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
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 Disease4
Signs & Symptoms
Signs and symptoms of CD may include:2,6
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
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
CD has no known cause, but some factors may increase the risk of developing the disorder, such as:6
Disease & Clinical Trial Tools
The tools listed below offer a measure of CD disease.
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.
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
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