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Ulcerative Colitis Diseases

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Ulcerative Colitis Diseases

Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis, may occur. Long-term risk of colon cancer is high. Diagnosis is by colonoscopy. Treatment is with 5-aminosalicylic acid, corticosteroids, immunomodulators, anticytokines, antibiotics, and occasionally surgery.

Ulcerative Colitis Diseases
Ulcerative Colitis Diseases

Pathophysiology

Ulcerative colitis (UC) usually begins in the rectum. It may remain localized to the rectum (ulcerative proctitis) or extend proximally, sometimes involving the entire colon. Rarely, it involves most of the large bowel at once.

The inflammation caused by UC affects the mucosa and submucosa, and there is a sharp border between normal and affected tissue. Only in severe disease is the muscularis involved. In early cases, the mucous membrane is erythematous, finely granular, and friable, with loss of the normal vascular pattern and often with scattered hemorrhagic areas. Large mucosal ulcers with copious purulent exudate characterize severe disease. Islands of relatively normal or hyperplastic inflammatory mucosa (pseudopolyps) project above areas of ulcerated mucosa. Fistulas and abscesses do not occur.

Toxic or fulminant colitis occurs when transmural extension of ulceration results in localized ileus and peritonitis. Within hours to days, the colon loses muscular tone and begins to dilate.
Photographs

Pseudopolyps

The terms toxic megacolon or toxic dilation are discouraged because the toxic inflammatory state and its complications can occur without frank megacolon (defined as transverse colon > 6 cm diameter during an exacerbation). Toxic colitis is a medical emergency that usually occurs spontaneously in the course of very severe colitis but is sometimes precipitated by opioid or anticholinergic antidiarrheal drugs. Colonic perforation may occur, which increases mortality significantly.

Symptoms and Signs

Bloody diarrhea of varied intensity and duration is interspersed with asymptomatic intervals. Usually an attack begins insidiously, with increased urgency to defecate, mild lower abdominal cramps, and blood and mucus in the stools. Some cases develop after an infection (eg, amebiasis, bacillary dysentery).

When ulceration is confined to the rectosigmoid, the stool may be normal or hard and dry, but rectal discharges of mucus loaded with RBCs and WBCs accompany or occur between bowel movements. Systemic symptoms are absent or mild. If ulceration extends proximally, stools become looser and the patient may have > 10 bowel movements per day, often with severe cramps and distressing rectal tenesmus, without respite at night. The stools may be watery or contain mucus and frequently consist almost entirely of blood and pus.

Toxic or fulminant colitis presents with sudden violent diarrhea, fever to 40° C (104° F), abdominal pain, signs of peritonitis (eg, rebound tenderness), and profound toxemia.

Systemic symptoms and signs, more common with severe UC, include malaise, fever, anemia, anorexia, and weight loss. Extraintestinal manifestations (particularly joint and skin complications—see Inflammatory Bowel Disease (IBD): Extraintestinal Manifestations) are most common when systemic symptoms are present.

Diagnosis

*
Stool cultures and microscopy (to exclude other causes)
*
Sigmoidoscopy with biopsy

Initial presentation: Diagnosis is suggested by typical symptoms and signs, particularly when accompanied by extraintestinal manifestations or a history of previous similar attacks. UC should be distinguished from Crohn’s disease (see Table 1: Inflammatory Bowel Disease (IBD): Differentiating Crohn’s Disease and Ulcerative ColitisTables) but more importantly from other causes of acute colitis (eg, infection; in elderly patients, ischemia).

In all patients, stool cultures for enteric pathogens should be obtained, and Entamoeba histolytica should be excluded by examination of fresh stool specimens. When amebiasis is suspected because of epidemiologic or travel history, serologic titers and biopsies should be obtained. History of prior antibiotic use or recent hospitalization should prompt stool assay for Clostridium difficile toxin. Patients at risk should be tested for HIV, gonorrhea, herpesvirus, chlamydia, and amebiasis. Opportunistic infections (eg, cytomegalovirus, Mycobacterium avium-intracellulare) or Kaposi’s sarcoma must also be considered in immunosuppressed patients. In women using oral contraceptives, contraceptive-induced colitis is possible; it usually resolves spontaneously after hormone therapy is stopped.

