Overview

Erythromelalgia is a rare condition that affects the small blood vessels and nerves in the extremities. It is characterised by repeated episodes of burning pain, visible redness and increased warmth in the body.¹ During a flare-up, the affected areas may feel so hot that patients describe them as “on fire”. These episodes can last from minutes to hours and are often triggered by heat, exercise, stress, or simply wearing socks and shoes. Cooling the skin by using fans, cool water, or elevation usually provides temporary relief, which is an important clue to the diagnosis.

Delayed recognition of erythromelalgia is partly due to its symptoms resembling those of other conditions that cause red, painful, or warm limbs.

This overlap can make diagnosis challenging and sometimes leads to delays in receiving the correct therapy, allowing symptoms to persist or worsen.¹

Epidemiology

Erythromelalgia is officially classified as a rare disorder, with a prevalence of 0.36–1.3 cases per 100,000 people.²

Age of onset

• Typical onset: Most cases are diagnosed between the ages of 40 and 60, but this may reflect when symptoms become severe enough to prompt investigation
• Childhood and teenage onset: Primary (inherited) erythromelalgia can start much earlier. Parents may notice their child complaining of burning or “hot” feet after running or playing, especially in warm weather

Gender distribution

Females assigned at birth are affected slightly more often than males assigned at birth, with some studies reporting a female-to-male ratio of up to 2:1.³

Primary vs secondary erythromelalgia

There are two types of erythromelalgia, primary (occurring on its own) and secondary (linked to another condition). Recognising whether erythromelalgia is primary or secondary is important for treatment:

Primary erythromelalgia

• It can be sporadic (no family history) or familial, caused by genetic mutations, most commonly in the SCN9A sodium channel gene
• Symptoms often start in childhood or adolescence and are triggered by heat and activity
• Pain episodes can last for hours and may be severe enough to limit normal activities²

Secondary erythromelalgia

• Occurs as a result of another disorder
• Most commonly associated with myeloproliferative disorders (such as essential thrombocythaemia, polycythaemia vera, or myelofibrosis)
• It can also be linked to peripheral neuropathies such as diabetic neuropathy, autoimmune diseases or medication reactions
• Treating the underlying disease, for example, lowering platelet counts in myeloproliferative disease, can lead to significant improvement or even resolution of symptoms²

Pathophysiology

The exact mechanism of erythromelalgia is complex and involves both nerve dysfunction and abnormal blood vessel behaviour.

• Small fibre neuropathy, which is damage or dysfunction of the tiny nerve fibres that control pain and temperature sensation, can cause exaggerated pain responses
• Microvascular dysregulation, which is the small blood vessels in the skin, may over-dilate, causing increased blood flow, redness and heat
• Genetic links like Mutations in the SCN9A gene (encoding the sodium channel NaV1.7), which can cause inherited erythromelalgia by making pain nerves overactive¹
• Triggers such as warm environments, exercise, spicy food, alcohol, stress, and even wearing socks or shoes can precipitate attacks
• Relief, such as cooling the affected area, resting or elevating the limb, can often bring temporary relief, which is an important diagnostic clue

Clinical presentation of erythromelalgia

The hallmark features include:⁴

• Redness (erythema): bright red or dusky discolouration of the feet, hands or sometimes the ears and face
• Heat: the skin feels warm or even hot to the touch during episodes
• Pain: burning, throbbing or searing pain that can range from mild discomfort to disabling agony
• Symmetry: usually affects both feet or both hands in a fairly symmetrical pattern
• Timing: episodes last from minutes to hours, often worse in the evening
• Triggers: heat, activity or stress make symptoms flare
• Relief: cooling measures such as fans, cold water, and air conditioning can all help to provide relief

Why is it confused with other conditions

Erythromelalgia causes red, painful, warm limbs; hence, it can be mistaken for other conditions:

• Raynaud’s phenomenon, which causes colour changes in response to cold
• Complex regional pain syndrome (CRPS) is a chronic pain disorder with colour change and swelling, often triggered by injury or surgery
• Cellulitis: it is a bacterial skin infection that presents with redness and swelling

Distinguishing between these conditions is crucial because their treatments are very different.

