Case and Research Letter
Primary Erythromelalgia: A Case Report
Eritromelalgia primaria: a propósito de un caso
A. Ballano Ruiz
, B. Aldea Manrique, A. Diago Irache, Y. Gilaberte Calzada
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Servicio de Dermatología, Hospital Miguel Servet, Zaragoza, Spain
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"apellidos" => "Ballano Ruiz" "email" => array:1 [ 0 => "adrian.baru@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Aldea Manrique" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Diago Irache" ] 3 => array:2 [ "nombre" => "Y." "apellidos" => "Gilaberte Calzada" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Miguel Servet, Zaragoza, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eritromelalgia primaria: a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 538 "Ancho" => 805 "Tamanyo" => 69402 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythema with fine palmar scaling.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Primary erythromelalgia is a rare autosomal dominant disorder linked to the <span class="elsevierStyleItalic">SCN9A</span> gene, implicated in sodium channels. Mutations in this gene give rise to functional gain and hyperexcitability in nociceptive nerve fibers. The triad of acral erythema, skin pain, and heat is the most common clinical manifestation.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 33-year-old man, with no family history of interest and with a personal history of allergic asthma, attended the clinic because of the presence of erythema, accompanied by pain and burning sensation, on the palms of both hands from infancy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In addition, he reported muscle and joint pain and dry skin with a tendency to pruritus from childhood. The results of the blood workup and electromyogram were within normal ranges. A genetic study was performed, showing a point mutation giving rise to an amino acid substitution in the <span class="elsevierStyleItalic">SCN9A</span> gene (c.296G>A; p[Arg99His]). The study was negative for the panel of genes implicated in mucopolysaccharidoses. The patient was treated with gabapentin and a compounded formula of ketamine and amitriptyline, with unsatisfactory results. Currently, the patient is in follow-up without any other treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Erythromelalgia was first described by Mitchel in 1878. Currently, this condition is classified as either primary or secondary. In the secondary cases, there is an underlying cause (myeloproliferative disorders, autoimmune neuropathies, rheumatological diseases, diabetes, poxvirus infections, drugs, etc.). The primary cases, however, can be inherited or sporadic.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Primary erythromelalgia is caused by a mutation in the <span class="elsevierStyleItalic">SCN9A</span> gene, first reported by Yang et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> in 2004. <span class="elsevierStyleItalic">SCN9A</span> encodes Nav1.7, a membrane protein belonging to the sodium channel family. It is preferentially expressed in small-fiber nociceptive neurons. The gene is upregulated in an inflammatory environment and establishes the threshold for action potentials. There are more than 70 mutations in the <span class="elsevierStyleItalic">SCN9A</span> gene, leading to different phenotypes such as extreme paroxysmal pain (AD), congenital insensitivity to pain associated with channel disorders (AR), and primary erythromelalgia (AD). More than 20 of these mutations have been reported for erythromelalgia.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Clinically, onset of symptoms occurs before the patient is 20 years old, with erythema accompanied by a painful and burning sensation, mainly on the hands and feet, triggered by heat, exercise, or standing. Some patients experience facial involvement or outbreaks of pain at other sites such as the limbs or trunk.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Diagnosis is largely clinical, based on age of onset, family history, and the patient's history to rule out possible secondary causes. Histologically, a perivascular lymphocyte infiltrate is observed in the skin, with endothelial edema, arteriolar smooth muscle hyperplasia, and, in some cases, decreased number of small nerve fibers.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Genetic study should be considered in those cases with early onset, with or without a family history, once other secondary causes have been ruled out.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Differential diagnosis should include Fabry disease, other peripheral neuropathies, perniosis, Raynaud phenomenon and other vascular diseases, dermatosis involving the acral regions, cellulitis, and erysipelas, among others.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Treatment is usually unsatisfactory. Sodium channel blockers may be effective in some cases, while lidocaine, carbamazepine, and gabapentin are reserved for highly symptomatic cases.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> Topical treatment with a compounded formulation of ketamine and amitriptiline,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> botulinic toxin,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> and nonpharmacological methods such as cooling the hands can be considered.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">This study did not receive any funding.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 538 "Ancho" => 805 "Tamanyo" => 69402 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythema with fine palmar scaling.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Yang" 1 => "Y. Wang" 2 => "S. Li" 3 => "Z. Xu" 4 => "H. Li" 5 => "L. Ma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmg.2003.012153" "Revista" => array:5 [ "tituloSerie" => "J Med Genet" "fecha" => "2004" "volumen" => "41" "paginaInicial" => "171" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14985375" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary erythromelalgia: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Z. Tang" 1 => "Z. Chen" 2 => "B. Tang" 3 => "H. Jiang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13023-015-0347-1" "Revista" => array:5 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26419464" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0045" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histopathologic findings in primary erythromelalgia are nonspecific: special studies show a decrease in small nerve fiber density" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.D. Davis" 1 => "R.H. Weenig" 2 => "J. Genebriera" 3 => "G. Wendelschafer-Crabb" 4 => "W.R. Kennedy" 5 => "P. 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Sandroni" 5 => "M.D. Davis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Drugs Dermatol" "fecha" => "2013" "volumen" => "12" "paginaInicial" => "308" "paginaFinal" => "310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23545913" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0060" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.H. Lin" 1 => "S.J. Wang" 2 => "J.L. Fuh" 3 => "S.P. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcma.2013.01.003" "Revista" => array:6 [ "tituloSerie" => "J Chin Med Assoc" "fecha" => "2013" "volumen" => "76" "paginaInicial" => "296" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23683264" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000011400000009/v1_202310020456/S0001731023005896/v1_202310020456/en/main.assets" "Apartado" => array:4 [ "identificador" => "6160" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas científico-clínicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00017310/0000011400000009/v1_202310020456/S0001731023005896/v1_202310020456/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023005896?idApp=UINPBA000044" ]
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