炎症性肠病共病研究进展

摘要

炎症性肠病(inflammatory bowel disease, IBD)作为一种全身性疾病, 除肠道表现外, 尚伴有肠外器官受累, 显著增加临床管理难度与医疗负担. 本文综述了IBD共病的流行病学特征与发病机制, 重点分析精神心理、神经系统、皮肤及心血管系统共病的临床特点, 阐述免疫炎症通路共享及肠-器官轴交互等核心病理机制. 提出临床应遵循早期筛查与个体化干预原则, 建立规范化的多学科协作诊疗模式, 以改善患者预后.

关键词: 炎症性肠病; 共病; 多学科协作; 肠-器官轴

核心提要: 本文综述了炎症性肠病共病的流行病学特征与发病机制, 重点分析精神心理、神经系统、皮肤及心血管系统共病的临床特点, 阐述免疫炎症通路共享及肠-器官轴交互等核心病理机制. 提出临床应遵循早期筛查与个体化干预原则, 建立规范化的多学科协作诊疗模式, 以改善患者预后.

Advances in research on comorbidities in inflammatory bowel disease

Shi-Ming Zhou, Yang Yang

Shi-Ming Zhou, Yang Yang, Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China

Corresponding author: Yang Yang, MD, Associate Chief Physician, Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing 102218, China. yya05205@btch.edu.cn

Received: April 3, 2026
Revised: May 6, 2026
Accepted: May 25, 2026
Published online: May 28, 2026

Abstract

Inflammatory bowel disease (IBD) is now recognized as a systemic disease that, beyond intestinal manifestations, involves extraintestinal organs, significantly increasing both the complexity of clinical management and the overall healthcare burden. This review summarizes the epidemiological characteristics and pathogenesis of IBD comorbidities, with a particular focus on the clinical features of psychiatric, neurological, dermatological, and cardiovascular comorbidities. It elucidates the core pathological mechanisms underlying these associations, including shared immune-inflammatory pathways and interactions along the gut-organ axes. The paper proposes that clinical management should adhere to the principles of early screening and individualized intervention, and emphasizes the importance of establishing a standardized multidisciplinary team model to improve patient outcomes.

Key Words: Inflammatory bowel disease; Comorbidity; Multidisciplinary team; Gut-organ axis

核心提要: 本文综述了炎症性肠病共病的流行病学特征与发病机制, 重点分析精神心理、神经系统、皮肤及心血管系统共病的临床特点, 阐述免疫炎症通路共享及肠-器官轴交互等核心病理机制. 提出临床应遵循早期筛查与个体化干预原则, 建立规范化的多学科协作诊疗模式, 以改善患者预后.

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0 引言

炎症性肠病(inflammatory bowel disease, IBD)主要包括克罗恩病(Crohn's disease, CD)和溃疡性结肠炎(ulcerative colitis, UC), 临床常表现为慢性腹泻(伴或不伴出血)、腹痛及体重减轻, 确诊需综合病史、体格检查、实验室检测及内镜评估[1,2]. 既往IBD高发于北美、欧洲及大洋洲等早期工业化地区[3], 但21世纪以来, 其在非洲、亚洲和拉丁美洲等新兴工业化地区的发病率显著上升[4,5]. 预计未来IBD患病率将在高收入国家持续攀升, 并在发展中国家加速蔓延, 进一步加剧全球医疗负担[6].

传统观念视IBD为局限于肠道的疾病, 然而现代医学证实其为一种全身性疾病, 许多患者除肠道表现外, 尚伴有肠外器官受累[7,8]. 除与IBD有直接病理关联的肠外表现(如关节、皮肤及眼部病变等)[8]外, 患者常合并其他与原发病无直接病理生理联系的疾病, 即"共病". 此类共病并非原发病的直接后果、治疗不良反应或解剖后遗症, 而是独立存在的伴随疾病[9,10]. 共病的存在显著增加了临床管理的复杂性与医疗成本[11,12], 并严重影响患者的生活质量及疾病预后[13,14].

本文旨在系统综述IBD共病的流行病学特征、发病机制及临床管理策略, 以期为临床诊疗提供参考.

