Erythromelalgia
What is Erythromelalgia?
Erythromelalgia is a rare neurovascular condition characterized by episodes of intense burning pain, redness, warmth, and swelling in the extremities (usually bilaterally), most commonly the hands and feet. These symptoms are typically triggered or worsened by heat, exercise, or prolonged standing. There are two forms of disease: primary and secondary. Primary Erythromelalgia mostly occurs in the first decade of life and occurs due to gene mutations in certain sodium channels involved in nervous system signaling. Secondary Erythromelalgia usually manifests after age 40 and is a complication of other underlying disorders such as myeloproliferative disorders. This is a group of blood and bone marrow cancers that includes myelofibrosis, polycythemia vera, and essential thrombocytosis.
Synonyms
- Erythermalgia
- Mitchell's disease
- Weir-Mitchell disease
- Gerhardt’s disease
- Burning feet syndrome
Erythromelalgia is a rare neurovascular condition characterized by episodes of intense burning pain, redness, warmth, and swelling in the extremities (usually bilaterally), most commonly the hands and feet. These symptoms are typically triggered or worsened by heat, exercise, or prolonged standing. There are two forms of disease: primary and secondary. Primary Erythromelalgia mostly occurs in the first decade of life and occurs due to gene mutations in certain sodium channels involved in nervous system signaling. Secondary Erythromelalgia usually manifests after age 40 and is a complication of other underlying disorders such as myeloproliferative disorders. This is a group of blood and bone marrow cancers that includes myelofibrosis, polycythemia vera, and essential thrombocytosis.
Erythromelalgia has a combined prevalence of 0.36 to 2 per 100,000 persons. In patients with myeloproliferative disorders, the reported prevalence of erythromelalgia is 3-65%. The primary form is reported to have a male-to-female ratio of 1:2.5. Secondary erythromelalgia was reported to have a male-to-female ratio of 3:2.
| Name | Abbreviation |
|---|---|
| Erythermalgia | |
| Mitchell's disease | |
| Weir-Mitchell disease | |
| Gerhardt’s disease | |
| Burning feet syndrome |
Primary Erythromelalgia can be idiopathic (of unknown origin), but is usually caused by a gain-of-function mutation in the SCN9A, SCN10A, or SCN11A gene, which encodes the alpha subunit of the voltage-gated NaV 1.7, NaV 1.8, and NaV 1.9 sodium channel, respectively. These mutations are inherited in an autosomal dominant manner, meaning you only need to inherit one mutated copy from either parent (see RareShare Guide on Genetic Inheritance). The affected peripheral sodium channels are expressed within the dorsal root ganglion of the sympathetic ganglion neurons. These mutations lead to hyperexcitability of the nociceptive fibers (nerve endings that sense pain) causing them to fire at subthreshold stimuli. This, in turn, leads to a previously non painful stimulus eliciting a painful response.
Secondary Erythromelalgia typically occurs due to the presence of an underlying disorder. Myeloproliferative disorders including essential thrombocytosis, polycythemia vera, and myelofibrosis are some of the most common ones. Secondary Erythromelalgia associated with myeloproliferative disorders involves abnormal platelet aggregation and consumption. Other underlying causes include infectious agents (HIV, influenza, syphilis, and poxvirus), autoimmune diseases (systemic lupus erythematosus and rheumatoid arthritis), diabetes mellitus type 1 and 2, solid tumors (astrocytoma, colon, and breast cancer), medications (bromocriptine, nifedipine, verapamil, topical isopropanol, pergolide, simvastatin), gout, multiple sclerosis, hypertension, venous insufficiency, pernicious anemia, thrombotic thrombocytopenic purpura, mushroom intoxication, and mercury poisoning.
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Pain: mild itching sensation progressing to intense burning pain, often described as severe and debilitating.
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Redness: The affected areas become red or flushed.
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Heat and warmth: The skin feels hot to the touch.
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Mainly in hands and feet
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Rarely involves other areas such as ears, face, genitals
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Swelling: Mild swelling may occur in the affected areas.
