Health Questions and Answers

Ulcerative colitis

What is ulcerative colitis?
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. It is distinct from Crohn’s disease (CD) of the colon in that the inflammation is restricted mostly to the mucosa and involves only the colon. The rectal segment is almost always involved, whereas in CD of the colon the rectum is usually spared.

Define backwash ileitis.
Backwash ileitis refers to unusual cases of ulcerative colitis that involve the terminal ileum. The endoscopic, histologic, and radiologic appearances of backwash ileitis is the same as those of ulcerative colitis. When deep linear ulcers and strictures are seen in the ileum, Crohn’s ileitis is the more likely diagnosis.

What is indeterminate colitis?
As more information is gathered about the pathogenesis of ulcerative colitis and CD, the distinction between them at times can be unclear. In about 7% of patients, when the inflammatory process is limited to the colon (no ileal involvement), the endoscopic, histologic, or radiologic findings are insufficiently distinct to separate the two diseases. The colitis is then referred to as “indeterminate.” Other patients carry the diagnosis of UC for many years until a change in signs and symptoms, consistent with CD, influences a change in diagnosis. In some patients, the diagnosis of CD of the colon is recognized only after colectomy and the development of recurrent ileitis in the ileostomy or ileoanal pouch performed for what was thought to be UC.

Why is it important to distinguish between ulcerative colitis and Crohn’s disease?
Medical treatment of the two diseases overlaps, but ulcerative colitis is “curable” by total colectomy, whereas CD can never be considered cured by resection. Therefore, the correct diagnosis is of the utmost importance.

What causes ulcerative colitis?
The cause is unknown. The greatest risk factor is a positive family history. Approximately 15% of patients with inflammatory bowel disease (IBD) have a first-degree relative with the disease, but the familial association is less in UC than in CD. Similarly, the incidence of IBD in first-degree relatives of patients with IBD is 30-100 times higher than in the general population. The cause remains technically unknown, although research has clarified that there are genetic, environmental, and immunologic contributions. The exact genetic link for UC has not been identified. Dietary antigens and bacteria have been proposed as possible triggers, but no evidence supports these theories. The incidence of UC is significantly higher in nonsmokers than in smokers and higher still in ex-smokers than in nonsmokers, supporting a protective effect of smoking. Whether this protective effect is secondary to nicotine or other constituents of cigarettes has not been fully established.

Who gets ulcerative colitis?
In most patients, UC has its onset in the second or third decades of life. However, there may be a second peak in the fifth or sixth decades, although this peak may be false because of other types of colitis that mimic UC. The disease has been described in all nationalities and ethnic groups but is more common in whites than in nonwhites. It is also more common in Jews than non-Jews. The hereditary link is supported by population-based studies.

What are the signs and symptoms of ulcerative colitis?
The predominant symptom at onset of UC is diarrhea, with or without blood in the stool. If inflammation is confined to the rectum (proctitis), blood may be seen on the surface of the stool; other symptoms include tenesmus, urgency, rectal pain, and passage of mucus, without diarrhea.
Other distributions of UC are proctosigmoiditis; left-sided disease, which extends more proximal to the descending colon, splenic flexure, or distal transverse colon; and universal colitis, which involves any length proximal to the mid-transverse colon and often the entire colon. The inflammation is almost always confluent in distribution and almost always involves the rectum, when it is untreated with medication by enema.
More extensive colitis may be accompanied by systemic symptoms, such as weight loss and malaise, in addition to bloody diarrhea. Although pain is not a dominant feature, patients may complain of crampy abdominal discomfort relieved by a bowel movement and may have abdominal tenderness, localized usually to the left lower quadrant. Occasionally, patients may present with “constipation” secondary to rectal spasm. Although patients may present with extraintestinal manifestations before bowel symptoms, more often they parallel the severity of the primary bowel disease.

Is there a diagnostic blood test for UC?
Two antibodies have been helpful in differentiating UC from Crohn’s colitis. Patients with ulcerative colitis have higher levels of peripheral anti-neutrophil cytoplasmic antibody (p-ANCA) and lower levels of anti-saccharomyces antibody (ASCA) than patients with Crohn’s disease. However, these tests lack sufficient sensitivity and specificity to be used alone for diagnostic purposes. The combination of both tests may be helpful in a select group of patients with indeterminate colitis, together with other parameters such as clinical, endoscopic, pathologic, and radiologic features.

