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Ulcerative Colitis: Therapy |
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Overview
The primary goal of therapy in ulcerative colitis is to reduce acute and chronic inflammation ultimately resulting in complete clinical and endoscopic remission. Medical therapies, as well as surgical intervention, are the current modalities for treatment of ulcerative colitis. Approximately 70% of patients respond favorably to medical regimens and go into remission. Surgery cures ulcerative colitis. Surgery is indicated for those patients who are unresponsive to medical therapy and have a severely compromised quality of life. Growth failure in children, life-threatening complications such as severe bleeding, toxic megacolon, impending perforation, intolerance to immunosuppression, colonic strictures, and dysplasia or carcinoma are also indications for surgery.
Medical Therapy
Anti-inflammatory drugs (adrenocorticosteroids and compounds containing 5-aminosalicylic acid) are the mainstays of medical therapy. These medications in a variety of forms are used orally and topically to reduce inflammation of the colon and rectum.  | | Table 02. |
Treatment Approaches
Treatment in ulcerative colitis is individualized to the specific needs of the patient and alterations in treatment strategies are made according to the response attained. Nevertheless, we present a guide to the most common approaches used with our patients.
Mild Acute Relapsing Ulcerative Colitis
Mild disease is associated with four or fewer loose bowel movements daily with occasional blood, abdominal cramps, and, infrequently, tenesmus. Systemic symptoms are not present. For proctitis or proctosigmoiditis, symptomatic treatment with antidiarrheals, rectal steroids (or rectal 5-aminosalicylic acid [5-ASA]), and occasionally oral 5-ASA is recommended. Left-sided colitis or pancolitis is treated with rectal steroids and oral 5-ASA.
Moderate Acute Relapsing Ulcerative Colitis
In patients with moderate disease, bowel movements range from 4–8 daily with urgency, a nocturnal pattern, blood in the stool, abdominal discomfort, and some systemic symptoms such as weight loss, mild anemia and low-grade fever (less than 100º F). Proctitis or protosigmoiditis is treated symptomatically (antidiarrheals, bulk agents). Rectal steroids (rectal 5-ASA) and oral 5-ASA are used in increasing doses. In left-sided or pancolitis, oral steroids are added and 5-ASA is used for maintenance therapy.
Severe Acute Relapsing Ulcerative Colitis
Severe attacks are characterized by the passage of six or more bloody stools daily accompanied by systemic symptoms such as fevers of 100º F or greater, weight loss, tachycardia, anemia with hemoglobin count of 10 g/dl or less, and hypoalbuminemia. For proctitis or protosigmoiditis, double-dose rectal steroids (plus rectal 5-ASA) along with increased oral 5-ASA or oral or intravenous steroids, are recommended. In left-sided or pancolitis, no antidiarrheal medications are recommended. A combination of oral 5-ASA, rectal steroids, intravenous steroids, and intravenous antibiotics (i.e., ciprofloxacin and/or metronidazole) is recommended. In protracted cases, the addition of intravenous cyclosporine is considered. The usual dose is 4 mg/kg given in a four-hour intravenous infusion (2–6 pm) for a period of 5–7 days. Trough levels are followed (normal range 100–250 mg/dl) as well as renal (kidney) function while on intravenous cyclosporine. If there is no major improvement of symptoms within one week after the initiation of intravenous cyclosporine, the patient is usually referred for surgery.
Surgical Therapy
Surgery in ulcerative colitis should be reserved for those patients with refractory disease, complications associated with the medical therapy, or complications of colitis. Colectomy may be used in pediatric patients for amelioration of growth retardation in prepubescent children affected by ulcerative colitis. Current surgical alternatives include total proctocolectomy (Figure 16A) with Brooke ileostomy (Figure 16B), the intra-abdominal Koch pouch (Figure 16C), and restorative proctocolectomy with ileal pouch-anal anastomosis (Figure 16D).
Elective colectomy cures ulcerative colitis and has a very low mortality rate (less than 1%). The procedure should almost always be a total colectomy (Figure 17A) with ileostomy or one of two internal ileal pouch alternatives. The Brooke ileostomy (standard) is a half-dollar–sized segment of terminal ileum that protrudes and is spouted from the right lower quadrant of the abdomen (Figure 17B). The patient attaches a double-faced adhesive ring to the skin and then to an opaque sack (which can be emptied) that collects the 750-1000 ml of material that the ileum produces daily (Figure 17C). Ostomy societies can be very helpful in adjusting to the inconvenience and psychological issues of an ileostomy. The Koch pouch (continent) ileostomy is an alternative to the Brooke ileostomy. An internal reservoir is created from reshaped ileum with a nickel-sized nipple valve opening onto the lower abdominal wall. The patient catheterizes the pouch through a nipple valve to remove ileal contents. The main disadvantage of this approach is that the valve may become incontinent within 2–5 years in 25–30% of patients, necessitating surgical repair (Figure 18 A-C). The most popular ileostomy alternative is the ileal pouch-anal anastomosis. The surgery involves creation of a new rectum from the small bowel and attaching the pouch of ileum to the anal canal (Figure 19). The pouch-anal anastomosis may be performed using a hand-sewn or stapled technique (Figure 20).
