erythromelalgia

Erythromelalgia is a rare neurovascular disorder characterized by episodic redness (erythema), warmth, and burning pain in the extremities, most commonly the feet and sometimes the hands. Attacks are typically intermittent and may last from minutes to hours. Symptoms are usually bilateral and worsened by heat or physical activity, with relief often obtained by cooling and elevation of the affected limbs.

There are primary (inherited) and secondary forms. Primary erythromelalgia commonly has a familial pattern and is often associated with gain-of-function mutations in the SCN9A gene, which encodes the voltage-gated sodium channel Nav1.7. Secondary erythromelalgia occurs with other medical conditions, notably myeloproliferative disorders such as polycythemia vera, essential thrombocythemia, or inflammatory or autoimmune diseases. In some cases, medications can also trigger erythromelalgia. The pathophysiology involves dysregulation of small-fiber nerves and cutaneous blood vessels, leading to enhanced nociceptor excitability and abnormal vasodilation.

Diagnosis is primarily clinical, based on the characteristic history and examination. It is important to exclude mimics such as cellulitis, deep vein thrombosis, venous insufficiency, complex regional pain syndrome, and Raynaud phenomenon. Laboratory testing may be guided by suspected secondary causes (for example, complete blood count and inflammatory markers to screen for myeloproliferative disease).

Treatment focuses on trigger avoidance and symptom control. Measures during attacks include cooling and limb elevation. Pharmacologic options vary and may include NSAIDs or acetaminophen for pain, aspirin when a myeloproliferative disorder is present, and agents that improve vascular tone or nerve excitability such as calcium channel blockers, gabapentinoids, duloxetine, and topical lidocaine or capsaicin. In inherited cases, sodium channel blockers like mexiletine can be helpful. Severe or refractory cases have been reported to respond to various immunomodulatory or intravenous therapies in some individuals, but evidence is limited.

Prognosis is variable; erythromelalgia can be chronic and disabling for some, while others experience periods of remission. Management is individualized and often requires a combination of lifestyle modifications and pharmacologic strategies.

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