptoms are triggered by exposure to the cold, though experts aren’t sure why. It’s the mildest type of cryopyrin-associated periodic syndrome (CAPS).

When you have FCAS, a protein called cryopyrin doesn’t work the right way. Cryopyrin serves as scaffold for a set of molecules that work together to fight germs or fix injuries. They jumpstart inflammation, which tells your immune system to start the healing process. With FCAS, your cryopyrin is overactive. That can lead to inflammation when you don’t need it. You can get symptoms like rash, fever, and joint pain.

Signs of FCAS tend to show up shortly after you’re born. But it’s possible to get your first symptoms as a child or young adult. Your attacks may come and go throughout your life. There isn’t a cure, but lifestyle changes and medication can help you manage FCAS.

Causes

Experts think you get FCAS when there’s a change, or mutation, in your NLRP3 gene. This gene gives your body directions on how to use cryopyrin. You can also have a mutation in your NLRP12 gene. That controls your monarch-1, a protein that acts as your “inflammation off switch.”

It seems that when there’s a glitch in these genes, your immune system ends up making too much interleukin-1. That’s a protein that promotes inflammation.

You get this condition when you inherit a mutated gene from one of your parents. Sometimes your genes can change on their own during conception and you can get FCAS. Males and females are just as likely to get FCAS. If you have it, there’s a 50% chance you’ll pass the gene mutation to your child.

Scientists only recently discovered FCAS. No one knows exactly how many people have it. So far, it’s mostly found in people from North America or Europe. Experts think there’s about a one-in-a-million chance you’ll get it.

Symptoms

You can have some mild skin issues on a daily basis. Or you may go for long stretches with no signs of FCAS. When you do have an attack, your symptoms may show up within 10 minutes or up to 8 hours after cold exposure. But they’ll most likely happen within a couple of hours.

Each episode usually lasts less than 24 hours, but they could go on for a few days. Here are the most common symptoms you’ll get:

Rash. FCAS causes hives. Your skin may itch and burn. You may get big red areas called patches or plaques. Purple-brown spots called petechiae may show up. Your rash may start out on the parts of your arms and legs exposed to the cold. It may spread to the rest of your body. Sometimes the affected body parts can swell.

Fever. Your body temperature may go up for a few hours or a few days. You may get chills at the same time.

Joint pain. This may happen about 4-6 hours after cold exposure. It’ll most likely affect your hands, knees, and ankles.

Eye problems. The white parts of your eyes may get red and irritated. That’s called conjunctivitis. Your eyes may hurt or get watery. Your vision may get blurry.

You may also get:

It’s rare, but FCAS can cause AA amyloidosis. That’s when ongoing inflammation causes a protein called amyloid A to build up. It can cause kidney disease. Your doctor may want to check how well your kidneys work every now and then.

Getting a Diagnosis

Your doctor will give you a physical exam and ask about your medical history. Tell them about all of your symptoms. That’ll help them rule out similar conditions. That includes acquired cold urticaria and other periodic fever disorders. Your regular doctor may refer you to a specialist who knows more about genetic disorders.

For a diagnosis of FCAS, your doctor will check for four of the following measures:

  • You get repeat episodes of fever and rash after cold exposure.
  • You have other family members with FCAS.
  • Your attacks start before you’re 6 months old.
  • Your symptoms usually go away within 24 hours.
  • You get eye redness (conjunctivitis) at the same time.
  • You don’t get deafness or swelling in your eyes, lymph nodes, or serous membranes (serositis).

Your doctor may also order:

Blood tests. They may want to check your levels of C-reactive protein or serum amyloid A protein. These are often higher in people who have autoinflammatory conditions like FCAS.

Genetic testing. A lab technician can check your blood for a change in your NLRP3 gene. This test is used to confirm your diagnosis. But not everyone with FCAS has this mutation. There may be more genetic tests available in the future.

