What causes erythromelalgia?

What causes erythromelalgia?

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.

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.

What is erythromelalgia

Erythromelalgia (EM) is a rare condition characterised 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 disorders or myeloproliferative conditions (secondary EM). Episodes may be triggered by increased body temperature, alcohol, and eating spicy foods. About 16% 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.

What are the signs and symptoms?

Erythromelalgia can be diagnosed clinically based on predetermined criteria and include the following: (a) burning pain in the extremities (b) pain provoked by heat (c) pain alleviate by cooling and elevation of the affected area (d) redness of the affected skin (e) increased temperature of the skin.

Erythromelalgia can be diagnosed through a clinical presentation (exam) and medical history (patient questioned). Additional tests may include a skin biopsy and thermography to evaluate skin temperature. Blood tests or other studies may be done to rule out other conditions that can cause similar symptoms (differential diagnoses).

There is no known diagnostic test for erythromelalgia. No single specialism looks after EM and a variety of specialists (alone or in combination) may be involved in the diagnosis and treatment of this condition. These may include vascular specialists, hematologists, dermatologists, neurologists, rheumatologists, and pain specialists. The type of specialist that is appropriate may depend on the underlying cause when secondary erythromelalgia is present. Since erythromelalgia is a rare disease, many doctors are not familiar with the condition. EM Warriors offers resources and support for persons looking for information and advice about the diagnosis and treatment of the syndrome.

Looking for genetic testing?

  • 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

Organisations Providing General Support

What treatments are available for EM?

There appear to be several subtypes of erythromelalgia and different subtypes respond to different therapies. Treatment consists of a trying various approaches until the best therapy is found [1]. Patients respond quite variably to drug therapy and no single therapy has proved consistently effective. Spontaneous remissions have also been known to occur [2].

Drugs shown to be effective in relieving pain in some individuals include: aspirin, prostaglandins (misoprostol), serotonin-norepinephrine reuptake inhibitors (venlafaxine and sertraline) and selective serotonin reuptake inhibitors (SSRIs), anticonvulsants (gabapentin), sodium channel blockers, carbamazepine, tricyclic antidepressants (amitriptyline and imipramine), calcium antagonists (nifedipine and diltiazem), magnesium, sodium nitroprusside infusion, and cyclosporine. Other treatments include: cooling or elevating the extremity, topical treatment with capsaicin cream, and surgical sympathectomy (a procedure where the sympathetic nerve fibres are selectively cut). Avoidance of triggers (such as warmth, prolonged standing, etc.) may reduce the number or severity of flare ups. 

We have extensive information on treatments and resources available on our EM Warriors website. Just register for free.

Video tutorial on seeking help for rare conditions

GARD Video Tutorial

  • Finding Treatment Information - A video developed by GARD Information Specialists that explains how you can find information about treatment for a rare disease.

Management guidelines

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. Click on the link to view the article on this topic.
Look on our EM Warriors website for detailed information on clinical trials.

Living with erythromelalgia

Medical Resources

Many individuals want to know about healthcare professionals or researchers who have knowledge of their conditions. When a condition is rare, it can be difficult to find someone who has seen many cases. Please ask us for details of EM-aware medics known to us for your area/country.
The EM Warriors website is packed with resources, including an international database of EM-aware medical professionals. Register for free.

Useful links

Join the EM Warriors Patient Information and Support Network for extensive resources. Registration and resources are free.