Crohn's disease

Crohn's disease may affect as many as 700,000 people in the U.S. Men and women are affected in equal numbers. While the condition can occur at any age, it is more common among adolescents and young adults between the ages of 15 and 35.

A variety of tests are used to diagnose and monitor Crohn’s disease. A combination of tests is often needed because some symptoms of the condition are similar to other intestinal disorders such as irritable bowel syndrome and to another type of inflammatory bowel disease (IBD) called ulcerative colitis.^[1] Tests used to narrow down the diagnosis may include blood tests, tissue tests, ultrasound, x-rays, CT scan, and/or endoscopy. A proper diagnosis also involves identifying the extent and severity of disease as well as any related complications.^[2]

Crohn's disease is a type of inflammatory bowel disease (IBD), the general name for conditions that cause inflammation in the gastrointestinal (GI) tract. Common signs and symptoms include abdominal pain and cramping, diarrhea, and weight loss. Other general symptoms include feeling tired, nausea and loss of appetite, fever, and anemia. Complications of Crohn's disease may include intestinal blockage, fistulas, anal fissures, ulcers, malnutrition, and inflammation in other areas of the body. Crohn's disease can occur in people of all age groups but is most often diagnosed in young adults.^[1][3] The exact cause is unknown, but is thought to be due from a combination of certain genetic variations, changes in the immune system, and the presence of bacteria in the digestive tract.^[1][3][4]  Many of the major genes related to Crohn disease, including NOD2, ATG16L1, IL23R, and IRGM, are involved in immune system function. The disease is not inherited but it appears to run in some families because in about 15% of the cases the disease is present in more than one relative.^[4] 

Treatment is aimed at relieving symptoms and reducing inflammation, and may include diet and medication, but some people require surgery.^[1][3] Surgery often involves removal of the diseased segment of bowel (resection), the two ends of healthy bowel are then joined together (anastomosis). In about 30% of people who have surgery for Crohn’s disease symptoms may come back within three years and up to 60% will have recurrence within ten years.^[5]

Crohn's disease causes inflammation of the digestive or gastrointestinal (GI) tract. It usually occurs in the lower part of the small intestine, called the ileum, but it can affect any part of the digestive tract, from the mouth to the anus. The inflammation extends deep into the lining of the affected organ, which can cause abdominal pain and diarrhea.^[1] Affected individuals may also have loss of appetite, weight loss, and fever.^[4]

About one-third of individuals with Crohn's disease have symptoms outside of the intestines, which may include arthritis, uveitis (inflammation of the covering of the eye), skin lesions, and sacroilitis (inflammation of the large joints of the tail bone and pelvis).^[6]

Symptoms of Crohn's disease may range from mild to severe. Most people will go through periods in which the disease flares up and causes symptoms, alternating with periods when symptoms disappear or decrease. People with Crohn’s disease who smoke tend to have more severe symptoms and more complications. In general, people with Crohn's disease lead active and productive lives.^[1][6]

The exact cause of Crohn's disease is not known, but it appears to be a multifactorial condition. This means that both genetic and environmental factors likely interact to predispose an individual to being affected. Studies suggest that Crohn's disease may result from a combination of certain genetic variations, changes in the immune system, and the presence of bacteria in the digestive tract.^[4]

Recent studies have found that variations in specific genes, including the ATG16L1, IL23R, IRGM, and NOD2 genes, influence the risk of developing Crohn's disease. These genes provide instructions for making proteins that are involved in immune system function. Variations in any of these genes may disrupt the ability of intestinal cells to respond to bacteria, leading to chronic inflammation and thus the signs and symptoms of the condition. There may also be genetic variations in regions of chromosome 5 and chromosome 10 that contribute to an increased risk to develop Crohn's disease.^[4]

Crohn's disease, like most other autoimmune diseases, is thought to be a multifactorial condition. This means it is likely associated with the effects of multiple genes, in combination with lifestyle and environmental factors.^[7] Once an autoimmune disease is present in a family, other relatives may be at risk to develop the same autoimmune disease, or a different autoimmune disease. However, if an autoimmune diseases such as Crohn's disease occurs in a family, it does not necessarily mean that relatives will develop an autoimmune disease.^[8] Having an affected family member means that there may be a genetic predisposition in the family that could increase an individual's chance of developing an autoimmune disease. Thus, having an affected family member is considered a risk factor for Crohn's disease.^[9]

More than 30 distinct genes, or presumed locations of genes (loci), have been suggested to be related to CD, including those related to susceptibility, age of onset, disease location, diagnosis, and prognosis.^[10] So far, the strongest associations with CD have been found with the NOD2 (also called CARD15), IL23R and ATG16L1 genes.^[10]

The search for specific susceptibility genes (genes in which variations may increase a person's risk) has been difficult due to complex genetics, including factors such as the lack of simple inheritance patterns and involvement of several genes. Studies have already led to the identification of a number of susceptibility genes: NOD2, DLG5, OCTN1 (also called SLC22A4), OCTN2 (SLC22A5), NOD1, IL23R, PTGER4, ATG16L1 and IRGM. The NOD2 gene is currently the most replicated and understood.^[10]

With respect to age of CD onset and more specifically to childhood or early-onset Crohn’s disease, the following genes/loci have been implicated: TNFRSF6B, CXCL9, IL23R, NOD2, ATG16L1 rs2241880, CNR1, IL-10, and MDR1 (also called ABCB1).^[10]

In terms of genes related to CD location, studies have suggested that upper GI Crohn’s disease has been related to NOD2 and MIF variants. Ileal CD has been related to the IL-10, CRP, NOD2, ZNF365 and STAT3 genes. Genes/loci associated with ileocolonic CD are 3p21, ATG16L1 and TCF-4 (TCF7L2).^[10]

Variations in a number of genes have also been found to be associated with other aspects of CD, such as disease behavior, risk for cancer, and presence of extraintestinal manifestations.^[10] To view a free, full-text journal article published in 2012 about the role of genetics in CD, click here. To view only a table from this article listing the genes that appear to be associated with Crohn's disease, click here.

Because the information provided here is complex, individuals seeking to better understand this information may benefit from meeting with a genetics professional or other qualified health care provider.