How are patients with ulcerative colitis classified?
Truelove and Witts divided patients into those with severe, moderate, and mild disease based on symptoms, physical findings, and laboratory values. We add to this list the severity of endoscopic and radiologic appearances. A plain film of the abdomen showing any degree of dilation of the colon or ulceration and edema of the mucosa outlined by air (even if not dilated) is indicative of a severe attack. Although endoscopic appearance does not always correlate well with clinical symptoms, the presence of severe mucosal disease indicates the need for more aggressive management. The clinical guide for severity of UC is as follows:
Mild: fewer than four stools daily, with or without blood, with no systemic disturbance and a normal erythrocyte sedimentation rate (ESR).
Moderate: more than four stools daily but with minimal systemic disturbance.
Severe: more than six stools daily with blood and systemic disturbance as shown by fever, tachycardia, anemia, or ESR >30.

What is colitic arthritis?
Colitic arthritis is a migratory arthritis affecting the knees, hips, ankles, wrists, and elbows. Usually, the joint involvement is asymmetric not bilateral. It responds well to corticosteroids.

Discuss the hepatic complications of ulcerative colitis.
Hepatic complications include fatty liver, pericholangitis, chronic active hepatitis, cirrhosis, and primary sclerosing cholangitis. Although most patients with sclerosing cholangitis have UC, only a minority of patients with UC develop sclerosing cholangitis. It is usually suspected with the finding of an abnormally elevated alkaline phosphatase or gamma glutamyl transferase (GGTP) enzyme. Sclerosing cholangitis is sometimes improved with ursodeoxycholic acid therapy (Actigal). Patients with sclerosing cholangitis and UC have a higher risk of developing colon cancer than those without. In addition, they are also at risk of developing cholangiocarcinoma. Cholestyramine may help in alleviating the pruritus associated with the disease, but the only cure is liver transplantation.

What are the ocular complications of ulcerative colitis?
Ocular complications include uveitis and episcleritis. Uveitis causes eye pain, photophobia, and blurred vision and requires prompt intervention to prevent permanent visual impairment. It usually responds to topical steroids, but, sometimes, systemic steroids are required.

Describe the association between ulcerative colitis and thromboembolic events.
Patients with IBD are at increased risk of thromboembolic events, most commonly deep venous thrombosis of the lower extremities. After a search for other causes of a hypercoagulable state, patients should receive standard therapy for the thrombosis.

How do I evaluate a patient with ulcerative colitis?
The management of UC depends on the severity and location of disease activity, which are best assessed by a careful clinical history with emphasis on the duration and severity of symptoms and physical examination, followed by endoscopic evaluation to determine the extent and severity of mucosal involvement. Although flexible sigmoidoscopy may indicate the severity of the disease, full colonoscopy is essential to determine the extent as well as the full severity. A plain radiograph of the abdomen should also be performed in flat and upright positions to recognize depth of ulceration and early or advanced toxic megacolon, which may be suspected by the presence of tympany in any of the segments of the abdomen

How do I treat proctitis and proctosigmoiditis?
For mild-to-moderate ulcerative proctitis, topical therapy may suffice. If disease is limited to the anorectal region, a Canasa suppository can be used once or twice daily. Hydrocortisone foam (cortifoam) or hydrocortisone enemas (Cortenema) may also be used either alone or in alternation with the 5-ASA product. For proctosigmoiditis, the Rowasa enema, used alone or in alternation with a hydrocortisone enema, is effective. Only the Rowasa enema-not the Cortenema- has maintenance value. The patient must lie on the left side for at least 20 minutes after introducing the enema to ensure adequate delivery to the affected area. In some instances when tenesmus is severe, the enema is better introduced in the knee-chest position, taking advantage of the downhill gravity. Occasionally, oral therapy may work better than enemas or suppositories; in other cases, a combination is required.

