Ulcerative colitis, one of the inflammatory bowel diseases, is characterized by recurring episodes of inflammation of the mucosal layer of the large bowel not related to an intestinal infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
The inflammation always involves the rectum and can extend proximally in a continuous fashion. Ulcerative proctosigmoiditis refers to inflammation extending into the sigmoid colon.
Left-sided colitis refers to inflammation extending up to, but not beyond, the splenic flexure.
Pancolitis refers to disease that extends proximally to the splenic flexure.
Approximately 50% of patients present with proctosigmoiditis, 30% with left-sided colitis, and 20% with pancolitis. Interestingly, about 50% progress to more extensive disease over the first 5 years of disease.
The inflammation is characterized by superficial ulcerations, granularity, and a distorted vascular pattern. Histologic features include an expansion of the lamina propria with inflammatory cells and crypt abscesses.
There are usually no fistulae or granulomas, the usual histologic features of Crohn disease.
The cause of ulcerative colitis remains unknown.
The immune system in the mucosa of the large intestine is exposed to a variety of antigens from food products and billions of bacteria live there.
In theory, any of these may trigger the release of proteins that sets off an immune reaction, bringing inflammatory cells to the colon lining. Recently, scientists searching for the cause of UC have developed three major hypotheses:
That unidentified pathogens, most likely harmful bacteria or viruses in the colon, trigger the body’s immune response, which is natural. But the immune cells are not effective in destroying the pathogens.
Therefore, chronic inflammation results, harming the lining of the colon.
That a common dietary antigen or a nonpathogenic microbe is present in the colon of people with UC. Their immune systems overreact, mounting an abnormally intense response to these common substances.
There is mounting evidence that people who develop UC are genetically predisposed to the immune overreaction and/or their immune system has not developed normal tolerance to these substances.
That UC is triggered by proteins present on the surface of the patient’s own intestinal cells. The theory holds that the body mounts an appropriate immune response to an antigen it discovers in the colon.
But because of similarities between the proteins on the surface of the antigen and those on cells in the colon, the immune system wrongly attacks the lining of the patient’s colon.
This is called an autoimmune response. It results in inflammation, which destroys the cells lining the colon. Auto-antibodies against antigens in white blood cells are common in ulcerative colitis (known as peripheral anti-neutrophilic cytoplasmic antibodies, or pANCA).
Further research may clarify which of these theories holds the most promise for future treatment.
Genetic factors play a role in who develops ulcerative colitis; indeed, the most firmly established risk factor is a family history of UC.
Approximately 10 percent of patients with ulcerative colitis have a first-degree relative with the illness, with approximately an 8-fold increased risk of the disease compared to those without a UC family history.
Jewish ancestry from middle and Eastern Europe (Ashkenazi Jews, the majority of Jews in the United States) heritage increases the risk of UC, but rates among Jews vary from country to country.
The prevalence of UC is higher among people born in Europe or North America than for those born in Asia or Africa, suggesting that environmental factors also play a role.
People with a family history of the other major chronic intestinal inflammatory bowel disease, Crohn’s disease, have a three-fold greater risk of developing UC.
In epidemiological studies of twins, identical twins share a stronger risk of UC than do fraternal twins.
However, there is only a modest increase in concordance of the disease among identical twins (approximately 6% concordance), providing further evidence that factors other than genetics, such as environment, also play a role.
Additionally, UC may develop from different causes, some having a greater genetic predisposition than others.
Presently about 15 unique regions of the human genome have been shown to contain DNA variations resulting in increased risk for UC.
Several of these genes influence the body’s immune function. These include variations in the human leukocyte antigen, known as HLA genes, which are required for the immune system to process antigens, and genes in proteins that regulate the chronicity of immune response, notably the interleukin 23 receptor.
Interestingly, the majority of the genes and genomic regions identified are also associated with risk for Crohn’s disease. It’s likely that the UC predisposing genes work together, and, influenced by environmental factors, lead to increased risk of ulcerative colitis.
Among the possible environmental factors, no specific foods have been identified as a cause of ulcerative colitis. However, some people with UC are intolerant of cows’ milk and find that dairy products may aggravate symptoms.
Cigarette smoking actually reduces the risk, though what component of tobacco has a beneficial effect on the colon lining is not entirely clear.
Smokers have only about 40 percent of the risk of developing ulcerative colitis of nonsmokers.
Among one group of 30 intermittent smokers with UC, resuming smoking a pack of cigarettes per day over a six-week period led to an improvement in symptoms in 50 percent of these patients. Stopping smoking seems to increase the risk of developing UC.
Former smokers are about 1.7 times more likely to develop the disease than are those who have never smoked. Some researchers have theorized that nicotine could be the element in tobacco that reduces the risk of UC.
Controlled trials of a nicotine patch as therapy for UC suggest nicotine may play a role in preventing the disease.
