Erythromelalgia · What Is It, Causes, Signs, Symptoms, and More

Erythromelalgia (EM) is a rare disorder characterized by intermittent, intense burning pain, warmth  and discoloration of the extremities, more commonly on the feet than the hands.  

The pain from erythromelalgia can last from minutes to days and is often brought on by exposure to heat or warm water and exercise. Erythromelalgia can be categorized into a primary and secondary type. Primary EM is inherited or sporadic, whereas secondary EM is associated with an underlying condition such as autoimmune, vascular, or nervous system disorders.  

The exact cause of erythromelalgia is unknown. It’s classified as a functional peripheral arterial disease where periodic dilation of the small arteries of the skin causes burning pain and erythema. 

Primary erythromelalgia can be sporadic (i.e., arises from a spontaneous mutation) or inherited (i.e., passed down from a parent to their offspring) due to an autosomal dominant mutation in the SCN9A gene that codes for voltage-gated sodium channels. 

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, whereas secondary form develops in adults.  

Secondary erythromelalgia results from an underlying condition, such as vascular disorders (e.g., essential thrombocytosis, chronic myelogenous leukemia, polycythemia vera, myelofibrosis); neurological conditions (e.g., peripheral neuropathy); or an autoimmune disease (e.g., multiple sclerosis, systemic lupus erythematosus or rheumatoid arthritis).  

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, burning pain, and  erythema in the feet and/or hands. In approximately 90% of individuals, erythromelalgia affects the feet (e.g., toes, soles of the feet, dorsum of the feet, or entire foot). Approximately 25% of individuals are affected in the fingers, dorsal hands, or whole hands.  

Symptoms are usually symmetrical; with asymmetrical presentation more common in secondary EM.  

The affected skin may look  erythematous and mottled and is typically warm or hot to the touch. The pain can range from mild to severe, potentially affecting mobility and one's quality of life. The sensation may be described as itching, tingling, pins and needles or burning. The pain is often intermittent, lasting a few minutes to hours once triggered. Other symptoms of erythromelalgia may include swelling of the affected parts of the body, sweating in the affected area, and skin discoloration.  

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

 It can also be helpful for individuals to take photographs of the affected areas during an episode to show their clinician as the symptoms of EM can be transient. Skin biopsies are typically non-specific to the diagnosis of erythromelalgia. However, they can help rule out other suspected conditions (e.g., Raynaud phenomenon, cellulitis). Additionally, there are no serologic tests that can help confirm the diagnosis at this time. 

The treatment of erythromelalgia includes prevention, such as avoiding strenuous exercise and excessive warming (i.e., submersion in warm water, wearing socks and gloves).  

During outbreaks, individuals can cool the affected extremities using fans, cold water, cooling socks or gloves, and ice packs, however, these should not be used in excess in case of tissue damage.   

Medications that have been used to treat EM include topical pain-relieving creams, gels, sprays, or patches. Examples include amitriptyline, lidocaine, capsaicin, and menthol topical preparations. The oral antiarrhythmic medication, mexiletine, is considered first-line in treatment. Other options include antidepressants (e.g., venlafaxine) and antiepileptics (e.g., gabapentin, carbamazepine).  

Treatment of secondary EM often involves treating the underlying condition, for example, using aspirin for those with thrombocytosis. If an inherited form of EM is present, genetic counseling may be considered. Other treatment modalities that may improve quality of life include rehabilitation programs targeted towards those with chronic pain, and counseling for those with extreme fears of precipitating pain episodes.    

There is currently no cure for erythromelalgia. However, interventions can improve quality of life and reduce symptoms.