How do I treat an exacerbation of ulcerative colitis?
When the disease extends more proximally, oral therapies are required in addition to, or instead of, topical therapy. Choice of oral 5-ASA product is determined by the extent of involvement. Pentasa (4 gm), Asacol (3.2 gm) or Colazal (6.75 gm) can be used for universal colitis and Dipentum (1 gm) for left-sided colitis. The dose of Asacol may be titrated within the limits of tolerability to a maximum of 4.8 gm/day. It is not yet known whether still higher doses of any of the three would have increased efficacy. If the disease fails to resolve with 5-ASA therapy or is moderately severe at presentation, a short course of oral corticosteroids should be prescribed to bring the disease under control. The maximal effective oral dose of prednisone is 60 mg daily. The dose may be tapered to 40 mg/day after 2-7 days, if the disease is brought under control. The formula for further tapering of prednisone is individualized. The 5-ASA drugs should be given concurrently with prednisone. Prednisone and other corticosteroids are not maintenance drugs.

What should I do if the disease is severe?
Severe disease requires admission to hospital for intravenous corticosteroids and fluids. Patients should be monitored carefully by serial physical examination, lab tests, and plain radiographs of the abdomen. Severe UC may progress to toxic megacolon and/or perforation. It is treated with intravenous corticosteroids, antibiotics, a small bowel tube attached to suction, “log rolling” from side to side and to the supine and prone positions, and sometimes by rectal tube. If these maneuvers are not successful, subtotal colectomy should be considered, preferably before a perforation occurs. If the colon is dilated and the mucosal surface is ragged on abdominal films, a surgical colleague should be involved in management decisions.
If there is no response to intravenous corticosteroids, intravenous cyclosporine should be considered. Rapid deterioration in clinical condition warrants early surgical intervention with ileostomy and subtotal colectomy. If there is time for a trial of cyclosporine, it should be administered only by physicians with extensive experience in its use. It is administered at a dose of 4 mg/kg/day intravenously by continuous infusion, with close monitoring of blood pressure, renal function, electrolytes, and drug blood levels. Cyclosporine should not be initiated if the serum cholesterol is low because it increases the risk of seizures. Bactrim is administered concurrently to prevent Pneumocystis carinii pneumonia. Failure to respond within 3 days portends a poor prognosis for medical therapy. Early medical intervention in expert hands can significantly reduce the number of severely ill patients who go to surgery. Severe UC sometimes responds to intravenous infliximab, even though more frequent success has been confirmed by trials in CD.

Define toxic megacolon.
Toxic megacolon is defined as a severe attack of colitis with total or segmental dilation of the colon (diameter of transverse colon usually >5-6 cm). It can be recognized by plain x-rays showing the colon to be outlined by air (not after endoscopy) even with a diameter less than 5 cm. Megacolon is considered toxic if two or more of the following criteria are positive, in addition to the colon persistently outlined by air:

  • Tachycardia with a pulse rate >100 beats/min
  • Temperature >101.5°F
  • Leukocytosis >10,000 cells/mm3
  • Hypoalbuminemia <3.0 gm/dL

How do I prevent a relapse?
Maintenance therapy should be initiated at the same time or soon after acute-phase therapy. For mild-to-moderate disease, a 5-ASA product may be all that is necessary. For more severe or recurrent disease, an immunosuppressive medication such as 6-mercaptopurine (6-MP) or azathioprine is more effective. 6-MP should be started at a dose of 50 mg/day, and the patient should be followed carefully with weekly blood counts for the first 3 weeks and less often thereafter. If the initial dose is tolerated well and the white cell count is normal, the dose may be increased gradually, if clinically warranted. Early toxic reactions to these medications include pancreatitis (3%), hepatitis, rash, fever, and leukopenia. The occurrence of pancreatitis or hepatitis precludes usually further use of the same drug. Patients with allergic-type reactions may be carefully desensitized to the same or the other immunosuppressive drug. High levels of the 6-MP metabolites 6-MMP (6-methyl mercaptopurine) and 6-TG (6-thioguanine) may predict which patients will develop toxicity. Anti-tumor necrosis factor is an established therapy for CD. There is evidence that it might also be effective in the treatment of UC.

