Inflammatory Bowel Disease

Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. The age of onset for ulcerative colitis and Crohn's disease is bimodal; the first peak occurs during the 20s, and the second occurs between ages 50 and 80. The reasons for this bimodality are unknown. The prevalence of inflammatory bowel diseases is increasing as more patients with these conditions live longer.

Ulcerative Colitis

A chronic inflammatory process of unknown origin that affects the superficial layers of the colonic wall in a continuous distribution.

Although incidence and prevalence data in the elderly are not precise, ulcerative colitis is probably as common in the elderly as in younger persons, affecting about 128/100,000 persons in the USA and Europe. Histologic examination reveals diffuse ulcerations, epithelial necrosis, depletion of goblet cells, and polymorphonuclear leukocyte infiltration extending from the superficial layers of the colon to the muscularis mucosa. Crypt abscesses are characteristic but not pathognomonic. The inflammatory process invariably involves the rectum and extends proximally for variable distances but not beyond the colon.

Symptoms and Signs

Ulcerative colitis may be classified as mild, moderate, or severe. Symptoms in the elderly are similar to those in younger persons. Most patients have diarrhea with or without blood in the stool, although elderly patients occasionally present with constipation or hematochezia. Systemic manifestations occur during more severe attacks and indicate a poorer prognosis. Although the disease may be less extensive in elderly patients, they present with a severe initial attack more often and have higher mortality and morbidity rates than younger patients.

Extraintestinal manifestations include arthralgias, erythema nodosum, pyoderma gangrenosum, uveitis, and migratory polyarthritis. These conditions occur more often in patients with increased disease activity and less often in patients with ulcerative colitis than in those with Crohn's disease.

Complications

Toxic megacolon, a serious complication of ulcerative colitis, occurs more often in elderly patients than in younger patients. Abdominal x-rays show colonic dilation; patients may be confused and have high fever, abdominal distention, and overall deterioration. Mortality is high.

The risk of developing colorectal cancer increases substantially in all patients beginning about 8 years after the onset of pancolonic disease. However, cancer may develop after many years of even quiescent disease. Therefore, despite some shortcomings in the interpretation of biopsies and in the outcome of surveillance programs, all patients with long-standing ulcerative colitis should have an annual colonoscopy with biopsy to detect mucosal dysplasia, which is considered a premalignant lesion in ulcerative colitis. Biopsies should be taken randomly throughout the colon and in areas that appear suspicious. If high-grade dysplasia is found, proctocolectomy is indicated.

Diagnosis

The diagnosis is made by sigmoidoscopy and rectal mucosal biopsies because the rectum is always involved. The extent of disease is determined by colonoscopy or barium x-ray; both procedures should be avoided in severely ill patients because of the risk of perforation and toxic megacolon. The characteristic findings are diffuse erythema, granularity, and friability of the mucosa without intervening areas of normal mucosa (skip areas). Inflammatory pseudopolyps indicate more severe erosion of the mucosa and must be distinguished from true polyps.

Diseases that may mimic ulcerative colitis, including Crohn's disease, ischemic colitis, radiation coloproctitis, and diverticulitis, must be excluded, particularly in the elderly. In acutely ill patients, stool cultures should be obtained to exclude infectious agents, including Salmonella, Campylobacter, Shigella, amebiasis, Yersinia, and Escherichia coli 0157:H7. Clostridium difficile-associated diarrhea and pseudomembranous colitis should be considered in elderly patients, particularly those who recently received antibiotics, were hospitalized, or are institutionalized.

Treatment

Treatment is based on the extent and severity of the disease (see Table 107-2). A number of effective drugs (eg, corticosteroids, 5-aminosalicylates [5-ASA], immunosuppressants) can be administered IV, orally, or rectally.

Severe disease: Patients with severe or fulminant disease, including toxic megacolon, should be hospitalized and receive IV hydrocortisone, methylprednisolone, or corticotropin infused in fluids containing enough potassium to avoid hypokalemia. One study suggests that corticotropin is more effective in patients who have not been treated previously with corticosteroids, whereas hydrocortisone may be more effective in those who have. If corticotropin does not produce significant improvement in 2 to 3 days, IV cyclosporine may be tried, but renal function should be closely monitored, especially in the elderly. When improvement is noted, IV therapy should be replaced with oral therapy.

Moderately severe disease: Oral corticosteroids are used to achieve a remission or to sustain one after IV therapy. Therapy consists of prednisone 40 to 60 mg/day initially given in two doses, then in a single morning dose. When the disease is controlled, the prednisone dose should be tapered rapidly to 20 mg every morning; then it can be tapered by 5 mg/day each week as long as the disease remains quiescent. The corticosteroid dose should be tapered while clinical activity and appropriate laboratory studies are monitored. Long-term corticosteroid therapy risks significant adverse effects related to both the dose and duration of therapy. These drugs may exacerbate diabetes mellitus, heart failure, osteoporosis, and hypertension, which are common in the elderly.

A 5-ASA drug should be given with oral corticosteroids. Sulfasalazine is effective and inexpensive, but its use is limited by adverse effects in up to 30% of patients. The adverse effects, which are often dose-dependent, include nausea, anorexia, headache, and sometimes a generalized rash; in most cases, these effects result from the inactive sulfapyridine carrier rather than the 5-ASA. If adverse effects occur, sulfasalazine should be replaced with a more expensive 5-ASA drug (eg, olsalazine, mesalamine). Diarrhea is a potential adverse effect of all 5-ASA drugs. Treatment should be maintained indefinitely for patients who can tolerate it.

Mild disease: Patients with mild disease may be treated effectively with 5-ASA drugs that can be given orally, by enema in patients with left-sided disease, or by suppositories in patients with limited proctitis. Rectal corticosteroids are also effective in left-sided disease but generally are not more effective than 5-ASA drugs. Because about 60% of a rectal corticosteroid may be absorbed, it is less suitable for maintenance therapy. Several poorly absorbed corticosteroid enema products and corticosteroids that do not affect the adrenal-pituitary-hypothalamic axis are under investigation and appear to be promising.

Maintenance therapy: For patients in remission, long-term maintenance with a 5-ASA drug reduces the frequency of relapses. The usual maintenance dose of sulfasalazine (1 g po bid) produces few or no long-term adverse effects. For patients who cannot tolerate sulfasalazine, olsalazine 500 mg po bid with meals is effective. For those with ulcerative proctitis or left-sided colitis, 5-ASA suppositories and enemas are effective when given every night to every third night. Nonsteroidal anti-inflammatory drugs have been reported to activate quiescent inflammatory bowel disease and should be avoided if possible.

Surgery: Surgery is indicated when drug therapy for acute fulminant disease fails, when patients cannot be weaned from long-term corticosteroid therapy, when surveillance studies reveal precancerous colonic lesions, and when drug therapy for chronic ulcerative colitis produces a suboptimal response.

In all age groups, the most common operation for acute fulminant colitis is subtotal colectomy and ileostomy. In elderly patients, proctocolectomy with ileostomy is the procedure of choice when long-term medical therapy fails or when premalignant changes develop. Procedures that avoid ileostomy, such as the ileoanal reservoir, are a good choice for many younger patients. However, the increased morbidity rate associated with this procedure limits its use in the elderly, who are already at greater risk for fecal incontinence because of age-related changes in anal sphincter function.

Crohn's Disease

A chronic inflammatory process of unknown cause that most often affects the terminal ileum or colon and is characterized by transmural inflammation, often with linear ulcerations and granulomas.

The general incidence is 76/100,000 persons in the USA and Europe. Histologic examination reveals transmural inflammation affecting all layers of the bowel and often associated with submucosal fibrosis. Other features that distinguish Crohn's disease from ulcerative colitis are linear ulcerations, fissures, fistulas, discrete mucosal ulcers, granulomas, and skip areas. Unlike ulcerative colitis, Crohn's disease often does not affect the rectum. Although the disease can involve any area of the GI tract from the mouth to the anus, the ileum and colon are most often involved. Crohn's disease confined to the colon (Crohn's colitis) occurs more often in the elderly than in younger persons, and left-sided colitis appears to be prevalent in elderly women.

Symptoms and Signs

The clinical picture in the elderly is similar to that in younger persons and includes diarrhea, fever, abdominal pain, and weight loss. However, elderly patients with Crohn's colitis tend to present more indolently than patients with ileal or ileocolonic involvement. In patients with colorectal involvement, perianal disease, a feature of Crohn's disease, may be an early manifestation characterized by rectal or anal strictures, fissures, fistulas, abscesses, prominent skin tags, or ulcers. The prevalence of extraintestinal manifestations (eg, migratory arthritis, pyoderma gangrenosum, iritis, erythema nodosum) is similar in elderly and younger patients. Common laboratory abnormalities (eg, leukocytosis, hypoalbuminemia, elevated erythrocyte sedimentation rate, abnormalities indicating anemia) vary with the severity of the illness. Rarely, the patient presents with peritonitis caused by bowel perforation, although it is more common with ileal involvement. An elderly patient with peritonitis may present atypically with mild abdominal pain, few abdominal findings, and mental confusion. Uncommonly, a patient with Crohn's colitis presents with massive lower GI bleeding or bowel obstruction.

Diagnosis

Prolonged delays in diagnosis probably occur more often in the elderly.

