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Crohn’s Disease: Diagnosis and Treatment

Digestion, General | March 8, 2016 | Author: The Super Pharmacist

Digestion

Crohn’s Disease: Diagnosis and Treatment

Crohn's disease is a chronic (long lasting) disease that causes inflammation—irritation or swelling—in the gastrointestinal (GI) tract. Most commonly, Crohn's affects the small intestine and the beginning of the large intestine. However, the disease can affect any part of the gastrointestinal tract, from the mouth to the anus. Crohn’s disease (named after Dr. Burrill B. Crohn, who first described the illness in 1932), is one of the two most common inflammatory bowel diseases, the other being ulcerative colitis.

Inflammatory bowel disease is a medical term that describes a group of conditions in which the intestines become inflamed (red and swollen). Inflammation affects the entire digestive tract in Crohn’s disease and affects the full thickness of the bowel wall whereas ulcerative colitis affects only the lining of the large intestine.

Crohn’s disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract, but it most commonly affects the end of the small bowel and the beginning of the large bowel. There can be normal healthy bowel between patches of diseased bowel.

Symptoms

Symptoms of Crohn’s disease include:

  • Persistent diarrheoa (loose, watery, or frequent bowel movements).
  • Cramping abdominal pain.
  • Fever.
  • Rectal bleeding (at times)
  • Loss of appetite and weight loss also may occur
  • Fatigue is another common complaint

Crohn’s Disease: Diagnosis and TreatmentCrohn’s disease can also affect the joints, eyes, skin, and liver. 

A few people may experience swollen joints, inflamed eyes, skin lumps or rashes, or jaundice (yellow discolouration of the skin).

The most common complication of Crohn’s disease is blockage of the intestine due to swelling and scar tissue. Symptoms of blockage include cramping pain, vomiting, and bloating.

Other complications can be sores or ulcers within the intestinal tract which turn into tracts—called fistulas.

Crohn’s patients may also have an increased risk of colon cancer. 

Those suffering with this condition often experience periods of symptomatic relapse and remission.

Risk Factors

Crohn’s disease can occur at any age, but is most frequently diagnosed in people ages 15 - 35. About 10% of patients are children under age 18. Men and women are equally at risk and the disease tends to run in families, with 20 - 25% of patients having a close relative who also has the disease.  According to the Digestive Health Foundation sponsored by the Gastroenterological Society of Australia (GESA), 61,000 Australians have an inflammatory bowel disease; approximately 28,000 have Crohn's disease and 33,000 have ulcerative colitis.

Causes of Crohn's disease

The exact cause of Crohn's disease is unknown. Researchers believe the following factors may play a role in causing the disease:

  • Autoimmune reaction
  • Genes
  • Environmental factors

Autoimmune reaction

Scientists believe one cause of Crohn's disease may be an autoimmune reaction—when a person's immune system attacks healthy cells in the body by mistake. Normally, the immune system protects the body from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances. Researchers believe bacteria or viruses can mistakenly trigger the immune system to attack the inner lining of the intestines. This immune system response causes the inflammation, leading to symptoms.

Crohn’s Disease: Diagnosis and TreatmentGenetics

Crohn's disease sometimes runs in families. Research has shown that people who have a parent or sibling with Crohn's disease may be more likely to develop the disease.

Researchers continue to study the link between genetics and Crohn's disease.

Environmental factors

Some studies suggest that certain things in the environment may increase the chance of a person getting Crohn's disease although the chance is low.

Drugs and Diet

Nonsteroidal anti-inflammatory drugs, antibiotics, and oral contraceptives and a high fat diet are implicated the chance of developing the disease.

Smoking has been shown to double the risk. 

Diagnosis

The following information describes the investigative work-up of individuals presenting with symptoms characteristic of inflammatory bowel disease. In order to make a diagnosis of Crohn’s disease, the work-up should include blood tests to check for anaemia, a stool sample to detect microscopic bleeding, x-rays of the upper gastrointestinal tract, a computerised tomography scan, and endoscopy.  Much of the following information in regard to diagnosis of Crohn's disease is obtained from the National Institute of Diabetes and Digestive and Kidney Diseases.

