What is Crohn's Disease?

The esophagus, stomach, large and small intestine, aided by the liver, gallbladder and pancreas convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

 

lower abdominal x-ray shows narrowing (stenosis) of the end of the small intestine (ileum), caused by Crohn's disease. Crohn's disease typically affects the small intestine, whereas ulcerative colitis typically affects the large intestine. A solution containing a dye (barium), was swallowed by the patient. When it passed into the small intestines, this x-ray was taken (lower GI series).

Clubbing may result from chronic low blood-oxygen levels. This can be seen with cystic fibrosis, congenital cyanotic heart disease, and several other diseases. The tips of the fingers enlarge and the nails become extremely curved from front to back.

 

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's disease is an inflammation of the intestines caused by immune response to an infection. The lining of the intestine may ulcerate and form channels of infection, called fistulas. Fistulas tunnel from the area of ulceration, creating a hole which may continue until it reaches the surface of the organ, or the surface of nearby skin. These holes typically spread the infection that creates them, and life-threatening conditions such as peritonitis (inflammation of the lining of the abdomen) may occur.

 

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Inflammatory Response

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

• B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
• T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

• Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
• Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

• TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
• TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

 

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

• Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
• Research indicates that patients with Crohn's disease have increased activity in TH1 helper cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural mechanism called apoptosis, a process whereby cells self-destruct. In such cases, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to accumulate on intestinal cells. E-selectin may be involved in the early stages of the disease (especially ulcerative colitis) and ICAM-1 in the persistence of either inflammatory bowel disease.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. Such increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Genetic Factors

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several candidate genes and chromosome locations have been identified that might prove to play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that they may have genetic defects in common. In either case, multiple genetic factors are likely to be responsible for susceptibility to these disorders.

Specific Genes Involved. One of the most important genetic discoveries to date was the identification of a genetic variant called NOD2, which appears to alter the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. This genetic factor might be involved in 15% of Crohn's disease cases. Those with one copy of the mutated gene have twice the average risk of developing Crohn's, and those with two defective genes face 20 - 40 times the risk.

 

Infections

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the injurious processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Dietary Factors

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Experts believe, then, that diet must play some role, although studies have been conflicting over its importance.

Crohn's Symptoms

Alternative Names:

Inflammatory bowel disease - Crohn's disease; Regional enteritis; Ileitis; Granulomatous ileocolitis

Symptoms:

• Abdominal pain
• Fever
• Diarrhea
• Loss of appetite
• Unintentional weight loss
• Abdominal mass
• Abdominal sounds (borborygmus, a gurgling or splashing sound heard over the intestine)
• Fatigue
• Gastrointestinal bleeding
• Foul-smelling stools
• Tenesmus (pain with passing stool)

Additional symptoms that may be associated with this disease include the following:

• Bloody stools
• Joint pain
• Anal Incontinence
• Swollen gums
• Constipation
• Abdominal fullness and gas

Signs and tests:

A physical examination may reveal an abdominal mass or tenderness, skin rash, swollen joints or mouth ulcers.

• Tests that show findings of Crohn's disease
  • Endoscopy, colonoscopy, or sigmoidoscopy with small bowel biopsy
  • Small bowel follow through
  • Barium enema
  • Upper GI series
• Positive stool guaiac

A stool culture may be done to rule out other possible causes of the symptoms.

This disease may also alter the results of the following tests:

• Fecal fat
• Liver function tests
• Albumin

Treatment Options for Crohn's Disease

Treatment focuses on relieving symptoms of the disease by inducing and then maintaining remission. This is accomplished by prescribing medicines that reduce the inflammation in the intestinal tract. Common drugs used to treat Crohn's disease are aminosalicylates, steroids, antibiotics, anti-TNF agents (see Infliximab below), and immunomodulators.

