Erythromelalgia

Abstract

Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1.8, and NaV1.9 neuronal sodium channels. Secondary forms might be associated with myeloproliferative disorders, connective tissue disease, cancer, infections, and poisoning. Between the pain episodes, the affected skin areas are usually asymptomatic, but there are patients with typical features of acrocyanosis and/or Raynaud's phenomenon preceding or occurring in between the episodes of erythromelalgia. Diagnosis is made by ascertaining the typical clinical features. Thereafter, the differentiation between primary and secondary forms should be made. Genetic testing is recommended, especially in premature cases and in cases of family clustering in specialized genetic institutions after genetic counselling. Multimodal therapeutic intervention aims toward attenuation of pain and improvement of the patient's quality of life. For this purpose, a wide variety of nonpharmacological approaches and pharmacological substances for topical and systemic use have been proposed, which are usually applied individually in a step-by-step approach. Prognosis mainly depends on the underlying condition and the ability of the patients and their relatives to cope with the disease.

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach

“…ncbi.nlm.nih.gov/ (accessed on 31 December 2020)), forming a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient [43]. The SCN10A protein plays a role in neuropathic pain mechanisms [44,45]. An SNP in the sodium-voltage alpha subunit 9 (SCN9A) has been previously associated with pain as well [46].…”

Chilblains

“…It presents with chronic coolness and violaceous discoloration of extremities [39]. Erythromelalgia evolves in paroxystic crisis and is characterized by the triad of burning pain, recurrent redness and warmth of the extremities [40,41]. These symptoms occur during exposure to heat, during exercise and in response to gravity and can be relieved by cooling and elevation.…”

Structure–Function and Therapeutic Potential of Spider Venom-Derived Cysteine Knot Peptides Targeting Sodium Channels

“…Voltage-gated sodium channels (Na V 1.1–1.9), in particular, are key players in the transmission of electrical signals in excitable cells and also involved in the pathophysiology of neurological disorders, including poorly treated conditions as chronic pain and epilepsy (Luiz and Wood, 2016; Klein-Weigel et al, 2018; Sloan et al, 2018; Szepetowski, 2018). The Na V channels α-subunit comprises four domains (DI–DIV), each formed by six transmembrane segments (S1–S6), including S4 which contributes transmembrane voltage sensitivity, the tip of S5–S6 which contributes to sodium ion selectivity, and the intracellular loop connecting S6 of DIII and S1 of DIV which contributes to fast inactivation (Figure 1).…”