Cardeza Foundation for Hematologic Research, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA, USA.
Division of Hematology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA.
Complement Ther Med. 2020 Mar;49:102327. doi: 10.1016/j.ctim.2020.102327. Epub 2020 Feb 3.
Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing curative therapies such as hematopoietic stem cell transplantation and gene therapy, effective pain management continues to lag behind. Palliative therapies continue to be the major approach to the management of SCD and its complications. The advent of hydroxyurea made partial success in preventing the frequency of vaso-occlusive crises and l-glutamine awaits post-trial confirmation of benefits. The search for additional pharmacotherapeutic agents that could be used singly or in combination with hydroxyurea and/or l-glutamine awaits their dawn hopefully in the near future. The purpose of this review is to describe the various manifestations of SCD, their pathophysiology and their current management. Recent impressive advances in understanding the pathophysiology of pain promise the determination of agents that could replace or minimize the use of opioids.
镰状细胞病（SCD）是一种高度复杂的血红蛋白结构遗传性疾病。尽管分子病变是单点突变，但镰状基因本质上是多效的，导致多种表型表达，构成疾病的各种并发症。其表现可以是急性、慢性、疼痛、神经病变，可以单独发生，也可以以各种组合发生。疼痛仍然是 SCD 表型并发症的主要因素，也是急诊科和/或医院就诊的最常见原因。尽管在理解 SCD 的病理生理学以及开发治疗方法（如造血干细胞移植和基因治疗）方面已经取得了进展，但有效的疼痛管理仍然滞后。姑息治疗仍然是 SCD 及其并发症管理的主要方法。羟基脲的出现部分成功地预防了血管阻塞性危象的发生频率，而 l-谷氨酰胺则等待试验后确认其益处。正在寻找其他可单独使用或与羟基脲和/或 l-谷氨酰胺联合使用的药物治疗剂，希望在不久的将来能取得进展。本文综述的目的是描述 SCD 的各种表现、其病理生理学及其当前的治疗方法。对疼痛病理生理学的理解的最新进展令人印象深刻，有望确定可以替代或减少阿片类药物使用的药物。