The cornerstone for inducing remission in severe Crohn's disease continues to be oral or intravenous corticosteroids such as prednisone. They also have a role in managing less severe disease and in treating small bowel involvement. They are used for short-term therapy and other medications are used to maintain remission following steroids. Steroids work by reducing inflammation throughout the body and thus long-term use is associated with many side effects like osteoporosis, diabetes, and hypertension. Promising results have been obtained with the use of budesonide (Entocort), a corticosteroid with high topical anti-inflammatory activity and low systemic activity (because of extensive hepatic metabolism). This medication, though costly, can reduce the intestinal inflammation while minimizing the side effects that would commonly be experienced with prednisone.

Another category of drugs often used in Crohn's disease is the topically acting 5-aminosalicylates such as mesalamine (Asacol, Pentasa), sulfasalazine (Azulfidine), and balsalazide (Colazal). These medicines are quite safe, but may require large doses. Antibiotic agents, such as metronidazole may be helpful in perianal and/or colonic Crohn's disease. How antibiotics help Crohn's disease is not well understood, but the benefit may be the result of altered concentrations of bacteria in the colon and small bowel.

Immunomodulatory drugs such as azathioprine (Imuran, Azasan), 6-mercaptopurine (Purinethol), or methotrexate are often effective in maintaining remission of Crohn's disease. These medications are used long-term and require monitoring to prevent adverse effects. They work by changing the way certain inflammatory cells in the intestinal lining respond to inflammatory triggers.

Infliximab (Remicade) is a powerful anti-inflammatory drug that blocks the action of a specific molecule called tumor necrosis factor (TNF), a key mediator of the inflammatory process in Crohn's disease. It is indicated for perianal Crohn's disease or intestinal disease not responding to the usual first-line medications. This drug is actually a synthetic antibody and is given as an intravenous infusion for both induction and maintenance of remission. Important side effects of this medication are infusion reactions (rash, fever) and, rarely, serious infections. Other medications known as biologicals, of which infliximab is one, are being studied and may emerge as viable therapies for Crohn's disease in the future.

 

HUMIRA® (adalimumab) is a TNF (tumor necrosis factor) blocker that was recently approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe Crohn's disease in adults who have not responded well to conventional therapy. HUMIRA is also approved for those adults who have lost response to, or are unable to tolerate REMICADE (infliximab). It can work fast - many patients experienced a response (significant difference in their symptoms) in just 4 weeks. In research studies of patients with Crohn's disease, HUMIRA helped relieve many of the symptoms of Crohn's disease, including painful cramps, persistent diarrhea and fatigue. It also helped patients experience remission (stop flare-ups for long periods of time). Patients with Crohn's disease take HUMIRA as an injection once every other week. Once your doctor shows you how to take HUMIRA, the injections can be taken in the convenience of your own home.

Despite advances in the medical treatment of Crohn's disease, surgery may be necessary to remove the diseased segment of bowel. Surgery is usually reserved for those in whom medical treatment has been ineffective. Other indications for surgery may include:

• permanent narrowing or an obstruction of the bowel
• development of a fistula between an involved segment and the bladder, vagina or skin
• infection in the area of the anus
• perforation of the bowel
• abscess (localized infection) within the abdomen

Surgery will result in remission but does not represent a cure of the disease. Most patients will have a recurrence of Crohn's disease after surgery and thus will require additional medical therapy.

Despite the serious nature of the disease, treatment often permits the person with Crohn's disease to lead an active and productive life with a normal lifespan. Dietary changes have not been shown to help treat Crohn's disease because diet does not appear to reduce the inflammation in the intestines. Because weight loss is common when Crohn's disease is active, it is important that patients maintain a healthy diet with adequate caloric intake. However, weight gain may only be successful after reducing the inflammation with prescription medications. If the bowel becomes narrowed (strictured) because of chronic Crohn's disease activity, then patients may be at risk of bowel obstruction. In this case, a low residue diet that eliminates non-digestible vegetables may be recommended. For all patients, stopping smoking is an important part of any therapy for this disease.

Reference Link:

http://www.healthcentral.com/chronic-pain/crohns