erythromelalgia

Erythromelalgia can be primary (idiopathic, often due to gain-of-function mutations in SCN9A encoding the Nav1.7 sodium channel, causing neuronal hyperexcitability) or secondary, most notably to myeloproliferative neoplasms like polycythemia vera and essential thrombocythemia, where it is thought to result from platelet aggregation and microvascular thrombosis induced by elevated platelet counts and activation. Secondary erythromelalgia is classically relieved dramatically by aspirin due to its antiplatelet effect, which is a key clinical pearl distinguishing it from other causes of extremity pain. Symptoms are typically bilateral and symmetric, involving the distal extremities, and are exacerbated by warmth, exercise, or dependency of the limb, while elevation and cooling (e.g., ice water) provide relief—though severe cases may lead to tissue damage from excessive cooling attempts. Other secondary causes include autoimmune diseases (e.g., SLE), diabetic neuropathy, certain drug exposures (e.g., calcium channel blockers, bromocriptine), and paraneoplastic syndromes. Diagnosis is clinical, supported by skin temperature measurements and response to aspirin in suspected myeloproliferative cases; CBC and JAK2 V617F mutation testing should be considered to evaluate for underlying polycythemia vera or essential thrombocythemia. Management includes treating the underlying cause (e.g., cytoreductive therapy for myeloproliferative disease), aspirin, and avoidance of triggers; sodium channel blockers (e.g., mexiletine) may be used in primary/genetic forms refractory to other treatments.