Devigili Grazia, Eleopra Roberto, Pierro Tiziana, Lombardi Raffaella, Rinaldo Sara, Lettieri Christian, Faber Catharina G, Merkies Ingemar S J, Waxman Stephen G, Lauria Giuseppe
Neurological Unit, University-Hospital "S. Maria della Misericordia", Udine, Italy Neuroalgology and Headache Unit, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands Department of Neurology, Spaarne Hospital, Hoofddorp, The Netherlands Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT, USA.
Pain. 2014 Sep;155(9):1702-1707. doi: 10.1016/j.pain.2014.05.006. Epub 2014 May 10.
Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.
瘙痒是一种常见的体验。它可发生于全身性疾病过程中，可能是过敏的表现，或是影响躯体感觉通路的疾病的后果。我们描述了一个家族，其特征为编码Nav1.7钠通道的SCN9A基因变异导致的阵发性瘙痒。患者接受了临床和躯体感觉特征评估，包括定量感觉测试、神经传导研究、自主心血管反射和交感皮肤反应检查、皮肤活检并量化表皮内神经纤维密度，以及SCN9A突变分析。索引患者、她的母亲和一个姐妹表现出一种典型的临床症状，其特征为阵发性瘙痒发作，累及肩部、上背部和上肢，随后是短暂的灼痛，由环境温暖、热饮和辛辣食物引发。躯体感觉特征评估显示，冷觉和痛觉阈值升高以及热感觉异常的模式显著相同。自主神经测试为阴性，而皮肤活检显示3例患者中有2例表皮内神经纤维密度降低。所有受影响成员在SCN9A基因第13外显子中均存在2215A>G I739V替换。普瑞巴林治疗降低了所有患者的瘙痒强度和发作频率。该家族中受影响成员I739V变异的共分离首次提供了证据，表明阵发性瘙痒可能与钠通道基因突变有关。
