Erythromelalgia (EM) is a rare condition that classically presents with intermittent symptoms of severe paroxysmal burning sensations, erythema, and warmth of the skin, usually involving the extremities (lower more often than upper). Feet are the most common area affected, followed by the hands. EM has also been reported to involve the face, ears, and genital area. Episodes often begin with pruritus that progresses to pain and can last from minutes to days. An erythromelalgic crisis is when changes extend proximally to involve the extremities. These crises tend to occur in the evening and are brought on by exercise, warm exposure, and dependency.

EM may be primary or secondary, with primary EM (PEM) further separated by some into a primary inherited form and an idiopathic group. Others consider only the inherited form as PEM. This primary inherited form is due to an autosomal dominant mutation in the SCN9A gene on chromosome 2q that encodes for Nav 1.7 (voltage-gated sodium channels present in small nociceptive neurons). In some cases, the mutation has occurred de novo.

By contrast, in secondary EM, there is an identifiable cause; it can be associated with a multitude of underlying conditions. These include myeloproliferative disorders with thrombocythemia in addition to vascular, connective tissue, neurological, and musculoskeletal conditions. In addition, drugs (such as bromocriptine, cyclosporin, simvastatin, iodinated contrast media, and thrombopoietin receptor agonists) are also known to trigger EM, as are poisonings and intoxication.

Poisoning from ingestion of the mushroom Paralepistopsis (formerly Clitocybe) acromelalga causes a self-limited form of EM. Onset is within 2-3 days of ingestion, and symptoms usually resolve in 1-2 weeks but may persist for months.

Incidence estimates have ranged from 0.3 to 1.3/100 000 for all forms of EM. These estimates are considered low due to underdiagnosis. Some studies suggest a female predominance of up to 2-3:1, and there does not appear to be a racial / ethnic predilection.