Blood tests. Blood tests may be done to check for anaemia (low red blood cell count), which could be caused by bleeding from the intestines.  Blood tests may also uncover a high white blood cell count which is a sign of inflammation somewhere in the body.

Stool sample. A stool sample may be tested for blood to detect gastrointestinal bleeding.

X-rays. An upper gastrointestinal series (also called an upper ‘GI’) may be performed to look at the small intestine. For this test, the person drinks barium, a chalky solution that coats the lining of the small intestine, before x-rays are taken. The barium shows up white on x-ray film, revealing inflammation or other abnormalities in the intestine. If these tests show Crohn’s disease, more x-rays of both the upper and lower digestive tract may be necessary to see how much of the GI tract is affected by the disease.

Computerised Tomography Scan (CT scan). Computerised tomography scans use a combination of x-rays and computer technology to create images. A CT scan of the abdomen can diagnose both Crohn's disease and the complications seen with the disease.

Intestinal endoscopy. Intestinal endoscopies are the most accurate methods for diagnosing Crohn's disease and ruling out other possible conditions, such as ulcerative colitis, diverticular disease, or cancer. Intestinal endoscopies include:

  • Upper GI endoscopy and enteroscopy. An upper GI endoscopy is a procedure that uses an endoscope—a small, flexible tube with a light—to directly visualise the lining of the upper GI tract. During the procedure, a nurse or technician may give the patient a liquid anaesthetic to gargle or will spray the anesthetic on the back of a patient's throat. The anesthetic numbs the throat and calms the gag reflex. The nurse or technician will then normally use an intravenous (IV) needle to provide a sedative. The physician carefully feeds the endoscope down the patient's oesophagus and into the stomach. A small camera on the endoscope sends a video image to a monitor, allowing close examination of the GI tract.
     
  • Capsule endoscopy. Although this procedure can examine the entire digestive tract, physicians use it primarily to examine the small intestine. The patient swallows a capsule containing a tiny camera. As the capsule passes through the GI tract, the camera will record and transmit images to a small receiver device worn by the patient. When the recording is done, the physician downloads the images and reviews them on a video monitor. The camera capsule leaves the patient's body during a bowel movement and is safely flushed down the toilet.
     
  • Colonoscopy or sigmoidoscopy. Colonoscopy is a test that uses a long, flexible, narrow tube with a light and tiny camera on one end, called a colonoscope or scope, to look inside a patient's rectum and entire colon. In most cases, light anesthesia and pain medication help patients relax for the test. A sigmoidoscopy allows the doctor to examine the lining of the lower part of the large intestine, while a colonoscopy allows the doctor to examine the lining of the entire large intestine.

Tissue biopsy. A biopsy is a procedure that involves taking small pieces of tissue for examination with a microscope.

Treating Crohn's Disease

Crohn's treatment includes medications directed at symptoms (specifically, diarrheoa), medications intended to suppress the active inflammatory disease itself, nutrition supplements, surgery, or a combination of these options.

Anti-diarrheoal and fluid replacement

Diarrhoea and crampy abdominal pain are often relieved when the inflammation subsides, but additional medication may also be necessary. Several antidiarrheoal agents could be used, including diphenoxylate, loperamide, and codeine. Patients who are dehydrated because of diarrhoea can be treated with fluids and electrolytes. In most cases, people only take loperamide for short periods of time since it can increase the chance of developing megacolon (an abnormal dilation of the colon or large intestine).

Anti-inflammatory and immunosuppressant therapy for active Crohn's disease

Treating Crohn's DiseaseSuccessful medical treatment accomplishes two important goals: it allows the intestinal tissue to heal and it also relieves the symptoms of fever, diarrheoa, and abdominal pain.

Once the symptoms are brought under control (this is known as inducing remission), medical therapy is used to decrease the frequency of disease flares (this is known as maintaining remission, or maintenance).

The goals of anti-inflammatory and immunosuppressant therapy are to induce and maintain remission and improve the person’s quality of life.

Drugs in this category include:

  • aminosalicylates
  • corticosteroids
  • immunomodulators
  • biologic therapies

Medications used to treat Crohn’s disease are designed to suppress the abnormal inflammatory response of the immune system.  In addition to controlling and suppressing symptoms (inducing remission), medication can also be used to decrease the frequency of symptom flare-ups (maintaining remission). With proper treatment over time, periods of remission can be extended and periods of symptom flare-ups can be reduced.   

