Causes

The cause of Crohn's disease remains undefined, due to the diverse nature of the possible contributing factors, however, some of these have been investigated.

It is most likely that Crohn's disease occurs as a result of the interaction between genetics and environment.

Below are some of the genetic and environmental factors that are most commonly related to the disease. 

Environmental Factors

Although all of these factors have been proven to increase relapse and the severity of the assocated symptoms, it is unknown whether any of them are responsible for causing Crohn's Disease.

• Smoking has been found to increase the risk of disease relapse.
• Diet, including high fat, refined foods, have been found to increase the risks
• Location, i.e, living in industrialised, high pollution, urban areas.

Genetic Factors

No one gene has been found to be entirely responsible for Crohn's Disease. Evidence shows that there may be a variety of genes which contribute, and that these may differ from patient to patient. Mutations of certain genes may either directly cause a given defect, or be a mediator in the development of the defect.

Gene mutations that have been identified in relation to Crohn's Disease are those on the CARD1 (NOD2), and the XBP1 gene. It is likely also that there are numerous genes which may be up or down regulated in Crohn's patients, possibly due to mutations of the genes themselves, or of the regulatory sequences which control the expression of the genes.

This is still however, a very vague and undefined are in the disease and is currently an important subject of genetic research studies.

Other Possible Factors

Abnormalities in the immune system may also play a role in the development of Crohn's Disease. Evidence shows that Crohn's has been associated with upper class populations, living in cleaner conditions. This suggests that children born into these families are not being exposed to many pathogens and are therefore, potentially, not developing an effective immune defense system . Supporting this notion is the evidence that shows the lack of crohns disease in third world countries, where children are exposed to more unhygenic conditions, allowing them to develop an acquired immunity to such diseases.

It is also possible that Crohn's disease could be as a result of pathogenic bacteria. The combination of lowering the immune response, either by gene mutations, or by the increased cleanliness of western society, and the presence of certain pathogens (e.g. Mycobacterium avium subspecies paratuberculosis), could hold the key to the increase of Crohn's Disease seen today.

 Pathophysiology

Characteristically, Crohn's disease presents the following abnormalities:

• Transmural inflammation of the intestinal wall.
• Ulceration of the GI tract
• Metaplasia of the digestive epithelium
• Fistulas (tissue connections between organs or between organs and the perotineum)
• Fissures
• Abscesses (infected and inflamed, pus filled growths, which can rupture and result in internal bleeding)

Below is an endoscopic image showing the loss of the normal structure of the sigmoid colon in Crohn's Disease.

Image taken from Wikipedia.