Erythromelalgia

Overview

Erythromelalgia is a rare neurovascular pain syndrome characterized by recurrent episodes of burning pain, erythema, and increased temperature, most commonly affecting the extremities (feet > hands). These episodes are typically triggered or exacerbated by heat, exercise, or emotional stress, and are relieved by cooling. The clinical diagnosis is based on the presence of these intermittent symptoms, which can be severe and disabling, often leading to significant impairment in quality of life.

Erythromelalgia can be classified as primary (often due to gain-of-function mutations in the SCN9A gene encoding the NaV1.7 sodium channel) or secondary (associated with underlying conditions such as myeloproliferative disorders, autoimmune diseases, or neuropathies). Pathophysiologically, it involves dysregulation of distal vasculature and/or small fiber neuropathy, with evidence of increased blood flow, vascular ectasia, and autonomic denervation in affected tissues.

Management is challenging and individualized. First-line strategies include trigger avoidance and symptomatic relief with cooling. Pharmacologic options may include sodium channel blockers (e.g., mexiletine, carbamazepine, lidocaine) for primary erythromelalgia, and aspirin for cases associated with thrombocythemia. Other agents such as gabapentinoids, antidepressants, and prostaglandin analogs have been used with variable success. Severe, refractory cases may require multidisciplinary pain management approaches.

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What is Erythromelalgia?

• From Greek:
  • “erythros” = red
  • “melos” = limb
  • “algia” = pain
• A neurovascular pain disorder involving small nerve fibers and dysregulated blood flow in the extremities

Clinical Features

Symptom	Description
Pain	Severe, burning, stinging or throbbing pain
Redness (erythema)	Bright red discoloration of affected areas
Warmth	Increased skin temperature
Swelling	May be present during flares
Triggers	Heat, exercise, tight shoes, or even emotional stress
Relief	Cooling the limbs (e.g. cold water or air)

History of Medicine

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Pathophysiology

• Often linked to dysfunction in small sensory and autonomic nerves and vascular dysregulation
• May involve mutations in SCN9A, a sodium channel gene associated with pain signaling
• Leads to inappropriate vasodilation, resulting in warm, congested extremities

Classification

• Primary
  • Idiopathic or genetic (e.g., SCN9A mutation)
• Secondary
  • Associated with other conditions:
    • Myeloproliferative disorders (especially essential thrombocythemia)
    • Autoimmune diseases
    • Diabetes
    • Toxins
    • Medications

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Diagnosis

• Clinical diagnosis based on history and appearance during attacks
• Rule out secondary causes with blood tests (e.g., CBC for platelet count)
• Skin biopsy may show small fiber neuropathy

Treatment

• Lifestyle:
  • Cooling, trigger avoidance, elevation
• Medications:
  • Aspirin (esp. in myeloproliferative cases)
  • Gabapentin
  • Pregabalin
  • Duloxetine
  • Tricyclics
• Topicals:
  • Lidocaine
  • Capsaicin (with caution)
• Advanced:
  • Nerve blocks
  • Spinal cord stimulation

Comparison with Raynaud’s

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Summary

Erythromelalgia is red, hot, and painful, and often relieved by cold. Always rule out secondary causes, especially myeloproliferative neoplasms like essential thrombocythemia, where aspirin can dramatically help.