First described in the mid-1800s, ulcerative colitis is a chronic disease with recurrent, uncontrolled inflammation of the colon. It is the most common form of inflammatory bowel disease worldwide, followed by Crohn’s disease. Ulcerative colitis usually presents itself in patients between the ages of 15 to 30. The highest incidence and prevalence of inflammatory bowel disease are seen in the populations of northern Europe and North America, in particular, the Caucasian and Jewish population, and the lowest in continental Asia. There are many risk factors and theories on the pathogenesis of ulcerative colitis, environmental influence, genetic predisposition, and immunologic response theory.
Starting with the environment, inflammatory bowel disease is associated with high social-economic status, diets high in fat and sugar, and medication, such as the oral contraceptive pill. Interestingly, smoking is associated with milder progression of the disease. Having an appendectomy in early life is also associated with a decreased incidence of ulcerative colitis. A family history of inflammatory bowel disease is a significant risk factor, evident from a high concordance in monozygotic twins.
However, ulcerative colitis is not inherited in a classic Mendelian pattern, again, suggesting the influence of environmental factors on an individual’s susceptibility. To date, we know that patients with ulcerative colitis display specific values in groups HLA and DR2. There is also an immunologic response theory in the pathogenesis of ulcerative colitis. Abnormalities in humoral and cellular adaptive immunity occur in ulcerative colitis.
For instance, elevated IgM, IgA, IgG levels are common in inflammatory bowel disease, with a disproportionate increase in IgG1 antibodies in ulcerative colitis. Autoimmunity may play a role in ulcerative colitis. In addition top-ANCA, ulcerative colitis is characterized by circulating IgG1 antibodies against a colonic epithelial antigen, Tropomyosin 5, that is shared with the skin, eye, joints, and biliary epithelium, which are also the extraintestinal involved in ulcerative colitis. Bloody diarrhea, with or without mucus, is the hallmark of ulcerative colitis. The onset is typically gradual, often followed by periods of spontaneous remission and subsequent relapses.
Active disease is manifested as mucosal inflammation commencing in the rectum (proctitis), working it’s way proximally to the colon, generally sparing the anus. The mucosal inflammation extends in a continuous uninterrupted fashion, unlike Crohn’s disease, where there are typically skipped lesions. This is a summary table of the intestinal and extra-intestinal manifestation of ulcerative colitis.
The intestinal involvement of ulcerative colitis will be discussed later, together with their management. For the extra-intestinal manifestation of ulcerative colitis, arthritis, ankylosing spondylitis, erythema nodosum, and pyoderma gangrenosum occur typically in association with active intestinal disease, and they typically improve or completely resolve after a colectomy. Colectomy, however, has no effect on the cause of primary sclerosing cholangitis. Most patients who have inflammatory bowel disease who develop primary sclerosing cholangitis tend to be less than 40 years of age, male, and have an increased risk of cancer.
For the management of ulcerative colitis, we’ll discuss the diagnosis, medical, and surgical therapies available. The diagnosis of ulcerative colitis involves defining the extent and severity of inflammation. Endoscopy and biopsy and the tests of choice to diagnose ulcerative colitis, as well as to assess the extent of the disease. On endoscopy, the characteristic changes include a loss of the typical vascular pattern, friability, exudates, ulcerations, and granularity in a continuous circumferential pattern.
The characteristic findings on histology include inflammation of mucosa and submucosa, sparing of the muscular layers of the colon, crypt abscesses, goblet-cell depletion, distorted crypt architecture, diminished crypt density, and ulcerations. Laboratory investigations are not diagnostic but are helpful in assessing and monitoring disease activity and in differentiating ulcerative colitis from other forms of colitis.
Full blood count, erythrocyte sedimentation rate, p-ANCA, level of fecal lactoferrin, or calprotectin can help determine the severity of inflammation. Stool cultures for Clostridium difficile, Campylobacter species, and E. coli are recommended to rule out an infectious cause of the complication. Neither the American College of Gastroenterology nor the British Society of Gastroenterology recommends routine radiographic testing in persons with suspected ulcerative colitis.
