炎症性肠病的肠外表现与治疗

炎症性肠病(IBD)病变主要累及肠道,但亦常合并各种肠外表现。许多肠外表现可作为IBD的首发症状出现,有些甚至危及生命。目前关于IBD肠外表现的报道较多,但大样本的流行病学调查不多,而其特有的治疗更少。     

炎症性肠病的肠外表现和并发症

<正>克罗恩病(CD)和溃疡性结肠炎(UC)都属于炎症性肠病(IBD)。IBD肠外表现的病因可能涉及到多种因素,有时候IBD的肠外表现(IBD本身累及其他器官)与IBD继发的肠外并发症(如营养不良、慢性炎症、药物的不良反应等所致)比较难鉴别。一般而言,IBD的肠外表现与IBD的活动性一致,但有些可能与IBD的活动性不一样,例如原发性硬化性胆管炎和强直性脊柱炎。这些肠外表现的症状可     

炎症性肠病肠外表现的临床特点及治疗

炎症性肠病(inflammatory bowel disease, IBD)是一种慢性、易复发、免疫性疾病,主要累及肠道。IBD可出现多种肠外表现,增加发病和死亡的风险。因此早期识别肠外表现至关重要,可促进更好的临床管理。在仔细回顾了最新的文献之后,本文旨在向读者介绍IBD患者肠外表现的最新治疗管理。     

炎症性肠病的肠外表现

炎症性肠病（IBD）肠外表现多种多样，发生率一般为1／3左右。多累及关节、皮肤、眼部以及肝胆系统。一些肠外表现可先于肠道原发病出现，而一旦出现某一种肠外表现，患者发生其他肠外表现的风险亦随之升高。发病机制仍然不确定，目前认为结肠上皮内有些蛋白质可能与眼、关节、皮肤及胆道存在交叉反应；或由于粘膜免疫细胞和内皮细胞间黏附分子间存在交互作用。现将一些临床常见及相对罕见的肠外表现作一综述，以期引起重视。     

炎症性肠病合并胆系疾病的诊治策略

炎症性肠病(IBD)是一类肠道慢性非特异性炎症性疾病,主要包括溃疡性结肠炎和克罗恩病。IBD患者除消化道症状外,常合并其他肠外表现,可累及骨骼肌肉、皮肤、眼部、肝胆、胰腺、神经、泌尿生殖、肺部、心脏、血液等多系统。胆系疾病是IBD的肠外表现之一,主要包括原发性硬化性胆管炎、IgG4相关性硬化性胆管炎、原发性胆汁性胆管炎、胆石症等。胆系疾病可表现为无症状患者一过性肝功能异常,也可能是威胁生命的肝衰竭,但不同的胆系疾病治疗及预后大有不同,需仔细鉴别诊断。就IBD合并胆系疾病进行评述,以期帮助临床医师熟悉IBD患者胆系疾病的临床表现及诊治策略。     

肠易激综合征与炎症性肠病

近年发现,炎症性肠病(IBD)患者发病早期或缓解期时常表现为肠易激综合征(IBs)症状,且IBD与IBS的临床表现具有一定的相似性。因而IBS与IBD的相关性受到广泛的重视。此文就IBS与IBD的发病机制及临床相关性予以阐述,以期为临床个体化治疗提供借鉴。     

溃疡性结肠炎的肠外皮肤表现

溃疡性结肠炎(UC)的发病率呈逐年上升趋势,其发病机制尚未完全明确。UC肠外表现(EIM)多样,可涉及骨关节、皮肤、肝胆、眼等全身多个器官系统,一种EIM的出现增加了其他EIM的发生风险。皮肤表现是UC重要的EIM,可分为反应性皮肤表现、免疫相关性皮肤表现、营养不良和治疗导致的皮肤表现。本文就UC肠外皮肤表现的临床症状、诊断、治疗等作一综述。     

炎症性肠病血栓栓塞机制的研究进展

静脉血栓栓塞(VTE)是炎症性肠病(IBD)公认的肠外表现,发病率和死亡率均较高。IBD血栓栓塞的机制尚不完全清楚,涉及多种获得性和遗传性因素。目前主要指南推荐给予IBD患者机械或药物治疗以预防血栓栓塞,但临床上尚未广泛应用。本文就IBD血栓栓塞的机制作一综述。     