Differentiating features

Raynaud’s phenomenon

• Typical colour sequence: white (pale) to blue (cyanosis) to red (reactive flushing)
• Triggers: cold exposure or emotional stress
• Symptoms: numbness, tingling, or discomfort, but usually not intense burning pain
• Relief: warming the hands or feet⁵

Erythromelalgia vs Raynaud’s

• Erythromelalgia is triggered by heat, not cold
• Pain is burning and intense
• Redness is persistent during attacks and associated with warmth

Complex regional pain syndrome (CRPS)

• Symptoms: Severe pain out of proportion to the injury, swelling, colour changes (red, purple, or blue), temperature changes (hot or cold phases), hair/nail growth changes
• Distribution: Usually affects one limb (asymmetrical)⁶

Erythromelalgia vs CRPS

• Erythromelalgia tends to be symmetrical
• CRPS often has a clear history of injury or surgery
• CRPS can present with skin thinning, sweating changes and muscle weakness, which are features less common in erythromelalgia
• Cooling provides dramatic relief in erythromelalgia but may worsen pain in CRPS

Cellulitis

• Symptoms: redness, warmth, swelling, tenderness, fever and feeling generally unwell
• Investigations: raised white blood cell count, elevated C-reactive protein (CRP)

Erythromelalgia vs cellulitis

• Cellulitis is almost always unilateral (one side)
• Systemic symptoms (fever, chills) are common
• Does not improve with cooling; requires antibiotics⁷

Management of erythromelalgia

Lifestyle and self-care

• Avoid overheating: use fans, keep rooms cool
• Wear open footwear or breathable socks
• Elevate limbs during attacks
• Caution: Avoid prolonged ice water immersion to prevent skin damage

Medications

• Aspirin: very effective in erythromelalgia linked to platelet disorders⁸
• Sodium channel blockers: such as mexiletine or carbamazepine, reduce nerve overactivity⁹
• Gabapentin or duloxetine: for neuropathic pain control¹⁰
• Topical therapies: lidocaine patches or capsaicin cream in some cases^11,12

Treating secondary causes

• Manage underlying myeloproliferative disease (hydroxyurea for thrombocytosis)
• Address peripheral neuropathy or autoimmune disease

Complications and prognosis

Complications

• Skin damage from excessive cooling (ulcers, frostbite)¹
• Sleep disturbance and depression from chronic pain
• Mobility limitations during severe flares

Prognosis

• It can vary. Some patients achieve good control with medication and lifestyle changes
• Others may have a chronic, relapsing course requiring long-term pain management

Research and future directions

• Biologic therapies: targeting nerve sodium channels and inflammatory pathways¹³
• Neuromodulation: spinal cord stimulation and sympathetic nerve blocks are being studied for refractory cases¹⁴

FAQs

Can erythromelalgia and Raynaud’s happen together?

Yes. Some patients experience both, with cold-triggered Raynaud’s attacks and heat-triggered erythromelalgia flares.

How can I tell cellulitis apart from erythromelalgia?

Cellulitis is usually one-sided, accompanied by fever and responds to antibiotics. Erythromelalgia is typically bilateral, recurrent and improves with cooling.

Is erythromelalgia curable?

There is no cure. 

Summary

Erythromelalgia is a rare condition that causes burning pain, redness and heat in the extremities, usually triggered by warmth and relieved by cooling. It can easily be mistaken for Raynaud’s phenomenon, CRPS, or cellulitis, but several clues help differentiate it:

• Heat vs cold triggers – erythromelalgia flares with heat, Raynaud’s with cold
• Symmetry – erythromelalgia is usually bilateral, cellulitis and CRPS are often unilateral
• Relief with cooling – dramatic in erythromelalgia, not in cellulitis or CRPS
• Lack of systemic illness – erythromelalgia does not cause fever or raised infection markers

Correct diagnosis enables timely treatment, including lifestyle changes, pain management, and, when appropriate, disease-specific therapies such as aspirin for myeloproliferative disorders or sodium channel blockers for primary disease.