Sigmoidoscopy should be performed; it allows visual confirmation of colitis and permits direct sampling of stool or mucus for culture and microscopic evaluation, as well as biopsy of affected areas. Although visual inspection and biopsies may be nondiagnostic, because there is much overlap in appearance among different types of colitis, acute, self-limited, infectious colitis can usually be distinguished histologically from chronic idiopathic UC or Crohn’s colitis. Severe perianal disease, rectal sparing, absence of bleeding, and asymmetric or segmental involvement of the colon indicate Crohn’s disease rather than UC (see Table 1: Inflammatory Bowel Disease (IBD): Differentiating Crohn’s Disease and Ulcerative ColitisTables). Colonoscopy is usually unnecessary initially but should be performed electively if inflammation has extended proximal to the reach of the sigmoidoscope.

Laboratory tests should be done to screen for anemia, hypoalbuminemia, and electrolyte abnormalities. Liver function tests should be done; elevated alkaline phosphatase and γ‑glutamyl transpeptidase levels suggest possible primary sclerosing cholangitis. Perinuclear antineutrophil cytoplasmic antibodies are relatively specific (60 to 70%) for UC. Anti–Saccharomyces cerevisiae antibodies are relatively specific for Crohn’s disease. However, these tests do not reliably separate the two diseases and are not recommended for routine diagnosis. Other possible laboratory abnormalities include leukocytosis, thrombocytosis, and elevated acute-phase reactants (eg, ESR, C-reactive protein).

X‑rays are not diagnostic but occasionally show abnormalities. Plain x‑rays of the abdomen may show mucosal edema, loss of haustration, and absence of formed stool in the diseased bowel. Barium enema shows similar changes, albeit more clearly, and may also demonstrate ulcerations, but the enema should not be performed during an acute presentation. A shortened, rigid colon with an atrophic or pseudopolypoid mucosa is often seen after several years’ illness. X‑ray findings of thumbprinting and segmental distribution are more suggestive of intestinal ischemia or possibly Crohn’s colitis rather than of UC.

Recurrent symptoms: Patients with known disease and a recurrence of typical symptoms should be examined, but extensive testing is not always required. Depending on duration and severity of symptoms, sigmoidoscopy or colonoscopy may be done and a CBC obtained. Cultures, ova and parasite examination, and C. difficile toxin assay should be done when there are atypical features to the relapse or when there is an exacerbation after prolonged remission, during a contagious outbreak, after antibiotic exposure, or whenever the clinician is suspicious.

Fulminant symptoms: Patients require further evaluation during severe flare-ups. Flat and upright abdominal x‑rays should be obtained; they may show megacolon or intraluminal gas accumulated over a long, continuous, paralyzed segment of colon—a result of lost muscle tone. Colonoscopy and barium enema should be avoided because of the risk of perforation. CBC, ESR, electrolytes, PT, PTT, and type and crossmatch should be obtained.

The patient must be watched closely for progressive peritonitis or perforation. Percussion over the liver is important because loss of hepatic dullness may be the first clinical sign of free perforation, especially in a patient whose peritoneal signs are suppressed by high-dose corticosteroids. Abdominal x‑rays are obtained every 1 or 2 days to follow the course of colonic distention and to detect free or intramural air.

Prognosis

Usually, UC is chronic with repeated exacerbations and remissions. In about 10% of patients, an initial attack becomes fulminant with massive hemorrhage, perforation, or sepsis and toxemia. Complete recovery after a single attack occurs in another 10%.

Patients with localized ulcerative proctitis have the best prognosis. Severe systemic manifestations, toxic complications, and malignant degeneration are unlikely, and late extension of the disease occurs in only about 20 to 30%. Surgery is rarely required, and life expectancy is normal. The symptoms, however, may prove stubborn and refractory. Moreover, because extensive UC may begin in the rectum and spread proximally, proctitis should not be considered localized until it has been observed for ≥ 6 mo. Localized disease that later extends is often more severe and more refractory to therapy.

Colon cancer: The risk of colon cancer is proportional to the duration of disease and amount of colon affected, but not necessarily to the clinical severity of the attacks. Some recent studies suggest that sustained microscopic inflammation is a risk factor, and that use of aminosalicylate to control inflammation is protective. Cancer begins to appear by 7 yr from onset of illness in patients with extensive colitis. The cumulative likelihood of cancer is about 3% at 15 yr, 5% at 20 yr, and 9% at 25 yr, representing an annual risk of about 0.5 to 1% after the 10th yr. There is probably no higher absolute cancer risk among patients with childhood-onset colitis independent of the longer duration of disease. However, patients who have inflammatory bowel disease and primary sclerosing cholangitis (PSC) are at a higher risk of cancer from the time of colitis diagnosis.

