Skip to main content
U.S. Department of Health & Human Services
National Institutes of Health
NCATS

COVID-19 is an emerging, rapidly evolving situation.

Get the latest public health information from CDC: https://www.coronavirus.gov (link is external)
Get the latest research information from NIH: https://covid19.nih.gov (link is external)

National Center for Advancing and Translational Sciences National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences
1-888-205-2311
Menu Search
1-888-205-2311
Menu
  • Home
  • Diseases expand submenu for Diseases
    • Browse A-Z
    • Find Diseases By Category expand submenu for Find Diseases By Category
      • Autoimmune / Autoinflammatory diseases
      • Bacterial infections
      • Behavioral and mental disorders
      • Blood Diseases
      • Chromosome Disorders
      • Congenital and Genetic Diseases
      • Connective tissue diseases
      • Digestive Diseases
      • Ear, Nose, and Throat Diseases
      • Endocrine Diseases
      • Environmental Diseases
      • Eye diseases
      • Female Reproductive Diseases
      • Fungal infections
      • Heart Diseases
      • Hereditary Cancer Syndromes
      • Immune System Diseases
      • Kidney and Urinary Diseases
      • Lung Diseases
      • Male Reproductive Diseases
      • Metabolic disorders
      • Mouth Diseases
      • Musculoskeletal Diseases
      • Myelodysplastic Syndromes
      • Nervous System Diseases
      • Newborn Screening
      • Nutritional diseases
      • Parasitic diseases
      • Rare Cancers
      • RDCRN
      • Skin Diseases
      • Viral infections
    • List of FDA Orphan Drugs
    • GARD Information Navigator
    • FAQs About Rare Diseases
  • Guides expand submenu for Guides
    • Patients, Families and Friends expand submenu for Patients, Families and Friends
      • How to Find a Disease Specialist
      • Tips for the Undiagnosed
      • Support for Patients and Families
      • Tips for Finding Financial Aid
      • Help with Travel Costs
      • How to Get Involved in Research
      • FAQs About Chromosome Disorders
      • Medical and Science Glossaries
    • Healthcare Professionals expand submenu for Healthcare Professionals
      • Caring for Your Patient with a Rare Disease
      • ICD Coding for Rare Diseases
      • FindZebra Diagnosis Assist Tool
    • Researchers expand submenu for Researchers
      • Finding Funding Opportunities
    • Teachers and Students expand submenu for Teachers and Students
      • Teaching Resources
  • News expand submenu for News
    • In The Spotlight
    • News Archive
    • Connect with GARD
    • Media Requests
  • About GARD expand submenu for About GARD
    • Contact GARD
    • About GARD
    • Videos
    • Brochures and Publications
  • En Español expand submenu for En Español
    • Enfermedades
    • Contacte GARD
    • Guías de Información expand submenu for Guías de Información
      • Preguntas Más Frecuentes Sobre Enfermedades Raras
      • Como Encontrar un Especialista en su Enfermedad
      • Consejos Para una Condición no Diagnosticada
      • Consejos Para Pacientes y Familias
      • Consejos Para Obtener Ayuda Financiera Para Una Enfermedad
      • Participe en Estudios de Investigación
      • Preguntas Más Frecuentes Sobre los Trastornos Cromosómicos
    • Sobre GARD
  • Home
© Positive Exposure
banner showing people with disabilities and/or their relatives
  1. Home
  2. Diseases
  3. Familial cold autoinflammatory syndrome
print
  • Table of Contents expand submenu for Table of Contents
    • Summary
    • Symptoms
    • Cause
    • Inheritance
    • Diagnosis
    • Treatment
    • Prognosis
    • Find a Specialist
    • Research
    • Organizations
    • Learn More
    • News & Events
    • GARD Answers
    • References
  • Browse A-Z
  • Find Diseases By Category expand submenu for Find Diseases By Category
    • Autoimmune / Autoinflammatory diseases
    • Bacterial infections
    • Behavioral and mental disorders
    • Blood Diseases
    • Chromosome Disorders
    • Congenital and Genetic Diseases
    • Connective tissue diseases
    • Digestive Diseases
    • Ear, Nose, and Throat Diseases
    • Endocrine Diseases
    • Environmental Diseases
    • Eye diseases
    • Female Reproductive Diseases
    • Fungal infections
    • Heart Diseases
    • Hereditary Cancer Syndromes
    • Immune System Diseases
    • Kidney and Urinary Diseases
    • Lung Diseases
    • Male Reproductive Diseases
    • Metabolic disorders
    • Mouth Diseases
    • Musculoskeletal Diseases
    • Myelodysplastic Syndromes
    • Nervous System Diseases
    • Newborn Screening
    • Nutritional diseases
    • Parasitic diseases
    • Rare Cancers
    • RDCRN
    • Skin Diseases
    • Viral infections
  • List of FDA Orphan Drugs
  • GARD Information Navigator
  • FAQs About Rare Diseases
You can help advance
rare disease research!
You can help advance rare disease research!
toolbox
Find out how with the NCATS Toolkit.