Because the rectum is often unaffected and the distribution in the colon is often discontinuous, colonoscopy and barium x-ray are the tests of choice. Both procedures can identify the characteristic ulcerations, skip lesions, and areas of colonic narrowing. Barium studies are better able to identify fistulas to adjacent visceral organs, whereas colonoscopy provides better visualization of the mucosa and allows mucosal biopsies to be taken. Biopsies should be taken from affected areas and from mucosa that appears grossly normal. Biopsies help distinguish Crohn's colitis from diseases that mimic it, including diverticulitis, which is common in the elderly, and ischemic colitis, which often occurs in a discontinuous distribution.

CT provides better definition of the colonic wall than colonoscopy and can identify extraintestinal abdominal abnormalities (eg, abscesses in patients with fever or palpable masses). CT and ultrasound may also identify renal lithiasis and ureteral obstruction, which occur with increased frequency in Crohn's ileocolitis.

Sexually transmitted diseases and carcinoma should be excluded. Infectious agents should be excluded by appropriate studies.

Treatment

Treatment is based on extent, severity, distribution, and complications. Drug therapy includes all drugs used for ulcerative colitis; in some patients, selected antibiotics are also useful (see Table 107-3).

Ileocolitis and colitis: Patients with mild to moderate disease often respond to sulfasalazine; those who cannot tolerate it may respond to one of the other 5-ASA drugs (eg, olsalazine, mesalamine). Dosages are similar to those used for ulcerative colitis and are listed in Table 107-3. If the patient responds inadequately and the disease remains mild or moderate, metronidazole 250 mg po tid or ciprofloxacin 500 mg po bid may be tried.

If the disease worsens despite these therapies or if the patient has moderate to severe symptoms, prednisone 20 to 30 mg po bid is given, followed by conversion to a single morning dose when disease activity significantly lessens. After remission is induced, the prednisone dose should be reduced by 5 to 10 mg/week until it is 20 mg/day. Subsequently, the dose should be tapered about 5 mg/day every 3 weeks while clinical activity and laboratory findings such as hemoglobin, white blood cell count, electrolytes, glucose, and albumin are monitored until the patient is weaned.

About 60% of patients who cannot be weaned from oral corticosteroids respond to azathioprine (up to 2 mg/kg/day po) or mercaptopurine (up to 1.5 mg/kg/day po). A therapeutic response may not develop for 6 to 9 months. These drugs may be continued indefinitely, but at least one attempt to discontinue them should be made after 1 year from the time of therapeutic response to determine if remission can be maintained. Other drugs with demonstrated efficacy are methotrexate (25 mg IM/week) and infliximab, an antitumor necrosis factor (5 mg/kg IV). Optimal duration has not been established but is likely to be prolonged.

Perianal disease: Perianal fistulas and abscesses can be debilitating for the patient and frustrating to treat. Although perianal disease often improves with standard therapy for bowel inflammation and control of diarrhea, perianal symptoms may persist in some patients. Short-term success has been reported with metronidazole 1.5 to 2.0 g/day po; however, adverse effects are common at these doses, and relapses occur when the drug is stopped or the dosage is tapered. Ciprofloxacin 500 mg po bid, a more expensive alternative, also has a high relapse rate. If an abscess develops, it should be incised and drained.

Azathioprine, mercaptopurine, or infliximab may be useful in some patients with refractory disease. Infliximab should be given in a dose of 5 mg/kg IV in patients with perianal fistula.

Surgery: Unlike ulcerative colitis, Crohn's disease is not cured by surgery. Therefore, surgery should be reserved for patients who do not respond to drug therapy. If perianal disease does not respond to therapy, the colon may be diverted surgically, but surgery may also fail to heal the disease.

For patients with extensive Crohn's colitis, proctocolectomy with ileostomy is the best surgical option. For elderly patients who are debilitated or malnourished, an initial subtotal colectomy with ileostomy is less debilitating; it also gives the patient an opportunity to gain weight and to improve physically. If a subsequent proctectomy is required, the risk of complications is reduced; if rectal disease is mild or absent, a proctectomy may not be needed. More limited colonic resections may be appropriate if severe disease is localized or if obstructive symptoms are caused by relatively circumscribed bowel involvement.

Patients with small bowel disease may require laparotomy for intestinal obstruction, peritonitis, abscess formation, or occasionally for a suspicion of malignancy. Indications for surgery in elderly patients with Crohn's disease are the same as those for younger patients.

Surgery for ileal disease is generally well tolerated in the elderly, and the prognosis is comparable with that in younger patients. Elderly patients with extensive colitis or severe ileocolitis have higher morbidity and mortality, especially when emergency surgery is needed.

Recurrence rates after surgical resection for Crohn's disease vary; this variation relates in part to the initial site of disease. Proximal extension of distal colonic disease appears to be uncommon in elderly patients, and data suggest that recurrence rates are lower in elderly patients than in younger ones. Mortality rates associated with Crohn's disease do not appear to be significantly higher in the elderly.