{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:45:46Z","timestamp":1790419546161,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sara Page Mayo Endowment for Pediatric Pain Research"},{"name":"Boston Children\u2019s Hospital Children\u2019s Rare Disease Cohorts (CRDC) Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Erythromelalgia is a descriptive term for severe burning pain and erythema in the distal extremities relieved by cold and exacerbated by heat. Pediatric case series to date are relatively small. We extracted and analyzed medical record data for 42 pediatric patients to describe clinical characteristics, associated conditions, and responses to treatments. Informed consent was obtained according to an IRB-approved protocol that included gene discovery. Three patients had confirmed Nav1.7 sodium channelopathies, with six additional patients under investigation with novel gene candidates. There was a female predominance (2.5:1), and the median onset age was 12 years (IQR = 3\u201314). Patients saw a median of three specialists (IQR = 2\u20133) for a diagnosis. The majority (90%) reported bilateral symptoms. Cooling methods usually provided partial relief, while heat and exercise exacerbated pain. No medication appeared to be consistently effective; commonly prescribed medications included sodium channel blockers (n = 37), topical analgesics (n = 26), gabapentin (n = 22), and aspirin (n = 15). Based on the currently published literature, we believe this cohort is the largest pediatric study of erythromelalgia to date. Many findings are consistent with those of previously published case series. Work is in progress to establish a prospective cohort and multi-center registry.<\/jats:p>","DOI":"10.3390\/children10081282","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:27:46Z","timestamp":1690421266000},"page":"1282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series"],"prefix":"10.3390","volume":"10","author":[{"given":"Jenny","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don Daniel","family":"Ocay","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Halpin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafni F. T.","family":"Frohman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Donado","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-0340","authenticated-orcid":false,"given":"Catherine A.","family":"Brownstein","sequence":"additional","affiliation":[{"name":"Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casie A.","family":"Genetti","sequence":"additional","affiliation":[{"name":"Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Madden","sequence":"additional","affiliation":[{"name":"Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Berde","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","first-page":"80","article-title":"Clinical Features and Management of Erythromelalgia: Long-Term Follow-up of 46 Cases","volume":"35","author":"Parker","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.2147\/JPR.S154462","article-title":"Current Pain Management Strategies for Patients with Erythromelalgia: A Critical Review","volume":"11","author":"Tham","year":"2018","journal-title":"J. Pain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jpeds.2018.10.024","article-title":"Pediatric Erythromelalgia and SCN9A Mutations: Systematic Review and Single-Center Case Series","volume":"206","author":"Arthur","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jaad.2011.01.010","article-title":"Pediatric Erythromelalgia: A Retrospective Review of 32 Cases Evaluated at Mayo Clinic over a 37-Year Period","volume":"66","author":"Tollefson","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","unstructured":"Jha, S.K., Karna, B., and Goodman, M.B. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.neuron.2010.04.030","article-title":"A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome","volume":"66","author":"Kremeyer","year":"2010","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5315\/wjh.v6.i3.32","article-title":"Aspirin Cures Erythromelalgia and Cerebrovascular Disturbances in JAK2-Thrombocythemia through Platelet-Cycloxygenase Inhibition","volume":"6","author":"Michiels","year":"2017","journal-title":"World J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1136\/jnnp-2012-303719","article-title":"Infrequent SCN9A Mutations in Congenital Insensitivity to Pain and Erythromelalgia","volume":"84","author":"Klein","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8232","DOI":"10.1523\/JNEUROSCI.2695-04.2004","article-title":"Electrophysiological Properties of Mutant Nav1.7 Sodium Channels in a Painful Inherited Neuropathy","volume":"24","author":"Cummins","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1093\/brain\/awh514","article-title":"Gain-of-Function Mutation in Nav1.7 in Familial Erythromelalgia Induces Bursting of Sensory Neurons","volume":"128","author":"Rush","year":"2005","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1172\/JCI33297","article-title":"Mutations in Sodium-Channel Gene SCN9A Cause a Spectrum of Human Genetic Pain Disorders","volume":"117","author":"Drenth","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pain.2009.06.032","article-title":"Functional and Structural Nerve Fiber Findings in Heterozygote Patients with Fabry Disease","volume":"145","author":"Rasmussen","year":"2009","journal-title":"PAIN"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.pain.2009.07.025","article-title":"Fabry Disease\u2014Pain Doctors Have to Find the Missing Ones","volume":"145","author":"Naleschinski","year":"2009","journal-title":"PAIN"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/ced.13891","article-title":"Review of Primary and Secondary Erythromelalgia","volume":"44","author":"Mann","year":"2019","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1542\/peds.2005-0697","article-title":"Erythromelalgia: Small-Fiber Neuropathy by Any