Pathogenesis and management principles of extraintestinal manifestations in inflammatory bowel disease

doi:10.16138/j.1673-6087.2025.02.03

Abstract

Abstract:

Inflammatory bowel disease (IBD) is a group of chronic relapsing inflammatory gastrointestinal diseases, including Crohn disease (CD) and ulcerative colitis (UC). 30%-50% of IBD patients develop extraintestinal manifestations (EIM), which affect multiple organs such as the musculoskeletal, skin, eyes, and hepatobiliary systems. The occurrence of some EIM parallels the activity of IBD inflammation, while others may progress independently. The pathogenesis of EIM involves multiple factors, including genetic susceptibility, dysbiosis of the gut microbiota, and immune dysregulation. The diagnosis and management of EIM require multidisciplinary team (MDT) collaboration. EIM associated with IBD activity can be alleviated by controlling the underlying IBD, while EIM with independent progression requires individualized treatment strategies according to its pathogenesis. In addition to conventional treatments, tumor necrosis factor (TNF)-α inhibitors are core biological agents suitable for the treatment of most EIM. In the future, precision diagnosis, personalized treatment, and multidisciplinary collaboration will be essential directions in EIM research.

Key words: Inflammatory bowel disease, Extraintestinal manifestation, Multidisciplinary team collaboration, Personalized diagnosis and treatment

CLC Number:

R574

CAO Zhijun, LU Juntao. Pathogenesis and management principles of extraintestinal manifestations in inflammatory bowel disease[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(02): 112-119.

Figures/Tables 2

Table 1

Table 2

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器官和系统	EIM	临床特征	与肠道表现的关系
肌肉骨骼	外周关节炎Ⅰ型	少关节炎（<5 个关节），累及大关节，常见于下肢，急性发作	平行于肠道表现
	外周关节炎Ⅱ型	多关节炎（≥5 个关节），对称性，慢性炎症	独立进展
	AxSpA	慢性腰背痛、晨僵、骶髂关节炎、部分与HLA-B27相关	独立进展
皮肤	结节性红斑	触痛性红色结节，多见于小腿前侧	平行于肠道表现
	坏疽性脓皮病	坏死性皮肤溃疡、边缘隆起	独立进展
	Sweet综合征	发热、白细胞增多、痛性红斑样皮损	平行于肠道表现
眼部	葡萄膜炎	眼痛、畏光、视力下降，前葡萄膜炎更常见	平行于肠道表现
	巩膜外层炎	自限性，结膜充血、灼热感、瘙痒及轻度不适和疼痛	平行于肠道表现
	巩膜炎	眼部充血、疼痛，可能引起视功能损害	独立进展
肝胆	PSC	胆汁淤积、黄疸、肝纤维化，可进展至胆管癌	独立进展
肝胆	AIH	转氨酶升高、IgG增高，部分患者对免疫抑制治疗敏感	不确定

EIM分类	传统治疗	生物制剂
与IBD活动平行的EIM
外周关节炎^1）	NSAID（选择性COX-2抑制剂）；柳氮磺吡啶、甲氨蝶呤	TNF-α抑制剂；其他生物制剂疗效尚存争议
结节性红斑	支持治疗；短期口服糖皮质激素[0.5~1.0 mg/(kg·d)，1~2 周]	TNF-α抑制剂（基于IBD活动）
Sweet综合征	控制IBD原发疾病；系统性糖皮质激素[0.5~1.0 mg/(kg·d)]	有报道使用TNF-α抑制剂（IFX）
葡萄膜炎	前葡萄膜炎：局部糖皮质激素滴眼液；中间型、后葡萄膜炎、全葡萄膜炎：玻璃体内注射或全身糖皮质激素+免疫抑制剂（二线）	严重或伴IBD活动：TNF-α抑制剂（三线）
巩膜外层炎	人工泪液、冷敷；难治性病例可使用局部糖皮质激素滴眼液	无明确生物制剂适应证
独立进展的EIM
AxSpA	NSAID；柳氮磺吡啶、甲氨蝶呤无效	TNF-α抑制剂；JAK抑制剂^2）
巩膜炎	轻症：选择性COX-2抑制剂、局部糖皮质激素滴眼液（短期）；重症：系统性糖皮质激素1.0 ~1.5 mg/(kg·d)，逐步减量+免疫抑制剂（甲氨蝶呤、硫唑嘌呤、吗替麦考酚酯、钙调磷酸酶抑制剂）	TNF-α抑制剂（难治性病例）
坏疽性脓皮病	轻度：局部糖皮质激素、钙调磷酸酶抑制剂；重度：糖皮质激素[0.5~2.0 mg/(kg·d)，口服或静脉注射]、环孢素	TNF-α 抑制剂（IFX）
PSC	UDCA；肝移植（终末期）	TNF-α抑制剂、VDZ对于改善肝脏生化指标无效
AIH^3）	诱导缓解：泼尼松龙；维持治疗：硫唑嘌呤（一线），吗替麦考酚酯、 6-巯基嘌呤（二线）	难治性：TNF-α 抑制剂（IFX）