Familial cold autoinflammatory syndrome


Title


How can we make GARD better? We want to hear from you.
Provide Feedback

Other Names:
FCAS; Familial polymorphous cold eruption; Familial cold urticaria
Categories:
Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases; Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases; Skin Diseases See More

Summary Summary


Listen
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.[1][2]
Last updated: 10/30/2013

Symptoms Symptoms


Listen
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.[1]

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.[1]

Last updated: 11/1/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 27 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Arthritis
Joint inflammation
0001369
Dysesthesia 0012534
Erythema 0010783
Fatigue
Tired
Tiredness
[ more ]
0012378
Fever 0001945
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased
[ more ]
0000975
Myalgia
Muscle ache
Muscle pain
[ more ]
0003326
Pruritus
Itching
Itchy skin
Skin itching
[ more ]
0000989
Urticaria
Hives
0001025
30%-79% of people have these symptoms
Headache
Headaches
0002315
Nausea and vomiting 0002017
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain
[ more ]
0002027
Arthralgia
Joint pain
0002829
Conjunctivitis
Pink eye
0000509
Dehydration 0001944
Polydipsia
Extreme thirst
0001959
Sensorineural hearing impairment 0000407
1%-4% of people have these symptoms
Aphthous ulcer
Canker sore
0032154
Elevated C-reactive protein level 0011227
Renal amyloidosis 0001917
Uveitis 0000554
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Chills 0025143
Infantile onset
Onset in first year of life
Onset in infancy
[ more ]
0003593
Leukocytosis
Elevated white blood count
High white blood count
Increased blood leukocyte number
[ more ]
0001974
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever
[ more ]
0001954
Skin rash 0000988
Showing of 27 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 2/1/2021
Do you have updated information on this disease? We want to hear from you.

Cause Cause


Listen
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.[2]
Last updated: 11/1/2013

Inheritance Inheritance


Listen
Familial cold autoinflammatory syndrome is inherited in an autosomal dominant manner.[2] 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.[1]
Last updated: 11/1/2013

Diagnosis Diagnosis


Listen
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.[3] Diagnostic criteria have been proposed in order to distinguish FCAS from acquired cold urticaria and other periodic fever disorders. 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.[1][3] 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.[3]
Last updated: 11/1/2013

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment


Listen
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.[4] 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.[5][4] These agents reportedly have a significant beneficial effect on quality of life for individuals with FCAS.[4]
Last updated: 11/14/2013

FDA-Approved Treatments

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

  • Rilonacept (Brand name: Arcalyst) - Manufactured by Regeneron Pharmaceuticals, Inc.
    FDA-approved indication: February 2008, rilonacept (Arcalyst) was approved for treatment of cryopyrin-assisted periodic syndromes (CAPS).
    National Library of Medicine Drug Information Portal
  • Canakinumab (Brand name: Ilaris) - Manufactured by Novartis Pharmaceuticals Corporation
    FDA-approved indication: June 2009, canakinumab (Ilaris) was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS), in adults and children 4 years of age and older. In May 2013, it was also approved for the treatment of active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 through 16 years.
    National Library of Medicine Drug Information Portal

Prognosis Prognosis


Listen
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.[1][5]  
Last updated: 12/12/2016

Find a Specialist Find a Specialist


Listen

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Research Research


Listen

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Familial cold autoinflammatory syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • The National Institute of Allergy and Infectious Diseases (NIAID) study, Pathogenesis of Physical Induced Urticarial Syndromes is currently recruiting participants. The study aims to investigate mechanisms that may cause physical hives or urticaria and to reproduce urticaria through challenge testing (procedures to test the skin for a reaction to a stimulus), followed by mast cell studies, measurement of IL-1, genetic studies, and other molecular studies to lead to a better understanding of urticaria and to design safe and more effective treatments.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Familial cold autoinflammatory syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Familial cold autoinflammatory syndrome:
    United States Immunodeficiency Network (USIDENT) Registry
     

Organizations Organizations


Listen

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

  • FMF & AID Global Association
    Schüracherstrasse 25a
    8306 Brüttisellen
    Switzerland
    Telephone: +41 76 415 4010
    E-mail: info@fmfandaid.org
    Website: https://www.fmfandaid.org/

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

  • American Autoimmune Related Diseases Association (AARDA)
    19176 Hall Road, Suite 130
    Clinton Township, MI 48038
    Toll-free: 800-598-4668
    Telephone: 586-776-3900
    Fax: 586-776-3903
    E-mail: aarda@aarda.org
    Website: https://www.aarda.org/
Do you know of an organization? We want to hear from you.