However, a double-contrast barium enema is useful when endoscopy is not readily available or when colonic strictures prevent a thorough evaluation. This is an example of a barium enema demonstrating the classic stovepipe or lead pipe sign of contiguous, superficial inflammatory process associated with loss of haustration, suggestive of ulcerative colitis. In this patient, there is also a colonic stricture.
The choice of treatment for patients with ulcerative colitis should take into consideration the level of clinical activity, be it mild, moderate, or severe. Combined with the extent of the disease, is it a proctitis, left-sided disease, extensive disease, or pancolitis? The cause of the disease, during follow-up, and the patient’s preferences. The main aims of medical therapy are the induction of remission and the maintenance of remission. The main therapeutic agents are aminosalicylates gates and steroids.
Immunomodulatory therapy is now also in use to induce remission of ulcerative colitis. Remission is clinically defined by three or fewer stools per day, without any presence of blood or increased urgency of defecation. The major goal of maintenance therapy is a steroid-free remission to avoid severe and partially disabling long-term side effects of corticosteroid treatment. And the main drugs used for the maintenance of remission are 5-aminosalicylates and thiopurines when 5-ASA is ineffective or not well tolerated.
Probiotic therapy also has a role in the maintenance of ulcerative colitis. There are other alternative therapies proposed but are still in trials. The indications of surgical management of ulcerative colitis include intractable disease with persistent symptoms and the complications of ulcerative colitis. First, massive gastrointestinal bleeding. This is an uncommon event, occurring in less than 5% of patients requiring an operation. Pre-operative resuscitation and stabilization is vital before surgery, and this involves the replenishment of extracellular volume and transfusions. Subtotal colectomy is the procedure of choice.
But if bleeding continues from the remaining rectal mucosa, an emergency proctocolectomy may be required. Toxic megacolon is a serious life-threatening condition that should not be missed. Patients with toxic megacolon typically present with symptoms of colitis that may be refractory to treatment and are usually septic, and may even have an altered mental status. In this condition, bacterial infiltration of the walls of the colon creates a dilatation of the colon of more than five centimeters in diameter as shown by the arrow in this abdominal x-ray.
And this progresses to the point of imminent perforation. This decompensation results in a necrotic thin-warped bowel in which pneumatosis can often be seen radiographically. Aggressive pre-operative stabilization is vital. Again, volume resuscitation with crystallite solutions, broad-spectrum antibiotics, and with stress dose steroids for patients previously on steroids. The goal of surgery is to remove all the colonic or dysplastic mucosa. Total abdominal colectomy with ileostomy and preservation of the rectum is the preferred operation for this condition. Patients with ulcerative colitis have been an increased risk of developing colon carcinoma.
Patients with prolonged duration of the disease, pancolonoic disease, continuously active disease, severe inflammation, primary sclerosing cholangitis have an increased risk of developing colon cancer. Colorectal carcinoma arising in ulcerative colitis tends to be poorly differentiated and highly aggressive tumors. The cumulative risk of cancer increases with the duration of the disease to as much as 65% after 40 years of active disease. As such, active surveillance, i.e. colonoscopy, is important and recommended for patients with ulcerative colitis.
The rationale in the surgery is to remove the diseased portion of the colon, as well as the rest of the large bowel as the remaining colon still poses a risk for further ulcerative colitis relapses, and more importantly a risk of malignant transformation. Total proctocolectomy with ileostomy is one surgical option, whereby the entirety of the colon and rectum are removed and the patient’s fecal content is brought out through the ileostomy. As you can imagine, it can be disturbing to the patient to have a stoma pouch and to have to regularly empty his ileostomy bag. Hence, the preferred surgical treatment is the restorative proctocolectomy with an ileal pouch-anal anastomosis, as shown in the diagram.
This option preserves the anal sphincter complex and provides the patient with a better quality of life. To summarize, we have learned epidemiology and multiple risk factors associated with ulcerative colitis. We have also gained an appreciation of the vast clinical presentation of ulcerative colitis, both intestinal and extra-intestinal involvement. Importantly, patients with ulcerative colitis have an increased risk of developing colorectal carcinoma. We have also gained an understanding of the management of ulcerative colitis, in diagnosing ulcerative colitis, the medical therapies, the role of endoscopy in diagnosis, and active surveillance, and the role of surgery in managing ulcerative colitis and their complications.