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Disease Profile


Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset

All ages





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Primary erythermalgia; Mitchell disease (formerly); Primary erythromelalgia


Congenital and Genetic Diseases; Nervous System Diseases; Skin Diseases


Erythromelalgia (EM) is a rare condition characterized by episodes of burning pain, warmth, swelling and redness in parts of the body, particularly the hands and feet. This condition may occur spontaneously (primary EM) or secondary to neurological diseases, autoimmune diseases, or myeloproliferative disorders (secondary EM). Episodes may be triggered by increased body temperature, alcohol, and eating spicy foods. About 15% of cases are caused by mutations in the SCN9A gene and are inherited in an autosomal dominant manner. Other cases may be caused by unidentified genes or by non-genetic factors. Treatment depends on the underlying cause and may include topical and/or oral medications. In some cases, the condition goes away without treatment.[1][2]


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.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Peripheral neuropathy
30%-79% of people have these symptoms
Itchy skin
Skin itching

[ more ]

5%-29% of people have these symptoms
Abnormal autonomic nervous system physiology
Abnormal thrombocyte morphology
Platelet abnormalities
Abnormally low body temperature
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

Inflammation of blood vessel
Percent of people who have these symptoms is not available through HPO
Abnormality of the musculature
Muscular abnormality
Abnormality of the nervous system
Neurologic abnormalities
Neurological abnormality

[ more ]

Autosomal dominant inheritance
Blurred vision
Watery stool
Excessive sweating
Increased sweating
Profuse sweating
Sweating profusely
Sweating, increased

[ more ]

Jaw pain
Juvenile onset
Signs and symptoms begin before 15 years of age
Keratoconjunctivitis sicca
Dry eyes
Muscle ache
Muscle pain

[ more ]

Missed heart beat
Skipped heart beat

[ more ]

Dry mouth
Dry mouth syndrome
Reduced salivation

[ more ]



About 15% of cases of erythromelalgia are caused by mutations in the SCN9A gene. The SCN9A gene gives instructions for making part of a sodium channel which carries sodium into cells and helps them make and transmit electrical signals. These sodium channels are found in nerve cells that transmit pain signals to the spine and brain. Mutations that cause erythromelalgia cause increased transmission of pain signals, leading to the signs and symptoms of the condition. In some of these cases, an affected individual inherits the mutation from an affected parent. In other cases, a new mutation occurs for the first time in an individual with no history of the condition in the family.[2]

In the remainder of cases, the exact underlying cause is not currently known. Evidence suggests that it results from abnormalities in the normal narrowing and widening of certain blood vessels, leading to abnormalities in blood flow to the hands and feet. There may be a variety of non-genetic causes, or mutations in other genes that have not yet been identified.[3]


There is no specific diagnostic test for most cases of erythromelalgia (EM), so making a diagnosis usually relies on symptoms, a clinical exam, and the medical history.[4][5]

Testing that may be done to support a suspected diagnosis or rule out other medical disorders includes:[5][6]

  • a complete blood count (CBC) with differential to search for evidence of a myeloproliferative disorder
  • imaging studies such as X-ray of the hands and feet, which typically show no specific findings
  • thermography, which may reveal elevated skin temperatures in affected areas (but this is not necessary for the diagnosis)
  • biopsy which may reveal characteristic findings in people with primary erythromelalgia

SCN9A-related inherited EM can be confirmed with genetic testing of the SCN9A gene.[7]

The first step to diagnosing EM is seeing your primary care doctor, who can test for some of the common causes of EM or its symptoms, and refer you to a specialist to confirm a suspected diagnosis. There is not a specific type of doctor that always diagnoses and treats EM. A variety of specialists (alone or in combination) may be involved in the diagnosis and treatment. These may include dermatologists, neurologists, vascular specialists, hematologists, rheumatologists, or other types of physicians. The type of specialist that is appropriate after diagnosis may depend on the underlying cause when secondary erythromelalgia is present.[6] 

The Erythromelalgia Association (TEA) has a Patient Guide which includes helpful information about diagnosing EM. This guide can be used as an educational and awareness tool for patients, family and friends, and health care providers. They also have a Doctor Directory with contact information for doctors and researchers who have been suggested by TEA members over time. Please note that neither GARD nor TEA recommends or endorses any doctors or researchers and that contact information may have changed since it was originally provided.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.


    No single therapy works well for every person with erythromelalgia (EM). Often it is necessary to try different treatments or combinations of treatments until the best therapy is found.[5][7][8] In some cases EM may go away on its own.[1][5] For both primary and secondary EM, avoiding triggers of symptoms is helpful in preventing flares. Treating secondary EM involves treating the underlying disease, which can be helpful in controlling symptoms in some people. However, results are inconsistent.[9]

    Treatments for EM that have been used with varying results include creams applied to the skin (topical creams), various oral medications, infusions of certain medications or anesthetics, supplements, and mind-body therapies (such as cognitive behavioral therapy). More invasive approaches to treatment when other therapies have failed have included epidural anesthesia, nerve blocks, and surgical procedures.[5][6][8][9]

    The resources below provide more detailed information about the many treatment options for EM, including evidence supporting the effectiveness of the treatments (which in most cases is very limited).


    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

      Learn more

      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

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • MedlinePlus Genetics contains information on Erythromelalgia. This website is maintained by the National Library of Medicine.
      • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
      • 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

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • 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 Erythromelalgia. Click on the link to view a sample search on this topic.


          1. de Menezes S. Erythromelalgia. DermNet NZ. May 2016; https://www.dermnetnz.org/topics/erythromelalgia/.
          2. Erythromelalgia. MedlinePlus Genetics. February 2016; https://ghr.nlm.nih.gov/condition/erythromelalgia.
          3. Mark Denis P. Davis. Erythromelalgia. NORD. 2015; https://rarediseases.org/rare-diseases/erythromelalgia/.
          4. FAQ: How is EM diagnosed?. The Erythromelalgia Association. https://erythromelalgia.org/resources/faqs/. Accessed 9/20/2018.
          5. Saliba AN. Erythromelalgia. MedScape Reference. September 17, 2018; https://emedicine.medscape.com/article/200071-overview.
          6. A Patient’s Guide to Erythromelalgia. The Erythromelalgia Association. https://erythromelalgia.org/resources/patients-guide/. Accessed 9/20/2018.
          7. Hisma FM, Dib-Hajj SD, Waxman SG. SCN9A-Related Inherited Erythromelalgia. Gene Reviews. August 15, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1163/.
          8. Davis MDP. Erythromelalgia. UpToDate. May 31, 2017; https://www.uptodate.com/contents/erythromelalgia.
          9. Mann N, King T, Murphy R. Review of primary and secondary erythromelalgia. Clin Exp Dermatol. July, 2019; 44(5):477-482. https://www.ncbi.nlm.nih.gov/pubmed/30609105.

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