Gastroenterology

Gastroenterology

Volume 161, Issue 4, October 2021, Pages 1118-1132
Gastroenterology

Reviews in Basic and Clinical Gastroenterology and Hepatology
Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management

https://doi.org/10.1053/j.gastro.2021.07.042Get rights and content

Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.

Section snippets

Epidemiology, Frequency, and Chronology of Extraintestinal Manifestations in Inflammatory Bowel Disease

The prevalence and incidence of EIMs are dependent on the types of EIMs included in definitions, as outlined. More stringent definitions of EIMs, as suggested by the European Crohn’s and Colitis Organization’s working group on EIM, will result in lower estimates of prevalence: “An inflammatory pathology in a patient with IBD that is located outside the gut and for which the pathogenesis is either dependent on extension/translocation of immune responses from the intestine, or is an independent

Pathophysiology of Extraintestinal Manifestations in Inflammatory Bowel Disease

It has been assumed that the factors relevant for the pathogenesis of EIMs are similar or the same as for the intestinal inflammation.5 Genetic risk factors seem to play a role, as several are shared between IBD and various EIMs. Furthermore, environmental factors appear to play a role. The innate and adaptive immune system certainly plays an important role in the initiation and perpetuation of organ inflammation. In addition, the interaction with components of the microbiota can be important.

Summary

EIMs in patients with IBD contribute significantly to the burden of disease. Specific anti-inflammatory and symptomatic treatments and therapies in a multidisciplinary team approach are necessary to address EIMs adequately and improve the quality of life of our patients. In the absence of specific therapeutic biomarkers for EIMs, considerations of co-existing EIMs in patients with IBD can inform treatment selection and decisions.

Acknowledgments

All of the authors contributed equally to the conceptualization, writing, editing, and review of final draft of this manuscript.

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    Conflicts of interest Gerhard Rogler has consulted for Abbvie, ARENA, Augurix, Biogen, BMS, Boehringer, Calypso, Celgene, FALK, Ferring, Fisher, Genetech, Gilead, Janssen, MSD, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillots, Vifor, Vital Solutions, and Zeller; has received speaker's honoraria from Astra Zeneca, Abbvie, BMS, FALK, Janssen, MSD, Pfizer, Phadia, Takeda, Tillots, UCB, Vifor, and Zeller; has received educational grants and research grants from Abbvie, Ardeypharm, Augurix, Calypso, FALK, Flamentera, MSD, Novartis, Pfizer, Roche, Takeda, Tillots, UCB, and Zeller; and is co-founder of PharmaBiome. Abha Singh receives grant support from Pfizer and Novartis. Arthur Kavanaugh has consulted for Abbvie, Pfizer, Amgen, BMS, Eli Lilly, Novartis, and UCB. David T. Rubin serves as a consultant for Abbvie, Altrubio, Allergan, Inc, Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd, Bristol-Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, Glycominds, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, and Techlab, Inc; and receives grant support from Takeda.

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