Erythromelalgia is characterised by a painful burning sensation, redness and warmth in the feet and hands. Erythromelalgia is considered very rare, as it affects only 2 in 100,000 people, with a slightly higher incidence in people assigned female at birth.¹ A normal, active life is possible with Erythromelalgia, but exposure to heat can be devastating to the patient, impeding daily activities such as walking under the sun or wearing shoes. In this article, we will take a closer look at what erythromelalgia is,  a historical overview, types and symptoms, diagnosis, and the current treatments.

Historical overview of erythromelalgia 

Erythromelalgia has been recognised for over a century, and its nomenclature and comprehension have evolved over this time:

• 1872: American neurologist, Dr Silas Weir Mitchell, provided the first description of the condition, which came to be known as Mitchell’s disease for many years
• 1892: German paediatrician, Dr Carl Jakob Gerhardt, reported cases triggered by excessive heat in children, subsequently referred to as Gerhardt’s disease
• 1964: Dr Babb studied 51 patients and observed that many of them also had myeloproliferative diseases-disorders of the blood. That helped link Erythromelalgia to other underlying diseases
• 1990: Drenth and Michiels, Dutch doctors, suggested the term Erythromelalgia when the disease occurred in association with another disease or drug, and Erythermalgia when the cause was unknown
• 2004: A significant milestone was reached when Erythromelalgia was discovered to be the first human disease with a mutation in a sodium channel gene. This finding described the manner in which dysfunctional nerve signalling could result in the burning sensation, connecting it to chronic nerve pain disorders²

Symptoms of erythromelalgia

The main symptoms of Erythromelalgia are:

• Severe burning pain that can feel like a scorching of the skin
• Swelling in the affected areas
• Redness or flushed skin of the extremities
• Increased warmth in the skin

The symptoms are often episodic, occurring in episodes that can last from a few minutes to sometimes hours. Triggers can be as simple as exercise or even a hot shower. Relief can be found in various cooling techniques, for example: putting feet on a cold floor, using a fan, or dipping in cool water. It must be noted that prolonged exposure to lower temperatures can also be harmful to the skin.³

Types of erythromelalgia

• Primary Erythromelalgia: This type is linked to genetic changes and appears without any other linked diseases. Symptoms typically arise in childhood or early adulthood.
• Secondary Erythromelalgia: Develops later in life and is related to other co-occurring health conditions such as blood disorders, autoimmune diseases, or nerve damage.

Why does it happen? understanding the science

• Primary Erythromelalgia is associated with a change in a gene called SCN9A, which produces a protein in the nerves called Nav1.7. This protein assists nerves in transmitting pain messages. With the mutation, the nerves send pain signals too quickly, resulting in a burning sensation even when no harm has occurred
• Secondary Erythromelalgia occurs in association with other diseases. Some blood-related disorders, such as Thrombocythemia, cause the blood to become thicker or create circulation problems that can trigger the existing symptoms. Autoimmune and metabolic diseases, or even certain drugs, may trigger similar symptoms of Erythromelalgia
• When researchers have examined a patient's tissue samples under a microscope, they find evidence of irritation of the small blood vessels, abnormal nerve endings and hyperactivity of the immune system, signalling that both blood flow and nerves are involved⁴

How is erythromelalgia diagnosed?

One of the most challenging aspects of living with Erythromelalgia is that there is no single test that can provide a diagnosis.. Diagnosis is mainly based on:

• History: Experiences of burning pain, redness of the skin, and warmth that worsens with heat and that improves with cooling
• Physical examination: Doctors observe the skin during flare-ups for redness, warmth and swelling
• Exclusion of other causes: The doctor might perform tests to rule out other conditions, such as infections or arthritis
• Blood tests: These may be useful in identifying secondary causes, such as blood disorders

Since these symptoms can be intermittent, patients don’t always display visible symptoms during appointments, further complicating diagnosis. It can take years for people to get the right answer.⁶

What are the treatment options?

There is no universal cure for Erythromelalgia currently. What’s helpful for one person won’t be the same for another. A multidisciplinary treatment plan with the involvement of dermatologists, neurologists, pain specialists, and occasionally haematologists is required.

Lifestyle and self-care

• Avoiding known triggers, such as heat, tight shoes or intense exercise
• Seeking relief with fans, cool liquids or air conditioning, but steering away from extreme cold or extended cold water soaking to prevent skin damage
• Putting on comfortable, light clothing and wearing open footwear

Medications

• Topical creams and gels: Lidocaine patches, capsaicin cream, or special combinations (for example, amitriptyline with ketamine) might numb the nerve pain
• Pain relief drugs: Some pain medications, such as gabapentin, pregabalin, carbamazepine or certain antidepressants, can calm overactive nerves
• Drugs affecting blood flow: Medications such as aspirin (if due to a blood condition), misoprostol, or prostacyclin
• Sodium channel blockers: Drugs such as mexiletine (Mexitil) or similar medications can block the overactivity of the nerves in primary erythromelalgia

Procedures

• Nerve-targeted injections can bring temporary relief from the nerve pain
• Sympathectomy: Surgical or chemical interruption of specific nerve pathways, reserved for very severe cases⁷

How does it affect daily life?

For patients with erythromelalgia, the constant threat of painful flare-ups can shape how a person plans their life. When there are no flare-ups, this condition is invisible. That often makes it worse, as family, friends or teachers may not realise how much pain the affected person is in. Many patients experience:

• Mobility problems, such as difficulty walking or standing for a long time
• Sleep disturbances, as patients may be unable to sleep at night due to flares
• Emotional stress, such as worrying when and where the next flare-up occurs
• Problems at work or school resulting in social isolation

What's in the future?

Erythromelalgia is not fully understood by scientists and doctors. With further progress in research, patients may have better and safer treatment options. Current research is focused on:

• Genetics: Studying the sodium channel gene mutations further and examining how they lead to the overactivity of nerves
• Improved treatments: Creating drugs that target the flawed sodium channels, which could provide greater pain relief
• Registries and studies: Gathering patient data around the world to identify patterns, enhance diagnosis and find the most effective treatments
• Skin and nerve studies: Analysing biopsies of skin to detect damage to small nerve fibres and changes in blood vessels that might lead to newer treatment targets⁸

Summary

Erythromelalgia is a rare but severely debilitating syndrome that is characterised by intense pain, redness, and heat in the extremities. It may be primary, associated with genetic factors, or secondary, related to other medical conditions. Diagnosis is based on the identification of the symptoms and the exclusion of other causes, therefore challenging to reach. There’s no cure yet, but symptoms can be managed through lifestyle changes, medications and procedures to improve quality of life. Continuing investigation of the disease offers promise for more directed therapies in the future.