What is erythromelalgia?

What is Erythromelalgia?

Erythromelalgia is a rare neurovascular disorder characterized by episodic burning pain associated with redness, warmth, and increased temperature of the extremities, most commonly affecting the feet and hands. 1

Clinical Characteristics

The condition presents with a classic triad of symptoms that occur in episodes:

• Intense burning pain primarily in the feet, less frequently in the hands 2
• Erythema (redness) of the affected skin during symptomatic episodes 1, 2
• Warmth and increased temperature of the extremities 1, 3
• Swelling may be present during symptoms, though not universally reported 1

Triggering Factors and Relief

Episodes are characteristically triggered by specific circumstances:

• Physical activity and exercise commonly precipitate symptoms 1, 4
• Exposure to warm temperatures or increased ambient heat 1, 3
• Pain is relieved by cooling the affected areas, which patients often accomplish through ice water immersion or fans 1

Classification: Primary vs Secondary

Primary (Inherited) Erythromelalgia

• Accounts for approximately 5% of cases with identifiable genetic mutations in the SCN9A gene 4
• These gain-of-function variants cause Nav1.7 sodium channels to open more easily and stay open longer, resulting in prolonged neuronal activation and disproportionate pain 4
• Some familial cases occur without detectable SCN9A variants, suggesting other genes are involved 4, 2
• Strongly associated with small fiber neuropathy, with marked abnormalities on thermoregulatory sweat testing in approximately 90% of patients 4

Secondary Erythromelalgia

• Myeloproliferative disorders (essential thrombocythemia, polycythemia vera) are present in approximately 5% of cases 4, 5
• Pathogenesis involves platelet-mediated endothelial cell injury resulting in inflammation and transient thrombotic occlusion 4
• Autoimmune conditions such as systemic lupus erythematosus can trigger secondary forms 4
• Certain medications including calcium channel blockers and ergot derivatives may precipitate the condition 4, 6

Clinical Impact and Complications

This is not merely a benign condition—it significantly affects patient outcomes:

• Lower quality of life compared to the general population 1
• Increased morbidity and mortality 1
• Increased risk for suicide due to severe, unrelenting pain 1
• Patients may engage in extreme cooling behaviors that lead to tissue damage, ulcerations, immersion foot, or trench foot 1

Diagnostic Challenges

Because symptoms are intermittent and extremities may appear normal during consultation, the diagnosis is frequently missed. 1 Patients often self-diagnose or seek help across multiple specialties including primary care, dermatology, vascular medicine, neurology, and pain medicine before receiving the correct diagnosis 1.

Pathophysiological Mechanisms

The underlying mechanisms involve:

• Endogenous temperature control dysfunction, likely through vasodilation of thermoregulatory arteriovenous anastomoses 1
• Small fiber neuropathy is present in approximately 90% of patients on thermoregulatory sweat testing 4
• Large fiber neuropathy is found on electromyography and nerve conduction studies in almost 50% of patients 4
• A bidirectional relationship between neuropathy and erythromelalgia may exist 4