Some research has indicated that Crohn’s may have a genetic link 5 . It runs in families and those with a sibling who has the disease are 30 times more likely to develop it than the normal population. Ethnic background is also a risk factor.
Mutations in the CARD15 gene – also known as the NOD2 gene – are associated with Crohn’s disease as well as susceptibility to certain phenotypes 6 of disease location and activity. Earlier studies indicated only two (2) genes were linked to Crohn’s, but researchers now believe there are over thirty (30) genes which indicate that genetics do play a role – either directly through causation or indirectly as with a mediator variable.
Diet is believed to be linked to a higher prevalence of Crohn’s disease in the more industrialized parts of the world. Additionally, smoking has also been shown to increase the likelihood of return of the active disease or lead to flare-ups 7 . Research has also shown that the introduction of hormonal contraception in the United States in the 1960s was also linked to a dramatic increase in the incidence rate of Crohn’s disease. Although a link has not been effectively determined, it is thought that these drugs (hormonal contraceptives) effect the digestive system similar to the way that smoking does.
Researchers have long suspected that abnormalities in the immune system as a cause of Crohn’s disease. Researchers believe that Crohn’s is an autoimmune disease and that inflammation is stimulated by an over-active Th1 cytokine response. However, more recent research that Th17 is of greater importance in regard to the disease. Another gene has also been implicated in Crohn’s. The ATG16L1 gene may reduce the effectiveness of autophagy and hinder the body’s ability to attack invasive bacteria.
In contrast to the prevailing view that Crohn’s is the result of a T-cell autoimmune disorder, there is an increasing body of evidence that favors the hypothesis that, instead, it results from an impaired innate immunity.
A variety of pathogenic bacteria were initially suspected of being causative agents of Crohn’s disease. However, most health care professionals now believe that a variety of microorganisms take advantage of their host’s weakened mucosal layer and inability to clear bacteria from the intestinal walls, both of which are symptoms of the disease. Some studies have suggested that Mycobacterium avium (sub-species: para tuberculosis) plays a role in the disease, in part because it causes a very similar disease – Johne’s disease – in cattle. Other studies have linked specific strains of enteroadherent E. coli to the disease..However, the exact relationship between specific types of bacteria and Crohn’s disease remains unclear.
How is the disease diagnosed?
Certain factors often make the diagnosis challenging, and a number of tests are often required to assist in making the diagnosis. In addition, sometimes with even a full battery of test, it may not be possible with complete certainty that the condition is indeed Crohn’s disease. One of the best tests for confirming the disease is a colonoscopy with is approximately seventy percent (70%) effective in diagnosing the disease, with further test being less effective.
A colonoscopy is the best means of diagnosing Crohn’s disease as it allows direct visualization of the colon and terminal ileum, thereby identifying the pattern of disease involvement. Occasionally, the colonscope can travel past the terminal ileum, but it varies from patient to patient. During the colonoscopy, the gastroenterologist can also perform a biopsy, where a small tissue sample can be taken for laboratory analysis. Since approximately thirty percent (30%) of Crohn’s involve only the ileum, a cannulation of the terminal ileum is otherwise required.
The use of a small bowel follow-through may suggest the diagnosis of Crohn’s and is useful when the disease only involves the small intestines. Because a colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and the beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through x-ray, where barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over a set period of time. This is particularly helpful in locating inflammation as well as narrowing of the small bowel. The advent of the colonoscopy has done away with the need to give patient’s a barium enema and then use fluoroscope as a part of the initial work-up to detect Crohn’s disease.
Both the CT scan and MRI are useful in evaluating the small bowel utilizing enteroclysis protocols 8 . They are also valuable when looking for intra-abdominal complications of Crohn’s such as abscesses, small bowel obstruction, or fistulae.
A complete blood count can reveal anemia, which can be caused by either blood loss or vitamin B12 deficiency. The latter may be seen with ileitis because vitamin B12 is absorbed in the ileum. Erythrocyte sedimentation rate (ESR) and C-reactive protein levels are also useful in gauging the degree of inflammation.
Calprotectin is a protein found in neutrophil cytosol. Neutrophils are integral to the inflammatory process caused by Crohn’s disease. The fecal concentration of calprotectin correlates well with inflammation and disease activity. Findings of a normal fecal calprotectin level in a patient presenting with active gastrointestinal symptoms would exclude inflammatory bowel disease as a likely diagnosis and, in many cases, negates the need for a colonoscopy or radio labeled white cell scan.
Comparison with ulcerative colitis
The most common disease that mimics the symptoms of Crohn’s disease is ulcerative colitis, as both are IBDs that can affect the colon with similar symptoms. It is important to differentiate these diseases, however, since the course of the disease as well as treatments may be different. In some cases, it may not be possible to tell the difference, in which case the condition is classified as indeterminate colitis.
5 “Crohn’s disease has strong genetic link: study” Crohn’s and Colitis Foundation of America (http://www.ccfa.org/reuters/geneticlink)
6 A Phenotype is defined as an organism’s observable traits or characteristics such as its biochemical or physiological properties.
7 “Tobacco and IBD: relevance in the understanding of disease mechanisms and best practices” Best Pract Res Clin Gastroenterol, pp 481-496
8 Rajesh, A. (2006) “Multi-slice CT enteroclysis: technique and clinical application,” Clinical Radiology, pp 31-39
9 Stenosis is an abnormal narrowing of a blood vessel or other tubular organ.
Source: Wikipedia.com (http://en.wikipedia.org/wiki/Stenosis)