Management of Inflammatory Bowel Disease

Deanna D. Nguyen

James M. Richter

Ulcerative colitis and Crohn disease account for most of the inflammatory bowel disease (IBD) seen in primary care practice. Abdominal pain, diarrhea, and bleeding are the principal presenting manifestations. The first priority is to distinguish IBD from other causes of diarrhea (see Chapter 64). The chronicity, potentially disabling symptoms, risk of malignancy (in the case of ulcerative colitis or Crohn colitis), potency and serious adverse effects of medications, and occasional refractoriness to medical therapy make management a major challenge. The primary care physician needs to know how to treat exacerbations, maintain remissions, and psychologically sustain these patients through difficult times. Competent care is based on a thorough understanding of the roles for medical and surgical therapy, skill in providing psychological support, and a good working relationship with consultants. Although patients with severe or refractory disease may need to be referred to the gastroenterologist, most of the others can be well-managed by the primary care physician.

PATHOPHYSIOLOGY, CLINICAL PRESENTATION, AND COURSE (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13)

Ulcerative Colitis

Ulcerative colitis is an idiopathic diffuse inflammatory disease of the colonic mucosa. Although pathogenesis is poorly understood, there is growing evidence of a dysregulated immune response to colonic flora. Established risk factors include stress, smoking cessation, and geographic latitude. Interestingly, frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) (at least 15 d/mo) but not aspirin is associated with increased incidence of IBD in an older population. The disease typically begins in adolescence or young adulthood but may occur at almost any age. Whites are affected more often than African Americans. Prevalence is highest among Jews of eastern European descent and among first-degree relatives of patients.

Clinical Presentation

The cardinal symptoms are urgency, tenesmus, and bloody diarrhea; in severe cases, fever, anorexia, and weight loss are also present. Patients may present with constipation due to proctitis or complain of abdominal cramping with bowel movements. The variability of presentations is remarkable, ranging from malaise and no symptoms referable to the colon, to fever, prostration, abdominal distention, and passage of large volumes of liquid stool. The disease need not be confined to the bowel; extracolonic manifestations include arthropathy, uveitis, jaundice, and skin lesions. The course is characteristically chronic, recurrent, and unpredictable. An insidious presentation does not predict a benign course, and a fulminant onset may be followed by long, relatively asymptomatic periods.

Ulcerative colitis almost always involves the rectum, making diagnosis possible by sigmoidoscopy. The mucosa becomes edematous, obscuring the fine network of submucosal vessels. The moist, glistening mucosal surface is lost, and a granular appearance develops. The bowel wall is friable, bleeding spontaneously or when touched with the colonoscope. In advanced cases, pseudopolyps and discrete ulcers may be seen. Smears of mucus from the bowel wall show polymorphonuclear leukocytes. Radiologic findings include bowel wall thickening on CT and a loss of haustral markings and a tubular appearance on barium enema. There are no skip areas on initial colonoscopic exam, but this may change after treatment.

Liver involvement occurs in the form of small-duct primary sclerosing cholangitis (formerly called pericholangitis) and fatty infiltration, which are common histologic findings in ulcerative colitis but are seldom symptomatic. Much less frequently, autoimmune hepatitis, primary biliary cirrhosis, or sclerosing cholangitis is seen. A migratory pauciarticular arthritis affecting principally the large joints develops in 10% of patients. This arthritis often coincides with an exacerbation of colitis and resolves with control of the underlying disease. Ankylosing spondylitis also occurs but runs a course independent of the colitis. Uveitis may be seen at any time during the course of the disease, whereas episcleritis or scleritis usually mirrors bowel symptoms. Erythema nodosum, oral aphthous ulcerations, and pyoderma gangrenosum are found in about 5% of patients; the first two usually during active colitis, whereas the last may occur independent of bowel inflammation.

Course

The prognosis for patients with ulcerative colitis seen in the primary care setting is far better than that for patients studied in referral centers, who are likely to have more severe disease. Long-term, community-based studies find that nearly 90% of patients go into complete remission after the first attack and less than 10% develop chronic persistent disease. Among those with chronic disease, less than half have disease limited to the distal bowel (rectum or rectosigmoid). Overall mortality in community-based populations of ulcerative colitis patients is no different from that of the general population, although it is increased in patients with severe first attacks or extensive disease.

There is an increased risk of cancer, which correlates with the extent and duration of disease and age at diagnosis. Risk begins to increase substantially after 8 years of illness at a rate of approximately 0.5% to 1% per year. A meta-analysis showed a risk of 2% at 10 years after diagnosis, 8% after 20 years, and 18% after 30 years. However, more recent data suggest that the risk may be lower (<10% at 30 years) perhaps due to better management of the disease.

