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This site is intended for US Healthcare Professionals only.

Introduction

Crohn's disease (CD) is a type of IBD that may affect any segment of the gastrointestinal tract from the mouth to the anus.1 Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, and weight loss.2 Bowel obstruction may occur as a complication of chronic inflammation, as will fistulas and abscesses. In addition, those with the disease are at greater risk of colon cancer. Other complications of CD include malnutrition and inflammation in other areas of the body, such as joints, eyes, and skin.1

Overview

The etiology of CD is unknown, but some factors are thought to influence its pathogenesis; including genetics, abnormal immune responses in the gut, and gut microbiota. Several genes related to immune regulation have been linked with CD. The interleukin TH23/ TH17 pathway is also associated with CD. In genetically susceptible individuals, disease onset can be stimulated by changes in the environment that disrupt the mucosal barrier, alter the balance of gut microbiota, or trigger an exaggerated immune response. An altered gut microbiota may affect the regulation of mucosal regulatory T cells (Tregs). The imbalance of effector T cells and Tregs in CD may facilitate and perpetuate intestinal inflammation.3

Goals of CD therapy vary according to disease severity and the extent of GI tract involvement. Current research includes a focus on patients demonstrating primary nonresponse or loss of response over time due to immunogenicity.5

Possible cellular mechanisms of Crohn's Disease

Possible cellular mechanisms of Crohn’s Disease4
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Signs & Symptoms

Signs and symptoms of CD may include:2,6

  • Diarrhea
  • Abdominal pain and cramping
  • Blood in the stool
  • Fever
  • Fatigue
  • Weight loss

Patient signs and symptoms may range from mild to severe. Clinical course can vary between patients, with periods of remission—during which the patient has no signs or symptoms for weeks or even years—alternating with periods of increased symptoms.2,6

Since signs and symptoms of CD overlap with UC and other conditions, endoscopy often plays an important part in establishing a CD diagnosis. Moreover, endoscopy is a useful tool for assessing inflammation extent and activity, as well as response to treatment.7

Risk Factors

CD has no known cause, but some factors may increase the risk of developing the disorder, such as:6

  • Genes: There are several inheritable genetic mutations that can predispose patients to developing CD.
  • Smoking: Cigarette smoking can increase the risk of getting CD, in some estimates by as much as double.

Disease & Clinical Trial Tools

The tools listed below offer a measure of CD disease.

Crohn’s Disease Activity Index (CDAI) and Patient Reported Outcome (PRO2)8,9

The Crohn’s disease activity index (CDAI) is a numerical measure of disease activity based on eight weighted variables: number of liquid stools, abdominal pain rating, general well-being, extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. The CDAI has long served as an outcome measure in clinical trials. Scores range from 0 to 600, with higher scores signaling greater CD activity.

The CDAI was adapted to derive Patient Reported Outcome 2 (PRO2), which assesses average weekly abdominal pain and liquid stool frequency using the same CDAI weighting factors, as seen in the table.

Download CDAI and PRO2

Simplified Endoscopic Score for Crohn’s Disease (SES-CD)

The Simplified Endoscopic Score for Crohn’s Disease (SES-CD) was developed to serve as an easy, practical score for assessing mucosal lesions in CD. The score comprises four variables: presence and size of ulcers, extent of ulcerated surface, extent of affected surface, and presence and type of narrowing. Each variable is scored from 0 to 3 within five ileocolonic segments, as displayed in the table.10

Download SES-CD

Colonic and Ileal Global Histologic Disease Activity Scores (iGHAS and cGHAS)

A commonly used index for assessing histologic disease activity in CD clinical trials, the Global Histologic Disease Activity Score (GHAS) evaluates chronicity of structural changes and inflammatory infiltrate. GHAS assigns a score between 0 and 4 to structural change and chronic inflammatory infiltrate, and a score between 0 and 8 for neutrophils in the lamina propria, neutrophils in the epithelium, epithelial damage, erosion or ulceration, and epithelioid granuloma. The total GHAS score ranges from 0 to 12, with higher scores indicating more severe inflammation.11

Modifications of the GHAS, the ileal GHAS (iGHAS) and the colonic GHAS (cGHAS) score the GHAS within specific segments of the bowel. The iGHAS assesses the highest GHAS within the ileum, while the cGHAS assess the highest segmental GHAS among the rectum, descending/sigmoid colon, transverse colon, and ascending colon.11

References

  1. NIH CD. https://www.niddk.nih.gov/health-information/digestive-diseases/crohns-disease/all-content. Accessed September 28, 2020.
  2. Crohn’s Disease. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes. Accessed May 28, 2020.
  3. Boyapati R, Satsagi J, Ho G-T. Pathogenesis of Crohn’s disease. Prim Report. 2015;7:44.
  4. Clough JN, Omer OS, Tasker S, et al. Regulatory T-cell therapy in Crohn’s disease: challenges and advances. Gut. 2020;69:942-952.
  5. Weisshof R, Juri KE, Zmeter N, Rubin DT. Emerging therapies for inflammatory bowel disease. Adv Ther. 2018;35:1746-1762.
  6. Crohn’s Disease. Cleveland Clinic. http://my.clevelandclinic.org/health/diseases/9357-crohns-disease. Published May 29, 2020. Accessed June 2, 2020.
  7. Spiceland CM, Lodhia N. Endoscopy in inflammatory bowel disease: Role in diagnosis, management, and treatment. World J Gastroenterol. 2018;24(35):4014-4020.
  8. Best WR, Becktel JM, Singleton JW, et al. Development of a Crohn’s Disease Activity Index: National Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70(3):439-444.
  9. Khanna R, Zou G, D’Haens G, et al. A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn’s disease activity.
    Ailment Pharmacol Ther. 2015;41:77-86.
  10. Daperno M, D’Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
  11. Danese S, Sandborn WJ, Colombel J-F, et al. Endoscopic, radiologic, and histologic healing with vendolizumab in patients with active Crohn’s disease. Gastroenterology. 2019;157(4):1007-1018.