1 IBD共病的分类

1.1 精神心理共病

IBD与精神心理疾病之间存在显著关联, 其共病模式复杂且呈谱系分布, 除焦虑与抑郁外, 尚涵盖多种精神障碍[15-17]. 一项2025年针对154例IBD患者的前瞻性研究显示[18], 57%的患者至少患有一种精神共病, 27%存在多重诊断; 其中重度抑郁症患病率达41.7%, 焦虑障碍为39.6%, 物质使用障碍为16.2%, 此外亦可见创伤后应激障碍、强迫症及双相情感障碍等.

二者共病的病理机制核心在于共享的免疫-炎症通路及肠-脑轴功能紊乱[19-21]. IBD与精神心理疾病均涉及免疫-炎症激活、氧化与硝化应激、色氨酸代谢异常及肠道屏障功能障碍等病理过程[22-28]. 肠道菌群失调通过迷走神经、炎症介质及代谢产物(如短链脂肪酸)影响中枢神经系统, 构成"菌群-肠-脑轴"的双向交互[29,30]; 在慢性炎症状态下, 促炎细胞因子[如肿瘤坏死因子α、白细胞介素(interleukin, IL)-6、IL-1β]穿透血脑屏障, 可诱发神经炎症及抑郁样行为[31-35]. IBD精神共病的发病机制尚存争议, 除特异性炎症外, 慢性躯体应激与社会心理因素亦为精神共病的重要维度. 未来亟待依托前瞻性队列与脑影像学, 量化炎症驱动与心理应激的独立权重及交互效应.

精神心理共病显著增加了IBD患者的临床与经济负担. 合并精神健康诊断的IBD患者, 其医疗费用约为无合并症者的两倍[36,37]. 此类共病不仅是IBD症状严重程度的独立预测因子, 亦会降低患者生活质量, 增加医疗服务利用率与照护者负担[38-40]. 在疾病管理方面, 针对共病的抗抑郁治疗可减少皮质类固醇需求、降低疾病复发率及相关检查需求[41,42]. 然而, 患者获取心理健康服务仍面临诸多障碍, 存在显著的未满足需求[43,44]. 有效识别并干预精神心理共病, 有助于改善患者的自我管理能力与治疗依从性, 减少非计划性医疗支出, 从而优化临床预后[45]. 因此, 将心理健康评估纳入IBD常规诊疗, 并建立多学科协作机制, 对改善患者预后至关重要.

1.2 神经系统共病

神经系统是IBD常见的肠外受累部位, 文献报道的合并率差异较大, 介于0.2%-67.0%之间[46]. 依据病因与病理机制, IBD合并神经系统疾病主要分为三类: 神经系统肠外表现、神经系统共患病以及神经系统并发症或药物不良反应. 明确分类对制定治疗策略及改善患者预后具有重要意义[10,47-49].

神经系统肠外表现与IBD病情活动密切相关, 常呈同步波动, 随着肠道炎症控制, 神经症状多可相应缓解[50-52]. 中枢神经系统受累可见脑血管炎、脑白质病变等, 临床表现包括偏瘫、偏盲、头痛及癫痫等; 部分病例神经系统症状先于IBD确诊前出现, 且神经功能恢复受限, 预后较差[52,53]. 周围神经系统病变在IBD患者中更为常见, 发生率约为0.9%-3.6%, 临床表现多为感觉异常, 可呈局灶性、多灶性或全身性, 患者经免疫抑制剂治疗后多见好转[54]. 中枢及周围神经系统均可发生脱髓鞘改变, IBD患者发生脱髓鞘疾病的风险显著增加, 其中CD和UC患者的患病风险分别为对照组的1.54倍和1.75倍[55].

神经系统共患病主要包括多发性硬化(multiple sclerosis, MS)、帕金森病(Parkinson's disease, PD)及重症肌无力(myasthenia gravis, MG)等[48]. 流行病学显示, IBD人群MS发生率是非IBD人群的1.5-1.7倍, 两者共享IL2RA、IL7R等遗传易感基因[56]. IBD患者的PD风险亦显著增高, 尤其是UC患者, 这可能与LRRK2基因介导的炎症反应及α-突触核蛋白清除障碍有关; 研究亦发现PD患者结肠活检中存在IL-6、干扰素γ等促炎因子表达, 提示两者存在潜在的重叠致病机制[57-59]. IBD合并MG的发生率约为0.9%, 常以眼睑下垂、复视等眼肌受累表现为首发症状[60].

