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Ulcerative colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. UC has evolved into a global burden given its high incidence in developed countries and the substantial increase in incidence in developing countries. An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. Since the early 2000s, anti-tumour necrosis factor (TNF) treatment has significantly improved treatment outcomes. Advances in medical treatments have enabled a paradigm shift in treatment goals from symptomatic relief to endoscopic and histological healing to achieve better long-term outcomes and, consequently, diagnostic modalities have also been improved to monitor disease activity more tightly. Despite these improvements in patient care, a substantial proportion of patients, for example, those who are refractory to medical treatment or those who develop colitis-associated colorectal dysplasia or cancer, still require restorative proctocolectomy. The development of novel drugs and improvement of the treatment strategy by implementing personalized medicine are warranted to achieve optimal disease control. However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

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Fig. 1: Global incidence of ulcerative colitis.
Fig. 2: Pathophysiology of ulcerative colitis.
Fig. 3: Endoscopic and histological features of ulcerative colitis.
Fig. 4: Proposed diagnostic flow for ulcerative colitis in the future.
Fig. 5: Management of ulcerative colitis according to disease severity.
Fig. 6: Ileal pouch-anal anastomoses.
Fig. 7: Main ulcerative colitis drugs in the pipeline and their targets.

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Acknowledgements

B.S. acknowledges the DFG (German Research foundation) for funding her research (CRC-TRR 241 and CRC1340).

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Authors and Affiliations

Authors

Contributions

Introduction (T.H., T.K. and S.D.); Epidemiology (C.N.B.); Mechanisms/pathophysiology (B. Siegmund); Diagnosis, screening and prevention (S.C.W.); Management (M.F. and B. Shen); Quality of life (C.L.B. and L.P.-B.); Outlook (T.K.); Overview of Primer (T.K. L.P.-B and T.H.).

Corresponding authors

Correspondence to Taku Kobayashi or Toshifumi Hibi.

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Competing interests

T.K. receives research support from AbbVie GK, Alfresa Pharma, EA Pharma, Kyorin Pharmaceutical Co., Ltd, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Thermo Fisher Scientific and ZERIA; receives advisory fees from AbbVie GK, Activaid, Alfresa Pharma, Bristol-Myers Squibb, Celltrion, CovidienÐ, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Kissei, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical and Thermo Scientific and receives lecture fees from AbbVie GK, Astellas, Alfresa Pharma, Celltrion, EA Pharma, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Takeda Pharmaceutical and ZERIA. B. Siegmund received speaker’s fees from Abbvie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, and Takeda (B. Siegmund served as representative of the Charité) and has served as consultant for AbbVie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus and Takeda. C.L.B. receives honoraria from AbbVie and Ferring. S.C.W. reports consultancy fees from AbbVie, AbGenomics, Celltrion, Ferring Pharmaceuticals Inc., Gilead, Janssen, Pfizer, Takeda, and Tanabe and receives lecture fees from AbbVie, Celltrion, Eisai, Excelsior Biopharma Inc., Ferring Pharmaceuticals Inc., Janssen, Takeda, Tanabe, Tillotts Pharma, and TSPC (Taiwan Specialty Pharma Corp.). M.F. receives research grants from Amgen, Biogen, Janssen, Pfizer, and Takeda and receives consultancy fees from AbbVie, Boehringer-Ingelheim, Janssen, MSD, Pfizer, Sandoz, and Takeda and receives speaker fees from AbbVie, Amgen, Biogen, Boehringer-Ingelheim, Falk, Ferring, Janssen, Lamepro, MSD, Mylan, Pfizer, and Takeda. B. Shen receives consultant fees for AbbVie, Takeda and Janssen. C.N.B. has received educational grants from AbbVie Canada, Janssen Canada, Pfizer Canada, Shire Canada, and Takeda Canada and a research grant from AbbVie Canada. C.N.B. has performed contract research for AbbVie, Boehringer Ingelheim, Celgene, Janssen, Pfizer and Roche. He is on the advisory boards for AbbVie Canada, Janssen Canada, Pfizer Canada, Takeda Canada, and Shire Canada and consulted to Mylan Pharmaceuticals. S.D. receives consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ely Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB Inc., and Vifor. L.P.-B. receives research grants from AbbVie, MSD, and Takeda and reports personal fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, BMS, Celltrion, Celgene, Enterome, Enthera, Ferring, Fresenius, Genentech, Gilead, Hikma, Index Pharmaceuticals, Janssen, Lilly, MSD, Mylan, Nestle, Norgine, Oppilan Pharma, OSE Immunotherapeutics, Pfizer, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Sublimity Therapeutics, Takeda, Vifor, and Tillots and stock options from CTMA. T.H. has received research grants from AbbVie, EA Pharma, JIMRO, Otuska Holdings, and Zeria Pharmaceuticals and lecture fees from Aspen Japan KK, AbbVie GK, Ferring, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Mitsubishi-Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku Pfizer, Takeda Pharmaceutical, and Zeria Pharmaceutical and advisory or consultancy fees from AbbVie, Bristol-Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Gilead Sciences, Janssen, Kyorin, Mitsubishi-Tanabe Pharma, Nichi-Iko Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Zeria Pharmaceuticals.

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Nature Reviews Disease Primers thanks O. H. Nielsen, D. Rubin, J. Schölmerich and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Stricture

An abnormal narrowing of the digestive tract.

Fistula

An abnormal connection between two organs or spaces.

Moon face

A medical sign of facial swelling with deposition of fat.

Tenesmus

An abnormal feeling of incomplete defecation.

Megacolon

Dilation of the colon without any mechanical obstruction.

Colonic crypt

A repetitive invagination of colonic surface epithelium.

Crypt abscess

A collection of neutrophils in an intestinal crypt.

Basal plasmocytosis

The presence of plasma cells beneath the base of the crypts.

Metaplasia

A transformation of one differentiated cell type to another.

Goblet cells

A type of colonic epithelial cell that secrete mucus.

Mucosal friability

An abnormally fragile surface of the intestine due to inflammation.

Ileostomy

A surgically created opening of the small intestine in the abdominal wall.

Sinus

A space or a cavity in a bone.

Nephrolithiasis

The process of formation of a kidney stone.

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Kobayashi, T., Siegmund, B., Le Berre, C. et al. Ulcerative colitis. Nat Rev Dis Primers 6, 74 (2020). https://doi.org/10.1038/s41572-020-0205-x

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