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Erythromelalgia Causes and Treatment

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Last Updated on September 12, 2023

Erythromelalgia is a rare disorder characterized by burning pain, warmth, and redness of the hands, feet, arms and legs.

The condition was described by Silas Weir Mitchell in 1872. Another scientist from Germany, Gerhardt also described the same disease. The disease had also been known by the names of their discoverers as Mitchell disease or Gerhardt’s disease.

The condition gets its name derived from three Greek words:

erythros (red)+ melos (limb)+ algos (pain).

The mean age of onset is about 50 to 60 years.

Erythromelalgia is also called acromelalgia,  red neuralgia, or erythermalgia.

It occurs in intermittent episodes in most of the individuals. The onset is often gradual and  it may remain mild for many years.

However, varied presentation is known too and it could be acute onset and become severe within months or weeks.

The specific cause is not known though it is thought to result from disturbances in muscles functioning of the blood vessels [vasomotor abnormalities].

Types of Erythromelalgia

Primary

The severity of the disorder is variable within the family members suggesting autosomal dominant inheritance.

The primary form could be classified according to the age of onset

  • Early – when it appears in the first two decades of life [before 10 years of age]
  • Late  – When it appears after the second decade

The age of onset of the symptoms has been correlated with Na+ channel voltage activation.

It is the main type of disease in children under 10 years of age.

It presents as recurrent painful bilateral limbs and arterial hypertension. Feet soles and hand palms are affected primarily. It can occur as frequently as daily and could cause incapacitation or compromise of the upper and lower limbs.

Secondary

In this type,  there is an underlying cause.  It could be present in children as well as in adults.

A list of causes of secondary erythromelalgia is given below in the table.

  • Collagenopathies
    • Lupus erythematosus
    • Rheumatoid arthritis
    • Mixed connective tissue diseases
    • Sj0gren syndrome
    • Leukocytoclastic vasculitis
  • Hematological Diseases
    • Polycythemia Vera
    • Essential thrombocytosis
    • Leukaemia
    • Spherocytic anemia
    • Pernicious anemia
    • Cryoglobulinemia
    • Systemic mastocytosis
  • Drug Reactions
    • Iodinated contrasts agents
    • Calcium channel blockers (Nicardipine, Nifedipine, Felodipine)
    • Cyclosporine
    • Rosuvastatin
    • Bromocriptine
    • Topical Isopropanolol
    • Pergolide
    • Norephedrine
  • Vascular diseases
    • Venous insufficiency
    • Thromboembolism
    • Arterial hypertension
  • Neuropathies
  • Physical diseases
    • Trauma
    • Burn
  • Intoxications
    • Mushrooms
    • Metals (plumb, mercury, arsenic)
  • Neoplasias
    • Paraneoplastic syndrome
    • Colon and breast cancer
    • Malignant thymoma
    • Astrocytoma
    • Subcutaneous panniculitis-like T-cell lymphoma
  • Miscellaneous
    • Influenza and hepatitis vaccine
    • Lichen sclerosis
    • Genetic diseases
    • HIV infection
    • Diabetes mellitus
    • Venous insufficiency
    • Rheumatoid arthritis
    • Gout

Most reported cases of secondary erythromelalgia are due to myeloproliferative disorders.

Pathophysiology

The pathophysiology is not clear though the understanding is evolving with new approaches in molecular biology.

The following things/events are thought to be contributory

  • Abnormal hyperaggregability of platelets
  • Dysfunction of sympathetic fibers
  • Hypersensitivity of C-fibers that carry pain sensation
    • May involve  sodium channels
  • Arteriovenous shunting
    • imbalance of perfusion in the skin

Known Triggers

  • Following are the known triggers that can lead to erythromelalgia
    • Exposure to heat
    • Prolonged standing
    • Physical activity
    • Stress
    • Alcohol
    • Spicy food
    • Drugs that dilate vessels
    • Exposure to chronic vibration

Clinical Presentation of Erythromelalgia

Erythromelalgia - different images

Both primary and secondary types of erythromelalgia are characterized by episodes of

  • Redness
    • varies from mild to moderate
  • Warmth
  • Burning sensation of the limbs.
    • Intense pain
    • May preclude waking

Lower limbs are affected more commonly than upper limbs.

The soles of feet and toes are most commonly involved. Rarely, the limb is involved as high as knees.

Involvement is usually bilateral but can occur in a single limb as well.

The warm environment can exacerbate symptoms whereas cooling and elevating the extremity can relieve symptoms.

A typical episode lasts about 2-3 hours. The limb may appear normal in between the episodes or may become blue [cyanosis] in some cases.

Anxiety and mental issues may develop due to repeated episodes. Walking long distances or playing may become difficult.

In adults, a secondary cause should always be looked for and clinical history should be obtained accordingly.

Examination during the episode may reveal

  • Bounding pulse
  • Warm tender limb
  • Dusky or red discoloration of the limb
  • Cyanosis
  • Swelling
  • Numbness
  • Dry skin due to lack of sweating

Patients should be examined in detail for myeloproliferative disorders as they are highly associated.

Differential Diagnoses

Work Up

The diagnosis is clinical mainly. Investigations are done to look for secondary causes

  • Blood counts
    • May suggest or rule out myeloproliferative disorders
    • High platelet count and hematocrit is suggestive
  • X-rays – often normal
  • Bone Scans – Indicated in unilateral cases to look for pathology if present

Treatment of Erythromelalgia

There is no curative or definitive treatment. Supportive treatment aims to alleviate symptoms. These measures can be

  • Cooling the limb
  • Elevation of limb
  • Drugs
    • Lidocaine, Mexiletine, Prostacyclin
      • Provide limited benefits
    • Systemic steroids effective in subgroup of patients
  • Preventive Measures
    • Trigger avoidance – avoid warmth, smoking, stress
    • Non-impact exercise only

References

    • Davis MD, Sandroni P, Rooke TW, Low PA. Erythromelalgia: vasculopathy, neuropathy, or both? A prospective study of vascular and neurophysiologic studies in erythromelalgia. Arch Dermatol. 2003;139:1337–1343. [link]
    • Waxman SG, Dib-Hajj SD. Erythromelalgia: a hereditary pain syndrome enters the molecular era. Ann Neurol. 2005;57:785–788. [Link]
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