Hot feet: erythromelalgia and related disorders

Erythromelalgia is an extraordinary pain syndrome first described by S. Weir Mitchell in 1878. Episodes of severe burning pain in the distal limbs, accompanied by striking redness and warmth of the skin, are precipitated by heat or activity and can be terminated only by cooling the affected part. Primary erythromelalgia is a sporadic or autosomal-dominant hereditary disorder whose symptoms begin in childhood. Secondary erythromelalgia occurs in association with thrombocythemia, collagen-vascular diseases, diabetes mellitus, 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, especially 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 (angry backfiring C nociceptors) syndrome, it seems plausible to regard erythromelalgia as a problem of sensitized skin polymodal C-fiber receptors. C-fiber threshold to activation by heat would be lowered to 32 degrees C to 36 degrees C; activated C fibers would cause vasodilation via axon reflexes with redness, heat, and swelling. Cooling would bring the nociceptors below threshold. Secondary erythromelalgia may result from humoral factors released from platelets or ischemic tissues or from C-fiber injury in some cases of neuropathy, whereas primary erythromelalgia could be due to a mutation of the capsaicin receptor.