中国大陆地区炎症性肠病肠外表现的汇总分析

目的:总结我国大陆地区炎症性肠病(IBD)肠外表现,为临床医师快速准确诊断本病提供线索.方法:对我国近30年来报道的IBD文献进行计算机CBM与文献追溯检索,对符合标准的肠外病变部位数据进行摘录、登记、统计分析.结果:1979-01/2008-01符合标准的文献169篇.报道UC患者14963例,CD患者3659例,大约15%UC患者与31%CD患者存在多种多样的肠外表现.结论:IBD除累及消化系外,常同时累及多个系统,易导致误诊,给临床诊断带来困难.     

炎症性肠病相关肺部病变的研究进展

炎症性肠病(inflammatory bowel disease,IBD)是一种系统性疾病,不仅累及肠道,亦可出现多种肠外表现(extraintestinal manifestations,EIMs)。IBD的肠外表现涉及多个系统,累及肺部者相对少见,常被忽视。IBD相关肺部异常包括药物不良反应、气道疾病、肺间质疾病、血管疾病、胸膜疾病及其他形式的肺损伤。本文归纳了炎症性肠病合并肺部异常的类型、临床特点和治疗等方面的进展,旨在为IBD合并肺部异常的诊疗提供参考。     

Pathogenesis and clinical approach to extraintestinal manifestations of inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC), both should be considered as systemic diseases as they are associated with clinical manifestations involving the organs outside the alimentary tract. In a genetically susceptible host with inflammatory bowel disease (IBD), complex interaction of bacterial or other local factors in the colon with antigen presenting cells may trigger an immune reaction to a shared antigen in the involved organs. These extraintestinal manifestations (EIM) are observed in up to 20-40% of the patients with IBD. Patients with CD are more susceptible to EIMs than patients with UC. Joints, eyes, skin and biliary tract are the most commonly involved organ systems. Some manifestations such as uveitis, episcleritis may precede the onset bowel disease and some may occur in conjunction with or subsequent to the diagnosis of active bowel disease. Although many EIMs tend to follow the clinical course of IBD and respond to the treatment of underlying bowel disease, some EIMs such as primary sclerosing cholangitis and ankylosing spondylitis tend to follow a course independent of the bowel disease activity. Biological agents, particularly anti-TNFa based therapies now assume an important role in the treatment of EIMs. Early recognition and treatment of EIMs are crucial in preventing major morbidity.     

Extraintestinal Manifestations in Patients with Inflammatory Bowel Disease: Study Based on the ENEIDA Registry

Background

Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others.

Aims

Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date.

Methods

Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018.

Results

The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2–19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9–13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7–5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9–2.2) for ocular manifestations, and 0.7% (95% CI 0.6–0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn’s disease, p?<?0.001), gender (female, p?<?0.001), the need for an immunomodulator (p?<?0.001) or biologic drugs (p?<?0.001), a previous family history of IBD (p?<?0.001), and an extensive location of IBD (p?<?0.001) were risk factors for the presence of EIMs.

Conclusions

One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn’s disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

     

Efficacy of infliximab for extraintestinal manifestations of inflammatory bowel disease

Opinion statement Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are associated with extraintestinal manifestations (EIMs) in approximately 40% of patients. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor-α, is effective for induction and maintenance of remission of CD and UC. The role of infliximab for EIMs related to IBD has been less studied, but it is likely as effective. The EIMs may run a course that parallels IBD activity or may present separately. The EIMs that parallel intestinal inflammation (eg, peripheral arthritis, pyoderma gangrenosum, erythema nodosum, and episcleritis) generally respond to infliximab. Therefore, treating patients with IBD who have one of these EIMs will more often than not improve the EIM. The EIMs that run a separate course from IBD are more difficult to treat. Ankylosing spondylitis (AS), uveitis, and primary sclerosing cholangitis (PSC) have variable responses to IBD medications. Infliximab is efficacious for uveitis and is approved by the US Food and Drug Administration for treatment of AS. The efficacy of infliximab for PSC is unknown. The dosing schedule of infliximab for IBD patients with EIMs should be induction doses with 5 mg/kg at 0, 2, and 6 weeks followed by every 8 weeks. Whether long-term infliximab therapy is necessary to maintain remission of EIMs, as in the case of IBD, has not been established.     