Regular colonoscopic surveillance, preferably during remission, is advised for patients with disease duration > 8 to 10 yr (except for those with isolated proctitis). Endoscopic biopsies should be taken every 10 cm throughout the colon. Newer techniques, especially chromoendoscopy, may better identify areas of suspicion in preference to totally random biopsies. Any grade of definite dysplasia within an area affected by colitis is liable to progress to more advanced neoplasia and even cancer and is a strong indication for total colectomy unless the dysplasia is strictly confined to a discrete, completely excisable polyp. It is important to distinguish definite neoplastic dysplasia from reactive or regenerative atypia secondary to inflammation. However, if the dysplasia is unequivocal, delaying colectomy in favor of repeated follow-up surveillance is a risky strategy. Pseudopolyps have no prognostic significance but may be difficult to distinguish from neoplastic polyps; thus, any suspect polyp should undergo excision biopsy.

The optimal frequency of colonoscopic surveillance has not been established, but some authorities recommend every 2 yr during the 2nd decade of disease and annually thereafter.

Long-term survival after diagnosis of colitis-related cancer is about 50%, a figure comparable to that for colorectal cancer in the general population.

Treatment

*
Loperamide Some Trade Names
IMODIUM
Click for Drug Monograph
and dietary management for symptom relief
*
5-Aminosalicylic acid (5-ASA)
*
Corticosteroids and other drugs depending on symptoms and severity
*
Sometimes surgery

Details of specific drugs and regimens are discussed above (see Approach to the Patient with Upper GI Complaints: Treatment).

General management: Avoiding raw fruits and vegetables limits trauma to the inflamed colonic mucosa and may lessen symptoms. A milk-free diet may help but need not be continued if no benefit is noted. Loperamide Some Trade Names
IMODIUM
2 mg po bid to qid is indicated for relatively mild diarrhea; higher oral doses (4 mg in the morning and 2 mg after each bowel movement) may be required for more intense diarrhea. Antidiarrheal drugs must be used with extreme caution in severe cases because they may precipitate toxic dilation.

Mild left-sided disease: Patients with proctitis, or colitis that does not extend proximally beyond the splenic flexure, are treated with 5‑ASA ( mesalamine Some Trade Names
ASACOL
ROWASA
enemas once/day or bid depending on severity. Suppositories are effective for more distal disease and are usually preferred by patients. Corticosteroid and budesonide Some Trade Names
PULMICORT
RHINOCORT
enemas are slightly less effective but should be used if 5‑ASA is unsuccessful or not tolerated. Once remission is achieved, dosage is slowly tapered to maintenance levels. Oral 5‑ASA drugs theoretically have some incremental benefit in lessening the probability of proximal spread of disease.

Moderate or extensive disease: Patients with inflammation proximal to the splenic flexure or left-sided disease unresponsive to topical agents should receive an oral 5‑ASA formulation in addition to 5‑ASA enemas. High-dose corticosteroids are added for more severe symptoms; after 1 to 2 wk, the daily dose is reduced by about 5 to 10 mg each wk. Immunomodulater therapy with azathioprine Some Trade Names
IMURAN
or 6- mercaptopurine Some Trade Names
PURINETHOL
can be used in patients who are refractory to maximal doses of 5-ASA and would otherwise need long-term corticosteroid therapy. Additionally, infliximab Some Trade Names
REMICADE
is beneficial in some patients and may be considered for those refractory to immunomodulator or corticosteroid therapy as well as those who are corticosteroid dependent.

Severe disease: Patients with > 10 bloody bowel movements per day, tachycardia, high fever, or severe abdominal pain require hospitalization to receive high-dose IV corticosteroids. 5‑ASA may be continued. IV fluids and blood transfusion are given as needed for dehydration and anemia. The patient must be observed closely for the development of toxic megacolon. Parenteral hyperalimentation is sometimes used for nutritional support but is of no value as primary therapy; patients who can tolerate food should eat.

