Primary erythromelalgia: a review
- PDF / 1,013,778 Bytes
- 11 Pages / 595.276 x 793.701 pts Page_size
- 97 Downloads / 194 Views
REVIEW
Open Access
Primary erythromelalgia: a review Zhaoli Tang1, Zhao Chen1, Beisha Tang1,2,3 and Hong Jiang1,2,3*
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 voltagegated 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. Keywords: Primary erythromelalgia, Voltage-gated sodium channel, Pain, Genetics, Electrophysiology, Hyper-excitability, Therapy
Introduction Pain, under physical conditions, informs body of harmful stimuli, elicits protective reflexes, making it essential for survival. Pathological pain, on the other hand, is one of the most prevalent symptoms seen in patients. Chronic pain has become a global health problem which is estimated to affect about 30 % of adults worldwide [1]. Currently used drugs such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs) show limited efficacy [2]. Thereby more precise medications for various types of pain rising from different etiologies are required. As one of the human heritable pain disorders, primary erythromelalgia (PE) is characterized by the triad of recurrent * Correspondence: [email protected] 1 Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha 410008, Hunan, China 2 Key Laboratory of Hunan Province in Neurodegenerative Disorders, Cen
Data Loading...
