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Ulcerative colitis

According to a review published in the American journal, Gastroenterology, the prevalence of ulcerative colitis in Europe was 505 per 100,000 persons and 249 per 100,000 persons in North America.

Ulcerative colitis more frequently affects non-smokers compared to smokers.

Overview

Ulcerative colitis is a type of inflammatory bowel disease (IBD). It is a chronic disease that causes inflammation and ulcers in the inner lining of the large intestine (colon). The disease is characterized by alternating periods of flare-ups (active disease) and remissions (few or no symptoms). The severity of the disease ranges from mild to severe.  

The exact cause of ulcerative colitis has yet to be identified. However, risk factors for developing ulcerative colitis include an abnormal immune response where the immune system mistakenly attacks the bacteria living in the colon, family history of the disease and environmental factors like air pollution. Other possible factors that minimally increase the risk include using NSAIDs, oral contraceptives and consuming milk products.

In patients with ulcerative colitis, alterations in the structure and function of the immune system, such as the presence of anti-colon antibodies, have been observed. The immune system ends up attacking the cells in the inner lining of the colon causing inflammatory polyps to appear.

Diarrhea, usually accompanied by blood or pus and abdominal discomfort is a most frequent symptom in ulcerative colitis patients. In the diagnosis of ulcerative colitis, endoscopies are considered to be the best and most accurate method. Two methods are commonly used, a colonoscopy or a flexible sigmoidoscopy. Sometimes, a biopsy may be taken from the intestine during the endoscopy. The doctor may also require additional tests such as blood or stool tests.

In the treatment of ulcerative colitis, the purpose is to manage the symptoms of the disease, increasing the duration between flare-ups (onset of symptoms) and decreasing their severity. Treatment usually begins with different types of medications, depending on the severity of the disease and possibly surgery. Surgery is required in specific cases where the disease is very severe, there are life-threatening complications or the patient is not responding to medication.

Medications prescribed for patients with ulcerative colitis include aminosalicylates, corticosteroids, immunomodulators, and biologics, which is known as anti-tumor necrosis factor (TNF) therapies. Surgical treatments include proctocolectomy and ileostomy.

Some complications of ulcerative colitis include blood in the stools, malabsorption, dehydration, increased risk of colon cancer, liver disease and megacolon (widening of the colon as a result of inflammation).

Since the exact cause of ulcerative colitis is unknown, it is not possible to prevent it. In patients with ulcerative colitis, prevention entails preventing future episodes by maintaining active treatment. Although dietary factors have not been indicated as a cause of ulcerative colitis flare-ups, some patients may find relief from their symptoms by avoiding certain types of foods such as dairy products, caffeine, spicy foods, and alcohol.

The overall prognosis for patients with ulcerative colitis is good. Patients with the higher risk of mortality include those with acute and severe flare-ups, those with extensive inflammation of the large intestine, older patients, those who develop liver disease and those who develop colon cancer. Patients in whom the disease progresses to the point of needing surgical intervention suffer from psychosocial limitations as a result of living with an ileostomy or an ileoanal pouch.

Definition

Ulcerative colitis is a chronic disease that affects the large intestine (colon). It is a major type of inflammatory bowel disease (IBD). Ulcerative colitis causes inflammation and ulcers on the inner lining of the large intestine which may produce pus and blood. The disease is characterized by alternating periods of flare-ups (active disease) and remissions (few or no symptoms).

Subtypes

Ulcerative colitis has differing degrees of severity. Types of ulcerative colitis based on severity are:

  • Mild ulcerative colitis, sometimes called ulcerative proctitis, is characterized by rectal bleeding (blood in the stool) accompanied by less than four bowel motions per day.

  • Moderate ulcerative colitis: This type is characterized by rectal bleeding accompanied by more than four bowel motions per day.

  • Severe ulcerative colitis: This type is characterized rectal bleeding accompanied by more than four bowel motions per day and systemic illness accompanied by an abnormally low level of albumin (a protein) in the blood (hypoalbuminemia).

Causes

The exact cause of ulcerative colitis has yet to be identified. Researchers consider that there are three main factors that may be related to developing ulcerative colitis. These factors are an abnormal immune response, genetic, and environmental factors, which are described in further detail under risk factors.

Risk Factors

Factors that may play a role in causing ulcerative colitis include:

  • An abnormal immune response: There are varying theories regarding the role of the immune system in causing ulcerative colitis. One theory is that the immune system incorrectly identifies the bacteria living in the colon as an infection, attacking these bacteria, resulting in inflammation of the colon and rectum. Another theory hypothesizes that a bacterial or viral infection prompts an immune response which does not switch off even after the infection is resolved/ comes to an end.. This results in an ongoing inflammation of the large intestine.

  • Genetic factors: Hereditary factors appear to play a role in increasing the probability of developing ulcerative colitis since the disease is more common in people with a family history of the disease. Furthermore, certain genetic studies have found genes that predispose people to develop ulcerative colitis.

  • Dietary factors: The role of dietary factors in causing ulcerative colitis symptoms has yet to be proven. However, some patients may find that dietary changes help reduce their symptoms. Specifically, consumption of large quantities of dairy products or low intake of dietary fiber may be associated with a higher risk of relapse.    Sulfur-rich foods which contain large amounts of sulfur-rich amino acids such as red meat, fish, nuts, cheese, milk, alcohol, and eggs have been suspected to play a role in increasing the likelihood of relapse.

  • Other factors: Some studies hypothesize that specific environmental factors such as air pollution may predispose people to develop ulcerative colitis, however, the risk remains low. 

Other factors that may cause a small increase in the risk of developing ulcerative colitis include:

  • Using NSAIDs,

  • Not consuming enough antioxidants, particularly vitamin A and E,

  • Stress,

  • Using milk products,

  • Using antibiotics,

  • Using oral contraceptives,

  • Eating a diet high in fat,

  • Age - ulcerative colitis is more likely to affect people between 15 and 30 and older than 60.

Pathophysiology

Several changes in the structure and function of the immune system have been observed in patients with ulcerative colitis. Subsets of T cells gather in the lamina propria of the diseased part of the colon. The lamina propria is a thin layer of connective tissue located under the epithelium, together with the epithelium it makes up the mucosa.

These T cells are cytotoxic to the epithelium of the colon in patients with ulcerative colitis. This causes an increase in the number of B cells and plasma cells leading to an increase in the manufacture of the antibodies immunoglobulin G (IgG) and immunoglobulin E (IgE).

The presence of anti-colon antibodies in patients with ulcerative colitis is well documented. Smooth muscle and anti-cytoskeletal antibodies have also been detected in a small number of ulcerative colitis patients.

Histologically, untreated ulcerative colitis patients display signs of chronic active colitis (inflammation of the inner lining of the colon). In active colitis, neutrophils (immune system cells) invade the epithelium of the intestinal gland cells (also called crypts of Lieberkühn) and may gather in the lumen (inside space) of these cells.

After a period of time, these invasions lead to alterations in the architecture of the intestinal gland cells, including

  • Shortening of crypts (space appears between the upper edge of the intestinal lamina and the bottom of the crypts),

  •  Differences in the sizes and shapes of crypts, and basal lymphoplasmacytosis (the base of the crypts is separated from the mucosa).

In addition to these microscopic changes, intestinal goblet cells discharge mucus.

In patients with severely active ulcerative colitis, erosion or ulceration of the intestinal mucosa occurs. After some time, granulation tissue (new connective tissue that forms on the surfaces of a wound as part of the healing process) covers the ulcerated areas. The erosion of the intestinal mucosa in addition to the presence of an excess of granulation tissue causes the formation of inflammatory polyps (also called pseudopolyps).

Signs And Symptoms

Ulcerative colitis is a progressive disease; it usually starts mildly and worsens with time. The severity of the symptoms ranges from mild to severe, depending on how much of the colon is affected.

Patients with ulcerative colitis most commonly display the following signs and symptoms.

  • Diarrhea, usually accompanied by blood or pus

  • Abdominal discomfort.

Other symptoms include:

  • Tenesmus (occasionally) – an urgent need to defecate,

  • Inability to defecate despite urgency,

  • Weight loss,

  • Fatigue,

  • Nausea or loss of appetite,

  • Anemia.

Less common symptoms include:

  • Pain or soreness in the joints,

  • Irritation of the eye,

  • Certain rashes.

In around 10% of people, ulcerative colitis has a fulminant course (the onset is sudden and severe). These people may suffer from severe symptoms including:

  • Severe pain and cramping in the abdomen,

  • Severe dehydration (the elderly are particularly susceptible),

  • Fever,

  • Severe diarrhea,

  • Leukocytosis (an increase in the total number of white blood cells in the body),

  • Abdominal distention (swelling of the abdomen).

Diagnosis

Ulcerative colitis is diagnosed using patient history, a physical exam, laboratory tests and endoscopies of the large intestine.

  • Patient History: The doctor will ask about family history of ulcerative colitis, the symptoms the patient is experiencing, including onset (beginning) of the disease, any medical conditions the patient is suffering from as well as past medical conditions, in addition to any medication the patient is taking.

  • Physical Exam: During the physical exam, the doctor will examine the abdomen and will check for any distension, tenderness or pain.

  • Lab Tests: Lab tests used to aid in the diagnosis of ulcerative colitis include blood and stool tests. A blood sample will be collected from the patient and used to check for signs of inflammation or infection, anemia, low albumin (protein), which is a sign of severe ulcerative colitis.

Furthermore, the sample will be tested for immunological markers (specific antibodies) that are commonly associated with ulcerative colitis. The stool test is usually used to rule out other possible causes of gastrointestinal disease, particularly infections.

  • Endoscopies: Endoscopies are considered to be the best and most accurate method for diagnosing ulcerative colitis. Two methods are commonly used, a colonoscopy or a flexible sigmoidoscopy.

  • Flexible sigmoidoscopy: The doctor passes a flexible, narrow tube that contains a light and a camera through the rectum to look inside it and lower colon. During the sigmoidoscopy, a biopsy may be taken. During this procedure, the doctor will look for any indication of bowel diseases such as irritated and swollen tissue, ulcers, and polyps.

  • Colonoscopy: A colonoscopy is used to look inside the rectum and colon. During the colonoscopy, a biopsy may be taken. By using this test, the doctor will be able to identify any irritated or swollen tissue, polyps, ulcers, and cancer.

  • Biopsy: This is considered useful for confirming the disease by checking for microscopic changes in the intestinal cells, for noting the severity of the disease, monitoring disease progression, and to check for dysplasia (pre-cancer) or cancer.

Treatment

A medical cure for ulcerative colitis has yet to be found.However, the purpose of ulcerative colitis treatment is to manage the symptoms of the disease, increasing the duration between flare-ups (onset of symptoms) and decreasing their severity. Treatment options include:

  • Medication: Medications are used to control the symptoms of ulcerative colitis, improving a patient’s quality of life. Medications prescribed for patients with ulcerative colitis include:

  • Aminosalicylates: These can help regulate inflammation and are mostly used to treat people with mild or moderate symptoms. Examples of aminosalicylates used include:

  1. Olsalazine

  2. Balsalazide

  3. Sulfasalazine

  4. Mesalamine

  • Corticosteroids (steroids): These can help reduce immune system activity, leading to a decrease in inflammation. They may be prescribed for patients who do not respond to aminosalicylates and for patients who display more severe symptoms. Examples of corticosteroids used include:

  1. Budesonide

  2. Prednisone

  3. Hydrocortisone

  4. Methylprednisolone

  • Immunomodulators: These can help decrease the activity of the immune system, leading to a decrease in inflammation in the colon. They may be prescribed for patients who do not respond to aminosalicylates. Examples of immunomodulators used include:

  1. 6-mercaptopurine, or 6-MP

  2. Azathioprine

  • Biologics: These medications target tumor necrosis factor (TNF), a protein created by the immune system. These medications nullify TNF, reducing inflammation in the large intestine. Examples of biologics used include:

  1. Infliximab

  2. Adalimumab

  3. Vedolizumab

  4. Golimumab

Other medication used to treat patients with ulcerative colitis could include:

  • Acetaminophen: This mostly used treat mild pain. However, ulcerative colitis patients should try not to use ibuprofen, naproxen, and aspirin since these medications can aggravate their symptoms.

  • Loperamide: This can help reduce or stop diarrhea, but this medication should not be used in patients with significantly active ulcerative colitis.

  • Cyclosporine: This can be used to treat people with severe ulcerative colitis.

  • Antibiotics.

  • Surgery: Surgery has historically been seen as a curative treatment for ulcerative colitis. Two different types of surgery are generally used in the treatment of ulcerative colitis:

  • Proctocolectomy and ileostomy: A proctocolectomy is a surgery to remove the entire colon and rectum. As a result of colonic removal, the surgeon creates an opening in the abdomen from part of the ileum (ileostomy). That opening is connected to a removable external collection pouch.  Contents of the intestine empty through the stoma into external collection pouch instead of passing through the anus. The ileostomy is permanent.

  • Proctocolectomy and ileoanal reservoir: A proctocolectomy is a surgery to remove the entire colon and rectum. An internal pouch from the patient’s ileum is created by the surgeon. This pouch is connected to the end of the rectum. Waste is stored in this pouch and leaves the body through the anus. An ileoanal reservoir is also called a pelvic pouch, a J-pouch or an ileoanal pouch.

Complications

Ulcerative colitis has several complications including:

  • Bleeding from the rectum (blood in the stools): Ulcers on the lining of the intestine may open and bleed. The bleeding may cause anemia. The bleeding may rarely be severe.

  • Malabsorption and dehydration: Inflammation of the intestinal lining renders the cells less able to absorb fluids and nutrients. In addition, consistent diarrhea plays a role.

  • Osteoporosis: Some medication used to treat ulcerative colitis such as corticosteroids may cause osteoporosis. It may also be a result of dietary changes such as avoiding dairy products, which may trigger symptoms in some people.

  • Megacolon: A rare complication where inflammation causes the large intestine to swell and stop working. Toxic megacolon is an acute and life-threatening inflammation of the large intestine, requiring immediate surgery.

  • Primary sclerosing cholangitis: A rare complication where the bile ducts become gradually inflamed and damaged over time.

  • Inflammation in other parts of the body: The immune system may cause sores in the lining of the mouth, inflammation in the joints, eyes, and skin.

  • Poor growth and development in children: Ulcerative colitis and some of its treatments may affect growth and delay puberty.

  • Increased risk of colon cancer: Particularly in males, if the patient has active ulcerative colitis, if the disease affects the entire colon, if the disease has been ongoing for 8 or more years and if the patient suffers from sclerosing cholangitis.

  • Other possible complications: These may include liver disease and increased risk of blood clots.

Some complications of surgery to treat ulcerative colitis include:

  • Fecal incontinence: Solid or liquid stool or mucus are accidentally passed from the rectum.

  • Infertility in women.

  • Pouchitis: Inflammation or irritation of the ileoanal pouch.

  • Infections.

  • Anastomosis leakage: Leaking where the surgeon attaches the ileum to the rectum.

  • Abscesses.

  • Sexual dysfunctions.

  • Small bowel obstructions.

Prevention

Since the exact cause of ulcerative colitis is unknown, it is not possible to prevent it. However, in patients with ulcerative colitis, prevention entails avoiding flare-ups of the disease by maintaining active treatment. Most of the medications used to treat ulcerative colitis, aside from corticosteroids, may be used to prevent further episodes.

Patients are recommended to keep a food diary to track if any foods help or worsen the symptoms of ulcerative colitis. Other dietary recommendations include limiting dairy products, avoiding foods high in fat, reducing fiber, particularly limiting foods such as cabbages and cauliflower, avoiding alcohol, spicy foods and caffeine, drinking plenty of water.

Stress may play a role in causing episodes of ulcerative colitis, as such methods of managing stress including exercising, relaxation and breathing techniques may help in preventing flare-ups.

Prognosis

The overall prognosis for patients with ulcerative colitis is good. The outcome of the disease depends on the rate of relapse and the complications that may arise.  The risk of mortality is at its highest in patients with acute and severe flare-ups, those with extensive inflammation of the large intestine, older patients, those who develop liver disease and those that develop colon cancer.

The disease’s clinical course ranges from inactive (long periods without flare-ups) to fulminant (severe and sudden) 21. In approximately one-fifth of the patients, the disease worsens with time despite treatment; however, in the majority of patients, the disease responds to treatment and becomes inactive or intermittent.

Despite improving the general physical health of the patient and reducing the risk of colorectal cancer, the colectomy imposes psychosocial limitations on patients living with an ileostomy or an ileoanal pouch.

Epidemiology

According to a review published in the American journal, Gastroenterology, the prevalence of ulcerative colitis in Europe was 505 per 100,000 persons and 249 per 100,000 persons in North America.

Ulcerative colitis more frequently affects non-smokers compared to smokers.

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