Aminosalicylates: Aminosalicylates contain 5-aminosalicyclic acid (5-ASA), which helps control inflammation. Sulfasalazine is the most commonly used of these drugs. Patients who do not benefit from it or who cannot tolerate it may be put on other mesalamine-containing drugs. Aminosalicylates include:

  • balsalazide
  • olsalazine
  • sulfasalazine
  • mesalazine also known as mesalamine or 5-aminosalicylic acid (5-ASA)

Some of the common side effects of aminosalicylates include abdominal pain, diarrhoea, headaches, heartburn, and nausea and vomiting.

Corticosteroids: Corticosteroids suppress the entire immune system and thereby, decrease inflammation. Corticosteroids are used to treat people with moderate to severe symptoms. Corticosteroids include:

  • budesonide
  • hydrocortisone
  • methylprednisone
  • prednisone
  • prednisolone

In most cases, corticosteroids are preferred not to be prescribed for long-term use. Side effects of corticosteroids include:

  • acne
  • a higher chance of developing infections
  • bone mass loss
  • high blood glucose
  • high blood pressure
  • mood swings
  • weight gain

Immunosuppressants: Immunosuppressants (also called immunomodulators) reduce immune system activity, resulting in less inflammation in the GI tract. These medications are used to help people with Crohn’s disease go into remission or to help persons who do not respond to other treatments. These medications can take several weeks to 3 months to start working. They are the drugs of choice in the management of disease that is dependent on or resistant to corticosteroids. Cyclosporin is only prescribed to people with severe Crohn’s disease because of the medication’s serious side effects. Immunosuppressants include: 6-mercaptopurine (or 6-MP), azathioprine, cyclosporine and methotrexate.

  • Azathioprine and 6-mercaptopurine (6-MP): Azothioprine and 6-mercaptopurine are medications that weaken the body's immunity by reducing the population of a class of immune cells called lymphocytes (white blood cells). Azathioprine and 6-MP are chemically related. Specifically, azathioprine is converted into 6-MP inside the body.
  • Methotrexate: Methotrexate  is used to treat patients with moderate to severe Crohn's disease who are either not responding to 6-MP and azathioprine or are intolerant of these two medications.  One major complication of methotrexate is the development of liver cirrhosis when the medication is given over a prolonged period of time (years).
  • Cyclosporin: Cyclopsporin is a potent immunosuppressant used to treat patients with severe Crohn's disease. Since the approval of infliximab (Remicade) for treating severe Crohn's disease, cyclosporin will likely be used primarily in the treatment of severe ulcerative colitis. Cyclosporin can be very effective in rapidly controlling severe colitis and avoiding or delaying surgery. Side effects of cyclosporin include high blood pressure, impairment of kidney function, and tingling sensations in the extremities. More serious side effects include anaphylactic shock and seizures.

Antibiotics Antibiotics: Antibiotics may be used when infections—such as abscesses—occur in Crohn’s disease. Antibiotics are used to treat bacterial overgrowth in the small intestine caused by stricture, fistulas, or prior surgery. Antibiotics may play a role in preventing postoperative recurrence of Crohn's disease.  The doctor may prescribe one or more of the following antibiotics: ampicillin, sulfonamide, cephalosporin, tetracycline, or metronidazole.

Biologic Therapies

Biologics are the newest group of Crohn's disease treatments. Unlike corticosteroids, which suppress the entire immune system, biologics are a newer, non-steroidal group of medications that act selectively

Biological therapy refers to the use of medication that is tailored to specifically target an immune or genetic mediator of disease. 

Prior to the development of biological therapies to treat inflammatory bowel disease, other medications that modulate the immune system—including 5-aminosalicylates, steroids, azathioprine, and other immunosuppressants—were primarily used in treatment. Patients with Crohn's disease that developed complications, including fistulae (abnormal connections to the bowel) were treated with surgery.

Inflammatory bowel disease is characterised by an inappropriate immune response to the body's own gut microbiota in the setting of a genetically susceptible individual. The consequence of this dysregulated process is activation of the innate immune system which in turn produces cytokines (pro-inflammatory molecules) such as tumour necrosis factor (TNF) and activation of the adaptive immune system with subsequent recruitment of pro-inflammatory white blood cells to the colon or small bowel.

