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What causes Crohn's disease?

The cause of Crohn's disease remains uncertain. Although there are a number of theories, none have yet been proven. What is known is that factors like a person's genetic makeup, the environment in which one lives, and an individual's immune system all play a role in the development of the disease, but exactly how this occurs is not clearly understood at this time. However, many potential mechanisms for how Crohn's disease may develop are currently under study.

The most widely accepted theory is that a person's immune system abnormally overreacts to some type of substance in the gut (gastrointestinal tract), which is most likely the bacteria that normally reside in the intestines, and that this overactive immune response is somehow triggered by exposure to something in the person's environment. Why one person develops this type of immune response while another person does not is thought to relate to an individual's genetic makeup or genetic susceptibility; in other words, the person who develops Crohn's disease has inherited some type of defective gene or genes that causes their immune system to react in this abnormal way. This activation of the immune system leads to an influx of inflammatory cells to the intestine. In patients with Crohn's disease, once the immune system is activated, it does not properly shut itself off, which results in the chronic inflammation that is characteristic of Crohn's disease. This is why many of the current treatments for Crohn's disease focus on suppressing the body's overactive immune response.

Genetic Factors

There is a substantial amount of evidence that genetic factors contribute to the development of Crohn's disease. Crohn's disease is more commonly seen among certain racial and ethnic groups; Caucasians, particularly persons of Jewish descent whose relatives come from Eastern Europe (Ashkenazim), are especially at risk. Additionally, there is a higher risk for Crohn's disease if one has a first degree relative with Crohn's disease. In fact, as mentioned previously, up to 20% of patients with Crohn's disease also have a first degree relative affected with the disease.

Some of the major recent advances in the field have been in the area of the genetics of Crohn's disease. A number of genes (>30) have been discovered in the past several years that have been shown to increase the risk for developing Crohn's disease. It should be emphasized that not one genetic defect will cause Crohn's disease; there are a number of genes that can predispose a person to develop the disease. Currently, there is no role for genetic testing outside of clinical studies, but this may change in the future.

The hope is that once the Crohn's susceptibility genes are discovered, scientists can begin to discover their function, which will provide insight into what actually causes Crohn's disease. Once we understand what causes the disease, the next step will be to design better medications to help control the symptoms, and even potentially cure the disease.

Environmental Factors

Environmental factors appear to combine with an individual's genetic predisposition to lead to the development of Crohn's disease. Certain environmental factors also affect the course of the disease. Unfortunately the environmental factors are not well studied. However, it is likely that they either cause the lining (mucosa) of the intestine to become more permeable - a characteristic associated with smoking and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) - or alter the bacteria that normally live in the colon, a situation that can occur with the introduction of antibiotics or gastrointestinal infections.

The two best studied environmental factors are smoking and NSAIDs. Smoking has been shown not only to increase the risk for Crohn's disease but also worsen the course of the disease. Smokers may be less responsive to certain treatments and are more likely to develop a recurrence of Crohn's disease after surgery. Quitting smoking is one of the best things a patient with Crohn's can do.

NSAIDs (non-steroidal anti inflammatory medications such as ibuprofen, Motrin, Advil, naproxen, and Aleve) may trigger the development of Crohn's disease, although the data in the medical literature is not overwhelming. Additionally, these drugs can cause flares of established inflammatory bowel disease (Crohn's or ulcerative colitis) in approximately 25% of patients. Studies suggest that these flares occur within a week of starting regular use of the NSAIDs. Acetaminophen (Tylenol) and aspirin appear to be safe and do not lead to exacerbations of Crohn's disease. Celecoxib (Celebrex) is a specific type of NSAID called a cox-2 inhibitor that appears to be safe, at least in short-term studies of patients in remission and on medicine for their inflammatory bowel disease (IBD).

Diet - Does It Play a Role?

Diet likely has a role as a risk factor for Crohn's disease, but little is known. Certainly, there is no one compelling dietary factor that has been shown to cause the disease or cause a flare of the disease. The most consistent factor identified as a risk factor for Crohn's disease is a diet high in refined sugars. Once Crohn's disease is established, there are no specific foods that a patient should definitely eat or should try to avoid, and usually patients are just advised to just follow a healthy, balanced diet.

No special diet has been shown to be effective for ameliorating the symptoms of Crohn's disease. Many patients mistakenly restrict dairy products and fruit and vegetables in their diet, which can compound nutritional deficiencies without any reduction in the risk of disease flares. Only those patients with tight small bowel strictures (narrowings) or recent small bowel obstructions need to follow a low residue diet. Patients on a low residue diet are instructed to avoid foods that cannot be readily digested such as skins of fruits, nuts, seeds, pineapple, mushrooms, and raw vegetables. Additionally, only those patients with a concomitant lactose intolerance need to avoid milk products.

What Is the Effect of Stress?

A lot of chronic illnesses are blamed on stress, and many patients with Crohn's disease will associate flares of their disease to a particular stress in their life. There is no evidence demonstrating that stress causes Crohn's disease. Although some medical studies have suggested that stress may trigger a flare of Crohn's disease, other studies have come to the opposite conclusion. At least one of the reasons for these disparate findings is that stress is a very difficult variable to measure. As a result, it becomes quite challenging to design a study examining how stress affects the course of a disease. Although the data is conflicting, we nonetheless will recommend stress reduction or relaxation techniques for patients who feel that stress worsens their symptoms.

Contact Information

Inflammatory Bowel Disease Program
Digestive Disease Center
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215