Learn More Learn More


Listen

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The Cleveland Clinic provides an overview of the different types of periodic fever syndromes.
  • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
  • Genetics Home Reference (GHR) contains information on Familial cold autoinflammatory syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Familial cold autoinflammatory syndrome. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

  • Leigh D Church, Sinisa Savic, and Michael F McDermott; Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap), Biologics. 2008 December; 2(4): 733–742.

News & Events News & Events


Listen

News

  • Rare Disease Day at NIH 2021
    March 1, 2021

GARD Answers GARD Answers


Listen

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I have the syndrome, as did my mother, my second brother, and his oldest son. I had biopsies taken of the so-called hives and were told that they were neutrophiles from the blood. Is it common to have so many in one family to have this syndrome? Also, how often does it skip a generation? See answer


Have a question? Contact a GARD Information Specialist.

References References


  1. Simon A, Van Der Meer S, Drenth J. Familial autoinflammatory syndromes. In: Harris et al.,. Harris: Kelley's Textbook of Rheumatology, 7th ed. Philadelphia, PA: Saunders; 2005;
  2. Familial cold autoinflammatory syndrome. Genetics Home Reference. September 2008; http://ghr.nlm.nih.gov/condition/familial-cold-autoinflammatory-syndrome. Accessed 10/28/2013.
  3. Hoffman HM. Familial Cold Autoinflammatory Syndrome. Orphanet Encyclopedia. February 2005; https://www.orpha.net/data/patho/GB/uk-FCAS.pdf.
  4. Delwyn Dyall-Smith. Familial cold autoinflammatory syndrome. DermNet NZ. March 2011; http://www.dermnetnz.org/systemic/fcas.html. Accessed 10/30/2013.
  5. Marwan Shinawi. Hereditary Periodic Fever Syndromes. Medscape Reference. January 11, 2013; http://emedicine.medscape.com/article/952254-overview#aw2aab6b7. Accessed 12/12/2016.
  6. Familial cold autoinflammatory syndrome. Genetics Home Reference. September 2008; http://ghr.nlm.nih.gov/condition=familialcoldautoinflammatorysyndrome.
Do you know of a review article? We want to hear from you.
You can help advance
rare disease research!
You can help advance rare disease research!
toolbox
Find out how with the NCATS Toolkit.

Share this content:

Share this content:

twitter-icon facebook-icon contact-icon link-icons

Copy Link

Link copied to your clipboard.

printer-icon

You May Be Interested In

How to Find a Disease Specialist

How to Find a Disease Specialist

Tips for the Undiagnosed

Tips for the Undiagnosed

Support for Patients and Families

Support for Patients and Families

Tips for Finding Financial Aid

Tips for Finding Financial Aid

Help with Travel Costs

Help with Travel Costs

How to Get Involved in Research

How to Get Involved in Research

FAQs About Chromosome Disorders

FAQs About Chromosome Disorders

Medical and Science Glossaries

Medical and Science Glossaries

Caring for Your Patient with a Rare Disease

Caring for Your Patient with a Rare Disease

ICD Coding for Rare Diseases

ICD Coding for Rare Diseases

FindZebra Diagnosis Assist Tool

FindZebra Diagnosis Assist Tool

Finding Funding Opportunities

Finding Funding Opportunities

Teaching Resources

Teaching Resources

placeholder for the horizontal scroll slider Back to top
GARD Home NCATS Home Site Map Browse Glossary A-Z Privacy Notice Disclaimer Accessibility FOIA OIG

If you have problems viewing PDF files, download the latest version of Adobe Reader

For language access assistance, contact the NCATS Public Information Officer

Genetic and Rare Diseases Information Center (GARD) - PO Box 8126, Gaithersburg, MD 20898-8126 - Toll-free: 1-888-205-2311

contact gard Office of Rare Disease Research Facebook Page Office of Rare Disease Research on Twitter
Listen