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Inflammatory Bowel Disease (Ulcerative colitis & Crohn's Disease)

Inflammatory Bowel Disease (Ulcerative colitis & Crohn's Disease)

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Inflammatory Bowel Disease

Inflammatory bowel diseases are autoimmune disorders characterized by chronic or remitting intestinal inflammation.

Ulcerative colitis is associated with inflammation of the mucosal and submucosal layers, and is restricted to the colon and rectum.

Crohn's disease is characterized by transmural inflammation (that is, inflammation can reach all layers of the GI tract) and can affect any segment of the GI tract.

In some patients, inflammation is present, but the designation of ulcerative colitis vs Crohn's disease is difficult – - About 5-15% of cases are considered "indeterminant" colitis (although this may be a temporary label, as some cases will become more definitive over time).

Diagnosis relies on endoscopy.

Most patients with inflammatory bowel disease are diagnosed in their teens/early 20s; with ulcerative colitis, we see a second "peak" in patients in their 60's or 70's.

Many studies suggest a female predominance in Crohn's disease.

Genetic factors play a role in development of disease; for example, mutations in NOD2 are associated with Crohn's disease.

Environmental factors are also important (ie., diet, cigarette smoking, medications ).

As autoimmune disorders, the pathogenesis of ulcerative colitis and Crohn's disease have much in common. They are the result of detrimental interactions between the host immune response, intestinal microbiota, and intestinal barrier defects.

However, there are key differences in the pathogenesis of the two disorders; for example, different types of T-helper cells are thought to play major roles in each.

Inflammatory bowel disease is associated with neoplasia, which is influenced by the duration and severity of the disease.

Crohn's disease

The so-called "skip lesions" can affect any segment of the GI tract, but most commonly involve the ileum and colon, and the rectum is usually spared ("skip" refers to its discontinuous pattern).

We draw the GI tract in section to show transmural inflammation with wall thickening and "creeping fat" that wraps around the GI tract.

Different types of lesions:

  • Aphthous erosions – these early signs of Crohn's disease are shallow, whitish or opaque sores in the mucous membrane.
  • Longitudinal, aka, rake or "bear claw" ulcers look as if someone dragged a rake down the lining of GI tract.
  • Eventually, the lining of the GI tract can take on a "cobblestone" appearance, as tissue becomes so crowded with ulcers that it resembles a cobblestone sidewalk.
  • Fissures in the wall form and can progress to form fistulas that open to abdominal/pelvic cavity or connect with other organs (such as the vagina).
  • As a result of chronic inflammation, fibrosis of the GI wall also occurs.

Histological Features:
Crohn's disease is associated with intestinal wall crypt distortion, fissures, and, in up to 60% of cases, noncaseating granuloma formation.

Crohn's disease is characterized by Th1/Th17 cell-mediated inflammation.

Signs/Symptoms:

  • Abdominal cramping (often on the right side, where the ileum meets the large intestine)
  • Diarrhea (potentially bloody diarrhea)
  • Fever and malaise
  • Weight loss (due to malabsorption)
  • Perianal lesions (25% of patients) - we show skin tags near the anus and fistulas that form in the anal canal and open to the perianal region.

Complications:
Problems related to fistulas, fissures, and obstructive strictures; dysplasia and adenocarcinoma; and, anemia from chronic blood loss.

Treatments:
Patients are advised to avoid cigarette smoking and nicotine, as nicotine exacerbates inflammation in Crohn's disease. Patients are often prescribed anti-inflammatories and/or immune suppressors; in some cases, surgery is necessary to remove parts of the colon.

Ulcerative colitis

UC primarily targets the colon and rectum, and is characterized by continuous lesions (in contrast to Crohn's disease, which typically spares the rectum and causes patchy inflammation).

We draw a portion of the GI tract in section to show the mucosal and submucosal inflammation.

Inflammation creates sunken, red/bloody ulcers with a friable or crumbly appearance (the remaining tissue of the GI tract appears as light/beige patches rising above the sunken ulcers).