Extraintestinal manifestations of inflammatory bowel disease

The idiopathic inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, may be complicated by extraintestinal manifestations (EIMs) in up to 40% of patients. Reports suggest that almost every organ system may be affected. The EIMs are a significant cause of morbidity and may be particularly distressing for the patient. Recent attempts have been made to define the phenotype of IBD in patients of different ethnicities. These studies have highlighted potential racial variations in the prevalence of specific EIMs, findings that are perhaps not surprising given the influence of genetic factors in their pathogenesis. Certain EIMs are related to the activity of the bowel disease, and their management often involves careful monitoring while the IBD is brought under control. Other EIMs, however, typically run a course independent of the IBD activity, and specific, targeted treatments may be required, even including biologic agents such as infliximab.     

Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study

BACKGROUND: Genetic factors may play a role in determining the development of extraintestinal manifestations (EIMs) and autoimmune diseases (AD) in patients with inflammatory bowel disease (IBD). We sought to determine the association between EIMs and AD in patients with first-degree familial IBD and sporadic IBD. METHODS: All patients evaluated in the IBD Clinic at the Mayo Clinic between January and September 1999 were offered enrollment. One clinic patient who was matched on age, gender, and geographic area of residence to each case served as controls. Information regarding EIMs and AD was obtained from a questionnaire completed by all IBD patients and controls. The adjusted odds ratios (95% CIs) for EIM as a function of first-degree familial IBD compared with sporadic IBD and AD as a function of first-degree familial IBD compared with sporadic IBD were estimated with a matched one-to-one conditional logistic regression model. RESULTS: Two hundred forty-three patients with IBD (47 first-degree familial IBD, 196 sporadic IBD) were enrolled. Forty percent of IBD patients had one or more EIMs compared with 14% matched controls [p < 0.001; OR = 3.1 (95% CI: 1.8 to 5.2)]. A total of 259 of the 1122 IBD patients and their first-degree family members indicated one or more EIM diagnoses (23%). The association between "familial versus sporadic" status and any EIM diagnosis was not significant [p = 0.59, the odds for an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.2 (95% CI: 0.8 to 1.7)]. Ten percent of IBD patients had one or more AD diagnoses compared with 19% matched controls [p = 0.04; OR = 0.4 (95% CI: 0.1 to 0.96)]. A total of 153 of the 1122 IBD patients and their first-degree family members indicated one or more AD diagnoses (14%). The association between disease status ("familial or sporadic") versus any AD diagnosis was not significant [p = 0.68, the odds for any AD in an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.4 (95% CI: 0.9 to 2.3)]. CONCLUSIONS: There was a positive association between IBD status (patient vs control) versus EIM, but not AD. A significant positive association between disease type (familial or sporadic) versus either EIM or AD was not detected.     

Extraintestinal manifestation of inflammatory bowel disease in Asian patients: A multinational study

Background/aimAlthough inflammatory bowel disease (IBD) incidence has increased over the past two decades in Asia, data on extraintestinal manifestations (EIMs) of IBD in Asian patients are limited. We aimed to evaluate the prevalence and clinical characteristics of EIMs in Asian IBD patients.MethodsIn total, 1,764 patients (1,130 with ulcerative colitis [UC] and 634 with Crohn's disease [CD]) were recruited from 10 tertiary centers in Asia. The medical records of IBD patients were retrospectively reviewed for the presence, clinical characteristics, chronological order, and therapeutic management of EIMs.ResultsEIMs were reported in 199 (11.3%) patients, of which 17 (1.0%) patients had multiple EIMs. EIMs were more prevalent in CD patients (P = 0.02). Multiple logistic regression analysis revealed that female sex (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.15–3.55), stricture (OR 2.49, 95% CI 1.41–4.39) and female sex (OR 2.57, 95% CI 1.52–4.34), extensive colitis (OR 2.63, 95% CI 1.57–4.41) were associated with EIMs in CD and UC patients respectively. EIMs appeared in 8% of patients before IBD diagnosis; 95% of cases with EIM could be managed via first-line therapy.ConclusionEIM prevalence is lower among Asian IBD patients than among patients from Western countries; however, the risk factors for EIM were similar between both populations.     

Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel disease

The inflammatory bowel diseases (IBD), notably Crohn's disease (CD) and ulcerative colitis (UC), are systemic inflammatory diseases primarily involving the gastrointestinal tract. Twenty percent to 40% of patients with IBD develop extraintestinal inflammation and symptoms, known as extraintestinal manifestations (EIMs).1-7 The most common EIMs affect the joints, skin, eyes, and biliary tract. The EIMs associated with IBD bear a negative impact on patients with UC and CD. Thus, the successful treatment of EIMs is essential for improving the quality of life of IBD patients. For most EIMs, their resolution often parallels that of the active IBD in both timing and therapy required. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis run a clinical course independent of IBD disease activity. The advent of biologic response modifiers, e.g., tumor necrosis factor-alpha (TNF) inhibitors, has improved the treatment of IBD and its associated EIMs. This article reviews the therapeutic experiences of the 2 most widely used anti-TNF neutralizing antibodies, infliximab and adalimumab, for immune-mediated EIM of IBD.     

Extraintestinal complications of inflammatory bowel disease

Recent studies of extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have demonstrated the importance of genetic predisposition in the etiology of musculoskeletal and cutaneous manifestations. In addition, small studies have shown infliximab to be effective in treating troublesome EIMs, particularly in pyoderma gangrenosum. Other trials have examined the safety of cyclooxygenase-2-specific nonsteroidal inflammatory drugs in IBD. Further work has been done on osteoporosis in IBD, and the American Gastroenterological Association has published a technical review and management guidelines for osteoporosis in a range of gastrointestinal disorders. However, despite further publications, debate remains concerning whether IBD patients with osteoporosis have a significant increase in fracture risk, and whether the bone loss is related to the disease or to its treatment.     

Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes

BACKGROUND & AIMS: There are few systematic studies on the natural history or immunogenetic associations of erythema nodosum (EN) or ocular inflammation in inflammatory bowel disease (IBD), but they are reportedly more common in patients with other extraintestinal manifestations (EIMs), particularly arthritis. Immunogenetic associations have previously been described in IBD arthritis and in EN associated with sarcoidosis. This study examined the clinical features and HLA-B, DR, and tumor necrosis factor alpha (TNF-alpha) associations of ocular inflammation and EN and their clinical and immunogenetic relationship to arthritis in IBD. METHODS: Details of EN and ocular inflammation were gathered by case-note review and questionnaire in 976 ulcerative colitis patients and 483 Crohn's patients. Sequence-specific PCR typing for polymorphisms in HLA-B, DR, and TNF-alpha was performed in 39 EN and 40 ocular patients. Results were compared with 490 IBD controls without EIMs, 38 patients with type 1 and 31 with type 2 peripheral arthritis, and 16 AS patients. RESULTS: EN and ocular inflammation were more common in women, were associated with IBD relapse, and recurred in approximately 30% of patients. They occurred more commonly with arthritis and AS than expected by chance. Ocular inflammation was strongly associated with HLA-B*27, B*58, and HLA-DRB1*0103. There is a weak association between EN and HLA-B*15 but a strong association with the -1031 TNF-alpha. CONCLUSIONS: EN, uveitis, and arthritis associated with IBD occur together commonly. They are associated with genes in the HLA region, and linkage disequilibrium between these genes may account for the clinical picture of overlapping but independent clinical manifestations.     

Combined therapeutic approach： Inflammatory bowel diseases and peripheral or axial arthritis

Inflammatory bowel diseases （IBDs）, particularly Crohn＇s disease （CD） and ulcerative colitis （UC）, are associated with a variety of extra-intestinal manifestations （EIMs）. About 36% of IBD patients have at least one EIM, which most frequently affect the joints, skin, eyes and the biliary tract. The EIMs associated with IBD have a negative impact on patients with UC and CD, and the resolution of most of them parallels that of the active IBD in terms of timing and required therapy; however, the clinical course of EIMs such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis is independent of IBD activity. The peripheral and axial arthritis associated with IBD have traditionally been treated with simple analgesics, non-steroidal anti-inflammatory drugs, steroids, sulfasalazine, methotrexate, local steroid injections and physiotherapy, but the introduction of biological response modifiers such as tumor necrosis factor-α blockers, has led to further improvements.