Other Name?","volume":"116","author":"Oaklander","year":"2005","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.2340\/actadv.v102.2316","article-title":"Erythromelalgia Associated with Neuropathy in Sj\u00f6gren\u2019s Syndrome: A Case Report","volume":"102","author":"Saito","year":"2022","journal-title":"Acta Derm. Venereol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1468-3083.2008.02938.x","article-title":"Incidence of Erythromelalgia: A Population-Based Study in Olmsted County, Minnesota","volume":"23","author":"Reed","year":"2009","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.spen.2016.10.008","article-title":"Neuropathic and Myopathic Pain","volume":"23","author":"Rodrigues","year":"2016","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/ana.21678","article-title":"A Novel Nav1.7 Mutation Producing Carbamazepine-Responsive Erythromelalgia","volume":"65","author":"Fischer","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4455","DOI":"10.1111\/bph.12788","article-title":"Mexiletine as a Treatment for Primary Erythromelalgia: Normalization of Biophysical Properties of Mutant L858F NaV1.7 Sodium Channels","volume":"171","author":"Cregg","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1001\/archderm.136.3.330","article-title":"Natural History of Erythromelalgia: Presentation and Outcome in 168 Patients","volume":"136","author":"Davis","year":"2000","journal-title":"Arch. Dermatol."},{"key":"ref_22","unstructured":"R Core Team (2023, February 27). R: A Language and Environment for Statistical Computing. Available online: https:\/\/r-project.org."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.nmd.2008.10.005","article-title":"Childhood Steroid-Responsive Acute Erythromelalgia with Axonal Neuropathy of Large Myelinated Fibers: A Dysimmune Neuropathy?","volume":"19","author":"Pfund","year":"2009","journal-title":"Neuromuscul. Disord."},{"key":"ref_24","unstructured":"(2023, May 21). Erythromelalgia Survey 2021. Available online: https:\/\/erythromelalgia.org\/wp-content\/uploads\/2021\/07\/Survey2021.Results.Presentation.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"374167","DOI":"10.1155\/2011\/374167","article-title":"Erythema and Burning Pain in the Vulva: A Possible Phenotype of Erythromelalgia","volume":"2011","author":"Johnson","year":"2011","journal-title":"Case Rep. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.pmn.2013.03.002","article-title":"Adolescent Pediatric Pain Tool (APPT) for Multidimensional Measurement of Pain in Children and Adolescents","volume":"15","author":"Jacob","year":"2014","journal-title":"Pain Manag. Nurs. Off. J. Am. Soc. Pain Manag. Nurses"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7459","DOI":"10.1038\/s41598-022-10911-8","article-title":"A Novel Non-Invasive Method of Measuring Microcirculatory Perfusion and Blood Velocity in Infants: A Pilot Study","volume":"12","author":"Fine","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"597768","DOI":"10.3389\/fcvm.2020.597768","article-title":"Carotid Intima-Media Thickness in Healthy Children and Adolescents: Normative Data and Systematic Literature Review","volume":"7","author":"Plesnik","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1155\/2013\/964352","article-title":"Children and Adolescents with Complex Regional Pain Syndrome: More Psychologically Distressed than Other Children in Pain?","volume":"18","author":"Logan","year":"2013","journal-title":"Pain Res. Manag. J. Can. Pain Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jadohealth.2021.12.003","article-title":"Rising Rates of Adolescent Depression in the United States: Challenges and Opportunities in the 2020s","volume":"70","author":"Wilson","year":"2022","journal-title":"J. Adolesc. Health Off. Publ. Soc. Adolesc. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrg.2017.116","article-title":"Paediatric Genomics: Diagnosing Rare Disease in Children","volume":"19","author":"Wright","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.pcl.2015.12.002","article-title":"Electronic Health Record\u2013Enabled Research in Children Using the Electronic Health Record for Clinical Discovery","volume":"63","author":"Sutherland","year":"2016","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejpn.2020.06.004","article-title":"Acute Monophasic Erythromelalgia Pain in Five Children Diagnosed as Small-Fiber Neuropathy","volume":"28","author":"Faignart","year":"2020","journal-title":"Eur. J. Paediatr. Neurol. EJPN Off. J. Eur. Paediatr. Neurol. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.neucli.2021.03.008","article-title":"A Reappraisal of the Presence of Small or Large Fiber Neuropathy in Patients with Erythromelalgia","volume":"51","author":"Reach","year":"2021","journal-title":"Neurophysiol. Clin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2534","DOI":"10.1212\/WNL.0000000000011919","article-title":"Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy","volume":"96","author":"Geerts","year":"2021","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1213\/01.ane.0000252965.83347.25","article-title":"Defining a Treatable Cause of Erythromelalgia: Acute Adolescent Autoimmune Small-Fiber Axonopathy","volume":"104","author":"Paticoff","year":"2007","journal-title":"Anesth. Analg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.nec.2022.02.003","article-title":"Health Care Disparity in Pain","volume":"33","author":"Hamilton","year":"2022","journal-title":"Neurosurg. Clin. N. Am."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/8\/1282\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:19:08Z","timestamp":1760127548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/8\/1282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,26]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["children10081282"],"URL":"https:\/\/doi.org\/10.3390\/children10081282","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,26]]}}}