药物不良反应与并发症亦是神经损害的重要原因. 药物诱发神经病变主要涉及环孢素A、甲硝唑、磺胺嘌呤类药物及生物制剂[61-65]. 并发症方面, 血栓栓塞相关脑血管病最为常见且后果严重. IBD患者血栓栓塞风险为常人的3.6倍, 活动期更增至15.8倍, 其中约26.1%的患者预后不良; UC患者的血栓栓塞风险增幅尤为显著[66]. 脑血管疾病在IBD患者中的发生率为0.12%-4%, 是导致患者致残致死的重要因素之一[67].

IBD神经系统共病的发病机制主要包括六大方面: 营养吸收不良(如维生素B1、B12、D、E及叶酸等缺乏)、代谢异常、免疫抑制相关感染、药物或手术医源性损伤、血栓栓塞以及免疫异常[68]. "肠-脑轴"交互作用被视为共病发病的核心机制. 针对该靶点的新型治疗策略, 如N-棕榈酰乙醇胺-恶唑啉, 已在实验研究中被证实可修复肠脑屏障并改善神经精神共病[69].

1.3 皮肤共病

IBD相关皮肤病主要分为三类: 特异性病变(如坏疽性脓皮病)、反应性皮肤病(如结节性红斑)及伴随性疾病(如银屑病、化脓性汗腺炎). 银屑病在普通人群中的患病率约为2%[70], 而在CD和UC患者中, 该比例分别显著上升至约10%和5.7%[71,72]. 银屑病患者罹患IBD的风险亦高于普通人群(约1.0% vs 0.4%)[73,74]. 临床表型方面, 银屑病合并CD患者通常发病年龄更早, 且肠道病变较重, 而皮肤表型相对较轻[75]. 两者发病机制高度重叠, 共享遗传背景及IL-23/Th17免疫炎症通路[76-78], 肠道中IL-23主要驱动Th17细胞分泌IL-17A、IL-22及IL-21, 进而引起肠上皮细胞间紧密连接损伤及中性粒细胞趋化浸润; 皮肤中IL-23活化的Th17细胞所分泌的IL-17A与IL-22主要靶向角质形成细胞, 导致其异常增殖与抗菌肽高表达.

结节性红斑是IBD最常见的反应性皮病, 多见于UC活动期, 典型表现为胫前疼痛性红色结节. 约1%-4%的结节性红斑由IBD引起, 其病情常与肠道炎症活动度平行, 随IBD有效控制多可缓解[76].

化脓性汗腺炎是一种慢性炎症性皮肤病, 好发于腋窝、腹股沟等间擦部位, 以反复发作的疼痛性结节、脓肿及窦道瘢痕形成为特征[79,80]. 研究表明, HS患者的IBD患病率高达3.3%(其中CD占2.5%, UC占0.8%), 显著高于普通人群(0.41%-0.74%)[81]. 与IBD共病患者无特异性HS表型, 但两者共享吸烟、肥胖及毛囊闭塞等危险因素, 且均涉及炎症小体激活与IL-17通路异常, 临床上需警惕两者并存的可能[81-83].

临床管理方面, IBD患者出现皮肤病变时, 需仔细鉴别其为IBD肠外表现、药物不良反应抑或独立共病. 早期识别并开展皮肤科与消化科的多学科协作(multidisciplinary team, MDT), 对改善患者预后至关重要.

1.4 心血管共病

IBD患者面临显著增加的心血管疾病风险, 主要涵盖静脉血栓栓塞(venous thromboembolism, VTE)、动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease, ASCVD)、心力衰竭及心律失常等[84]. IBD患者发生VTE的风险约为一般人群的2.5倍, ASCVD风险增加1.2倍, 心力衰竭风险增加2倍, 而年轻女性IBD患者的心律失常风险增加逾2倍[85-87].

IBD相关的血栓风险并非源于遗传性易栓症[88,89], 美国血液学会与欧洲心脏病学会均将IBD列为VTE的慢性中度风险因素[90,91]. 慢性全身性炎症是IBD心血管共病的核心机制: 持续的炎症状态不仅诱导高凝状态促进血栓形成[92,93]; 并加速动脉粥样硬化进程, 引发致动脉粥样硬化性血脂谱改变, 表现为小而密的低密度脂蛋白颗粒增多及高密度脂蛋白功能受损[84].