Inflammation destroys the submucosal vascular network.

Mucosa is bloody when inflammation is active.

We re-draw the GI tract in cross section to show the sunken ulcerous tissue with the remaining mucosa creating "pseudopolyps."

Histological Features:
UC is characterized by branching and distension of the intestinal crypts, with neutrophils present during active inflammation. We show crypt abscesses with neutrophils.

UC inflammation is Th2 cell-mediated.

Signs/Symptoms:
Patients experience bloody diarrhea with rectal bleeding, abdominal pain, fever, and weight loss.

Complications:
Toxic ulceritis, toxic megacolon, and intestinal perforation.

Dysplasia and adenocarcinoma can occur and are more likely when the entire colon is involved (pancolitis).

Treatments:
Anti-inflammatories, immune suppressors, and colectomy.
Oddly enough, patients who smoke cigarettes are more likely to experience bouts of ulcerative colitis upon quitting.

Extraintestinal manifestations and complications of inflammatory bowel disease:

Most common are skin lesions (in up to 40% of patients), uveitis, and arthritis.

Less common, but potentially deadly, include involvement of the liver/gallbladder, lung, pancreas, and kidneys.

Board Review

Inflammatory Bowel Disease

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USMLE & COMLEX-USA

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References

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  • Brand, S. "Crohn's Disease: Th1, Th17 or Both? The Change of a Paradigm: New Immunological and Genetic Insights Implicate Th17 Cells in the Pathogenesis of Crohn's Disease." Gut 58, no. 8 (August 1, 2009): 1152–67. https://doi.org/10.1136/gut.2008.163667.
  • Bsat, Marwa, Laurence Chapuy, Manuel Rubio, Ramses Wassef, Carole Richard, Frank Schwenter, Rasmy Loungnarath, Geneviève Soucy, Heena Mehta, and Marika Sarfati. "Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients." Frontiers in Immunology 10 (2019). https://www.frontiersin.org/article/10.3389/fimmu.2019.01177.
  • Corica, Domenico, and Claudio Romano. "Renal Involvement in Inflammatory Bowel Diseases." Journal of Crohn's & Colitis 10, no. 2 (February 2016): 226–35. https://doi.org/10.1093/ecco-jcc/jjv138.
  • "Crohn Skin Disease | DermNet NZ." Accessed January 14, 2022. https://dermnetnz.org/topics/crohn-skin-disease.
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  • Galitovskiy, Valentin, Jing Qian, Alexander I. Chernyavsky, Steve Marchenko, Vivian Gindi, Robert A. Edwards, and Sergei A. Grando. "Cytokine-Induced Alterations of Α7 Nicotinic Receptor in Colonic CD4 T Cells Mediate Dichotomous Response to Nicotine in Murine Models of Th1/Th17- versus Th2-Mediated Colitis." The Journal of Immunology 187, no. 5 (September 1, 2011): 2677–87. https://doi.org/10.4049/jimmunol.1002711.
  • Graham, Daniel B., and Ramnik J. Xavier. "Pathway Paradigms Revealed from the Genetics of Inflammatory Bowel Disease." Nature 578, no. 7796 (February 2020): 527–39. https://doi.org/10.1038/s41586-020-2025-2.
  • Guan, Qingdong. "A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease." Journal of Immunology Research 2019 (December 1, 2019): 1–16. https://doi.org/10.1155/2019/7247238.
    "Idiopathic Inflammatory Bowel Disease - ClinicalKey." Accessed January 12, 2022. https://www-clinicalkey-com.proxy.ulib.uits.iu.edu/#!/content/book/3-s2.0-B9781437709254000195.
