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Crohn's Disease and Ulcerative Colitis

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Crohn's Disease

Crohn's Disease: An Overview

Crohn's disease, a debilitating and chronic inflammatory disorder, can attack any part of the gastrointestinal tract, but is seen most commonly in the terminal ileum and small bowel. The disease is segmental in nature, meaning there will be areas of normal mucosa found between diseased segments. Crohn's disease can lead to severe disability and sometimes death. It is frequently a high cost disease as a result of, among other things, expensive hospitalizations.

The overall incidence of Crohn's disease has been increasing over the last several years to approximately 2 cases per 100,000 population. The incidence of the disease has also been increasing in the young. Typically, the age at diagnosis is the teens and early twenties with a range of 15 to 30 years of age1 but the disease is seen in every decade of life. A positive family history of Crohn's disease is found in 40% of all patients.1 The frequency among siblings is higher than with distant relatives, although no genetic basis has been found.

Pathophysiology

The cause of Crohn's disease is unknown. Several factors have been examined as possible causes:

  1. Infectious agents(bacteria and viruses)
  2. Altered susceptibility
  3. Immune-mediated intestinal damage
  4. Genetic factors
  5. Environmental factors.

None of these factors demonstrate conclusive findings of the cause of Crohn's disease but they all make a contribution and certainly impact treatment. Recent evidence suggests that Crohn's disease is characterized by an abnormal immune response controlled by the CD4+ T helper type 1 cells(Th 1). Th1 helper cells produce interferon-gamma (IFN-y), tumor necrosis factor-alpha (TNFa), and interleukin-2 (IL-2) that contribute to inflammation and a cytotoxic T cell response. The Th 1 responses are usually associated with immunity to viruses. The cellular mechanism of Crohn's disease may be caused by an exaggerated Th1 response to mucosal stimuli, or persistent T cell activation due to either excessive T cell proliferation or to a reduced level of T cell apoptosis. Regardless of the Th1 response, tumor necrosis factor alpha (TNFa), a proinflammatory cytokine, plays an important role in perpetuating the chronic inflammatory state that is characteristic of Crohn's disease. Increased levels of TNFa seen in inflammatory diseases, such as the inflamed mucosa common in Crohn's disease, suggest that TNFa plays a early, central role in the cytokine cascade, which causes the inflammation.. This finding has important implications for treatment.

Diagnosis

Clinically the individual with Crohn's disease presents with:

  1.  Fever
  2. Right lower quadrant pain
  3. Diarrhea
  4. Fatigue
  5. Weight loss.
  6. Anorexia, nausea and vomiting may be present.

Complications of the disease include:

  1. Intestinal obstruction
  2. Anal fissures
  3. Small bowel and colon cancers
  4. Bile salt malabsorption
  5. Urinary oxylate stones.
  6. Fistulas occur in 30% of patients.  (Passages between the bowel and the skin or other organs which allow the intestinal contents/flora to pass to the skin or other organs.)

The initial assessment should include an evaluation of the effect of the disease on the patient's quality of life. A complete history and physical examination along with diagnostic studies is necessary to formulate a treatment plan.

Diagnostic studies include: 

  1. Stool cultures
  2. Stool guiac
  3. Laboratory studies
  4. Lactose tolerance test
  5. Sigmoidoscopy
  6. Colonoscopy
  7. Biopsy
  8. Barium studies.

 After diagnosis, patients are classified into categories depending on signs and symptoms.

Mild-moderate disease

Ambulatory patients able to tolerate oral alli-mentation without manisfestations of dehydration, toxicity, abdominal tenderness,painful mass or obstruction.

Moderate-severe disease

Patients who have failed to respond to treatment for mild-moderate disease. Have prominent symptoms of fever, weight loss more than 10%, abdominal pain, vomiting or anemia.

Severe-fulminant disease

Patients with persisting ysmptoms despite steroids as an outpatient or indiviudals with high fever, persistent vomiting, intenstinal obstruction, rebound tenderness, cachexia, or an abscess.

Remission

Patients who are asymptomatic or without inflammatory sequelae; includes patients who have responded to acute medical intervention or have undergone surgical resections, without gross residual disease. Patients requireing systemic steroids are not usually considered to be in remission.

(Adapted from Hanauer, S. "Management of Crohn's Disease in Adults, The American Journal of Gastroenterology, 1997-92(4).

