Description

The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. It will review evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, potential therapeutic options, and surveillance for complications of this condition.

Methods

This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations.

Best Practice Advice Statements

Best Practice Advice 1

In patients believed to have celiac disease who have persistent or recurrent symptoms or signs, the initial diagnosis of celiac disease should be confirmed by review of prior diagnostic testing, including serologies, endoscopies, and histologic findings.

Best Practice Advice 2

In patients with confirmed celiac disease with persistent or recurrent symptoms or signs (nonresponsive celiac disease), ongoing gluten ingestion should be excluded as a cause of these symptoms with serologic testing, dietitian review, and detection of immunogenic peptides in stool or urine. Esophagogastroduodenoscopy with small bowel biopsies should be performed to look for villous atrophy. If villous atrophy persists or the initial diagnosis of celiac disease was not confirmed, consider other causes of villous atrophy, including common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy.

Best Practice Advice 3

For patients with nonresponsive celiac disease, after exclusion of gluten ingestion, perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, lactose or fructose intolerance, and small intestinal bacterial overgrowth.

Best Practice Advice 4

Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish between subtypes of refractory celiac disease and to exclude enteropathy-associated T-cell lymphoma. Type 1 refractory celiac disease is characterized by a normal intraepithelial lymphocyte population and type 2 is defined by the presence of an aberrant, clonal intraepithelial lymphocyte population. Consultation with an expert hematopathologist is necessary to interpret these studies.

Best Practice Advice 5

Perform small bowel imaging with capsule endoscopy and computed tomography or magnetic resonance enterography to exclude enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis at initial diagnosis of type 2 refractory celiac disease.

Best Practice Advice 6

Complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies in patients diagnosed with refractory celiac disease. Check albumin as an independent prognostic factor.

Best Practice Advice 7

Correct deficiencies in macro- and micronutrients using oral supplements and/or enteral support. Consider parenteral nutrition for patients with severe malnutrition due to malabsorption.

Best Practice Advice 8

Corticosteroids, most commonly open-capsule budesonide or, if unavailable, prednisone, are the medication of choice and should be used as first-line therapy in either type 1 or type 2 refractory celiac disease.

Best Practice Advice 9

Patients with refractory celiac disease require regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy. Identify local experts with expertise in celiac disease to assist with management.

Best Practice Advice 10

Patients with refractory celiac disease without response to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials.

中文翻译：

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AGA 难治性乳糜泻管理临床实践更新：专家评审

描述

本专家综述的目的是总结难治性乳糜泻的诊断和治疗。它将审查对患有持续性或复发性症状的乳糜泻患者的评估、鉴别诊断、营养支持、潜在的治疗选择以及对该病并发症的监测。

方法

该专家评审由美国胃肠病学协会 (AGA) 研究所临床实践更新委员会 (CPUC) 和 AGA 管理委员会委托和批准，旨在就对 AGA 成员具有高度临床重要性的主题提供及时指导，并由美国胃肠病学会内部同行评审CPUC 和通过胃肠病学标准程序进行的外部同行评审。这些最佳实践建议 (BPA) 声明来自对已发表文献的回顾和专家意见。由于没有进行系统评价，这些 BPA 声明没有对证据质量或所提出考虑的强度进行正式评级。

最佳实践建议声明

最佳实践建议 1

在被认为患有乳糜泻且有持续性或复发性症状或体征的患者中，乳糜泻的初步诊断应通过回顾先前的诊断测试来确认，包括血清学、内镜检查和组织学检查结果。

最佳实践建议 2

对于确诊患有持续性或复发性症状或体征的乳糜泻患者（无反应性乳糜泻），应通过血清学检测、营养师复查以及粪便或尿液中免疫原性肽的检测来排除持续摄入麸质作为这些症状的原因。应进行食管胃十二指肠镜检查和小肠活检以寻找绒毛萎缩。如果绒毛萎缩持续或乳糜泻的初步诊断未得到证实，请考虑绒毛萎缩的其他原因，包括常见的可变免疫缺陷、自身免疫性肠病、热带口炎和药物性肠病。

最佳实践建议 3

对于无反应性乳糜泻患者，在排除麸质摄入后，对其他潜在的症状原因进行系统评估，包括功能性肠病、显微镜下结肠炎、胰腺功能不全、炎症性肠病、乳糖或果糖不耐受和小肠细菌过度生长。

最佳实践建议 4

使用流式细胞术、免疫组织化学和 T 细胞受体重排研究来区分难治性乳糜泻的亚型并排除与肠病相关的 T 细胞淋巴瘤。1 型难治性乳糜泻以正常的上皮内淋巴细胞群为特征，2 型以存在异常的克隆性上皮内淋巴细胞群为特征。有必要咨询专家血液病理学家来解释这些研究。

最佳实践建议 5

在最初诊断为 2 型难治性乳糜泻时，使用胶囊内镜检查和计算机断层扫描或磁共振肠造影进行小肠成像，以排除肠病相关的 T 细胞淋巴瘤和溃疡性空肠炎。

最佳实践建议 6

完成详细的营养评估，调查诊断为难治性乳糜泻患者的微量营养素和常量营养素缺乏症。检查白蛋白作为一个独立的预后因素。

最佳实践建议 7

使用口服补充剂和/或肠内支持纠正大量和微量营养素的不足。考虑对因吸收不良导致严重营养不良的患者进行肠外营养。

最佳实践建议 8

皮质类固醇，最常见的开囊布地奈德或泼尼松（如果没有的话）是首选药物，应作为 1 型或 2 型难治性乳糜泻的一线治疗。

最佳实践建议 9

难治性乳糜泻患者需要由包括胃肠病学家和营养师在内的多学科团队定期随访，以评估对治疗的临床和组织学反应。确定具有乳糜泻专业知识的当地专家协助管理。

最佳实践建议 10

对类固醇没有反应的难治性乳糜泻患者可能会受益于转诊到具有管理或评估专业知识的中心以纳入临床试验。