Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA.
Division of Gastroenterology, Department of Internal Medicine, University of Florida College of Medicine, Jacksonville, FL, USA.
Arq Gastroenterol. 2024 Oct 21;61:e24053. doi: 10.1590/S0004-2803.24612024-053. eCollection 2024.
Microscopic colitis is a relatively new diagnosis that was first described in the 1980s. Patients usually present with chronic watery and non-bloody diarrhea and are typically characterized by an unremarkable gross appearance of the colon on lower endoscopy while having evidence of lymphocytic infiltration of the lamina propria and the epithelium on histology. Two subtypes have been described in the literature: Collagenous colitis, with marked thickening of the subepithelial layer, and Lymphocytic colitis. Multiple risk factors such as female gender, older age and celiac disease have been associated with this entity. A few studies have found an association between microscopic colitis and proton-pump inhibitor (PPI). The aim of our study was to evaluate the risk of developing microscopic colitis and its subtypes for patients who are on PPI therapy.
A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have been diagnosed with any autoimmune disease have been excluded. A multivariate regression analysis was performed to assess risk of developing microscopic, lymphocytic, and collagenous colitis by accounting for potential confounders including female gender, smoking history, and the use of proton pump inhibitor, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008).
78,256,749 individuals were screened in the database and 69,315,150 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with microscopic, lymphocytic, and collagenous colitis is seen in table 1. Using a multivariate regression analysis, the risk of developing microscopic, lymphocytic, and collagenous colitis was calculated and illustrated in table 2.
Our study showed that the risk of microscopic colitis, lymphocytic colitis and collagenous colitis was higher in females and smokers. Although medications like SSRI and NSAIDs showed a positive correlation with colitis, the highest likelihood of developing this disease was associated with PPIs. Lansoprazole has been documented to be associated with microscopic colitis as it is believed to inhibit colonic proton pumps, and subsequently promote diarrhea and inflammation. Interestingly, the prevalence of lymphocytic colitis and collagenous colitis was similar in the cohort of patients treated with PPIs, indicating no specific predisposition to either subtype. This study further confirms the risk factors associated with microscopic colitis. It can help guide physicians to recognize and eliminate these risk factors prior to initiating treatment for this disease. Future studies can focus on identifying the incidence of microscopic colitis with the different types of PPIs in the market.
显微镜结肠炎是一种相对较新的诊断，于 20 世纪 80 年代首次描述。患者通常表现为慢性水样且无血便腹泻，且在结肠镜检查下结肠大体外观通常无明显异常，而组织学上则表现为固有层和上皮的淋巴细胞浸润。文献中描述了两种亚型：胶原性结肠炎，伴有明显的上皮下层增厚；和淋巴细胞性结肠炎。许多危险因素，如女性、年龄较大和乳糜泻，与该实体相关。一些研究发现显微镜结肠炎和质子泵抑制剂（PPI）之间存在关联。我们的研究目的是评估接受 PPI 治疗的患者发生显微镜结肠炎及其亚型的风险。
本研究利用了一个来自美国 26 个不同医疗保健系统的 360 多家医院的验证性多中心和研究平台数据库，该数据库建立于 1999 年至 2022 年 9 月。纳入年龄在 18 岁及以上的患者。排除任何自身免疫性疾病诊断的个体。通过多变量回归分析，考虑到包括女性、吸烟史和质子泵抑制剂、非甾体抗炎药和选择性 5-羟色胺再摄取抑制剂的使用在内的潜在混杂因素，评估发生显微镜、淋巴细胞和胶原性结肠炎的风险。双侧 P 值<0.05 被认为具有统计学意义，所有统计分析均使用 R 版本 4.0.2（R Foundation for Statistical Computing，Vienna，Austria，2008）进行。
在数据库中筛选了 78256749 人，在考虑了纳入和排除标准后，最终分析中选择了 69315150 人。显微镜、淋巴细胞性和胶原性结肠炎患者的基线特征见表 1。使用多变量回归分析，计算并图示了发生显微镜、淋巴细胞性和胶原性结肠炎的风险（见表 2）。
我们的研究表明，女性和吸烟者发生显微镜结肠炎、淋巴细胞性结肠炎和胶原性结肠炎的风险更高。尽管 SSRI 和 NSAIDs 等药物与结肠炎呈正相关，但发生这种疾病的最大可能性与 PPI 相关。兰索拉唑已被证明与显微镜结肠炎有关，因为它被认为抑制结肠质子泵，从而促进腹泻和炎症。有趣的是，在接受 PPI 治疗的患者队列中，淋巴细胞性结肠炎和胶原性结肠炎的患病率相似，表明对任何一种亚型均无特定的易感性。本研究进一步证实了与显微镜结肠炎相关的危险因素。它可以帮助医生在开始治疗这种疾病之前识别和消除这些危险因素。未来的研究可以集中在确定市场上不同类型的 PPI 与显微镜结肠炎的发生率上。
