Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A case of inherited erythromelalgia


Background A 15-year-old boy presented with recurrent episodes of erythema and burning pain in the distal extremities, which he had experienced since early childhood. The episodes were triggered by heat or exertion. His medical history revealed an extensive six-generation family history of similar symptoms.

Investigations Neurological examination, MRI brain scan, electromyography, skin biopsy, laboratory blood testing, and DNA analysis.

Diagnosis Juvenile onset primary erythromelalgia.

Management Genetic counseling, and symptomatic management of neuropathic pain.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Figure 1: Photograph of the patient's feet showing erythema
Figure 2: The patient's family pedigree
Figure 3: Schematic diagram of a sodium channel showing the locations of the known mutations in Nav 1.7 in erythromelalgia
Figure 4: The effect of the F1449V mutation on the firing properties of dorsal root ganglion neurons


  1. Finley WH et al. (1992) Autosomal dominant erythromelalgia. Am J Med Genet 42: 310–315

    Article  CAS  Google Scholar 

  2. Dib-Hajj SD et al. (2005) Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 128: 1847–1854

    Article  CAS  Google Scholar 

  3. Kalgaard OM et al. (1997) Erythromelalgia: a clinical study of 87 cases. J Intern Med 242: 191–197

    Article  CAS  Google Scholar 

  4. Davis MD et al. (2003) Erythromelalgia: vasculopathy, neuropathy, or both? A prospective study of vascular and neurophysiologic studies in erythromelalgia. Arch Dermatol 139: 1337–1343

    Article  Google Scholar 

  5. Mork C et al. (2000) Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia. J Invest Dermatol 114: 643–646

    Article  CAS  Google Scholar 

  6. Drenth JP et al. (2001) The primary erythermalgia-susceptibility gene is located on chromosome 2q31–32. Am J Hum Genet 68: 1277–1282

    Article  CAS  Google Scholar 

  7. Yang Y et al. (2004) Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet 41: 171–174

    Article  CAS  Google Scholar 

  8. Cummins TR et al. (2004) Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J Neurosci 24: 8232–8236

    Article  CAS  Google Scholar 

  9. Waxman SG and Dib-Hajj S (2005) Erythermalgia: molecular basis for an inherited pain syndrome. Trends Mol Med 11: 555–562

    Article  CAS  Google Scholar 

  10. Rush AM et al. (2006) A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc Natl Acad Sci USA 103: 8245–8250

    Article  CAS  Google Scholar 

  11. Black JA et al. (2004) Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 108: 237–247

    Article  CAS  Google Scholar 

  12. Nassar MA et al. (2004) Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci USA 101: 12706–12711

    Article  CAS  Google Scholar 

  13. Han C et al. (2006) Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. Ann Neurol 59: 553–558

    Article  CAS  Google Scholar 

  14. Hisama F et al. (2006) SCN9A-related inherited erythromelalgia. In GeneReviews at GeneTests: medical genetics information resource [] (accessed 20 October 2006)

    Google Scholar 

  15. Nathan A et al. (2005) Primary erythromelalgia in a child responding to intravenous lidocaine and oral mexiletine treatment. Pediatrics 115: e504–e507

    Article  Google Scholar 

  16. Mork C et al. (2004) The prostaglandin E1 analog misoprostol reduces symptoms and microvascular arteriovenous shunting in erythromelalgia—a double-blind, crossover, placebo-compared study. J Invest Dermatol 122: 587–593

    Article  CAS  Google Scholar 

  17. Davis MD and Rooke T (2006) Erythromelalgia. Curr Treat Options Cardiovasc Med 8: 153–165

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Stephen G Waxman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Novella, S., Hisama, F., Dib-Hajj, S. et al. A case of inherited erythromelalgia. Nat Rev Neurol 3, 229–234 (2007).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing