Ulcerative Colitis: Causes, Symptoms, and Treatment
1. Introduction
Ulcerative colitis is a chronic, or long-lasting, disease that causes inflammation and sores, called ulcers, in the inner lining of the large intestine, which includes the colon and the rectum (the part of the colon located close to the anus). Ulcers form where inflammation has killed the cells that usually line the colon, then bleed and produce pus. Inflammation in the colon also causes the colon to empty frequently, causing diarrhea. When the cells and the body's defense mechanisms cannot clear the inflammation, the symptoms of ulcerative colitis can last a long time and can return. There may be long periods of remission, where you have few or no symptoms.
Ulcerative colitis is an inflammatory bowel disease (IBD), the general name for diseases that cause inflammation in the small intestine and the colon. It can be difficult to diagnose because its symptoms are similar to other IBD and irritable bowel syndrome (IBS). IBD is a term used for a group of diseases with the following features: inflammation of the GI tract, inflammation goes through the layers of the intestines, and it always involves ulcers of the intestines. The most common diseases are ulcerative colitis and Crohn's disease. Both diseases are similar and usually not very specific. The main difference between the two is the location and the nature of the inflammation. In Crohn's disease, the inflammation can occur anywhere in the GI tract and may have normal healthy bowel between areas of diseased bowel (skip lesions). Ulcerative colitis most often starts at the anus and continues up the rectum to the colon.
1.1 Definition and Overview
What is ulcerative colitis?
Ulcerative colitis is a chronic, or long-lasting, disease that causes inflammation and sores, called ulcers, in the inner lining of the large intestine, which includes the colon and the rectum - the end part of the colon. The inflammation makes the colon empty frequently, causing diarrhea. Ulcers form in places where the inflammation has killed the cells lining the colon; the ulcers bleed and produce pus. Because the cell lining is damaged, it does not hold the stool, and it is passed rapidly and emptily, causing diarrhea.
This disease affects the colon only and does not spread to other parts of the body. It is not the same as Crohn's disease, which can affect the entire digestive system and involve all layers of the bowel wall. While both Crohn's disease and ulcerative colitis are types of inflammatory bowel disease, it is important to note that ulcerative colitis and Crohn's disease are chronic diseases, but they are not usually lifelong, nor are they considered fatal. Ulcerative colitis has similar features to other diseases that cause inflammation of the bowel, such as irritable bowel syndrome and to an extent, Clostridium difficile colitis, but by having a colonoscopy or sigmoidoscopy will show the characteristic inflammation of the colon and rectum to confirm the diagnosis of ulcerative colitis.
1.2 Prevalence and Incidence
Prevalence is a measure of all individuals affected by a disease at a certain point in time. It is useful to policy makers and gives an indication of the burden of a certain disease. Incidence is a measure of the number of new cases of a disease in a certain period of time. Incidence "provides a measure of the risk of contracting the disease." Data for prevalence and incidence can be gathered by doctors seeing how many patients come in with a certain disease in a specific timeframe and recording this information.
Prevalence rates of Ulcerative Colitis vary depending on the location. UC is most prevalent in North America and Europe and is less prevalent in Asia, Africa, and the Middle East. Prevalence rates are higher in urban communities as opposed to rural ones, but the rates in rural communities have been increasing. The rates are also higher in higher socioeconomic classes and show no sex predominance. Prevalence also changes depending on the age of the individual. It has been discovered that UC is more prevalent in older individuals; however, an alternate peak of even higher incidence rates in newly industrialized countries shows that the disease may be moving towards a younger population. Prevalence rates also appear to show that UC incidence has been increasing in the past. This can be due to the improved diagnosis of the disease but also the possibility of newly industrialized countries moving towards a western lifestyle.
Incidence rates of Ulcerative Colitis have also shown to vary depending on the location. The highest rates are in North America and Europe, but the incidence is also increasing in newly industrialized countries. The incidence rates also peak in people ages 15-25 and then again in those ages 55-65. This bimodal distribution is unique to UC and shows that a higher proportion of older individuals are affected by UC compared to other IBDs. Just like prevalence, no sex predominance is shown in incidence. The worldwide distribution of UC, the changes in rates seen in the past, and the difference in rates depending on demographics all indicate that UC is a disease of modern society.
1.3 Risk Factors
Having a family history of ulcerative colitis increases your chances for developing the disease 10 times above normal. Abnormal responses of the immune system also appear to be a cause. The body's immune system is believed to react abnormally to the bacteria in the digestive tract. When the body's white blood cells attack the lining of the intestines, they cause ongoing inflammation. Heredity also seems to play a factor in that ulcerative colitis is more common in those with a family history of the disease or other bowel disorders. Lastly, although stress does not cause ulcerative colitis, it can make symptoms worse and harder to control. A current theory is that the stress response in the body can cause symptoms in the bowel. These factors combined can eventually lead to the development of ulcerative colitis.
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2. Causes and Pathophysiology
The exact cause of ulcerative colitis is still unknown. Ulcerative colitis is the result of an abnormal response by your body's immune system. However, the immune system, which is composed of various cells and proteins, is believed to be responding to a virus or bacterium by causing chronic inflammation in the intestines. The inflammation does not go away, which results in the chronic phase of the disease. There is a consensus among scientists that the interaction between genes of the host and microbes of the gut is a key factor in causing UC. Studies have determined that ulcerative colitis is caused by a complex interplay of genetic and environmental factors. Persons with a family history of IBD are more likely to develop UC. Twin studies have also shown that if one monozygotic twin has UC, the other twin is far more likely to develop UC than if they were dizygotic twins. HLA is a gene complex that encodes MHC in humans. MHC is a protein that presents an antigen to a T cell. Certain MHC II genotypes (for example the HLA-DRB1*0103 genotype) have been associated with UC. This is known as an example of genetic predisposition to UC. The explanation for how environmental factors contribute to UC includes the hygiene hypothesis and studies of smoking. The hygiene hypothesis states that children in Western countries are not exposed to the same types of infections that children in developing countries are exposed to, and thus their immune systems develop differently. Smoking is inversely related to the development of UC, and smoking cessation has been linked to an increased risk of UC. Smoking is also known to have many detrimental health effects, so the risks of starting to smoke are much greater than the potential benefits of preventing UC. When an environmental factor triggers a person's immune system to cause chronic inflammation in the colon, the symptoms of UC develop.
2.1 Immune System Dysfunction
This form of inflammatory bowel disease involves an abnormal response by the body's immune system. Normally, the immune system protects the body from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances. In patients with IBD, however, the immune system cannot tell the difference between foreign substances and the body's own healthy tissues. As a result, the immune system responds to the GI tract as if it were being invaded by bacteria, viruses, and other foreign substances. In so doing, the immune system causes chronic inflammation which does not subside. In the pop-up description of "Crohn's", either have a link to UC or have similar chronic inflammation language.
In ulcerative colitis, the inflammation is continuous and extends a variable distance up the colon. The inflammation involves the surface of the lining of the colon, and it is typically a combination of ulcerations and the body's attempts to heal the ulcers. By contrast, in Crohn's disease, inflammation involves all layers of the bowel wall and may extend deeply into adjacent tissues. Crohn's disease can be found anywhere in the digestive tract.
The chronic inflammation produces the symptoms of UC, such as abdominal pain, diarrhea, and rectal bleeding. It also produces the complications of UC, such as colon cancer and toxic megacolon. Unfortunately, medications only partially suppress the immune system's abnormal inflammatory response in UC, and there is still no cure. Consequently, a large portion of the research into UC pathogenesis aims to completely understand and eventually cure the immune system dysfunction in UC.
2.2 Genetic Factors
Genome-wide association studies have implicated several genetic loci as risk factors for UC. The strongest association is in the HLA complex on chromosome 6p, which accounts for 10% of the genetic risk. Non-HLA genes probably account for a further 10% of the genetic risk. Several recent review articles provide comprehensive lists of gene associations with UC, but useful recent links are also available at the National Institute of Diabetes and Kidney Disease readily assembled single nucleotide polymorphism database.
The mechanism by which genetic loci predispose to UC is not clear, although it is likely that they influence local immune or epithelial responses to luminal antigens. The HLA associations with UC differ significantly from those with Crohn's disease or primary sclerosing cholangitis (both of which are also inflammatory diseases of the colon), suggesting that different HLA-restricted responses are involved in these diseases. The observation that some gene associations differ between UC and Crohn's disease, combined with the rarity of extensive colitis and the mild course in some ethnic groups, suggests that genetic risk factors may influence the phenotype of colitis.
A family history of UC is a strong risk factor, and recent data suggest that the risk is affected by the number and sex of affected relatives. A large European study found that the relative risk is between 5 and 20 for a child whose mother had UC, especially if the child was female. A Danish study also found a significantly higher risk in children of the same sex as an affected sibling. These findings raise the intriguing possibility of in utero environmental effects that influence the developing immune system, although other genetic or environmental factors related to sex or shared environment cannot be excluded.
2.3 Environmental Triggers
Environmental triggers (Table 4): Environmental factors may initiate or perpetuate inflammation. Psychological stress has been thought, through undefined mechanisms, to play a role in the exacerbation of IBD. The social and economic consequences of IBD are substantial, and there is a high rate of psychiatric morbidity among patients, especially anxiety and depression. Exposure to cigarette smoke is the most important environmental factor linked to the development of IBD. A recent meta-analysis examining smoking in IBD demonstrated that smoking increases the likelihood of developing CD and worsens the disease course. There is also an inverse association between smoking and the development of UC, and smoking cessation is associated with disease onset in UC. The underlying pathophysiology regarding how smoking affects CD and UC still remains unclear and is an area that requires further research. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin have been implicated in disease flares and the onset of CD in a dose-dependent manner. Avoidance of NSAIDs may, therefore, influence the disease course. Appendectomy, which in many cases is performed due to appendicitis, is associated with the decreased development of UC but increased risk of CD.
Outdoor air pollution and exposure to sulfur or nitrogen dioxide have been associated with an increased risk of relapse in UC. A study examining dietary patterns in patients from Europe, its inflammatory bowel disease network showed that a diet characterized by meat and dessert consumption was associated with an increased risk in developing CD, whereas a diet high in fruits and vegetables was associated with an increased risk of developing UC. Industrialization has resulted in the westernization of societies, and there are many countries whereby IBD was previously rare and is now becoming more common. This may be attributed to either greater disease recognition and resource allocation for diagnosis or an epidemiological change due to global influences of the aforementioned environmental factors.
Several infections have been implicated in the development of IBD, and a recent inception cohort study has shown an increased risk of IBD development following acute appendicitis. Hormonal contraceptive use in women has also been associated with an increased risk, especially in UC. Primary sclerosing cholangitis in a patient with UC is an increased risk factor for developing colitis-associated colorectal cancer, and an understanding of disease pathogenesis is crucial for therapy development. This often-neglected area of research may ultimately be beneficial in preventing the development of IBD in certain high-risk groups.
3. Symptoms and Diagnosis
Pain on the left side followed by weight loss may be the first symptom of ulcerative colitis. It may be followed by skin lesions and joint pain, and then by diarrhea and bloody stool. Rectal urgency and incontinence are frequent symptoms. In extreme cases, ulcerative colitis can lead to anemia or life-threatening toxic megacolon. Symptoms are variable and depend on the extent and severity of the inflammation. Ophthalmological symptoms are rare, and when they occur, they generally reflect the extent of inflammation in the body.
Diagnosis of ulcerative colitis can be suspected from the patient's history and symptoms, but it is usually confirmed through endoscopy and biopsy. A flexible sigmoidoscopy or a colonoscopy allows examination of the entire colon and rectum, and can identify the extent of the disease. A biopsy will always confirm the diagnosis of ulcerative colitis because it takes on a specific appearance under the microscope. Sulfasalazine, although previously mentioned, should be questioned as it may mask the symptoms and delay the diagnosis of ulcerative colitis.
3.1 Common Symptoms
Symptoms of ulcerative colitis include abdominal pain, diarrhea, rectal bleeding, urgency to defecate, and tenesmus. Other symptoms may include fatigue, a reduced appetite, weight loss, and occasional fevers. Symptoms can vary depending on the severity of inflammation and the extent of the colon involved. For example, individuals with proctitis (inflammation confined to the rectum) may have rectal bleeding, but no other symptom. More systemic symptoms include anemia, arthralgias, and skin lesions, but these are less common. Eye inflammation, when it occurs, is more common in people with ulcerative colitis than in the general population. Primary sclerosing cholangitis is a progressive primary inflammatory disease of the bile ducts that affects children and adults in all age groups. It occurs more often in patients with ulcerative colitis, particularly men. Finally, an increased risk of blood clots, mainly in the legs (deep vein thrombosis) and lungs (pulmonary embolism).
Anemia is a condition where you do not have enough red blood cells or hemoglobin to carry oxygen to the body's tissues. It is a common symptom of ulcerative colitis, occurring in about 20% to 80% of patients, and it is usually due to chronic gastrointestinal blood loss. Other causes of anemia in ulcerative colitis are hemolysis (increase in destruction of red blood cells), deficiencies of vitamin B12 and/or folic acid, and anemia of chronic disease. Symptoms of anemia may include weakness, fatigue, and shortness of breath. Eye inflammation (uveitis) often manifests as iritis, which can cause eye pain, blurred vision, and photophobia. It may occur once or be recurrent. It is usually responsive to treatment and does not lead to permanent loss of vision. Skin lesions may appear as erythema nodosum, which appears as red, painful nodules under the skin, often on the shins. These may occur at the time of initial diagnosis or during flares of colitis. This condition may resolve when the underlying colitis is treated. A pyoderma gangrenosum is a less common but more severe, ulcerative lesion of the skin that can occur with underlying systemic inflammation. Deep vein thrombosis or pulmonary embolism can result from an increased rate of blood clotting due to underlying inflammation. In general, symptoms of ulcerative colitis are highly variable and depend on the location, severity, and extent of inflammation as well as the patient's overall health.
