Rubinstein Eitan, Stolz Leslie E, Sheffer Albert L, Stevens Chris, Bousvaros Athos
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, 300 Longwood Ave, Fegan 5th Floor, Boston, MA 02115, USA.
BMC Gastroenterol. 2014 Apr 9;14:71. doi: 10.1186/1471-230X-14-71.
Hereditary angioedema (HAE) is characterized by unpredictable attacks of debilitating subcutaneous and mucosal edema. Gastrointestinal attacks are painful, of sudden onset and often mistaken for acute abdomen leading to unnecessary surgery. The purpose of this study was to analyze symptom presentation of gastrointestinal angioedema in pediatric and adult HAE patients.
Information collected during the clinical development of ecallantide for treatment of acute HAE attacks included affected anatomic location, accompanying symptoms, medical history, and pain assessments. Efficacy endpoints included Treatment Outcome Score (TOS, maximum score = 100; minimally important difference = 30), a point-in-time measure of treatment response, and time to treatment response.
Forty-nine percent of 521 HAE attacks only involved abdominal symptoms. The most commonly reported abdominal symptoms were distension (77%), cramping (73%) and nausea (67%). The most common pain descriptors were tender, tiring-exhausting, aching, cramping and sickening. White blood cell counts were elevated (>10 × 10(9)/L) in 23% of attacks (mean ± SD: 15.1 ± 11.27 × 10(9)/L). A high proportion of patients reported a history of abdominal surgery, including appendectomy (23%), cholecystectomy (16.4%), and hysterectomy (8.2%). Mean TOS at 4 hours post ecallantide was 77 ± 33 versus 29 ± 65 for placebo. Median time to significant symptom resolution was 165 minutes (95% CI 136, 167) for ecallantide versus >4 hours (95% CI 161, >4 hours) for placebo. Anaphylactic reactions occurred in 6 of the 149 treated patients.
HAE should be considered in the differential diagnosis of patients with recurrent discrete episodes of severe, unexplained crampy abdominal pain associated with nausea.
The data used in the analysis were gathered across multiple clinical trials conducted during the clinical development program for ecallantide. All of the studies were conducted using Good Clinical Practices (GCP) and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. Each site that participated in the clinical trials obtained the appropriate IRB or Ethics Committee approval prior to enrolling any patients. All patients provided written informed consent prior to undergoing any study-related procedures. Pediatric patients provided written assent and their parents or guardians gave written informed consent.The following trials have been registered at http://www.clinicaltrials.gov: EDEMA2 (identifier NCT01826916); EDEMA3 (identifier NCT00262080); EDEMA4 (identifier NCT00457015); and DX-88/19 (identifier NCT00456508).
遗传性血管性水肿（HAE）的特点是不可预测地发作使人衰弱的皮下和黏膜水肿。胃肠道发作疼痛，起病突然，常被误诊为急腹症而导致不必要的手术。本研究的目的是分析儿童和成人HAE患者胃肠道血管性水肿的症状表现。
在艾替班特治疗急性HAE发作的临床研发过程中收集的信息包括受累解剖部位、伴随症状、病史和疼痛评估。疗效终点包括治疗结果评分（TOS，最高分=100；最小重要差异=30），这是治疗反应的即时测量指标，以及达到治疗反应的时间。
521次HAE发作中有49%仅涉及腹部症状。最常报告的腹部症状是腹胀（77%）、绞痛（73%）和恶心（67%）。最常见的疼痛描述词是压痛、疲倦-疲惫、酸痛、绞痛和令人作呕。23%的发作中白细胞计数升高（>10×10⁹/L）（平均值±标准差：15.1±11.27×10⁹/L）。高比例患者报告有腹部手术史，包括阑尾切除术（23%）、胆囊切除术（16.4%）和子宫切除术（8.2%）。艾替班特给药后4小时的平均TOS为77±33，而安慰剂组为29±65。艾替班特组症状显著缓解的中位时间为165分钟（95%CI 136，167），而安慰剂组>4小时（95%CI 161，>4小时）。149例接受治疗的患者中有6例发生过敏反应。
对于反复出现严重、原因不明的伴有恶心的痉挛性腹痛离散发作的患者，鉴别诊断时应考虑HAE。
分析中使用的数据来自艾替班特临床研发项目期间进行的多项临床试验。所有研究均按照良好临床实践（GCP）并依据源自《赫尔辛基宣言》的伦理原则开展。参与临床试验的每个研究点在纳入任何患者之前均获得了适当的机构审查委员会（IRB）或伦理委员会批准。所有患者在接受任何与研究相关的程序之前均提供了书面知情同意书。儿科患者提供了书面同意，其父母或监护人给予了书面知情同意。以下试验已在http://www.clinicaltrials.gov注册：EDEMA（标识符NCT01826916）；EDEMA3（标识符NCT00262080）；EDEMA4（标识符NCT00457015）；以及DX-88/19（标识符NCT00456508）。
