Is low dose hydroxyurea the solution to the global epidemic of sickle cell disease?
Is low dose hydroxyurea the solution to the global epidemic of sickle cell disease?
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低剂量羟基脲是全球镰状细胞病流行的解决方案吗？
DOI：
10.1002/pbc.25471
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发表时间：
2015
影响因子：
3.2
通讯作者：
Strouse,JohnJ
中科院分区：
文献类型：
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作者：
Strouse,JohnJ
镰状细胞病是一种慢性疾病，在卫生保健资源有限的地区被忽视。与肥胖症、心血管疾病、高血压、糖尿病和恶性肿瘤不同，这些疾病目前在中低收入国家流行，并且正在出现特定区域的数据，绝大多数镰状细胞病病例发生在非洲和印度。然而，大多数研究是针对美国和欧洲的患者进行的，这些国家的收入较高，新发镰状细胞病病例< 1%。[1]全球疾病负担研究估计，2013年全球有176，200人死于镰状细胞病，镰状细胞病比伤寒，白血病或麻疹造成更多的寿命损失。[2]在非洲和印度，大多数镰状细胞病患者可能在儿童早期死于常见的和可能可预防的感染，如疟疾和肺炎球菌。[3]他们的易感性和这些感染的死亡风险增加是未被认识的，因为新生儿筛查镰状细胞病是不可用的。即使诊断为镰状细胞病，对该疾病的全面护理也很少，并且仅限于预防感染性并发症和治疗一些急性和慢性并发症，但疾病修饰疗法，如羟基脲，长期输血镰状阴性血或造血干细胞移植通常不存在。羟基脲是这些疗法中最不复杂和最昂贵的，但在卫生保健资源有限的地区，剂量递增和定期实验室监测血液学毒性的标准方法不可行。Svarch及其在中美洲和加勒比海地区的同事率先使用基于体重的固定剂量的羟基脲来治疗镰状细胞性贫血儿童。他们报告说，住院人数中位数减少了80%，急性疼痛减少了70%以上。
Sickle cell disease is a chronic illness that has been neglected in regions with limited health care resources. Unlike obesity, cardiovascular disease, hypertension, diabetes mellitus, and malignancies, which are now epidemic in lower and middle income countries and for which regions-specific data are emerging, the vast majority of cases of sickle cell disease occur in Africa and India. However, most of the research is performed for patients in the United States and Europe, higher income countries with< 1% of the new cases of sickle cell disease.[1]The Global Burden of Disease Study estimated that 176,200 people died worldwide from sickle cell disease in 2013 and that sickle cell disease was responsible for more years of life lost than typhoid fever, leukemia, or measles.[2] Most people with sickle cell disease in Africa and India probably die during early childhood from common and potentially preventable infections, such as malaria and pneumococcus.[3] Their predisposition and increased risk of mortality from these infections is unrecognized, because newborn screening for sickle cell disease is not available. Even when a diagnosis of sickle cell disease is made, comprehensive care for the disease is available for few and is limited to prophylaxis for infectious complications and treatment of some acute and chronic complications, but disease modifying therapies, such as hydroxyurea, chronic transfusion of sickle negative blood, or hematopoietic stem cell transplantation are generally not. Hydroxyurea is the least complicated and expensive of these therapies, but the standard approach of dose escalation and regular laboratory monitoring for hematological toxicity is not feasible in areas with limited health care resources. Svarch and colleagues in the Central America and the Caribbean pioneered the use of fixed weight-based dosing of hydroxyurea to treat children with sickle cell anemia. They reported an 80 percent reduction in the median number of hospitalizations and a greater than 70 percent reduction in acute painful