Erythromelalgia

Reviewed November 2012

What is erythromelalgia?

Erythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.

The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life. As individuals with erythromelalgia get older and the disease progresses, the hands and feet may be constantly red, and the affected areas can extend from the hands to the arms, shoulders, and face, and from the feet to the entire legs.

Erythromelalgia is often considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.

How common is erythromelalgia?

The prevalence of erythromelalgia is unknown.

What genes are related to erythromelalgia?

Mutations in the SCN9A gene can cause erythromelalgia. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.

The SCN9A gene mutations that cause erythromelalgia result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of sodium ions into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the signs and symptoms of erythromelalgia. It is unknown why the pain episodes associated with erythromelalgia mainly occur in the hands and feet.

An estimated 15 percent of cases of erythromelalgia are caused by mutations in the SCN9A gene. Other cases are thought to have a non-genetic cause or may be caused by mutations in one or more as-yet unidentified genes.

Related Gene(s)

Changes in this gene are associated with erythromelalgia.

SCN9A

How do people inherit erythromelalgia?

Some cases of erythromelalgia occur in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some of these instances, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of erythromelalgia?

These resources address the diagnosis or management of erythromelalgia and may include treatment providers.

Gene Review: SCN9A-Related Inherited Erythromelalgia (http://www.ncbi.nlm.nih.gov/books/NBK1163/)
Genetic Testing Registry: Primary erythromelalgia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0014805)

You might also find information on the diagnosis or management of erythromelalgia in Educational resources (http://ghr.nlm.nih.gov/condition/erythromelalgia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/erythromelalgia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about erythromelalgia?

You may find the following resources about erythromelalgia helpful. These materials are written for the general public.

MedlinePlus - Health information
- Health Topic: Pain (http://www.nlm.nih.gov/medlineplus/pain.html)
- Health Topic: Peripheral Nerve Disorders (http://www.nlm.nih.gov/medlineplus/peripheralnervedisorders.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/6377/resources/resources/1)
Additional NIH Resources - National Institutes of Health
- National Institute of Neurological Disorders and Stroke: Chronic Pain Information Page (http://www.ninds.nih.gov/disorders/chronic_pain/chronic_pain.htm)
- National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page (http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm)
Educational resources - Information pages
- Cleveland Clinic: Neuropathy (http://my.clevelandclinic.org/disorders/neuropathy_peripheral/hic-neuropathy.aspx)
- Johns Hopkins Medicine: Peripheral Neuropathy (http://www.hopkinsmedicine.org/healthlibrary/conditions/adult/nervous_system_disorders/peripheral_neuropathy_134,51/)
- Merck Manual for Patients and Caregivers: Nociceptive Pain (http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/pain/types_of_pain.html)
- Merck Manual Home Edition for Patients and Caregivers (http://www.merckmanuals.com/home/heart_and_blood_vessel_disorders/peripheral_arterial_disease/functional_peripheral_arterial_disease.html)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1956)
- Washington University, St. Louis: Neuromuscular Disease Center (http://neuromuscular.wustl.edu/sensory-pain.html)
Patient support - For patients and families
- American Chronic Pain Association (http://www.theacpa.org/default.aspx)
- National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/245/viewAbstract)
- The Neuropathy Association (http://www.neuropathy.org/site/PageServer)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1163/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Primary erythromelalgia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0014805)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22erythromelalgia%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((erythromelalgia%5BTIAB%5D)%20OR%20(erythermalgia%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/133020)

What other names do people use for erythromelalgia?

erythermalgia
familial erythromelalgia
primary erythromelalgia

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about erythromelalgia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding erythromelalgia?

autosomal ; autosomal dominant ; cell ; channel ; familial ; gene ; increased body temperature ; ions ; mutation ; nervous system ; neuropathy ; nociceptors ; peripheral ; peripheral nervous system ; peripheral neuropathy ; prevalence ; sodium ; sodium channel ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. From genes to pain: Na v 1.7 and human pain disorders. Trends Neurosci. 2007 Nov;30(11):555-63. Epub 2007 Oct 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17950472?dopt=Abstract)
Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. Sodium channels in normal and pathological pain. Annu Rev Neurosci. 2010;33:325-47. doi: 10.1146/annurev-neuro-060909-153234. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20367448?dopt=Abstract)
Drenth JP, te Morsche RH, Guillet G, Taieb A, Kirby RL, Jansen JB. SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. J Invest Dermatol. 2005 Jun;124(6):1333-8. (http://www.ncbi.nlm.nih.gov/pubmed/15955112?dopt=Abstract)
Drenth JP, Waxman SG. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J Clin Invest. 2007 Dec;117(12):3603-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18060017?dopt=Abstract)
Estacion M, Han C, Choi JS, Hoeijmakers JG, Lauria G, Drenth JP, Gerrits MM, Dib-Hajj SD, Faber CG, Merkies IS, Waxman SG. Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7. Mol Pain. 2011 Dec 2;7:92. doi: 10.1186/1744-8069-7-92. (http://www.ncbi.nlm.nih.gov/pubmed/22136189?dopt=Abstract)
Han C, Dib-Hajj SD, Lin Z, Li Y, Eastman EM, Tyrrell L, Cao X, Yang Y, Waxman SG. Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation. Brain. 2009 Jul;132(Pt 7):1711-22. doi: 10.1093/brain/awp078. Epub 2009 Apr 15. (http://www.ncbi.nlm.nih.gov/pubmed/19369487?dopt=Abstract)
Waxman SG, Dib-Hajj S. Erythermalgia: molecular basis for an inherited pain syndrome. Trends Mol Med. 2005 Dec;11(12):555-62. Epub 2005 Nov 8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16278094?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.



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