3.2 Diagnostic Tests
There is no specific test for ulcerative colitis, but several may be used in order to diagnose the condition. Stool samples are the first test that might be carried out. This is to rule out any other causes for the symptoms such as infection. The inflammation caused by ulcerative colitis will, in turn, produce ulcers. Colonoscopy is used to diagnose many bowel conditions, including ulcerative colitis. This is a procedure which involves inserting a long, flexible, telescopic camera into the rectum and up into the colon. Biopsies can then be taken from the colon, which will show any inflammation. An X-ray of the colon called a barium enema or lower GI series, using a chalky liquid called barium to show up the colon on the x-ray, or a CT scan may be necessary to provide a clearer diagnosis. Blood tests can also be used to show inflammation in the body but may not necessarily demonstrate ulcerative colitis.
3.3 Differential Diagnosis
The differential diagnosis of ulcerative colitis is relatively sparse as the disease is distinctive in the pattern of distribution in the colorectum and to the variable degree of extra-intestinal manifestations. It is important to distinguish between CD and UC as the treatment approaches are different between the two diseases and a misdiagnosis has the potential to cause harm. In the differentiation between CD and UC alternative diagnosis, a non-inflammatory irritable bowel syndrome was given its own diagnostic criteria which excludes patients with IBD. In a study conducted, 2.2% of patients who thought to have UC were reclassified as having IBS. The main symptoms of IBS are bloating and abdominal pain relieved by defecation and onset associated with a change in stool frequency or form. The absence of rectal bleeding and weight loss should point to a diagnosis of IBS over a diagnosis of UC. Acute infective diarrhea is a common alternative diagnosis to UC and its presence must be excluded. Bacterial pathogens have been found to cause dysentery and a bloody diarrhea which can mimic a UC relapse. Flexible sigmoidoscopy should be used to differentiate between the two diseases as patients with infectious diarrhea generally have inflammation confined to the rectum. Once again, it's important to note that other causes of infective bloody diarrhea are more common in the third world. Ischemic colitis is an important alternative diagnosis in the elderly who present with fresh rectal bleeding. Finally, colonic malignancy is the most significant differential diagnosis as UC in long-standing disease in the left colon is a risk factor for the development of colonic cancer and dysplasia. An accurate histological diagnosis must be made and there are many characteristic features in the colonoscopic and radiological findings of UC that should allow differentiation from simulating diseases. An epidemiological study of 318 UC patients was conducted to discover the most common diseases wrongly diagnosed as UC. The main alternative diagnosis was CD (14.5%) and 37 cases of colonic cancer were discovered which had a severe impact on the survival of the patients. Evidently, there is a large psychiatric morbidity associated with IBD wherein a study conducted found a 21% prevalence of a primary mood disorder with most of the patients' symptoms not meeting the diagnostic criteria for a mood disorder. Wrong diagnosis of the patients' own psychiatric symptoms with the symptoms of UC can lead to overdiagnosis of disease severity and overtreatment of the patient with psychiatric drugs. Steps need to be taken to improve the distinction between UC and its simulating diseases as in many cases UC is wrongly assumed to be the correct diagnosis without logical reasoning and in only around 80% of the cases is the initial diagnosis of UC correct.
4. Treatment and Management
Smoking cessation is commonly advised and often successfully decreases the need for medication and increases the possibility of remission. In some cases, smoking can make some medications less effective, so it may have an effect on the type of medication that a patient would be prescribed. Recommending patients to stop smoking generally carries more weight if it is known that the patient's UC was triggered when they started smoking or decreased in severity when they quit. Some people with ulcerative colitis may not be able to absorb enough nutrients from food and will need to take a supplement. Special high-calorie liquid supplements are sometimes recommended to help patients maintain a healthy weight and improve their nutritional intake. If you have severe symptoms, you may need to eat a low residue diet to lower the amount of undigested food in the stool. This can help to control acute symptoms; however, it is not recommended for maintenance of remission or overall health.
