What is Erythromelalgia?

Erythromelalgia is a rare condition that leads to redness, warmth, and a burning sensation, often affecting the arms and legs. It’s most frequently found in the lower part of the body, namely the feet, but can also occur in the upper part such as the hands. People with this condition usually experience symptoms after physical activities and find relief when they cool down the affected parts. While erythromelalgia usually affects both sides of the body, it can occasionally affect just one side. In some very rare cases, symptoms can occur only in the face, which can often lead to misdiagnosis. Other names for erythromelalgia include burning feet syndrome, erythermalgia, Gerhardt disease, and Mitchell disease.

The name erythromelalgia comes from three Greek words: erythros, meaning “red,” melos, meaning “limb,” and algos, meaning “pain.” This condition was first identified in 1878 by Silas Weir Mitchell, who initially called it “Mitchell Disease.” In 1938, Smith and Allen introduced the term erythermalgia to highlight the warmth that people with the condition often feel. Then in 1990, two researchers from the Netherlands, Drenth and Michiels, proposed the name erythromelalgia.

The condition can be classified based on how it responds to aspirin, a common pain-reliever. This has been divided into the following three groups:

(a) Erythromelalgia in thrombocythemia: This type is often associated with a surplus of blood platelets and responds well to aspirin. It often occurs alongside increased platelet disorders and overproduction of red blood cells.

(b) Primary erythermalgia: This refers to a condition that occurs on its own without any identified cause or inherited disorder. It is also referred to as aspirin-resistant erythermalgia of unknown origin.

(c) Secondary erythermalgia: This type does not respond to aspirin and occurs in conjunction with different other health conditions.

What Causes Erythromelalgia?

Erythromelalgia is a condition often linked with blood disorders such as essential thrombocytosis and polycythemia vera.

Primary erythromelalgia could occur without a known reason (idiopathic) or could be inherited. The inherited type is due to a problematic change in one of the genes — SCN9A, SCN10A, or SCN11A. These genes control parts of the channel that allows sodium to enter nerve cells, specifically in a part of the nervous system called the dorsal root ganglion. The problematic change leads to overactivity in pain-sensing nerve fibers, causing them to respond to stimuli that shouldn’t be painful.

Secondary erythromelalgia is linked with a variety of medical conditions. Most commonly, it coincides with blood disorders, including essential thrombocytosis, polycythemia vera, and myelofibrosis (all conditions that involve an overproduction of blood cells). Other causes can range from infectious diseases such as HIV, flu, syphilis and poxvirus, autoimmune diseases like lupus and rheumatoid arthritis, both type 1 and type 2 diabetes, certain cancers (e.g. brain, colon and breast cancer), gout, multiple sclerosis, high blood pressure, vein problems, a type of anemia called pernicious anemia, a rare blood disorder (thrombotic thrombocytopenic purpura), to intoxication from mushrooms and mercury poisoning. Certain medications like bromocriptine, nifedipine, verapamil, topical isopropanol, pergolide, and simvastatin can also trigger secondary erythromelalgia.

People with secondary erythromelalgia usually have milder symptoms which often get better once the underlying disease is treated.

Risk Factors and Frequency for Erythromelalgia

Primary erythromelalgia usually shows up in the first two decades of a person’s life, while the secondary form tends to start around the age of 49. The number of people affected by primary erythromelalgia each year is somewhat unpredictable, ranging from 0.25 to 2 out of every 100,000 people. Some studies suggest that both men and women are equally likely to experience this condition, while some others suggest it might be a bit more common in women. Cases have been reported in many different parts of the world, in people from diverse backgrounds, including those of Chinese, American, French, Dutch, and Norwegian nationality. This condition is incredibly rare in kids, but if it does occur it can lead to severe health issues and even loss of life.

Primary erythromelalgia usually appears in the first 20 years of life.
Secondary erythromelalgia typically begins around the age of 49.
The incidence rate for primary erythromelalgia varies, affecting 0.25 to 2 people out of every 100,000 each year.
It’s unclear whether one gender is more likely to get erythromelalgia than the other.
People of all nationalities, including Chinese, American, French, Dutch, and Norwegian, can have erythromelalgia.
The disease is extremely rare in children, but very serious if it occurs.

Signs and Symptoms of Erythromelalgia

Erythromelalgia is a rare condition where parts of the body, especially the feet, become red, warm, and experience a burning pain. This typically occurs in episodes, and the classic symptoms are redness, warmth, and burning pain. The feet are most commonly affected, with about 90% of patients experiencing it here. Hands and fingers may also be affected in roughly 25% of cases, while a very small percentage (2-3%) may experience symptoms in areas such as the head, genitals, or neck region.