IBD的心血管管理策略亟需从被动治疗转向对高危患者的主动预防干预[94]. IBD患者ASCVD风险的增加无法仅通过传统心血管危险因素(如高血压、糖尿病等)来解释, 疾病活动度、女性性别及脂质谱的异常改变可能是其独特的独立危险因素[95,96]

2 临床管理策略与多学科协作

IBD共病受多因素影响(表1). 呈高度异质性: (1)亚型: CD易发皮肤及肛周病变, UC高发VTE与硬化性胆管炎; (2)活动度: 部分共病(如VTE)与肠道炎症同步, 重在控原发病; 部分(如银屑病)病程独立, 需多学科干预; (3)人群: 儿童多发育心理共病, 老年易发心血管及药源损害, 育龄女性需警惕心律失常及妊娠VTE; 和(4)激素增加精神、代谢与心血管风险, 免疫抑制剂及生物制剂等重塑感染与肿瘤共病图谱.

表1 炎症性肠病主要共病的流行病学特征及临床关联.

系统分类	共病疾病	流行病学数据	与IBD关联特征及临床备注
精神心理	重度抑郁症	IBD患者患病率41.7%	病理机制涉及免疫-炎症通路及肠-脑轴功能紊乱
	焦虑障碍	IBD患者患病率39.6%	与IBD病情严重程度相关
	物质使用障碍	IBD患者患病率16.2%	需关注药物相互作用及成瘾风险
神经系统	脱髓鞘疾病	CD和UC患病风险分别为对照组的1.54倍和1.75倍	中枢及周围神经系统均可受累
	多发性硬化	IBD人群发生率是非IBD人群的1.5-1.7倍	共享遗传易感基因(如IL2RA, IL7R)
	周围神经病变	IBD患者发生率0.9%-3.6%	较中枢病变更为常见, 多表现为感觉异常
	脑血管疾病	IBD患者发生率0.12%-4.0%	致残致死的重要因素, 与血栓栓塞密切相关
	重症肌无力	IBD合并MG发生率 0.9%	常以眼肌受累为首发表现
皮肤系统	银屑病	CD和UC患病率分别为10%和5.7%, 普通人群患病率约为2%	共享IL-23/Th17炎症通路及遗传背景
	化脓性汗腺炎	IBD患病率: 3.3%, 普通人群为0.41%-0.74%	共享吸烟、肥胖等危险因素及IL-17通路异常
	结节性红斑	1%-4%的结节性红斑由IBD引起	最常见的反应性皮病, 多见于UC活动期, 病情常与肠道炎症平行
心血管系统	静脉血栓栓塞	IBD发生风险约为一般人群2.5倍	IBD为VTE慢性中度风险因素
	动脉粥样硬化性心血管疾病	IBD发生风险增加1.2倍	慢性炎症诱导高凝状态及致动脉粥样硬化性血脂谱改变
	心力衰竭	IBD发生风险增加2.0倍	需关注药物心脏毒性及炎症对心肌的影响
	心律失常	IBD发生风险增加>2.0倍(年轻女性)	特定人群需密切监测心律变化

IBD: 炎症性肠病; CD: 克罗恩病; UC: 溃疡性结肠炎; MG: 重症肌无力; VTE: 静脉血栓栓塞症.

IBD共病的临床管理应遵循早期筛查、个体化干预及MDT的综合策略. 应将心理健康评估纳入IBD常规诊疗体系, 早期识别并干预可有效改善患者依从性、降低复发风险并减轻医疗负担. 临床需精准鉴别其为肠外表现、药物不良反应或独立疾病, 并据此采取免疫抑制治疗、药物调整或针对性的专科干预措施. 构建由消化科、精神科、神经科、皮肤科及心血管科等组成的MDT团队, 制定标准化临床路径, 是实现IBD共病规范化管理、改善患者预后的关键举措(图1).

图1 炎症性肠病共病临床管理. IBD: 炎症性肠病.

3 结论

IBD共病影响患者预后, 涉及精神心理、神经系统、皮肤及心血管等多个系统, 病理机制复杂, 涵盖免疫炎症通路共享、肠-器官轴交互及代谢异常等. 共病的存在显著增加了诊疗难度与医疗负担. 未来研究应聚焦于深入解析共病的遗传与分子机制, 挖掘早期预测生物标志物, 并探索针对肠-器官轴的干预靶点. 同时, 建立规范化的多学科协作诊疗模式, 加强早期筛查与个体化管理, 对优化IBD患者长期预后具有重要意义.

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备注

学科分类: 胃肠病学和肝病学

手稿来源地: 北京市

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科学编辑: 刘继红 制作编辑:张砚梁