The psychological effects of ulcerative colitis should not be underestimated. The variable and unpredictable course of the disease, the effects of medication and surgery, and the restrictions imposed by symptoms can be distressing for many patients. Symptoms of UC such as urgency, soiling, and incontinence can be discomforting, and patients with UC may fear leaving the house, traveling, or being without a toilet. Low mood and anxiety are common, and some people develop more severe psychological illnesses such as depression or anxiety. Optimal treatment of the underlying colitis can improve psychological symptoms. However, some patients may require specific treatment for their psychological health.
Ulcerative colitis increases your risk of developing colorectal cancer. If you have had UC that affects the whole colon for more than 10 years, it is recommended that you are entered into a surveillance program for colorectal cancer. This will usually involve having a colonoscopy (an examination of the colon using a flexible camera) at regular intervals, usually once every 1-2 years. During the colonoscopy, biopsies (small samples of tissue) can be taken to look for early changes in the lining of the colon. If these are detected, it may be possible to treat them to reduce the risk of developing colorectal cancer. The mechanism varies in different countries and regions.
4.1 Medications
There are several different types of medications used to treat ulcerative colitis. The type prescribed by a doctor will depend on the severity of symptoms and the location of the inflammation. The main goal of medication will be to reduce inflammation in the colon, in order to induce or maintain remission. Another goal is to bring about a steroid-free remission because steroids are associated with serious side effects. Currently available medications will not cure ulcerative colitis. Then, there are antibiotics used to treat infections in the tissues and the surrounding area. Many studies have investigated various regimens of mesalamine, which is available in a variety of different formulations and under many brand names. Mesalamine is effective in inducing remission in patients with mild to moderate ulcerative colitis and is as effective as sulfasalazine, which has similar properties. Long-term maintenance therapy with mesalamine reduces the risk of relapse of disease, particularly among patients with extensive colitis. Mesalamine is well tolerated and its use has been associated with a decreased need for corticosteroids, fewer hospitalizations, and fewer surgeries.
4.2 Lifestyle Modifications
There are several factors known to bring on and worsen the symptoms of ulcerative colitis, particularly in those who are in the midst of a flare-up in symptoms. Some of the more common irritants are: diet, stress, smoking, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin.
While the role of diet as a cause of ulcerative colitis has not been firmly established, it has long been recognized that some people notice an increase in abdominal symptoms with specific foods. It may be helpful to keep a food diary to try to identify any problem foods, which can then be excluded from the diet. If symptoms do improve, it may be worth altering the diet to try to prevent re-introduction of these foods. This approach would then be combined with the recommended healthy eating pattern.
Stress may also worsen symptoms of ulcerative colitis, although it is not thought to cause the disease. Any form of severe life stress (e.g. loss of job, family break-up) can lead to a flare of symptoms, but the most well-recognized form of stress-related worsening of symptoms is 'exam stress' in young adults. (Note: Stress does not cause flares of ulcerative colitis to develop into the more serious toxic dilatation or colitis). Strategies for stress reduction and improved coping should be discussed with someone trained in stress management techniques, or a clinical psychologist or psychiatrist if symptoms are severe. These strategies usually involve providing initial active treatments to reduce the symptoms that are then combined with approaches to prevent future symptoms. Concentration of stress-reducing interventions is a poor use of resources and is often best delivered by self-help approaches or individual support from qualified therapists.
4.3 Surgical Options
Ulcerative colitis can dramatically affect a person's quality of life. The disease is marked by abdominal pain, diarrhea, and bleeding. Over time, 80% of patients with ulcerative colitis may require surgery for cure of their disease. Surgery is not a treatment for ulcerative colitis, rather it is a curative procedure because the disease resides in the large intestine. There are several surgical options available, and the individual considerations for each patient will be discussed with the surgeon.
Colectomy: This is a surgical procedure to remove the large intestine. The entire large intestine is removed and the anus is usually sewn shut. There are various forms of colectomy - a total colectomy and removal of the rectum is called a proctocolectomy. If only part of the colon is removed, it is possible to reconnect the small and large intestine; however, this is not an option in the treatment of ulcerative colitis as the disease may persist in the remaining large intestine. Colectomy may be necessitated as a result of emergency treatment for severe colitis or it may be a planned procedure in cases of chronic disease. Step-by-step guide.
Peri-anal conditions (patients with disease around the anus) may undergo a removal of the colon and creation of an ileostomy, leaving the rectum in place with the possibility of reconnection at a later date. An ileostomy is a surgically created opening in the abdominal wall where a portion of the small intestine is brought to the skin's surface to create an outlet for stool. This may be temporary or a permanent solution. A total proctocolectomy as final treatment involves removal of the colon and rectum and closure of the anus with ileostomy formation. Finally, the ileostomy can be closed with a further operation.