{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:59:21Z","timestamp":1790150361635,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Erythromelalgia is a rare disorder characterised by burning pain, erythema and increased skin temperature in the extremities. Its pathophysiological heterogeneity, together with variable treatment responses, complicates management in the absence of evidence\u2010based guidelines. This systematic review appraised pain\u2010management strategies across reported aetiological subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Databases and Data Treatment<\/jats:title>\n                    <jats:p>\n                      Following PRISMA 2020 guidelines, the review was registered in PROSPERO (CRD420251232074). PubMed, Embase, the Cochrane Library and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      were searched for studies published or registered between 1 January 2000 and 30 April 2026. Randomised controlled trials, non\u2010randomised interventional studies, cohort studies and case series were eligible; non\u2010randomised studies required at least five individuals. Risk of bias was assessed using Joanna Briggs Institute tools and certainty of evidence using GRADE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 3372 records, 25 studies reporting 591 individuals were included. Aetiological subtype was reported for 277 individuals (46.9%). Mechanistic and aetiological characterisation varied substantially across domains, with haematological data available for 72.6% and\n                      <jats:italic>SCN9A<\/jats:italic>\n                      status for 19.0% of the overall population. Moderate\u2010certainty evidence supported aspirin in myeloproliferative neoplasm\u2010associated erythromelalgia. Low\u2010certainty evidence suggested benefit from mexiletine and carbamazepine in primary erythromelalgia, as well as from prostaglandin analogues, corticosteroids, selected topical therapies and sympathetic interventions in specific contexts. Evidence for selective Na\u1d651.7 inhibitors and most other interventions was of very low certainty.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment\u2010response patterns in better\u2010characterised populations suggest that aetiology and underlying mechanisms may be relevant to treatment selection. However, this mechanism\u2010informed approach remains hypothesis\u2010generating and requires prospective validation through systematic aetiological and mechanistic characterisation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>This systematic review provides a comprehensive, graded evaluation of the full spectrum of pain\u2010management strategies in erythromelalgia, including systemic, topical, interventional and non\u2010pharmacological approaches, across reported aetiological subtypes. Integrating risk\u2010of\u2010bias appraisal and GRADE certainty ratings, it identifies moderate\u2010certainty evidence for aspirin in myeloproliferative neoplasm\u2010associated disease and low\u2010certainty evidence for conventional sodium\u2010channel blockers in selected primary forms, while evidence for other interventions remains low or very low. These patterns suggest that aetiology may inform treatment selection, but require prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70368","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:53:07Z","timestamp":1788511987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pain Management in Erythromelalgia: A Systematic Review and Graded Appraisal Across Etiological Subtypes"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1248-7452","authenticated-orcid":false,"given":"Camille","family":"Racca","sequence":"first","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re (AP\u2010HP)  Paris France"},{"name":"R\u00e9seau Douleur Maladies Rares (REDOMA) Association Draw Your Fight  Paris 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