Hot feet: Erythromelalgia and related disorders

Erythromelalgia is an extraordinary pain syndrome first described by S. Wei r Mitchell in 1878. Episodes of severe burning pain in the distal limbs, ac companied by striking redness and warmth of the skin, are precipitated by h eat or activity and can be terminated only by cooling the affected part. Pr imary erythromelalgia is a sporadic or autosomal-dominant hereditary disord er whose symptoms begin in childhood. Secondary erythromelalgia occurs in a ssociation with thrombocythemia, collagen-vascular diseases, diabetes melli tus, peripheral neuropathy, and use of certain drugs. Aspirin is effective for patients with thrombocythemia, but most other cases are very resistant to treatment. The pathogenesis of erythromelalgia has remained puzzling, es pecially the peculiar switch-like manner in which symptoms are turned on by heat and turned off by cold. Following Ochoa's description of the ABC (ang ry backfiring C nociceptors) syndrome, it seems plausible to regard erythro melalgia as a problem of sensitized skin polymodal C-fiber receptors. C-fib er threshold to activation by heat would be lowered to 32 degreesC to 36 de greesC; activated C fibers would cause vasodilation via axon reflexes with redness, heat, and swelling. Cooling would bring the nociceptors below thre shold. Secondary erythromelalgia may result from humoral factors released f rom platelets or ischemic tissues or from C-fiber injury in some cases of n europathy, whereas primary erythromelalgia could be due to a mutation of th e capsaicin receptor.