Questions for Your Doctor

Write down everything you’d like to know before your appointment. That way you won’t forget what you’d like to ask.

Here are some questions to get you started:

  • What are all of my treatment options?
  • Will I need to take medicine for the rest of my life?
  • What side effects do drug treatments have?
  • Will biologics raise my chances of an infection?
  • What nonmedical options can help?
  • Will my symptoms change as I get older?
  • Is there a clinical trial I can join?

Your regular doctor may not be able to answer all of your questions. It’s OK to ask them to refer you to someone who can. Or you can look for a genetic specialist or clinic yourself. Check for resources through the American College of Medical Genetics or National Society of Genetic Counselors.

You can also talk to someone at the Genetic and Rare Diseases (GARD) contact center. Call 888-205-2311 between noon to 6 p.m. Eastern time Monday-Friday.

Treatment

Your doctor may suggest a mix of lifestyle changes and medication.

Treatment for FCAS may include:

Cold avoidance. It may seem obvious, but you may feel better if you stay warm. Some situations that might trigger your symptoms include:

  • Cold temperatures outside
  • A cold blast of wind
  • Damp mist or rain
  • Cold air from the refrigerator
  • Air conditioning

Biologics. It’s not always possible to avoid the cold. Your doctor may give biologics -- drugs made from living sources -- to prevent or ease symptoms. You’ll get them through a shot under your skin. They work in different ways to block the inflammatory protein interleukin-1.

Biologics used for FCAS include:

  • Anakinra
  • Canakinumab
  • Rilonacept

Canakinumab and rilonacept are FDA-approved to treat FCAS. Anakinra is sometimes used “off-label.” That means it hasn't been approved to treat FCAS, but doctors use it because it has been shown to help people with this condition.

Nonsteroidal anti-inflammatory drugs (NSAIDs). These may help ease your joint pain and fever.

Steroids. Your doctor may give you these for a short time to slow down your immune system. But they can cause some unwanted side effects. Your doctor can go over the pros and cons with you.

Taking Care of Yourself

Rest and get warm when you need to. Check in with your doctor if your FCAS symptoms aren’t under control. You have better treatment options than in the past. If your regular doctor can’t help you, it’s OK to find someone else.

What to Expect

FCAS is a lifelong condition, but drugs like biologics can help you feel better. Researchers continue to study how the disease works. There may be better treatments in the future.

If you’d like to join a study, check for clinical trials at ClinicalTrials.gov. You may also want to add your name and info to the United States Immunodeficiency Network (USIDNET) registry. Your unique experience can help the medical community understand a little more about FCAS. Visit Usidnet.org for more information.

Getting Support

There aren’t very many people with FCAS, but you aren’t alone. You can connect with others who understand your experience. That includes people with other kinds of autoinflammatory diseases.

If you’re not sure where to start, ask your doctor or social worker. They may know of a condition-specific or general support group you can join. Websites like Autoinflammatory Alliance or RareConnect can also point you in the right direction.

WebMD Medical Reference

Sources

SOURCES:

Medline Plus: “Familial cold autoinflammatory syndrome.”

British Journal of Nursing: “Recognising and understanding cryopyrin-associated periodic syndrome in adults.”

National Organization for Rare Disorders: “Familial Cold Autoinflammatory Syndrome.”

Genetic and Rare Diseases Information Center: “Familial cold autoinflammatory syndrome,” “Contact GARD.”

Autoinflammatory Alliance: “Familial Cold Autoinflammatory Syndrome (FCAS),” “Current Treatments for CAPS,” “Connect-Internet Links.”

Journal of Allergy and Clinical Immunology: “Familial Cold Autoinflammatory Syndrome.”

Cedars Sinai: “AA Amyloidosis.”

Revista Brasileira de Reumatologia: “Guidelines for the management and treatment of periodic fever syndromes: Cryopyrin-associated periodic syndromes (cryopyrinopathies – CAPS).” 

Rare Connect: “Connecting rare disease patients globally.”

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