In patients with persistent disease activity or the development of dysplasia or cancer, a mucosectomy (stripping) may be performed before the anastomosis. Those who do not advocate anal stripping believe that preservation of a few centimeters of rectal mucosa produces better functional results (Figure 21).
In the patient with fulminant colitis, the colon may be removed first, leaving the creation of the pouch, restoration, and the removal of the rectum for a time when the patient has recovered from the colitis and is in better nutritional condition. This is a three-stage procedure, as a temporary ileostomy is made above the pelvic pouch to allow healing. In patients with more chronic and stable disease, the procedure may be performed in two stages (with a temporary ileostomy). Select patients are candidates for a restorative proctocolectomy performed in a single step. After a temporary protective ileostomy is closed, patients can defecate through their anus. After one year, most patients have five bowel movements per day. Incontinence is uncommon, although some patients experience nocturnal soiling. Although pouchitis is a complication in 25% of patients, the ileoanal pouch is an acceptable and successful alternative to standard ileostomy.
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Overview The complications of ulcerative colitis can be divided into those that affect the colon and those that are extracolonic.
Toxic Megacolon Overview
The most feared complication of ulcerative colitis is the development of toxic megacolon. It occurs as a result of extension of the inflammation beyond the submucosa into the muscularis, causing loss of contractility and ultimately resulting in a dilated colon. Dilation of the colon is associated with a worsening of the clinical condition and development of fever and prostration.
Diagnosis
This diagnosis is based on radiographic evidence of colonic distention in addition to at least three of the four following conditions: fever higher than 38.6ºC, neutrophil leukocytosis greater than 10,500 cells/mm³, heart rate greater than 120 beats/minute, and/or anemia. At least one sign of toxicity must also be present (dehydration, electrolyte disturbance, hypotension, or mental changes). Physical exam reveals a tender abdomen over the distribution of the colon. There may be rebound tenderness, abdominal distention, and hypoactive or absent bowel sounds.
Perforation
Colonic perforations are usually a complication of toxic megacolon. However, perforation can also present in severe ulcerative colitis even in the absence of toxic megacolon. Most perforations occur in the left colon, commonly in the sigmoid colon. Perforations tend to occur more often during the first episodes of colitis. Steroid therapy has been suggested to be a risk factor for colonic perforation, but this is controversial. Surgical management is indicated for perforation.
Radiography
X-rays of the abdomen reveal colonic dilation, usually maximal in the transverse colon, which tends to exceed 6 cm in diameter. Segments of the right and left colon may also be dilated. Serial plain abdominal x-rays of the abdomen taken at 12–24-hour intervals are useful in following the clinical course.
Medical Therapy
The goal of medical therapy is to reduce the likelihood of perforation and to return the colon to normal motor activity. The patient should have nothing by mouth. A nasogastric tube is placed in the stomach for suction and decompression of the upper gastrointestinal tract. The use of the rolling technique, during which the patient lies on the abdomen for 10–15 minutes every 2 hours while awake, allows for passage of gas and easier decompression of the dilated colon. Intravenous fluids are given to replete water and electrolytes. Broad-spectrum antibiotic coverage is instituted in anticipation of peritonitis resulting from perforation. Intravenous steroids are usually administered in doses equivalent to more than 40 mg of prednisone per day. Close monitoring of the patient's clinical condition is essential, and signs of deterioration, such as increasing abdominal girth, development of rebound tenderness, or hypotension, should prompt immediate action.
Surgical Therapy
Colectomy occurs in about 25% of patients and is required in almost 50% of patients with pancolitis. Surgical intervention is undertaken if the patient does not begin to show signs of improvement during the first 24–48 hours of medical therapy, as the risk of perforation increases markedly. Colectomy with creation of an ileostomy is the standard procedure, although single-stage proctocolectomy is done occasionally. If surgical therapy is performed before there is colonic perforation, the mortality is approximately 2%. In cases in which there has been bowel perforation, however, the mortality risk increases to 44%.
Strictures
Clinically relevant strictures are uncommon in ulcerative colitis. However, some degree of narrowing may be seen in approximately 12% of surgical specimens. Histologically, strictures present with hypertrophy and thickening of the muscularis mucosa without evidence of fibrosis. Strictures tend to occur late in the course of disease, usually 10–20 years after onset of disease. Most strictures occur in the sigmoid and rectum, with an approximate length of 2–3 cm. The most common presenting symptoms are diarrhea and fecal incontinence. Strictures have been associated with malignancy, and biopsy of the strictures is warranted. In fact, in patients with long-standing history of ulcerative colitis, a stricture should be considered potentially malignant.
Primary Sclerosing Cholangitis
Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by fibrosing inflammation of extra- and intrahepatic bile ducts. It is frequently associated with ulcerative colitis (Figure 24). Patients may have symptoms of fatigue, pruritis, abdominal pain, fever, or jaundice. This usually appears in men after 10–15 years of very mild, even subclinical, pancolitis, and may necessitate liver transplantation in some patients.
 | | Figure 23. A, Primary sclerosing cholangitis with typical stricturing and dilation pattern; B, Cholangiogram (ERCP image) |
For more information about primary sclerosing cholangitis
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