Crohn's disease

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Diagram of the Human Intestine

Crohn's disease is a chronic inflammatory disease of the digestive tract and it can involve any part of it - from the mouth to the anus. It typically affects the terminal ileum as well as demarcated areas of large bowel, with other areas of the bowel being relatively unaffected. It is often associated with auto-immune disorders outside the bowel, such as aphthous stomatitis and rheumatoid arthritis. Crohn's disease should not be confused with a non-progressive and non-degenerative digestive disorder called irritable bowel syndrome. IBS is not an autoimmune disease. Ulcerative colitis is a sibling autoimmune disease to Crohn's but only impacts the colon while Crohn's can impact any part of the digestive tract. Furthermore, Crohn's tends to impact multiple layers of the bowel lining which can lead to many additional and hard-to-treat complications.

Contents

1 Symptoms

2 Incidence

3 Causes

3.1 Autoimmunity
3.2 Mycobacterial infection

4 Complications

4.1 Short-term
4.2 Long-term risks

5 Treatment

5.1 Acute treatment
5.2 Steroid-sparing
5.3 Surgery
5.4 Dietary

6 Differential diagnosis

7 History and name

8 External links

Symptoms

Crohn's patients typically suffer from chronic diarrhea and disrupted digestion, making it difficult for sufferers in the acute phase of the disease to eat and/or digest food. The inflammation can be extremely painful and debilitating. Other common complications of Crohn's include fistulas of the colon, hemorrhoids, lipid absorption problems, and anemia. Bleeding is seen in 20% cases, against 98% cases in ulcerative colitis. Bruising of the shins, varying fever symptoms, indirect minor brain damage, varying levels of pain, and psychological damage is seen in many cases.

Incidence

The disease typically first appears in a young adults in their late teens and twenties, although it is not unknown for symptoms to first appear quite late in life. Additionally, there has been an increase in cases occurring in young children. Recent studies suggest that up to 30% off all newly diagnosed cases are in children and teens under the age of 18. Estimates suggest that up to 60,000 people in the UK (about 1 in 1200) and 1,000,000 Americans have the disease (around 1 in 300). Some ethnic groups (such as Ashkenazi Jews) have a significantly higher rate of prevalence than others. Increased rates of disease have also been noted in some families, leading to speculation of a possible genetic link; in 2001 a susceptibility locus for Crohn's disease has been mapped to chromosome 16, and named NOD2/CARD15 gene. Epidemiological research indicates that Crohn's belongs to the group of diseases of affluence. In other words, the incidence of the disease is much higher in industrialized countries than elsewhere. However, Crohn's symptoms are typically diagnosed over a long period of time, in order to establish a pattern; in countries where medical help is expensive or less available, it may be difficult to arrive at a diagnosis.

Smoking increases the risk of Crohn's disease. Some women find that their disease is exacerbated by taking the birth control pill oral contraceptives, while others find it can help keep their flare ups at bay. More research needs to be done on the impact of hormones on Crohn's.

Causes

Autoimmunity

The efficacy of immunosuppression, as well as scanty reports of complete disease resolution after bone marrow transplant, is highly suggestive of an autoimmune pathogenesis. A definite epitope to which the autoimmunity is directed is unknown, which also hampers the search for a virus or other pathogen that could induce molecular mimicry.

Since Crohn's disease is often found in families, it is likely that it has a genetic component. Studies have identified a gene named CARD15 (or NOD2) which is suspected to participate in the inflammatory process at the heart of Crohn's disease. While mutations or polymorphisms (common variations) in this gene do not directly cause the disease, they may help determine who is affected or how serious one's symptoms are. One study reported that 50% of patients with Crohn disease carried one or more mutations in CARD15. Some mutations were associated with more severe cases or earlier age or onset. While a number of independent studies have reported the association of CARD15 with Crohn's disease, others have observed contrary results. Further studies are in progress to delineate the contribution of this gene.

Mycobacterial infection

The disease has long been suspected of being due to a Mycobacterium because of the similarity of many features to human tuberculosis and veterinary Johne's Disease. Mycobacterium avium subspecies paratuberculosis (MAP), which causes Johne's disease in cattle, is a primary area of research for many scientists and doctors involved in Crohn's disease. MAP has been proven to affect both cattle and human hosts and is passed on through the mammary glands. Current pasteurization methods have proved ineffective in ridding dairy products of Mycobacterium Paratuberculosis. This remains a controversial area of research, although recent studies have lent more credence to the theory, and government agencies in some countries have begun investigations into the possibility.

Nearly all practicing physicians and many researchers are unwilling to accept that MAP is a primary cause of Crohn's. Dozens of studies have been done in which evidence of MAP infection could not be found in tissue and blood samples of Crohn's patients. However, other studies have been performed which (with more stringent methodology) showing that MAP was found in up to 90% of the Crohn's patients in the study. Mycobacteria are known to be fastidious, which means they are extremely difficult to grow in culture. Therefore, unless very stringent precautions are taken, cultures for mycobacteria can underestimate the presence of the bacterium.

