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Review
. 2025 Feb 5;17(2):e78576.
doi: 10.7759/cureus.78576. eCollection 2025 Feb.

Primary Erythromelalgia: Historical Perspective and Current Update

Allison C Eaton  1 , Harvey N Mayrovitz  2
Affiliations
Review

Primary Erythromelalgia: Historical Perspective and Current Update

Allison C Eaton et al. Cureus. .

Abstract

Erythromelalgia is a condition characterized by intense burning pain, redness, and heat in the extremities that has garnered increasing attention in recent years. This literature review provides a comprehensive historical perspective and current update on primary erythromelalgia or PEM, categorizing and tracing the clinical knowledge of the condition and identifying key milestones of historical research. In a sequential fashion, the review explores the evolution of understanding of PEM, starting from its initial descriptions in the medical literature to the present day. Early case reports and pivotal studies that contributed to recognizing and characterizing the disorder are examined. Important discoveries, diagnostic criteria, and therapeutic approaches that have shaped the management of erythromelalgia over time are highlighted. Additionally, the impact of genetic studies and molecular investigations on current understanding of PEM is discussed. Identifying mutations in the SCN9A gene is emphasized as a significant breakthrough, shedding light on the role of sodium channels in the disorder's pathogenesis. Overall, this review consolidates the wealth of clinical knowledge and research milestones related to PEM. Integrating historical research milestones offers a comprehensive overview of the condition, from early descriptions to the current state of knowledge. This knowledge serves as a foundation for further research and can assist in improving diagnosis and management strategies for individuals with PEM.

Keywords: erythermalgia; erythromelalgia; nav1.7; neuropathic pain; scn9a; skin erythema; sodium channelopathy.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Milestone timeline
The timeline features the most notable historical developments traced to our current understanding of PEM: Graves, 1834 [10]; Mitchell, 1878 [6]; Smith and Allen, 1938 [5]; Drenth et al., 2001 [11]; Yang et al., 2004 [9]. This is an original figure courtesy of the authors.
Figure 2
Figure 2. Example of a primary erythromelalgia flare
Images (A and B) show two views of the left hand before the attack, and images (C and D) show two views of the left hand during the acute flare approximately 15 minutes later. This is an original figure courtesy of the authors.
See this image and copyright information in PMC

References

    1. Erythromelalgia: incidence and clinical experience in a single centre in Sweden. Alhadad A, Wollmer P, Svensson A, Eriksson KF. Vasa. 2012;41:43–48. - PubMed
    1. Primary erythromelalgia: a review. Tang Z, Chen Z, Tang B, Jiang H. Orphanet J Rare Dis. 2015;10:127. - PMC - PubMed
    1. Erythromelalgia. Klein-Weigel PF, Volz TS, Richter JG. Vasa. 2018;47:91–97. - PubMed
    1. Erythromelalgia. Part I: pathogenesis, clinical features, evaluation, and complications. Caldito EG, Kaul S, Caldito NG, Piette W, Mehta S. J Am Acad Dermatol. 2024;90:453–462. - PubMed
    1. Erythermalgia (erythromelalgia) of the extremities: a syndrome characterized by redness, heat, and pain. Smith LA, Allen EV. Am Heart J. 1938;16:175–188.

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