Triggered by exercise, warm climates, standing, or tight-fitting shoes
Symptoms may last from minutes to days
Relief often comes from cooling or elevating the affected area
Episodes often occur at night due to increased temperature
Initially presents as an itching sensation, later progresses to severe burning pain
Affected areas are usually normal between episodes

Some patients may also experience symptoms similar to Raynaud’s phenomenon in between episodes. It is also seen that after the start of symptoms, some patients may develop blood disorders like essential thrombocytosis and polycythemia vera. These disorders may cause additional symptoms like general fatigue, weight loss, itchiness, headaches, blurry vision, and discomfort from an enlarged spleen.

When diagnosing this condition, doctors may ask about your history of fever, recent injuries, joint pain, skin and mouth sores, as well as check your blood pressure and any medications you’re taking. This helps to rule out other potential causes like cellulitis, systemic lupus erythematosus (SLE), and rheumatoid arthritis.

During a physical examination, doctors may note redness, warmth, or mild swelling in the affected area. They may also observe signs like persistent blue discoloration (acrocyanosis), normal joint movement, and a normal or bounding pulse. Doctors may also check for ulcers in chronic cases, and for signs of underlying conditions like an enlarged spleen (splenomegaly) or swollen lymph nodes (lymphadenopathy), or characteristic skin symptoms in cases of systemic lupus erythematosus.

Testing for Erythromelalgia

When doctors suspect erythromelalgia, a condition that causes episodes of redness, warmth, and burning pain usually in the hands or feet, they look for classic signs and symptoms. These symptoms are often triggered by heat or exercise and can be relieved by cooling. Since this condition comes and goes, it can be challenging to diagnose. Your doctor may ask you to take photos of the affected area during an episode to help with the diagnosis.

There are two types of erythromelalgia: primary and secondary.

To diagnose primary erythromelalgia, doctors will look for the typical symptoms and may also test for specific genetic mutations in a gene called SCN9A.

On the other hand, secondary erythromelalgia is diagnosed by ruling out other diseases that could be causing the symptoms. This could involve a complete blood count to check for certain disorders like myeloproliferative disorder (a condition that can raise the number of red blood cells or platelets in your blood) and cellulitis (an infection that causes inflammation and can raise the number of white blood cells). Doctors might also test for other diseases like lupus, HIV, and rheumatoid arthritis, or conditions like gout. If you’ve recently had an injury or surgery, a certain type of bone scan could be recommended.

A skin biopsy, which involves taking a small sample of your skin for testing, is generally not done because the results are often inconclusive. But if it’s performed, doctors may see a slight decrease in the amount of nerves in the skin and around your blood vessels.

Tests like electromyography and nerve conduction velocity, which study the electrical activity in your muscles and how fast your nerves send signals, might be abnormal in patients with erythromelalgia. These tests could also support the use of certain medications for neuropathy (nerve pain) in erythromelalgia patients.

Treatment Options for Erythromelalgia

Managing erythromelalgia, a painful disorder characterized by redness and swelling in extremities, can be difficult and requires a team-based approach. Treatment is aimed at educating the patient about the condition, encouraging lifestyle changes, and advising them to avoid triggers that might worsen their symptoms. The main goal is not a cure, but helping manage symptoms and improve the patient’s quality of life. If erythromelalgia is a secondary condition – meaning it’s caused by an underlying disorder – treating the primary disorder could also improve or even eliminate the symptoms of erythromelalgia.

Treatment for both primary and secondary erythromelalgia frequently involves avoiding known triggers, which often include heat, exercise, and standing for long periods. Some helpful techniques could include staying cool, avoiding too much physical activity, keeping the limbs elevated, and not wearing excessive clothing. Some patients also find it soothing to immerse the affected area in cool water or use portable fans. However, repeated and excessive cooling using ice water could damage the skin, making it vulnerable to infection.

Topical (applied to the skin) treatments might provide some relief from the pain associated with erythromelalgia. Such treatments may include lidocaine patches, compounded (custom-mixed by the pharmacist) amitriptyline-ketamine cream, and capsaicin cream. There’s also a moisturizing cream containing a medicine named midodrine, which could help reduce erythromelalgia-related redness. These topical treatments are typically applied for two to four weeks to determine if they’re helping.

For erythromelalgia related to blood disorders (thrombocytopenia or myeloproliferative disorder), Aspirin is often the preferred drug. Other similar drugs, like Anagrelide, may also be used. Importantly, any underlying blood disorder should be diagnosed and treated as it can directly impact the erythromelalgia. In some cases, chemotherapy or bloodletting may help reduce symptoms associated with these disorders.

Primary erythromelalgia, which isn’t caused by an underlying condition, can be stubborn to treat. Certain medicines such as lidocaine, mexiletine, and carbamazepine that affect the body’s sodium channels have shown promise. Other drugs that may help manage primary and secondary erythromelalgia include gabapentin, pregabalin, venlafaxine, amitriptyline, iloprost, misoprostol, calcium-channel blockers, and beta-blockers.

For cases resistant to treatment, other therapies may be considered. These could include epidural infusions (delivery of drugs into the spinal canal), transcranial magnetic stimulation (a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain), subcutaneous injection of botulinum toxin A, and surgical interruption of part of the sympathetic nerve trunk, a group of nerves in the chest (thoracic) or lower back (lumbar).