For this reason, PCR is a more promising technique than culture. Researchers have identified an insertion sequence called IS900 that is unique to the MAP organism, and many studies have been performed using PCR to test for the presence of MAP. However, the problem with PCR is that it will detect dead or near-dead ("non viable") MAP organisms, so often times a combination of PCR and careful culture is needed to prove that MAP is present.

Researchers using PCR and careful culture have found that live MAP bacteria are present in significant numbers of Crohn's patients, and other studies using PCR and culture have shown that live MAP bacteria are present in significant percentages of pasteurized milk in the United States, the United Kingdom, and the Czech Republic.

Complications

Short-term

The bowel shows segmental "hose pipe" thickening and shows full thickness chronic inflammation, giant cell granulomas, and fissures with acute inflammation. Fistula formation is quite common in Crohn's. Bowel obstruction is a known complication which may require surgical resection. Approximately 50% of surgical cases require additional surgery within five years because the disease tends to reappear at the site where the bowel was rejoined, and some patients eventually develop short bowel syndrome which makes it extremely difficult to digest food. For this reason, surgery is considered by many doctors only as a last resort in the treatment of Crohn's.

Long-term risks

Some patients can be treated with the existing drugs quite effectively and can go into long-term remission, sufficient to allow the sufferer to lead a normal life. Patients are at somewhat larger risk of colon cancers, and should have regular colonoscopies both to check for precancerous growths and to monitor the success of treatment. It does not seem to have as great a risk of malignancy compared to ulcerative colitis.

Treatment

Acute treatment

Steroids are often necessary in initial stages and during flare-ups, although long-term steroid therapy is discouraged because of its well-known side effects.

Steroid-sparing

A well-established group of drugs, especially useful in mild-to-moderate disease, are salicylates - 5-ASA derivates - 5-aminosalicylic acid compounds such as sulfasalazine, mesalamine (Pentasa®, Asacol®), olsalazine, and balsalazide. Immunomodulating drugs such as azathioprine, 6-mercaptopurine and methotrexate are given mainly in moderate-to-severe cases. Research trials are being conducted on treatment with drugs in the same family as thalidomide. Infliximab (brand name Remicade®) is given in patients with therapy-resistant or fistulating Crohn's.

Surgery

Surgery (resection of parts of the bowel) is avoided, as this does not cure the disease - it can recur at any site in the digestive tract. 50% of all Crohn's patients eventually undergo one or more resections to control highly active disease. Most often, this is of the terminal ileum.

Dietary

Some patients find some foods (such as foods high in fiber, dairy foods, and sugars) make their symptoms worse, but the disease cannot be controlled simply through diet modifications. However, paying close attention to diet can help reduce the number of flare-ups for many sufferers.

Differential diagnosis

Crohn's disease and ulcerative colitis are quite distinct diseases but in practice there are sometimes difficulties distinguishing between them, especially in mild cases - these are usually simply classified as "chronic inflammatory bowel disease" or "indeterminate colitis".

Crohn's disease is often initially misdiagnosed as food poisoning, gastroenteritis, appendicitis (due to the common locus of pain in the lower right-hand quadrant of the abdomen), and irritable bowel syndrome.

History and name

Crohn's disease was first described by Giovanni Battista Morgagni (1682-1771), and subsequent cases were described by John Berg in 1898, and by Polish surgeon Antoni Leśniowski in 1904. Scottish physician T. Kennedy Dalziel described nine cases in 1913. Burrill Bernard Crohn, an American gastroenterologist, described fourteen cases in 1932, characterizing the disease as "Terminal ileitis: A new clinical entity"; the description was changed to "Regional ileitis" on publication. It is by virtue of alphabetization rather than contribution that Crohn's name appeared as first author: because this was the first time the condition was reported in a widely-read journal, and the disease has come to be known as Crohn's disease for reasons of publicity rather than precedence.

In Poland the disease is known as Leśniowski-Crohn disease. In Germany and in Europe the disease is known as Morbus Crohn.

External links

General Information
- Crohn's Disease (http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/) US National Institute of Diabetes and Digestive and Kidney Diseases
- Crohn's Disease - WebMed (http://my.webmd.com/content/article/5/1680_50985.htm)
- Crohn's Disease Clinical and Alternative Treatment (http://goldbamboo.com/topic-t1222.html)
- Crohn's Disease - HealthAtoZ (http://www.healthatoz.com/healthatoz/Atoz/ency/crohns_disease.html)
- How the disease came to be known as Crohn's disease (http://www.whonamedit.com/synd.cfm/1397.html)
Organizations
- National Association of Colitis and Crohn's Disease (http://www.nacc.org.uk)
- CrohnsZone.org - Self-help Group (http://www.crohnszone.org/index.php)
- Crohn's and Colitis Foundation of America (http://www.ccfa.org)