How often should patients have surveillance colonoscopy?
The current recommendations are as follows: for patients with left-sided colitis, surveillance should begin after 15 years of colitis. For patients with universal colitis, surveillance should begin after 8 years of colitis. Three biopsy specimens should be obtained every 10 cm throughout the colon. In addition, any strictured, raised, polypoid areas, or those with unusual shapes or textures, should be biopsied. Surveillance colonoscopy should be repeated annually for universal disease, perhaps less often for left-sided disease.

What should be done if a polyp or dysplasia is found?
Obvious polyps should be removed and the area surrounding the polyp biopsied. If the area is free of premalignant changes, nothing further need be done except for the usual surveillance. However, if dysplasia is found, colectomy is the treatment of choice. Dysplasia is a premalignant lesion classified as high-grade, low-grade, or indefinite. Although everyone agrees that high-grade dysplasia anywhere in the colon warrants proctocolectomy, there is less consensus about management of low-grade dysplasia. The diagnosis of low-grade dysplasia can be challenged when the biopsies are taken from areas of marked inflammation. Intensive treatment of the disease may lead to the recognition that the diagnosis of dysplasia was not accurate. Biopsies should be taken preferably from flat mucosa without inflammation. If a recommendation of colectomy depends on the diagnosis of dysplasia, a second expert gastrointestinal pathologist should review the biopsy slides before the final decision is made.

Define dysplasia-associated lesion or mass (DALM).
DALM is a dysplasia-associated lesion or mass and is an indication for total colectomy. If, however, the mass is a polyp and no dysplasia is present elsewhere in the colon, a simple polypectomy can be performed without colectomy and the surveillance routine continued.

Is surveillance effective?
Yes. Studies have shown that as many as 42% of patients with UC who are found to have high-grade dysplasia either already have cancer or develop it within a short time. The presence of low-grade dysplasia is also predictive of cancer: 19% of patients develop cancer of the colon or may even have cancer at the time of diagnosis. The finding of no dysplasia is predictive of a good short-term outcome. Outcome and case-controlled studies have shown that cancer in patients in a surveillance program is detected at an earlier and therefore more favorable stage. Patients who undergo screening have improved survival rates and lower cancer-related mortality rates.

Is diet important in the management of ulcerative colitis?
No evidence suggests that any one diet is beneficial in patients with UC. Apart from the advice that patients with lactose intolerance should avoid lactose-containing food, no dietary restrictions are necessary. Because chronically ill patients may be in a consistently negative caloric balance, maintaining a balanced diet is of the utmost importance.

Does stress exacerbate ulcerative colitis?
No studies to date support any role for psychological stresses, personality types, or overt psychiatric illness in the causation or exacerbation of UC. However, many physicians believe that psychosocial stress plays an important role not only in precipitating illness but also in preventing healing. This belief is validated by the fact that many patients experience exacerbations during times of emotional stress. When a patient remains ill, despite maximal medical therapy, consideration should be given to psychological factors. A psychopharmacologist can be invaluable in this setting. Sometimes, the addition of an anxiolytic agent or an antidepressant may be the final step required to bring UC under control.
As with any chronic illness, the approach to management should be multifaceted with expert medical and surgical teams, a psychopharmacologist, and knowledgeable ancillary staff.

How does menstruation affect ulcerative colitis?
Scattered information supplements our experience that the symptoms of both UC and Crohn’s disease are aggravated or provoked coincidentally with the premenstrual period and, in some cases, throughout menstruation. Occasionally, a 2- to 3-day course of steroids is warranted.

