Extraintestinal manifestations of inflammatory bowel disease: Epidemiology, diagnosis, and management

Larsen, Signe Benzon; Bendtzen, Klaus; Nielsen, Ole Haagen

doi:10.3109/07853890903559724

Cited by 257 publications

(186 citation statements)

References 148 publications

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“…Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), traditionally related to a Th2 cytokine profile mediated by 3], where immune homeostasis of the gastrointestinal tract is compromised. Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].Dendritic cells (DCs) are the most potent antigen presenting cells and determine the nature and type of immune responses [6,7]. Intestinal DCs control immune tolerance in the gastrointestinal tract [8][9][10].…”

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confidence: 99%

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IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

et al. 2012

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Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.Keywords: Dendritic cells r IL-6 r Mucosal immunity r Intestinal immunity r Ulcerative colitis Correspondence: Prof. Stella C. Knight e-mail: s.knight@imperial.ac.uk IntroductionThe gastrointestinal tract is in contact with a wide variety of commensal microbiota and diverse pathogens, and therefore C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 1338 David Bernardo et al. Eur. J. Immunol. 2012. 42: 1337-1353 requires a balance to be maintained between immunity and immune tolerance; the lack of immune responses against food antigens and/or the commensal microbiota is essential to maintain the homeostasis of the gastrointestinal tract [1]. Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), traditionally related to a Th2 cytokine profile mediated by 3], where immune homeostasis of the gastrointestinal tract is compromised. Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].Dendritic cells (DCs) are the most potent antigen presenting cells and determine the nature and type of immune responses [6,7]. Intestinal DCs control immune tolerance in the gastrointestinal tract [8][9][10]. DCs also maintain immune responses localized to specific tissues, since they imprint specific tissue-homing profiles on stimulated T cells [11]. Retinoic acid (RA), the active form of vitamin A following dehydrogenization by the RALDH2 enzyme controls some of the mechanisms of immune homeostasis of the gut [12][13][14]. RA-producing DCs mediate the IgA switching of B cells [15], the generation of T cells with a regulatory phenotype [10], and the imprinting of gut-homing markers on B and T cells [16,17], thereby keeping tolerogenic immune responses com...

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“…Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

et al. 2012

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“…Between 20-40% of the patients with CD develop chronic inflammatory conditions located in other organs and systems, which are known as extraintestinal manifestations (EIM) of the disease (1)(2)(3)(4)(5)(6)(7)(8)(9). EIM are associated with an additional and significant morbidity and impaired quality of life (10).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of adalimumab for the treatment of extraintestinal manifestations of Crohn's disease

Acosta

Lorenzo

Domínguez‐Muñoz

2012

Rev. esp. enferm. dig.

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Background and aims:Crohn's disease (CD) is commonly associated with inflammatory processes located in organs and systems others than the gut, which are known as extraintestinal manifestations (EIM) of the disease. The aim of this study was to assess the effectiveness of adalimumab (ADA) for the treatment of EIM in patients with CD.Methods: forty two consecutive CD patients with at least one EIM were prospectively included in a open-label study. Patients received ADA (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six months and the effectiveness and safety of ADA for EIMs were assessed. The influence of gender, age, smoking habits, family history of inflammatory bowel disease, phenotype and previous anti-TNF treatment on EIM resolution was also investigated.Results: at month six, 76.2% of the patients showed remission or response in CD (33.3% remission and 42.9% any response). EIM showed a parallel course with CD in most cases, and showed remission or response in 66.7% of patients (38.1% remission and 28.5% any response). Patients with any response of their EIM condition were younger than those with no response (p = 0.04). No relationship was found between sex, tobacco, family history of IBD, phenotype and previous treatment with anti-TNF, and EIM resolution.Conclusions: adalimumab is effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF-naïve status appears to influence the response.

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“…In the studies investigating the frequency of extraintestinal involvement in IBD patients, it was reported that systemic involvement was present in approximately one-third of the patients (6,7). Depending upon the areas of reporting, this rate ranges between 20% and 40% (6).…”

Section: Discussionmentioning

confidence: 99%

İnflamatuvar barsak hastalığı tanılı olgularımızda ekstraintestinal tutulum tipleri ve sıklığı

Yeşıl¹,

Şenateş²,

Kayataş³

et al. 2015

Endoskopi Gastrointestinal

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Extraintestinal manifestations of inflammatory bowel disease: Epidemiology, diagnosis, and management

Cited by 257 publications

References 148 publications

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

Efficacy of adalimumab for the treatment of extraintestinal manifestations of Crohn's disease

İnflamatuvar barsak hastalığı tanılı olgularımızda ekstraintestinal tutulum tipleri ve sıklığı

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