What is Primary erythromelalgia

Erythromelalgia is a rare disease of unknown cause, characterized by redness of the skin, increased temperature, and pain in the extremities (feet and hands), which usually occurs in response to warmth and moderate exercise. The prefix “erythro-” denotes redness, “mel-” is a combining form meaning limb or limbs, and the suffix “-algia” indicates pain.
Erythromelalgia may be:

  • Secondary to (occurring as a result of) other diseases (most commonly myeloproliferative disorders where the blood-producing cells in the bone marrow develop and reproduce abnormally)
  • Primary, i.e. arising spontaneously without any underlying disease causing it.
    It is the primary form of erythromelalgia that is being described here.

The specific underlying cause of erythromelalgia remains unknown. However, the condition is thought to result from vasomotor abnormalities or dysfunction in the normal narrowing (constriction) and widening (dilation) of the diameter (caliber) of certain blood vessels, leading to abnormalities of blood flow to the extremities.

Statistics on Primary erythromelalgia

Primary erythromelalgia is a rare disorder.
Patients are normally young (before 25 years old) when the symtpoms start – the average age being 10 years.
It affects more females than males, with the male to female ratio being 1 to 2.5.

Risk Factors for Primary erythromelalgia

Primary erythromelalgia is a pain disoder that is passed on in families in an autosomal dominant manner.

  • In the autosomal dominant mode of inheritance, a single, abnormal gene on one of the autosomal chromosomes (one of the first 22 “non-sex” chromosomes) from either parent can cause the disease.
  • One of the parents will usually have the disease (since it is dominant) in this mode of inheritance.
  • Only one parent needs to have an abnormal gene in order for the child to inherit the disease.Changes in the gene that controls pain sensation have been identified. Previous studies have associated primary erythromelalgia with 2 mutations (specific permanent changes in the gene). Recently, a third mutation has been described.

    Progression of Primary erythromelalgia

    The average time between the start of symptoms and diagnosis is 5.6 years. This is due to delays by patients and doctors (absence of symptoms when patients present in between attacks, therefore resulting in difficulty in diagnosis).
    The intensity of the disease varies from invidual to individual. Even mild erythromelalgia can greatly affect normal functioning and quality of life. When the disease progresses to a severe stage, patients may become house bound because of the continually painful symptoms. Some patients have to move to a cooler climate, and have to avoid wearing socks even in winter.

    How is Primary erythromelalgia Diagnosed?

    The doctor may perform a blood test to rule out erythromelalgia occuring as a result of bone marrow disorders.

    Prognosis of Primary erythromelalgia

    The prognosis depends on the severity of the disease. Complete cure of the disease is generally not likely in primary erythromelalgia.
    The disease is less distressing for patients who benefit from aspirin as a treatment option.
    Death is rare unless associated with ulceration, resulting infection and tissue death of affected extremities.

    How is Primary erythromelalgia Treated?

    Treatment aims to relieve symptoms.

  • Local measures, such as cooling or elevating the limb affected, are helpful. However, patients have to be cautious with soaking the feet in cold water as it can cause tissue breakdown of the skin, infections, reactive flaring and severe ulcers.
  • A consistent and comfortable environment with air conditioning or a fan can help.
  • Avoidance of vigorous exercises may reduce attacks.
  • Many patients show good response to aspirin, which is usually the medical treatment of choice. Other non-steroidal anti-inflammatory drugs provide relief of a much shorter duration.
  • Surgical sympathectomy (surgical interruption of sympathetic nerve pathways) has been attempted, but the results are variable.Recent studies demonstrate that in primary erythromelalgia, there are abnormal changes in the gene that codes for a specific sodium channel (which is present in nerves and is responsible for pain transmission). Therefore it has been suggested that medications that target the affected channel may possibly be efficacious.

    Primary erythromelalgia References

    1. Davis MD, Sandroni P. Lidocaine patch for pain of erythromelalgia. Arch Dermatol 2002; 138: 17-9.
    2. Dib-Hajj SD, Rush AM, CUmmins TR, Hisama FM, Novella S, Tyrrell L et al. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 2005; 128(8): 1847-54.
    3. Kalgaard OM, Seem E, Kvernebo K. Erythromelalgia: A clinical study of 87 cases. J Intern Med 1997; 242(4): 191-7.
    4. Kuhnert SM, Phillips WJ, Davis MD. Lidocaine and mexiletine therapy for erythromelalgia. Arch Dermatol 1999; 135: 1447-9.
    5. Legroux-Crespel E, Sassolas B, Guillet G, Kupfer I, Dupre D, Misery L. Treatment of familial erythermalgia with the association of lidocaine and mexiletine. Ann Dermatol Venereol 2003; 130: 429-33.
    6. Nardino RJ. Erythromelalgia [online]. 2004 [cited 2005 August 27th]. Available from: URL: http://www.emedicine.com/med/topic730.htm
    7. The Erythromelalgia Association website [online]. 2005 [cited 2005 August 27th]. Available from: URL: http://www.erythromelalgia.org/
    8. Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet 2004; 41: 171-4.