Patients who do not respond within 3 to 7 days should be considered for IV cyclosporine Some Trade Names
NEORAL
SANDIMMUNE

or infliximab Some Trade Names
REMICADE
or else for surgery. Patients who do respond to a medical regimen are switched within a week or so to prednisone Some Trade Names
DELTASONE
60 mg po once/day, which may be gradually reduced at home based on clinical response. Patients who are started on IV cyclosporine Some Trade Names
NEORAL
SANDIMMUNE
and respond to therapy are switched to oral cyclosporine Some Trade Names
NEORAL
SANDIMMUNE
and concomitant azathioprine Some Trade Names
IMURAN
or 6- mercaptopurine Some Trade Names
PURINETHOL
. Oral cyclosporine Some Trade Names
NEORAL
SANDIMMUNE
is continued for about 3 to 4 mo, during which time corticosteroids are tapered and cyclosporine Some Trade Names
NEORAL
SANDIMMUNE
levels are closely monitored. Some clinicians recommend prophylaxis against Pneumocystis jiroveci pneumonia during the interval of overlapping treatment with corticosteroids, cyclosporine Some Trade Names
NEORAL
SANDIMMUNE
, and an antimetabolite.

Fulminant colitis: If fulminant colitis or toxic megacolon is suspected, the patient should (1) discontinue all antidiarrheal drugs; (2) take nothing by mouth and have inserted a long intestinal tube attached to intermittent suction; (3) undergo aggressive IV fluid and electrolyte therapy with 0.9% NaCl, and potassium chloride Some Trade Names
K-LOR
K-TAB
KLOR-CON
and blood as needed; (4) be treated with high-dose IV corticosteroids; and (5) receive antibiotics (eg, metronidazole Some Trade Names
FLAGYL
500 mg IV q 8 h and ciprofloxacin Some Trade Names
CILOXAN
CIPRO
500 mg IV q 12 h).

Having the patient roll over in bed from the supine to prone position every 2 to 3 h may help redistribute colonic gas and prevent progressive distention. Passage of a soft rectal tube may also be helpful but must be done with extreme caution to avoid bowel perforation.

If intensive medical measures do not produce definite improvement within 24 to 48 h, immediate surgery is required or the patient may die of sepsis caused by bacterial translocation or even perforation.

Maintenance therapy: After effective treatment of a flare-up, corticosteroids are tapered based on clinical response and then discontinued because they are ineffective as maintenance. Patients should remain on 5‑ASA drugs indefinitely—oral or rectal, depending on location of disease—because stopping maintenance therapy often allows disease relapse. Dosage intervals for rectal preparations may be gradually lengthened to every second or third day.

Patients who cannot be withdrawn from corticosteroids should be given azathioprine Some Trade Names
IMURAN
or 6‑ mercaptopurine Some Trade Names
PURINETHOL
Surgery: Nearly 33% of patients with extensive UC ultimately require surgery. Total proctocolectomy is curative: Life expectancy and quality of life are restored to normal, the disease does not recur (unlike Crohn’s disease), and the risk of colon cancer is eliminated.

Emergency colectomy is indicated for massive hemorrhage, fulminating toxic colitis, or perforation. Subtotal colectomy with ileostomy and rectosigmoid closure or mucous fistula is usually the procedure of choice because most critically ill patients cannot tolerate more extensive surgery. The rectosigmoid stump may be electively removed later or may be used for ileoanal anastomosis with a pouch. The intact rectal stump should not be allowed to remain indefinitely because of the risk of disease activation and malignant transformation.

Elective surgery is indicated for cancer, symptomatic strictures, growth retardation in children, or most commonly, intractable chronic disease resulting in invalidism or corticosteroid dependence. Colectomy is also performed for high-grade and perhaps even low-grade mucosal dysplasia confirmed on pathologic consultation, unless the dysplasia is limited exclusively to a completely excisable polyp. Severe colitis-related extraintestinal manifestations (eg, pyoderma gangrenosum), now better controlled by intensive medical therapies, are only rarely indications for surgery.

The elective procedure of choice in patients with normal sphincter function is restorative proctocolectomy with ileoanal anastomosis. This procedure creates a pelvic reservoir or pouch from distal ileum, which is connected to the anus. The intact sphincter allows continence, typically with 8 to 10 bowel movements/day. Pouchitis is an inflammatory reaction occurring after this procedure in about 50% of patients. It is thought to be related to bacterial overgrowth and is treated with antibiotics (eg, quinolones). Probiotics may be protective. Most cases of pouchitis are readily controlled, but 5 to 10% prove refractory to all medical therapy and require conversion to a conventional (Brooke) ileostomy. For a minority of patients who are older, who have well-established families and lifestyles, who have poor sphincter tone or cannot tolerate frequent bowel movements, or who are simply unable or unwilling to face the consequences of frequent or chronic pouchitis, the Brooke ileostomy remains the procedure of choice.

In any event, the physical and emotional burdens imposed by any form of colon resection must be recognized, and care should be taken to see that the patient receives all the instructions and all the medical and psychologic support that is necessary before and after surgery.

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