title: Primary erythromelalgia: a review.
abstract: Primary erythromelalgia (PE ORPHA90026) is a rare autosomal dominant neuropathy characterized by the combination of recurrent burning pain, warmth and redness of the extremities. The incidence rate of PE ranges from 0.36 to 1.1 per 100,000 persons. Gender ratio differs according to different studies and no evidence showed a gender preference. Clinical onset of PE is often in the first decade of life. Burning pain is the most predominant symptom and is usually caused and precipitated by warmth and physical activities. Reported cases of PE contain both inherited and sporadic forms. Genetic etiology of PE is mutations on SCN9A, the encoding gene of a voltage-gated sodium channel subtype Nav1.7. Diagnosis of PE is made upon clinical manifestations and screening for mutations on SCN9A. Exclusion of several other treatable diseases/secondary erythromelalgia is also necessary because of the lack of biomarkers specifically for PE. Differential diagnoses can include Fabry disease, cellulites, Raynaud phenomenon, vasculitis and so on. Diagnostic methods often involve complete blood count, imaging studies and thermograph. Treatment for PE is unsatisfactory and highly individualized. Frequently used pain relieving drugs involve sodium channel blockers such as lidocaine, carbamazepine and mexiletine. Novel drugs such as PF-05089771 and TV-45070 could be promising in ameliorating pain symptoms due to their Nav1.7 selectivity. Patients' symptoms often worsen over time and many patients develop ulcerations and gangrenes caused by excessive exposure to low temperature in order to relieve pain. This review mainly focuses on PE and the causative gene SCN9A--its mutations and their effects on Nav1.7 channels' electrophysiological properties. We propose a genotype-channelopathy-phenotype correlation network underlying PE etiology which could provide guidance for future therapeutics.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha, 410008, Hunan, China. zhaoli.tang@outlook.com.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha, 410008, Hunan, China. czcf98@126.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha, 410008, Hunan, China. bstang7398@163.com.|Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, 87 Xiangya road, Changsha, 410008, Hunan, China. bstang7398@163.com.|State Key Lab of Medical Genetics, Central South University, 110 Xiangya road, Changsha, 410078, Hunan, China. bstang7398@163.com.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha, 410008, Hunan, China. jianghong73868@126.com.|Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, 87 Xiangya road, Changsha, 410008, Hunan, China. jianghong73868@126.com.|State Key Lab of Medical Genetics, Central South University, 110 Xiangya road, Changsha, 410078, Hunan, China. jianghong73868@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D004916:Erythromelalgia / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D009154:Mutation / Q000235:genetics*; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D010146:Pain / Q000175:diagnosis / Q000235:genetics; D059408:Pain Management / Q000379:methods
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel