Crohn's Disease & Ulcerative Colitis (CD & UC)

Crohn's Disease

Crohn’s disease (CD) belongs to a group of diseases collectively called Inflammatory Bowel Disease (IBD) which also includes Ulcerative Colitis (UC). It is a chronic disease that can cause inflammation anywhere from the mouth to the anus anywhere along the lining of the digestive tract. It most commonly affects the small intestine and the colon. The disease can show up along different parts of the digestive tract in a continuous or patchy distribution. It typically involves both the superficial and deep layers of the intestinal wall

Symptoms of CD

Symptoms of CD depend on the severity and location of the intestinal inflammation and can range from none or mild, to severe. Symptoms may develop gradually or come on suddenly, without warning. Abdominal pain and cramping, persistent diarrhea (loose, watery, numerous bowel movements), blood in the stool and fever are hallmark symptoms of CD. Ulcers of the mouth, a lack of appetite, fatigue, nausea and vomiting and unexplained weight loss may also develop. With severe diarrhea and the digestive tracks’ inability to absorb nutrients, nutritional deficiencies may occur over time

Causes of CD

We do not yet know an exact cause of CD. Similar to other chronic inflammatory disorders (e.g. asthma, rheumatoid arthritis, psoriasis, multiple sclerosis) there is a complex interaction between an individual’s genetic make-up, their immune system and foreign substances in the environment (including dietary factors and microbes living in our gut) that are responsible for the chronic uncontrolled inflammation in CD. The impact of the various factors (genes, immune system and environment) are different for each individual accounting for the broad spectrum of how patients present with inflammation in different segments of the intestine and in various degrees of severity. Unfortunately, it appears as if once this inflammatory process is set in motion it cannot be regulated or reversed by the body itself

Who gets CD and how common is it?

Men and women appear to be affected equally. Symptoms usually start between the ages of 15-35 but can develop at any time during one’s lifetime. It used to be thought that CD predominantly affects Caucasians in North America and Western Europe, however, we now see individuals being diagnosed with CD in populations from South America, Africa and Asia where the disease was unheard of 20 years ago. CD can run in families and having a sibling or another first degree relative afflicted with the disease can increase the risk of developing the disease by ten to fifteen times as compared to the general population. However, more than 80% of patients with CD do not have a recognized genetic disposition. Given the complex genetic makeup the disease it is not inherited in the classic sense. Smoking is an important controllable risk factor in CD. People who smoke with this disease tend to have more severe forms of the disease and are at higher risk of needing surgery. People who live in industrialized countries and urban areas are also at elevated risk of having the disease. Some other factors including the use of medications such as non-steroidal anti-inflammatory drugs (aspirin-like drugs) and particular infections have been theorized to exacerbate or cause the disease although none have been shown in a consistent fashion to be the cause

How is CD diagnosed?

There is no single test to confirm the diagnosis of CD. Instead, multiple tests are usually used in combination to help arrive at the diagnosis depending on the symptoms that lead individuals to seek care. Ultimately, a colonoscopy or flexible sigmoidoscopy must be performed to directly visualize the intestine internally and to obtain small tissue samples (biopsies) for evaluation under the microscope. Other imagines studies can be used in conjunction with a colonoscopy to help in the evaluation including a barium enema, upper gastrointestinal series (UGI series) with small bowel follow through, computerized tomography scans (CT scans or ‘cat scans’), magnetic resonance imaging (MRI) or a pill camera study (capsule endoscopy) but are not mandated. Blood tests which look for antibodies and markers of inflammation along with stool specimen tests for hidden blood and infection may also be used to help confirm or exclude the diagnosis of CD

What are the complications of CD?

CD may cause symptoms outside the digestive tract including: inflammation of the eye (conjunctivitis, episcleritis, uveitis, iritis), inflammation of joints (arthritis), weakening of bones (osteoporosis), skin rashes (erythema nodosum, pyoderma gangrenosum), inflammation of the liver or bile ducts (primary sclerosing cholangitis), kidney stones, gallstones and in children, delayed growth or sexual development due to the use of steroids, malnutrition and malabsorption. Crohn’s disease may also lead to several complications over time which may be related to the disease or due to the effects of medications used to treat the disease.

Listed below are some of the common complications:

  • Anal fissure. A crack, or cleft, in or around the skin of the anus which lead to painful bowel movements, blood in the stool and sometimes drainage around the anal canal.
  • Ulcers. Chronic inflammation can lead to open sores (ulcers) anywhere in the digestive tract, including the mouth, genital area (perineum) and anus.
  • Fistulas. Sometimes ulcers can extend completely through the intestinal wall, creating a fistula — an abnormal tunnel between different parts of the intestine, between the intestine and skin or other organs, such as the bladder or vagina. These abnormal connections affect up to a third of patients with CD. Internal connections lead to diversion of food contents while external connections can lead to drainage and infections. When a course of medical therapy fails, surgery may be necessary to fix these abnormal connections.
  • Bowel obstruction. Due to inflammation over time, parts of the bowel could form scar tissue resulting in a thickening and narrowing of the bowel, which may block the flow of digestive contents through the affected part of the intestine. Medications may be of help in decreasing the inflammation and opening up the narrowed areas but some cases require surgery to remove the disesed portion of the bowel.
  • Malnutrition. Symptoms of diarrhea, pain and cramping may make it difficult to eat. In addition, inflammation of the intestine can decrease absorption of vital nutrients needed to maintain nourishment. Deficiencies of proteins, calories and vitamins may occur over a prolonged period of time. Vitamin B-12 and iron deficiency frequently lead to anemia in patients with malnutrition.
  • Colon cancer. Patients with Crohn’s disease that involves the colon do have an increased risk of colon cancer depending upon the amount of the colon that is affected and the duration of disease. Less than 5% of patients develop colon cancer although this is higher than the general population. Therefore, after approximately 8 years from the start of symptoms a colonoscopy is performed every 1 to 2 years to look for precancerous changes called dysplasia. Identifying dysplasia allows the potential to remove dysplastic growths (polyps) prior to the development of cancer

What are different types of treatment for CD?

Currently, there is no cure for CD and the goal of treatment is to alleviate symptoms, prevent complications and improve quality of life. This can be achieved through suppression of the body’s immune response which is paramount to allow the intestinal tissue to heal and retain its normal function. Initially, the goal is to induce remission, which is to bring the symptoms under control. Once this step is achieved, medical therapy is used to maintain remission with the goal of decreasing the frequency of disease flares. Several groups of drugs are used to treat Crohn’s disease and are listed below:

  • Aminosalicylates (5-ASA): This class of anti-inflammatory drugs is often used to treat mild to moderate symptoms in the colon and includes oral formulations of sulfasalazine and mesalamine and drugs that may be administered rectally.
  • Corticosteroids: This class of medications has a general, nonspecific effect of suppressing the entire immune system and is used to treat moderate to severe forms of the disease. Prednisone, budesonide and methylprednisolone are most commonly used. These are drugs that are best utilized short-term to alleviate major flares of the disease and due to side effects, these should not be used for maintenance therapy. Owing to a significantly increased risk of osteoporosis with the use of corticosteroids, a baseline DEXA scan should be performed at the initiation of therapy. Supplementation of calcium and vitamin D, and consideration of a bisphosphonate are also warranted.
  • Immune modifiers: Azathioprine, 6-MP, cyclosporine A and methotrexate alter the immune system and are also referred to as immunomodulators, used to help decrease exposure to corticosteroids, maintain disease remission and to help heal fistulas.
  • Antibiotics: These are classically used to treat perianal disease, abscesses and sometimes acute flares of the disease. Metronidazole and ciprofloxacin are the most commonly used.
  • Biologic therapies: This newer group of medications was first approved in 1998 for moderate to severe CD that did not respond to conventional therapy or to treat fistulae. These medications work by blocking specific chemical messages between immune cells. Biologics, like ADALIMUMAB, used in treating moderate to severe Crohn’s disease specifically target a protein called tumor necrosis factor (TNF) to help reduce the symptoms of Crohn’s.

What is the clinical course and prognosis in CD?

Most people with CD with the proper medical care tend to live healthy, productive lives with a normal life span. Maintenance of remission and surveillance for complications are the major goals which lead to maintaining quality of life in patients with CD. Regular visits with a gastroenterologist and developing a longstanding relationship are vital to managing this disease

Ulcerative Colitis

What is Ulcerative Colitis?

Ulcerative colitis (UC) is a disease marked by inflammation of the lining of the colon and rectum, together known as the large intestine. This inflammation causes irritation in the lining of the large intestine which leads to the symptoms of UC. Though UC always affects the lowest part of the large intestine (the rectum), in some patients it can be present throughout the entire colon. UC belongs to a group of diseases called inflammatory bowel diseases which also includes Crohn’s disease (CD). Though it was once thought that UC and CD were two different diseases, as many as 10% of patients may have features of both diseases and this is called indeterminate colitis. It is important to note that inflammatory bowel disease (IBD) is different from irritable bowel syndrome (IBS).

Symptoms of UC

The symptoms of ulcerative colitis depend on the severity of inflammation and the amount of the colon that is affected by the disease. In patients with mild to moderate inflammation, symptoms can include rectal bleeding, diarrhea, mild abdominal cramping, stool urgency, and tenesmus (discomfort and the feeling that you have not completely emptied your rectum after a bowel movement). When more severe inflammation is present, patients often develop fever, dehydration, severe abdominal pain, weight loss, loss of appetite or growth retardation (in children and adolescents with UC). Individuals with moderate or severe inflammation may also have to wake up at night to have bowel movements and may lose control of bowel movements. Some of the symptoms of UC may be non-specific and could be caused by other diseases such as Crohn’s disease, irritable bowel syndrome, or infection. Your doctor can help determine the cause of your symptoms and should be consulted should you experience a significant change in your symptoms.

Causes of UC

The way in which patients get ulcerative colitis is still poorly understood. There seems to be an interaction between the unique genetic makeup of an individual, environmental factors, and a patient’s specific immune system that triggers the disease. UC is not an infection that can be passed from person to person. Men and women are equally affected by UC. UC is more common in first degree relatives (siblings, parents, and children) of patients affected by UC and up to 20% of patients will have an affected family member. Despite the influence of genetics, the majority of patients with UC do not pass the disease to their children. There is no way to predict those at higher risk. Cases of ulcerative colitis have been identified throughout the world though certain populations, including those living in Northern climates and those of Jewish descent, are at higher risk of developing UC. Individuals having their appendix removed prior to the age of 20 appear to be at lower risk of developing UC. No specific infectious agent has been linked to UC and diet, breast feeding, and various medications have also been examined but none have been found to cause UC. It has been observed that smokers have lower rates of UC than non-smokers. Furthermore, those who smoke and have UC tend to have a milder course of UC than those who do not smoke (note that this is the exact opposite effect that smoking has on Crohn’s disease). Despite the protective role smoking appears to have on the development and natural history of UC, it is not recommended that patients start smoking to prevent UC due to the fact that there are so many other illnesses and cancers in which smoking is a definite risk factor. UC is an immune-mediated disease in which there is loss of control of the normal bowel immune activity and the ongoing activity results in damage to the bowel wall

How is UC diagnosed?

Your doctor will usually suspect the diagnosis of ulcerative colitis based on your symptoms, but confirmation of the diagnosis requires testing. Blood work is often checked to look for markers of inflammation or anemia (low blood counts), though these tests can be normal in patients with mild disease. Tests of your stool to look for evidence of an intestinal infection are often obtained. Radiologic images including x-rays and CT scans are usually not recommended but may be performed. All patients with symptoms consistent with UC should have a colonoscopy or flexible sigmoidoscopy to confirm the diagnosis assuming that they are healthy enough to undergo the procedure. During this procedure, your gastroenterologist will be able to directly examine the lining of your colon and rectum to look for evidence of inflammation and take small biopsies to be examined under a microscope to look for the cause of the inflammation.

What are the complications of UC?

The complications of ulcerative colitis can be divided into those affecting the colon and those occurring outside of the colon. Within the colon, UC can rarely lead to toxic megacolon or colon cancer. Toxic megacolon describes a severe disease flare with a high risk of infection and colonic perforation (holes in the colon). Patients may occasionally present with toxic megacolon as their initial presentation of UC and this complication requires hospitalization and may lead to surgery to remove the colon (colectomy). UC is known to increase the risk of colon cancer. Those patients who have had UC for a long time and those with a longer length of the colon affected are at higher risk of developing colon cancer. In general, patients begin to have an increased risk of colorectal cancer 10 years after the onset of disease symptoms and should have colonoscopy every one or two years starting at this time. Colon cancer is a rare complication and it is thought that it may be preventable based on control of inflammation of the colon and careful colonoscopy examinations that look for any pre-cancerous changes called dysplasia. Overall, the risk of colon cancer increases 0.5% yearly after 10 years of disease though patients with inflammation throughout their colon may be at higher risk. Those patients with primary sclerosing cholangitis (PSC) are at greatest risk for colon cancer and need to start screening upon diagnosis. Patients with UC are also at risk for extra-intestinal manifestations of UC (complications outside of the colon). These complications most frequently involve the liver, skin, eyes, mouth, and joints. Within the liver, patients with UC may develop primary sclerosing cholangitis. This occurs in about 3% of patients with UC. Patients with UC can develop sores in the mouth or rashes on the skin that generally only appear when UC colon symptoms are active. The most common rashes that are seen in UC are erythema nodosum (EN) and pyoderma gangrenosum (PG). EN usually presents as a red, raised, painful area most commonly on the legs and is most often seen during flares of UC. PG also presents as raised lesions on the skin (most frequently on the legs) that often develops after trauma to the skin and can lead to the formation of ulcers. Unlike in EN, the appearance of skin lesions in PG may or may not mirror the activity of bowel symptoms. The eyes can become red and painful (uveitis) and vision problems should be reported to your doctor. Arthritis is commonly associated with UC and can affect either small (such as the fingers/toes) or large joints (often the knee), though involvement of the smaller joints may have a course that is not related to activity in the colon. The joints of the spine can be affected as well, though this is less common than it is in Crohn’s disease. As in other chronic medical conditions, anxiety and depression are common in patients with UC. The unpredictability of UC and the need to take medications on a daily basis can lead to feelings of frustration or anger. Though occasional feelings of frustration can be normal, feelings of significant anxiety or depression should be brought to the attention of your physician.

What are different types of treatment for UC?

Medical treatment of ulcerative colitis generally focuses on two separate goals: the induction of remission (making a sick person well) and the maintenance of remission (keeping a well person from getting sick again). Surgery is also a treatment option for UC and will be discussed separately. Medication choices can be grouped into four general categories: aminosalicylates, steroids, immunomodulators, and biologics. Aminosalicylates are a group of anti-inflammatory medications (sulfasalazine, mesalamine, olsalazine, and balsalazide) used for both the induction and maintenance of remission in mild to moderate UC. These medications are available in both oral and rectal formulations and work on the lining of the colon to decrease inflammation. They are generally well tolerated. The most common side effects include nausea and rash. Rectal formulations of mesalamine (enemas and suppositories) are generally used for those patients with disease at the end of their colon. Steroids (prednisone) are an effective medication for the induction of remission in moderate to severe UC and are available in oral, rectal, and intravenous (IV) forms. Steroids are absorbed into the bloodstream and have a number of severe side effects that make them unsuitable for chronic use to maintain remission. These side effects include cataracts, osteoporosis, mood effects, an increased susceptibility to infection, high blood pressure, weight gain, and an underactive adrenal gland. Immunomodulators include medications such as 6-mercaptopurine and azathioprine. These are taken in pill form and absorbed into the bloodstream. They are effective for maintenance of remission in moderate to severe ulcerative colitis, but are slow to work and can take up to 2-3 months to reach their peak effect. Because of this, these medications are often combined with other medications (such as steroids) in patients who are very ill. These medications require frequent blood work as they can cause liver test abnormalities and low white blood cell counts, both of which are reversible when the medication is stopped. Adverse reactions can include nausea, rash, liver and bone marrow toxicity, pancreatitis, and rarely lymphoma. Biologic agents are medications given by injection that are used to treat moderate to severe UC. Biologic treatments are engineered to target a specific protein in the body. Biologics, like ADALIMUMAB, used in treating moderate to severe ulcerative colitis (UC) specifically target a protein called tumor necrosis factor (TNF) and can help people who’ve not responded well to immunomodulators.