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Symptoms are often episodic and can last from minutes to hours, typically worsening with:
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Heat exposure
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Exercise
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Stress or emotional triggers
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Tight fitting shoes/gloves
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Clinical evaluation- classic signs of redness, warmth, burning pain
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Blood tests- check for blood/autoimmune disorders or inflammatory markers.
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Genetic testing- search for SCN9A, SCN10A, or SCN11A gene mutations
There is no cure for Erythromelalgia. Treatment aims to manage symptoms and improve quality of life for patients.
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Avoid triggers such as heat, excess exercise, excess clothing, stress
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Cooling or elevating the affected extremity
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Topical lidocaine, capsaicin, amitriptyline/ketamine compounds
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Pregabalin or Gabapentin (neuropathic pain agents)
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Mexiletine, Carbamazepine (sodium channel blockers)
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Hydroxyurea in patients with underlying polycythemia vera
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Aspirin in patients with underlying myeloproliferative disorders
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Treat the underlying disorder in Secondary Erythromelalgia patients
Outlook for Erythromelalgia varies based on the form of disease. Primary Erythromelalgia has chronic symptoms that are managed with treatment and monitoring by a multidisciplinary team that can include physicians in dermatology, neurology, vascular medicine, and pain medicine. Over time, ulceration, necrosis, and gangrene can develop in response to repeated ice water immersion or other forms of chronic cooling of the extremities. Quality of life has been shown to be dramatically affected and can lead to chronic depression due to fear of precipitating episodes. Counseling is recommended for those seeking mental health support. In addition, due to the autosomal dominant pattern of inheritance, genetic counseling is beneficial in those planning to have children. Secondary Erythromelalgia has a more favorable outlook as addressing the underlying disorder will alleviate symptoms. Further, these patients, especially those with underlying myeloproliferative disorders, are more likely to respond to aspirin therapy.
Erythromelalgia | DermNet. (n.d.). Dermnetnz.org. https://dermnetnz.org/topics/erythromelalgia
Erythromelalgia - Heart and Blood Vessel Disorders. (n.d.). Merck Manuals Consumer Version. https://www.merckmanuals.com/home/heart-and-blood-vessel-disorders/peripheral-arterial-disease/erythromelalgia
Erythromelalgia Treatment & Management: Approach Considerations, Pharmacologic Therapy. (2022). EMedicine. https://emedicine.medscape.com/article/200071-treatment
Jha, S. K., Karna, B., & Goodman, M. B. (2022). Erythromelalgia. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557787/
| Title | Description | Date | Link |
|---|---|---|---|
| The Erythromelalgia Association |
The Erythromelalgia Association (TEA) is an international, all volunteer, nonprofit organization dedicated to supporting people with erythromelalgia, funding research into the treatments and causes of EM, and increasing awareness of this rare disease and its symptoms among healthcare providers and the general public. |
03/20/2017 |
Clinical Trials
CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access.
Enrolling is easy.
- Complete the screening form.
- Review the informed consent.
- Answer the permission and data sharing questions.
After these steps, the enrollment process is complete. All other questions are voluntary. However, these questions are important to patients and their families to create awareness as well as to researchers to study rare diseases. This is why we ask our participants to update their information annually or anytime changes to their information occur.
Researchers can contact CoRDS to determine if the registry contains participants with the rare disease they are researching. If the researcher determines there is a sufficient number of participants or data on the rare disease of interest within the registry, the researcher can apply for access. Upon approval from the CoRDS Scientific Advisory Board, CoRDS staff will reach out to participants on behalf of the researcher. It is then up to the participant to determine if they would like to join the study.
Visit sanfordresearch.org/CoRDS to enroll.
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"MY HANDS ARE ON FIIIREEEEEEE"
- Alicia Keys, maybe?
Kidding. It's me bitching about my hands/feet/face/ears throwing a fit like a toddler over a temperature difference of 2 degrees...
Having read what I wrote here while confined to my hospital room on day three of my current stint for very low hematocrit values (<2.5) (July 2021)
I realize how atrocious what I had...
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