Treatment

Treatment options are usually determined by location of disease and severity of the symptoms. Treatment is divided into acute and maintenance phases. In the acute phase, treatment consists of intravenous fluids, nothing by mouth with bed rest or limited activity. If the patient is suffering from a small bowel obstruction, nasogastric suctioning is indicated to decompress the bowel. Depending upon the laboratory findings, the patient may need vitamin replacement along including folic acid and iron. Surgery may be indicated for obstructing stenoses, complications or intractable disease. Because the cause of Crohn's disease is unknown, medical management focuses on reducing inflammation.

Medications play an important role in the treatment of the patient with Crohn's disease and form the basis of both acute and maintenance therapies. Categories of medications include: corticosteroids, antibiotics, aminosalicylates and immunomodulatory agents as well as anti-diarrheal agents and vitamins.

Antibiotics

Metronidazole (Flagyl)TM is effective in treating patients with mild to moderate active disease. Long term therapy is required since relapse is likely once treatment is stopped. A long term side effect includes peripheral neuropathy.

Corticosteroids

Corticosteroid therapy, commonly PrednisoneŽ, is indicated primarily for the short-term induction of remission of the disease and not as a maintenance therapy because of the toxic effects related to dose and duration of therapy.

Aminosalicylates

Sulfasalazine (AzulfidineTM), mesalamine and 5-aminosalicylic acid formulations are commonly used to treat mildly or moderately active Crohn's disease and to maintain remission. Common side effects of sulfasalazine, which generally respond to a dose reduction, include headache, nausea and fatigue.

Immunomodulatory Drugs

Immunomodulatory drugs (6-mercaptopurine; azathioprine) are used for long-term treatment in some patients with Crohn's disease. The mechanism of action of these drugs involve inhibition of lymphocyte function, primarily the T cells. As mentioned, this is for long-term therapy and a clinical response takes between three to six months of therapy. This class of drugs has significant side effects in some patients: pancreatitis, bone marrow suppression, renal dysfunction and hepatic toxicity. Patients undergoing treatment with any of  these drugs need close clinical and laboratory monitoring.

A new drug, infliximab, (RemicadeTM) was approved by the Food and Drug Administration in August of 1998 for the treatment of moderately to severely active Crohn's disease and to close entercutaneous fistulas. TNFa has a central role in stimulating T-cell activation. Infliximab is an anti-TFNa monoclonical antibody which interferes with T-cell activation and is a benefit in patients with active Crohn's disease. Infliximab is administered by intravenous infusion.

References

1. Broadwell DC, Jackson, BS, Principles of Ostomy Care, St.Louis, 1982,Mosby.

2. Glickman RM, Inflammatory Bowel Disease. Ulcerative Colitis and Crohn's disease. In: Wilson JD, Braunwald E, Isselbacher KJ, et al, eds., 12th ed.Harrison's Principles of Internal Medicine.New York. McGraw-Hill, Inc.1991:1268-1281

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Colitis causes redness and swelling of the mucosa, making bleeding possible.

Crohn's and Colitis Links

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Crohn's: An Overview

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An Overview of Ulcerative Colitis

Ulcerative colitis is a chronic (ongoing) disease of the colon, or large intestine. The disease is marked by inflammation and ulceration of the colon mucosa. Tiny open sores, or ulcers, form on the surface of the lining, where they bleed and produce pus and mucus. Because the inflammation makes the colon empty frequently, symptoms typically include diarrhea (sometimes bloody) and often crampy abdominal pain.

The inflammation usually begins in the rectum and lower colon, but it may also involve the entire colon. When ulcerative colitis affects only the lowest part of the colon -- the rectum -- it is called ulcerative proctitis. If the disease affects only the left side of the colon, it is called limited or distal colitis. If it involves the entire colon, it is termed pancolitis.

Ulcerative colitis differs from another inflammatory bowel disease (IBD), Crohn's disease. Crohn's can affect any area of the gastrointestinal (GI) tract, including the small intestine and colon. Ulcerative colitis, on the other hand, affects only the colon. The inflammation involves the entire rectum and extends up the colon in a continuous manner. There are no areas of normal intestine between the areas of diseased intestine. In contrast, such so-called "skip" areas may occur in Crohn's disease. Ulcerative colitis affects only the innermost lining of the colon, whereas Crohn's disease can affect the entire thickness of the bowel wall.