  • "Inflammatory Disorders of the Small Intestine - ClinicalKey." Accessed January 12, 2022. https://www-clinicalkey-com.proxy.ulib.uits.iu.edu/#!/content/book/3-s2.0-B9781455707478000169?scrollTo=%23hl0001948.
  • Kaplan, Gilaad G., and Siew C. Ng. "Understanding and Preventing the Global Increase of Inflammatory Bowel Disease." Gastroenterology 152, no. 2 (January 2017): 313-321.e2. https://doi.org/10.1053/j.gastro.2016.10.020.
  • Kellermann, Lauge, and Lene Buhl Riis. "A Close View on Histopathological Changes in Inflammatory Bowel Disease, a Narrative Review." Digestive Medicine Research 4, no. 0 (March 30, 2021). https://doi.org/10.21037/dmr-21-1.
  • Langenfeld, Sean J. Inflammatory Bowel Disease, An Issue of Surgical Clinics. Elsevier Health Sciences, 2019.
  • Lee, Seung Hoon, Jeong eun Kwon, and Mi-La Cho. "Immunological Pathogenesis of Inflammatory Bowel Disease." Intestinal Research 16, no. 1 (January 2018): 26–42. https://doi.org/10.5217/ir.2018.16.1.26.
  • Mirsepasi-Lauridsen, Hengameh Chloé, Bruce Andrew Vallance, Karen Angeliki Krogfelt, and Andreas Munk Petersen. "Escherichia Coli Pathobionts Associated with Inflammatory Bowel Disease." Clinical Microbiology Reviews 32, no. 2 (January 30, 2019): e00060-18. https://doi.org/10.1128/CMR.00060-18.
  • Molnár, Tamás, László Tiszlavicz, Csaba Gyulai, Ferenc Nagy, and János Lonovics. "Clinical Significance of Granuloma in Crohn's Disease." World Journal of Gastroenterology : WJG 11, no. 20 (May 28, 2005): 3118–21. https://doi.org/10.3748/wjg.v11.i20.3118.
  • O'Brien, Claire L., Christopher J. Kiely, and Paul Pavli. "The Microbiome of Crohn's Disease Aphthous Ulcers." Gut Pathogens 10 (October 10, 2018): 44. https://doi.org/10.1186/s13099-018-0265-6.
  • Roda, Giulia, Margherita Marocchi, Alessandro Sartini, and Enrico Roda. "Cytokine Networks in Ulcerative Colitis." Ulcers 2011 (January 10, 2011): e391787. https://doi.org/10.1155/2011/391787.
  • Rogler, Gerhard, Abha Singh, Arthur Kavanaugh, and David T. Rubin. "Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management." Gastroenterology 161, no. 4 (October 2021): 1118–32. https://doi.org/10.1053/j.gastro.2021.07.042.
  • Schirmer, Melanie, Ashley Garner, Hera Vlamakis, and Ramnik J. Xavier. "Microbial Genes and Pathways in Inflammatory Bowel Disease." Nature Reviews. Microbiology 17, no. 8 (August 2019): 497–511. https://doi.org/10.1038/s41579-019-0213-6.
  • Seyedian, Seyed Saeid, Forogh Nokhostin, and Mehrdad Dargahi Malamir. "A Review of the Diagnosis, Prevention, and Treatment Methods of Inflammatory Bowel Disease." Journal of Medicine and Life 12, no. 2 (2019): 113–22. https://doi.org/10.25122/jml-2018-0075.
  • Stidham, Ryan W., and Peter D. R. Higgins. "Colorectal Cancer in Inflammatory Bowel Disease." Clinics in Colon and Rectal Surgery 31, no. 3 (May 2018): 168–78. https://doi.org/10.1055/s-0037-1602237.
  • Venkateswaran, Niranjani, Scott Weismiller, and Kofi Clarke. "Indeterminate Colitis – Update on Treatment Options." Journal of Inflammation Research 14 (November 30, 2021): 6383–95. https://doi.org/10.2147/JIR.S268262.

Textbooks:

  • Jameson, J. Larry, ed. Harrison's Principles of Internal Medicine. Twentieth edition. New York: McGraw-Hill Education, 2018.
  • Kumar, V, AK Abbas, JC Aster, and JA Perkins. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders, 2015.