Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO.
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Am J Surg Pathol. 2018 Apr;42(4):545-552. doi: 10.1097/PAS.0000000000001022.
Collagenous enteritis is an uncommon small intestinal injury pattern with unclear pathogenesis. While it has been speculated that collagenous enteritis represents a form of refractory celiac disease, recent clinical studies suggest a potential link to exposure to the antihypertensive medication olmesartan. Here we hypothesized that the pathogenesis of collagenous enteritis involves both genetic and environmental factors. All subjects with biopsy-proven collagenous enteritis diagnosed between 2002 and 2015 were identified from 2 tertiary care medical centers. Human leukocyte antigen (HLA)-DQ genotyping was performed by polymerase chain reaction on archived tissue. Celiac disease serology, past medical history, medications, smoking history, demographics, histology, clinical management, and follow-up were recorded. A total of 32 subjects were included. In contrast to celiac disease, subjects with collagenous enteritis were mostly elderly (median age at diagnosis, 69 y; range, 33 to 84 y). Seventy percent of collagenous enteritis subjects harbored celiac disease susceptibility alleles HLA-DQ2/DQ8; however, only 1 subject had elevated serum levels of celiac disease-associated autoantibodies while on a gluten-containing diet. Furthermore, 56% of subjects were taking nonsteroidal anti-inflammatory drugs, 36% proton-pump inhibitors, 28% statins, and 32% olmesartan at the time of diagnosis. Discontinuation of olmesartan and treatments with steroids and/or gluten-free diet resulted in symptomatic and histologic improvement. Neither lymphoma nor collagenous enteritis-related death was seen in this cohort. Therefore, while collagenous enteritis shares similar HLA genotypes with celiac disease, the difference in demographics, the lack of celiac disease-associated autoantibodies, and potential link to medications as environmental triggers suggest the 2 entities are likely distinct in pathogenesis.
胶原性肠炎是一种不常见的小肠损伤模式，其发病机制尚不清楚。虽然有人推测胶原性肠炎代表了一种难治性乳糜泻形式，但最近的临床研究表明，它与暴露于抗高血压药物奥美沙坦可能有关。在这里，我们假设胶原性肠炎的发病机制涉及遗传和环境因素。从 2 家三级保健医疗中心确定了在 2002 年至 2015 年间经活检证实的胶原性肠炎患者。通过聚合酶链反应对存档组织进行人类白细胞抗原（HLA）-DQ 基因分型。记录乳糜泻血清学、既往病史、药物使用史、吸烟史、人口统计学、组织学、临床管理和随访情况。共纳入 32 例患者。与乳糜泻不同，胶原性肠炎患者大多为老年人（诊断时的中位年龄，69 岁；范围 33 至 84 岁）。70%的胶原性肠炎患者存在乳糜泻易感等位基因 HLA-DQ2/DQ8；然而，仅有 1 例患者在食用含麸质饮食时血清中存在乳糜泻相关自身抗体水平升高。此外，56%的患者在诊断时正在服用非甾体抗炎药、36%质子泵抑制剂、28%他汀类药物和 32%奥美沙坦。停用奥美沙坦和使用皮质类固醇和/或无麸质饮食治疗导致症状和组织学改善。在该队列中，既未观察到淋巴瘤，也未观察到胶原性肠炎相关死亡。因此，虽然胶原性肠炎与乳糜泻具有相似的 HLA 基因型，但在人口统计学方面的差异、缺乏乳糜泻相关自身抗体以及与药物作为环境触发因素的潜在关联提示这两种疾病在发病机制上可能不同。