Both illnesses do have one strong feature in common. They are marked by an abnormal response by the body's immune system. The immune system is composed of various cells and proteins. Normally, these protect the body from infection. In people with IBD, however, the immune system reacts inappropriately. Mistaking food, bacteria, and other materials in the intestine for foreign or invading substances, it launches an attack. In the process, the body sends white blood cells into the lining of the intestines, where they produce chronic inflammation. These cells then generate harmful products that ultimately lead to ulcerations and bowel injury. When this happens, the patient experiences the symptoms of IBD.

Neither ulcerative colitis nor Crohn's disease should be confused with irritable bowel syndrome (IBS), a disorder that affects the motility (muscle contractions) of the colon. Sometimes called "spastic colon,"+or "nervous colitis" IBS is not characterized by intestinal inflammation. It is, therefore, a much less serious disease than ulcerative colitis. IBS bears no direct relationship to either ulcerative colitis or Crohn's disease.

The first symptom of ulcerative colitis is a progressive loosening of the stool. The stool is generally bloody and may be associated with crampy abdominal pain and severe urgency to have a bowel movement. The diarrhea may begin slowly or quite suddenly. Loss of appetite and subsequent weight loss are common, as is fatigue. In cases of severe bleeding, anemia may also occur. In addition, there may be skin lesions, joint pain, eye inflammation, and liver disorders. Children with ulcerative colitis may fail to develop or grow properly.

Approximately half of all patients with ulcerative colitis have relatively mild symptoms. However, others may suffer from severe abdominal cramping, bloody diarrhea, nausea, and fever. The symptoms of ulcerative colitis do tend to come and go, with fairly long periods in between flare-ups in which patients may experience no distress at all. These periods of remission can span months or even years, although symptoms do eventually return. The unpredictable course of ulcerative colitis may make it difficult for physicians to evaluate whether a particular course of treatment has been effective or not.

  • Proctosigmoiditis: Colitis affecting the rectum and the sigmoid colon.  Symptoms include bloody diarrhea, cramps, and tenesmus. Moderate pain on the lower left side of the abdomen may occur in active disease.
  • Left-sided colitis: Continuous inflammation that begins at the rectum and extends as far as the splenic flexure. Symptoms include loss of appetite, weight loss, diarrhea, severe pain on the left side of the abdomen, and bleeding.
  • Pan-ulcerative (total) colitis: Affects the entire colon. Symptoms include diarrhea, severe abdominal pain, cramps, and extensive weight loss. Potentially serious complications include massive bleeding and acute dilation of the colon (toxic megacolon), which may lead to perforation. Serious complications may require surgery.

Currently, there is no medical cure for ulcerative colitis. However, effective medical treatment can suppress the inflammatory process. This accomplishes two important goals: It permits the colon to heal and it also relieves the symptoms of diarrhea, rectal bleeding, and abdominal pain. As such, the treatment of ulcerative colitis involves medications that decrease the abnormal inflammation in the colon lining and thereby control the symptoms.

Three major classes of medication are used today to treat ulcerative colitis:

  1. Aminosalicylates include aspirin-like drugs that contain 5-aminosalicylic acid (5-ASA). Examples are mesalamine, olsalazine, and sulfasalazine. These drugs, which can be given either orally or rectally, alter the body's ability to generate and sustain inflammation. Without inflammation, symptoms such as diarrhea, rectal bleeding, and abdominal pain can be diminished greatly. Aminosalicylates are effective in treating mild to moderate episodes of ulcerative colitis, and are also useful in preventing relapses of this disease.
  2. Corticosteroids include prednisone, methylprednisolone, and budesonide These medications can be given orally, rectally, or intravenously. Corticosteroids are used for patients with moderate to severe disease. These drugs affect the body's ability to create and maintain inflammation. Although steroids can be quite effective for short-term control of acute episodes of colitis, they are not recommended for long-term use due to side effects.
  3. Immunomodulatory medicines include azathioprine, 6-mercaptopurine (6-MP), 6 thioguanine,(6-TG) and, recently, cyclosporine. As a group, they alter the immune cells' interaction with the inflammatory process. Immunomodulators are generally administered orally. They are used in selected patients when aminosalicylates and corticosteroids have been either ineffective or only partially effective. Azathioprine and 6-MP have been useful in reducing or eliminating some patients' dependence on corticosteroids. They also may be helpful in maintaining remission in selected refractory ulcerative colitis patients. However, these medications can take as long as three months before their beneficial effects begin to work.

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