Erythromelalgia

Erythromelalgia can be sporadic (i.e., arises from a spontaneous mutation) or inherited (i.e., passed down from a parent to their offspring). The more common form of erythromelalgia is sporadic and seen primarily in adults. Sporadic erythromelalgia sometimes results from an underlying condition, such as myeloproliferative disorders (e.g., essential thrombocytosis, chronic myelogenous leukemia, polycythemia vera, myelofibrosis); nerve damage (e.g., peripheral neuropathy); or an autoimmune disease (e.g., multiple sclerosis, systemic lupus erythematosus or rheumatoid arthritis). The cause of sporadic erythromelalgia is idiopathic, as the mechanism is unknown. It is classified as a functional peripheral arterial disease since periodic dilation of the small arteries of the skin causes burning pain and erythema. 

The inherited form of erythromelalgia, which is relatively rare, is caused by mutations in the SCN9A gene, which codes for a voltage-gated sodium channel. Mutations to these channels decrease the threshold for impulses in pain-sensing neurons and increase the sensation of extreme, burning pain. Inherited erythromelalgia typically presents in children and adolescents and is generally passed to an offspring in an autosomal dominant inheritance pattern, with only one mutated allele necessary to cause the disease.

Specific factors that trigger episodes of erythromelalgia include increased body temperature, which may be caused by exercise, warm weather, or wearing socks and shoes. Other triggers include feelings of stress, drinking alcohol, eating spicy foods, and dehydration. 

The signs and symptoms of erythromelalgia include heat, pain, and redness in the affected skin area. In approximately 90 percent of individuals, erythromelalgia affects the feet (e.g., toes, soles of the feet, dorsum of the feet, or entire foot). Approximately 25 percent of individuals are affected in the fingers, dorsal hands, or whole hands. Symptoms are usually symmetrical but may be unilateral or more prominent on one side of the body. Erythromelalgia is more common in those assigned females at birth and adults. 

Erythromelalgia is diagnosed by physical exam and thorough patient history, which allows recognizing characteristic signs and symptoms. The clinician making the diagnosis typically looks for the presence of five key criteria, including pain in the extremities that is burning in nature; the pain is aggravated by heat; the pain is relieved by cooling; the affected skin is erythematous, and the skin increases in temperature when affected.

Erythromelalgia is first treated by preventing flare-ups, such as stopping exercise or decreasing the room temperature. During outbreaks, individuals can cool the affected extremities using fans, cold water, or ice. Additionally, one can also use battery-powered cooling socks or gloves. Clinicians may prescribe topical pain-relieving medications in the form of creams, gels, sprays, or patches. Capsaicin creams or patches have proven to be effective in reducing pain due to decreasing sensitivity of the heat receptors in the skin. A local anesthetic, such as lidocaine, may also be prescribed. Certain oral medications can also be beneficial in treating the pain, including aspirin; anti-epilepsy medicines (e.g., gabapentin, carbamazepine); vasoactive medications (e.g., beta-blockers, calcium antagonists, sodium nitroprusside); low doses of antidepressants (e.g., duloxetine, venlafaxine, amitriptyline or nortriptyline), and systemic glucocorticoids. 

Individuals with refractory and debilitating pain may benefit from rehabilitation programs that use a multidisciplinary and behavioral therapy approach to assist those with chronic pain achieve a better quality of life. Counseling may help those with extreme fears of precipitating episodes of erythromelalgia and have thus altered their lifestyles negatively in fear of triggering attacks. Provided pain is adequately controlled, patients should be encouraged to engage in their everyday lifestyle as much as possible. There is currently no cure for erythromelalgia. However, interventions can improve quality of life and reduce symptoms.