Additionally, studies suggest that pain rehabilitation programs and counseling could help improve a patient’s physical health and emotional wellbeing.

When managing erythromelalgia, it’s typically advised to start with avoiding triggers, then try Aspirin for a month. If that doesn’t work, topical treatments could be used for up to a month, followed by systemic medicines like gabapentin, pregabalin, or venlafaxine for up to four months. If these measures don’t provide sufficient relief, consider trying other systemic drugs and pain rehabilitation programs. It’s important to note that each next step is usually tried only after the previous one doesn’t work. Any underlying blood disorder should be treated at the same time, if possible.

Erythromelalgia, a condition causing episodes of burning pain and redness in parts of the body, can often get confused with several other conditions. However, it can be distinguished with the help of typical symptoms linked with these other illnesses. Here’s a list of those conditions:

Polyneuropathy (a condition that affects the nerves in your feet and hands)
Acrocyanosis (a disorder that limits the supply of oxygen-rich blood to the hands and feet)
Peripheral arterial disease (narrowed arteries reduce blood flow to your limbs)
Lipodermatosclerosis (thickening skin on the lower legs)
Raynaud’s phenomenon (fingers and toes turn blue or white in response to cold temperatures)
Cellulitis (a skin infection)
Gout (a form of arthritis characterized by severe pain)
Fabry disease (a genetic disorder)
Vasculitis (inflammation of the blood vessels)
Frostbite (skin damage due to freezing)

These conditions have their distinct features which can help tell them apart from erythromelalgia. For instance, Fabry disease is associated with angiokeratomas and corneal opacities, cellulitis typically manifests after a fever or trauma and responds well to antibiotics, gout symptoms emerge with high uric acid levels, and polyneuropathy shows abnormal results in nerve conduction tests. Raynaud’s phenomenon occurs after exposure to cold and gets better when warmed.

Besides these, erythromelalgia can be confused with complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy. CRPS shares many symptoms with erythromelalgia. However, CRPS predominantly affects one side of the body and can manifest more towards the center of a limb. It often follows an injury or surgery. On the other hand, erythromelalgia is likely to show on both sides of the body and occur more at the ends of the limbs. Its episodes can often be triggered by heat and are alleviated with cooling methods.

Sometimes, when erythromelalgia symptoms appear only on the face, which is very rare, it can be misdiagnosed and treated incorrectly as rosacea, seborrheic dermatitis, or contact dermatitis.

What to expect with Erythromelalgia

Patients suffering from primary and secondary erythromelalgia, a rare condition characterized by episodes of burning pain and redness in parts of the body, can be challenging to treat. A type of erythromelalgia, secondary to conditions known as polycythemia vera and essential thrombocythemia, has been seen to respond favorably to aspirin therapy. Currently, there are differing views on the severity and outlook of primary versus secondary erythromelalgia.

Some studies suggest that patients who respond well to aspirin have less severity in their disease, while those with platelet-related disease experience more complications. Platelets are a type of blood cells that help with blood clotting.

Moreover, in response to long-term immersion in ice water or other consistent cooling practices, patients might develop ulceration, necrosis (the death of body tissue), or gangrene (a condition where body tissue dies due to a lack of blood flow or a bacterial infection). This can significantly hinder the quality of life and could lead to chronic depression because of the fear of episode triggers.

Possible Complications When Diagnosed with Erythromelalgia

Patients with this illness often try to ease their burning pain by cooling the affected body part. Some go to extremes such as sitting in front of the fridge for relief. However, many of these methods can result in a condition known as maceration, where the affected tissue softens and deteriorates, leading to skin damage.

Infections are the most frequently reported problem and are usually due to blistering, the formation of ulcers, cyanosis (turning blue), and gangrene (tissue death). If left untreated for a long time, this could potentially result in the need for amputation. In a few cases, patients have also experienced malnutrition and hypothermia.

Side Effects:

Maceration of the affected tissue
Damage to skin barrier
Infection due to blistering
Ulceration, cyanosis, and gangrene
Possible amputation in chronic untreated cases
Malnutrition and hypothermia in some patients

Preventing Erythromelalgia

People suffering from the two types of a condition called erythromelalgia, whether it’s primary (meaning it occurs on its own) or secondary (meaning it’s caused by another disease), need to have a clear understanding of the causes of the disease. A comprehensive check-up is needed to rule out certain diseases of the blood cells (myeloproliferative disorders) which are known to cause secondary erythromelalgia. This is an important step in both managing erythromelalgia and quickly diagnosing any underlying conditions.

Regular check-ups are necessary to find out how effective the treatment is. It’s also recommended that patients have a complete blood count with differential done yearly. This is a type of blood test which counts the different types of cells in your blood. This test helps doctors keep an eye on the development of any myeloproliferative disorder.