On the other hand, a high proportion of nonsmokers experienced unacceptable side effects from nicotine patches. Some studies have shown benefit using nicotine for treatment of UC, while others have not. Larger studies are needed.
Life-threatening complications can result from ulcerative colitis. These include toxic megacolon, colonic perforation, strictures, and a liver disorder called primary sclerosing cholangitis.
Toxic megacolon: The most feared complication from severe ulcerative colitis is toxic megacolon. This condition occurs as a result of extension of the inflammation beyond the submucosa of the colon into the smooth muscle layer in the wall of the colon.
This causes the colon to lose its ability to contract, ultimately resulting in a dilated colon, fever, weakness, racing heart, an abnormally elevated white cell count, abdominal tenderness, and other signs of toxicity.
X-rays of the abdomen are done to diagnose the condition. Colonic perforation, or a hole in the wall of the colon, is a common complication with toxic megacolon, leading to peritonitis, and possibly death.
Medical therapy to reduce the likelihood of perforation of the colon wall and to return the colon to normal motor activity is required to prevent toxic megacolon in patients with signs of fulminant colitis, where toxic megacolon is likely to develop.
Because patients should take nothing by mouth, a nasogastric tube is placed in the stomach for suction and decompression of the gastrointestinal tract.
The use of a rolling technique during which the patient lies on his abdomen for 10 to 15 minutes every two hours while awake, allows gas to pass and the dilated colon to decompress. Intravenous fluids are given.
Broad-spectrum antibiotics are begun in anticipation of possible peritonitis from a perforation.
Intravenous steroids to reduce inflammation are usually administered. The patient’s condition is closely monitored for signs of deterioration.
If the patient does not show signs of improvement during the first 24 to 48 hours of drug therapy, the risk of perforation increases markedly and surgical intervention is undertaken. If surgery is performed before there is colonic perforation, the mortality rate is only about 2 percent.
But in cases where there has been bowel perforation, the rate increases to 44 percent.
Perforation: Perforations can also occur in severe ulcerative colitis even if toxic megacolon does not develop. Most perforations occur in the left colon, commonly in the sigmoid colon.
Perforations tend to occur more often during first episodes of colitis. Perforations must be treated surgically.
Strictures: Though uncommon in ulcerative colitis, strictures, or narrowings of the colon, are evident in about 12 percent of surgically removed colons.
Strictures tend to occur late in the disease, usually 10 to 20 years after onset. The most common symptom is fecal incontinence. Strictures have been associated with colon cancer, and biopsy of the stricture is warranted.
Primary sclerosing cholangitis: This is a chronic liver disease in which the flow of bile in the liver is interrupted by fibrous tissue in the bile ducts.
The abnormal tissue forms as a result of chronic inflammation. The majority of people with this condition develop or have had ulcerative colitis.
People with this complication have symptoms of fatigue, abdominal pain, fever, or jaundice. It can appear in men after 10 or 15 years of very mild, even subclinical (i.e. asymptomatic) pancolitis, and it is associated with a high risk for colon cancer.
Primary sclerosing cholangitis can result in liver cirrhosis and necessitate liver transplant. Because primary sclerosing cholangitis does occur in patients without any evidence of UC (or Crohn’s disease) and because relatively few patients with UC develop primary sclerosing cholangitis, it is likely these are two distinct diseases but with overlapping causes.
The predominant symptom of ulcerative colitis is diarrhea, sometimes associated with blood in the stool.
Frequent bowel movements are common, as a result of irritability of the inflamed rectum. In severe cases, people may have eight or more bloody bowel movements a day.
Other symptoms include abdominal or rectal pain, fever, and weight loss. In some cases, anemia and weakness may result from blood loss.
About 50 to 60 percent of patients have mild disease, marked mainly by diarrhea and some bleeding. These cases usually respond well to drug therapy.
Moderate disease occurs in about 30 percent of people with UC and is characterized by bloody diarrhea, cramps, abdominal tenderness, and urgency to defecate; sometimes these symptoms are accompanied by anorexia and weight loss, fever, or mild anemia.
Only about 10 percent of UC patients have severe cases of the disease. The symptoms involve six or more bloody bowel movements per day, abdominal pain and tenderness, fever, anemia, an elevated white cell count, and a low level of albumin, a protein in the blood.
People who suffer severe UC may develop life-threatening complications, such as severe hemorrhage, or a condition called “toxic megacolon,” where the colon swells and may damage other organs.
Sometimes, people with ulcerative colitis experience symptoms that affect other systems of their body, known as extra-intestinal symptoms.
Extraintestinal Symptoms of UC
Symptoms of arthritis may occur in as many as 26 percent of patients with ulcerative colitis. Arthritic symptoms may show up even before inflammatory bowel disease is diagnosed.
About 12 to 23 percent of patients with ulcerative colitis have peripheral arthritis, or pain and swelling that affects the large, weight-bearing joints such as the knees and ankles.
If UC worsens or becomes exacerbated, arthritis signs and symptoms often accompany the change in condition.
Spondylitis, or inflammation of the vertebrae, occurs in about 3 percent of UC patients who also have arthritis complications.
Nineteen percent of patients with ulcerative pancolitis (UC that involves the entire colon) experience dermatological disorders.
These can include a skin condition called erythema nodosum, in which small, tender, red nodules appear under the skin, accompanied by fever and transitory arthritic symptoms. Another possible skin disorder is pyoderma gangrenosum.
Thought to be an immune reaction, this condition causes soft, red nodules on top of the skin that ulcerate, turning purple-red around the edges.
Pyoderma gangrenosum (and especially erythema nodosum) do occur alone and associated with other conditions that do not include UC.
However, because pyoderma gangrenosum is so commonly associated with UC, evaluation of the bowel is usually undertaken even in the absence of symptoms (as in primary sclerosing cholangitis).
Psoriasis, a common skin disease appearing as reddish, silvery-scaly skin, can accompany UC.
About 5 percent of patients with extensive ulcerative colitis also develop eye-related manifestations of the disease.
These may include uveitis, or inflammation of all or part of the uvea (the iris, ciliar body, and choroids); episcleritis, inflammation of the outermost layers of the eye; and keratoconjunctivitis, a condition characterized by dryness of the cornea due to lack of tears.
Symptoms of these ocular complications are often headache, abnormal sensitivity to light, blurred vision, burning, and increased secretions from the eyes.
Note that the majority of patients that have these ocular conditions do not have UC, however.
In most cases, when these systemic symptoms occur, they can be effectively treated with standard medications. Only in rare cases is removal of the colon necessary to control severe systemic complications associated with ulcerative colitis.
The diagnosis of ulcerative colitis is established by finding characteristic intestinal ulcerations and excluding alternative diagnoses, such as enteric infection, ischemia, diverticulitis, or NSAID-induced enteropathy.
The most common diagnosis that mimics ulcerative colitis is that of the infectious colitides. It is imperative to check stool for enteric pathogens, including ova and parasites, Escherichia coli O157:H7, cytomegalovirus, and Clostridium difficile.
Active disease in ulcerative colitis is characterized by the endoscopic appearance of superficial ulcerations, friability, a distorted mucosal vascular pattern, and exudates.
Patients with severely active disease can have pseudopolyps, and deep ulcers and friability that result in spontaneous bleeding.
The typical distribution of disease is continuous from the rectum proximally.
However, patients with partially treated ulcerative colitis might have discontinuous or patchy involvement.
Histologic features of ulcerative colitis include disease limited to the mucosa and submucosa with an expansion of inflammatory cells in the lamina propria, mucin depletion, ulcerations, exudate, and crypt abscesses.
What triggers ulcerative colitis to develop is unknown. Therefore, there is no way to effectively prevent the disease.
Medical care focuses on treatment to achieve remission of symptoms, prevention of relapses, and management of the disorder to avoid systemic symptoms, worsening of the disease, and life-threatening complications.
Management of ulcerative colitis is described in practice guidelines published in 2010.4 The severity of the ulcerative colitis flare is based on patient symptoms and on the extent of colitis, not on the histologic severity of inflammation .
For patients with mild to moderate distal or left-sided colitis, therapy includes oral or topical 5-ASA agents, or both.
The combination of oral and topical mesalamine is more effective than either alone for active disease.11 Mesalamine (5-ASA) enemas are commonly used topical agents and given at a dose of 4 g nightly.
This therapy is effective for both active colitis and for maintaining remission, and it is superior to rectal corticosteroids for distal disease.
Steroid enemas are effective in active disease, but they are not useful in maintaining remission.
Mesalamine suppositories are also useful for patients with proctitis.
Mesalamine therapy is not considered to have failed until a patient has been given maximum doses of the drug or has experienced intolerable side effects.
Oral 5-ASA doses of up to 4.8 g per day are given for active disease and 2.4 g per day for maintenance of remission. Sulfasalazine 2 g per day is given for maintenance, and up to 8 g per day for active disease.
Balsalazide 6.75g daily is particularly effective for left-sided colitis. Once-daily formulations of mesalamine are effective in inducing and maintaining remission.
Although sulfasalazine is less expensive than the other 5-ASA agents, it has a high incidence of side effects, such as nausea, vomiting, anorexia, dyspepsia, malaise, and headache.
Some rare idiosyncratic reactions include fever, rash, hepatitis, pancreatitis, pneumonitis, and agranulocytosis.
Folate supplementation is recommended, because sulfasalazine can inhibit folate absorption. The other 5-ASA agents can be more expensive but generally are better tolerated.