Do patients with ulcerative colitis have problems with fertility and pregnancy?
In considering the effects of UC on pregnancy and vice versa, two aspects are important: the effect of the disease itself and the effect of the medications used to treat the disease. Well-controlled disease appears to have no deleterious effects on fertility or pregnancy. However, if the disease is active at any time during pregnancy, the incidence of fetal loss may be increased. It is therefore important to maintain control of the disease before and during pregnancy.
Mesalamine (5-ASA) has a long record of safety in pregnancy. Corticosteroids have also proven to be safe during pregnancy. With regard to the immunosuppressants 6-MP and azathioprine, data from the transplant literature suggest safety during pregnancy. One study concerning UC and CD treated with immunosuppressives concluded that they are safe and need not be discontinued for pregnancy. In our experience, however, these medications may cause fetal loss when used by women before pregnancy and an increased incidence of congenital abnormalities and spontaneous abortions when used by men within 3 months of conception. We therefore suggest that patients should discontinue these drugs, if clinically feasible, at least 3 months before planned conception. If a woman is in remission, immunosuppressives may be stopped without expectation of early recurrence. If the disease is active, pregnancy should be postponed. Sulfasalazine causes defects in sperm morphology and motility. It should be replaced with one of the newer 5-ASA products in male patients who are contemplating starting a family.

What medications are contraindicated in patients with ulcerative colitis?
Evidence suggests that nonsteroidal anti-inflammatory drugs may precipitate exacerbations of the disease and, in some cases, may even be implicated in the onset of disease. These drugs, including aspirin, should be avoided in patients with UC.
Anticoagulant therapy, with warfarin, may lead to increased bleeding in patients with active disease and bloody diarrhea. Ironically, heparin therapy has been reported to improve disease activity in some patients. Although heparin therapy is not the standard of care, it may be useful when anticoagulation is required for patients with active UC. Opioid derivatives should be avoided, if possible, in patients with any type of colitis because of their propensity to cause toxic dilatation of the colon.

What new treatments are available for UC?
Probiotics are indigenous nonpathogenic microorganisms that are being used in mainstream medical therapy. Currently proposed mechanisms of action in IBD include (1) competition with microbial pathogens for cell surface receptors, (2) immunomodulation, (3) suppression of pathogens via release of antimicrobial factors, and (4) induction of T cell apoptosis in the lamina propria. Several open label studies have shown encouraging results with the use of combinations of lactobacilli in pouchitis and mild to moderate UC. These results have to be confirmed with randomized controlled trials.
Infliximab (anti-tumor necrosis factor) is well established as an effective therapy for Crohn’s disease. Several open label studies have demonstrated an approximately 50% clinical response rate in UC. Although at the time of writing, infliximab is not an FDA-approved treatment for UC, it is a useful therapy for this condition and will likely receive approval in the near future.
Natalizumab is a monoclonal anti-alpha4-integrin antibody that has emerged from recent trials as a promising new agent for the treatment of UC. Further trials are underway.

What are the surgical options for management of ulcerative colitis?
When medical management fails, or complications such as perforation or dysplasia occur, subtotal colectomy with ileostomy or ileoanal pouch is the procedure of choice. Many patients are frightened by the prospect of having an ileostomy, but education can do much to alleviate their fears. Fortunately, a large number of patients with ileostomies become accustomed to them and continue to lead normal lives.
The ileoanal pouch is a possible alternative. It consists of a double loop of ileum that is fashioned into a pouch and stapled to the rectal stump and stripped of its mucosa, thereby preserving the anal sphincter. Disadvantages of the pouch include recurrent inflammation or “pouchitis,” frequent bowel movements, nocturnal incontinence, and the continued need for surveillance endoscopy. Pouchitis responds well to metronidazole, Cipro or Bismuth, alone or in combination. These drugs can be used to treat the acute illness and also as maintenance therapy to prevent recurrence. Some patients with refractory pouchitis may require excision of the pouch and substitution of an ileostomy at a later date.

References

WEBSITES
http://www.niddk.nih.gov
http://www.ccfa.org/

BIBLIOGRAPHY

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  9. Sutherland LR, May GR, Shaffer EA: Sulfasalazine revisited: A meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Ann Intern Med 118:340-349, 1993.
  10. Truelove SC, Witts LJ: Cortisone in ulcerative colitis: Final report on a therapeutic trial. BMJ 2:1041-1048, 1955.
  11. Winawer SJ, Fletcher RH, Miller L, et al: Colorectal cancer screening: Clinical guidelines and rationale. Gastroenterology 112:594-642, 1997.
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