Understanding Biologic Therapies: TNF Inhibitors, or Anti-TNFs

In the late 1990s, a class of biologics known as anti-TNFs, or TNF inhibitors, was introduced for use in moderate to severe Crohn's disease in patients who did not respond to conventional treatments. Blocking TNF-alpha, one protein involved in triggering inflammation that often leads to painful, bowel symptoms, may be effective in relieving some Crohn's symptoms. Currently, there are three anti-TNF agents (infliximab, adalimumab and certolizumab) that have been approved for use in Crohn's disease.  Concerns regarding the risk of lymphoma, and specifically the risk of hepatosplenic T-cell lymphoma, exist with all of these agents.

Infliximab. Infliximab works by binding to TNF-α. It won its initial approval by the FDA for the treatment of moderate to severe Crohn's disease that does not respond to standard therapies (mesalamines, corticosteroids, immunosuppressants) and for the treatment of open, draining fistulas in August 1998. It was the first treatment specifically approved for Crohn's disease.

Adalimumab. Adalimumab is a monoclonal antibody that binds with high affinity and specificity to human TNF-alpha. It was approved by the FDA in 2007 for the treatment of moderate to severe Crohn's disease. Unlike infliximab, which requires an intravenous infusion, adalimumab is administered by subcutaneous injection.

Certolizumab pegol. Certolizumab is a therapeutic monoclonal antibody to tumor necrosis factor alpha (TNF-α) approved by the FDA in 2008 for the treatment of moderate to severe Crohn's disease in adult patients who have had an inadequate response to conventional therapy.

Integrin Receptor Antagonists

The mainstay of treatment of moderate to severe Crohn's disease has been therapeutic targeting of the pro-inflammatory cytokine, TNF. Unfortunately, a significant proportion of individuals will be refractory to these medications or eventually lose efficacy. Moreover, anti-TNFs involve a non-negligible risk for infections and/or malignancies. This has widened the search for other pathways that might be targeted to treat Crohn's disease. The most advanced of these treatments are the integrin inhibitors that target adhesion of lymphocytes to the gut.The anti-adhesion molecules are one of the most interesting new treatments for inflammatory bowel disease because of their gut-selectivity. The integrins are a family of cell-surface glycoproteins involved in the adhesion, migration, and activation of immune cells. Integrin receptor antagonists are another recent development in biologic Crohn's treatments. Unlike TNF inhibitors, these Crohn's treatments are believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood–brain barrier.

Natalizumab. The first molecule to successfully target gut-specific adhesion of pro-inflammatory cells in treating Crohn's disease was natalizumab which targeted the α4 integrin. This drug proved efficacious in patients with moderate to severe Crohn's disease.Unfortunately, some individuals treated with natalizumab developed progressive multifocal leucoencephalopathy which is a rare, fatal demyelinating disease of the brain caused by reactivation of JC virus.

Vedolizumab. Vedolizumab is another compound that specifically targets the α4 integrin which has been developed. It was given FDA approval for the treatment of moderate to severe Crohn's disease in May 2014, and ongoing safety data are being collected in the Gemini LTS study which is a 7-year study that aims to report in 2016.The majority of adverse events have been headache, nasopharyngitis, nausea, arthralgia, upper respiratory infections, and fatigue. Patients treated with vedolizumab are also at an increased risk of developing infections.

Other medications   

Paracetamol is indicated for mild pain. People with Crohn’s disease should avoid using ibuprofen, naproxen, and aspirin since these medications can make symptoms worse by irritating the GI tract.

Pharmacology for Crohn's Disease

Therapy for mild Crohn's disease is typically administered in a sequential “step-up” approach, in which less aggressive and less toxic treatments are initiated, followed by more potent medications or procedures if the initial therapy fails. For the treatment of moderate to severe Crohn’s disease, current recommendations include the “top-down” approach, which differs from the conventional step-up approach in that more potent agents are administered first.

Nutrition Supplementation for Crohn's Disease

Nutritional therapy is another important modality for the treatment of disease, malnutrition, and growth failure in Crohn's disease. Although ineffective as a primary therapy, nutritional manipulations that allow bowel rest can be effective adjuncts in the treatment of active Crohn's disease. A dramatic reversal of malnutrition and a change in growth velocity can be expected in all children treated with adequate nutrition in conjunction with medical therapy to control symptoms of Crohn's disease. Both parenteral (intravenous) and enteral nutrition (via the gastrointestinal tract; e.g. by means of a nasogastric tube) are effective. Additionally, exclusive enteral nutrition has been shown to be as effective as corticosteroids for the induction of remission and might promote better gastrointestinal tract mucosal healing. Consumption of at least 1200 kcal/day has been associated with lower rates of disease relapse, but patients frequently relapse after initiation of a normal diet.

When Is Surgery Indicated in Crohn's Disease?

When Is Surgery Indicated in Crohn's Disease?In contrast to ulcerative colitis, it is not possible to remove the entire bowel that may be affected by Crohn’s disease, so the disease cannot be cured by surgery. However, surgery is great for treating complications of the disease such as a blockage, leak or abscess in the bowel, and also to remove the worst affected areas if drug treatment is ineffective. Surgery may also be necessary for people with Crohn’s disease of the anus, especially to drain abscesses so that medical therapy can work more effectively.

In Crohn’s disease, when surgery is performed, a conservative approach is generally adopted, to keep
as much of the gut intact as possible. 

Because of the high rate of disease recurrence after segmental bowel resection, the guiding principle of surgical management of Crohn disease is preservation of intestinal length and function. 

In 2007, the Standards Practice Task Force of the American Society of Colon and Rectal Surgeons (ASCRS) published recommendations for surgery in patients with Crohn disease. The most common complication of Crohn disease, occurring in 30-50% of patients, is small bowel obstruction. Typically, it is due to intestinal strictures from repeated bouts of inflammation and subsequent fibrosis. For a complete obstruction or a partial one refractory to nonsurgical management, surgical intervention is required. As many as two-thirds to three-quarters of people with Crohn's disease will require surgery at some point during their lives. While surgery does not cure Crohn's disease, it can conserve portions of the GI tract and return the patient to the best possible quality of life.

Surgery for Crohn's Disease

Small bowel resection

A small bowel resection removes part of a patient's small intestine. When a patient with Crohn's disease has a blockage or severe disease in the small intestine, a surgeon may need to remove that section. The two types of small bowel resection are:

  • laparoscopic—procedure is performed through several small, half-inch incisions in the patient's abdomen. The surgeon inserts a laparoscope—a thin tube with a tiny light and video camera on the end—through the small incisions. While watching the monitor, the surgeon inserts tools through the small incisions and removes the diseased or blocked section of small intestine. The surgeon will reconnect the ends of the intestine.
  • open surgery—when a surgeon makes one incision about 6 inches long in the patient's abdomen and procedes to remove or repair the damaged small intestine.

Subtotal colectomy

A subtotal colectomy, also called a large bowel resection, is surgery to remove part of a patient's large intestine. When a patient with Crohn's disease has a blockage, a fistula, or severe disease in the large intestine, a surgeon may need to remove that section of intestine. A surgeon can perform a subtotal colectomy using one of two methods:

  • laparoscopy—when a surgeon makes several small, half-inch incisions in the abdomen. While watching the monitor, the surgeon removes the diseased or blocked section of the large intestine. The surgeon will reconnect the ends of the intestine.
  • open surgery—when a surgeon makes one incision about 6 to 8 inches long in the abdomen, locates and removes the diseased or blocked section.

Proctocolectomy and ileostomy

A proctocolectomy is surgery to remove a patient's entire colon and rectum. An ileostomy is a stoma, or opening in the abdomen, that a surgeon creates from a part of the ileum—the last section of the small intestine. The surgeon brings the end of the ileum through an opening in the patient's abdomen and attaches it to the skin, creating an opening outside of the patient's body. The stoma is about three-fourths of an inch to a little less than 2 inches wide and is most often located in the lower part of the patient's abdomen, just below the beltline. A removable external collection pouch, called an ostomy pouch or ostomy appliance, connects to the stoma and collects intestinal contents outside the patient's body.

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