Ulcerative Proctitis

Ulcerative proctitis is a variant of ulcerative colitis, distinguished by the limited extent of inflammation, its good prognosis, and the paucity of serious complications. Typically, the patient with ulcerative proctitis is a young adult who presents with rectal bleeding and tenesmus. The bleeding is usually not severe; it is sometimes mistakenly attributed to hemorrhoids. Diarrhea or constipation may accompany the bleeding, but often, there are only small, frequent bowel movements associated with a small amount of mucus. On sigmoidoscopy, an edematous friable rectal mucosa is observed; the bowel above the rectosigmoid is uninvolved. On barium enema or colonoscopy, the remainder of the large bowel is normal.

The clinical presentation of ulcerative proctitis is not pathognomonic; the condition must be distinguished from infectious forms of proctocolitis, including AIDS-related etiologies (see
Chapters 13 and 66). Although prognosis is good, relapses are common. Approximately 20% of cases progress to generalized ulcerative colitis. The distant complications of ulcerative colitis are rare, and the risk of carcinoma of the rectum is only slightly, if even at all, increased compared to unaffected individuals.

Crohn Disease

Pathophysiology

Crohn disease is a chronic relapsing inflammatory disorder of the alimentary tract. A leading purported mechanism includes a dysregulated response to intestinal microbial flora in a genetically predisposed individual. There are high levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-a, interferon-γ, and interleukin-17. The infusion of monoclonal antibodies directed against TNF-α can produce remission of otherwise refractory disease (see Management). There may also be inadequate production of counterregulatory substances. Frequent use of NSAIDs (>15 d/mo), but not aspirin, high geographic latitude, low vitamin D, and depression appear to increase risk of Crohn disease.

Pathologically, the distribution of bowel inflammation is discontinuous, with diseased segments of bowel separated by normal areas. Because the granulomatous inflammatory process may extend transmurally through all layers of the bowel wall, it has a tendency to cause perforation, strictures, fistulas, and abscesses.

Clinical Presentation

Peak onset is in the second and third decades, but the condition may begin late in life. It often affects the distal ileum and right colon but frequently involves only the small bowel or colon. It may occur in any portion of the alimentary tract, from the buccal mucosa to the anus. Symptoms vary, depending on the location and extent of disease. Diarrhea and abdominal pain (particularly in the right lower quadrant) are cardinal symptoms, occurring in almost 80% of patients. Weight loss, vomiting, fever, perianal discomfort, and bleeding are also common complaints. Constipation may be an early manifestation of obstruction. Symptoms can develop subtly or can present in fulminant fashion with the patient systemically toxic. Extraintestinal involvement occurs in approximately 20% of cases, with arthropathy, ankylosing spondylitis, uveitis, erythema nodosum, aphthous oral ulcers, and pyoderma gangrenosum being the predominant manifestations of disease outside the bowel. In addition, cholelithiasis and nephrolithiasis have a higher incidence in these patients than in the general population.

Physical examination may reveal a discrete abdominal mass, especially in the right lower quadrant, but usually, a normal abdomen or doughy loops of bowel are found. Abdominal or perianal fistulous tracts are noted on examination in up to 10% of patients. Extraintestinal findings include inflamed joints, spinal deformities, erythema nodosum, pyoderma gangrenosum, uveitis, and aphthous ulcers.

Sigmoidoscopy is abnormal in fewer than 20% of cases; fistulous tracts and discrete inflammatory ulcers are sometimes encountered in the rectosigmoid. Imaging studies show segmental involvement of large and small bowel, sometimes with strictures, fistulas, and lymphadenopathy. Because there are typically “skip” areas and cecal involvement, definitive diagnosis usually requires colonoscopy with ileal intubation (see Workup).

Prognosis

Although it is difficult to extrapolate from referral center data to patients seen in primary care settings, a pattern emerges of disease activity that waxes and wanes over many years. Disease-free intervals may last as long as several years or even decades, but recurrences are the rule. Several years of relief from symptoms may be afforded by surgical resection. Needs for surgery and hospitalization have decreased over the past decade associated with the advent of better medical therapy.

WORKUP (4, 5 and 6,9,14)

Proper management requires establishing a working diagnosis and determining the extent of disease.

Ulcerative Colitis

Diagnosis

Clinical presentation and sigmoidoscopic demonstration of mucosal inflammation usually suggest the diagnosis; stool culture and examination for ova and parasites help to exclude potentially mimicking bacterial and parasitic infections (see Chapter 64). Because the disease almost invariably affects the rectum, sigmoidoscopy or colonoscopy is an essential component of the workup. In acute phases of the illness, the mucosa appears friable and inflamed; there is loss of the normal vascular pattern. As the disease progresses, a purulent exudate and discrete small ulcers may form. With severe colitis, there may be pus, spontaneous bleeding, and large ulcers. A granular mucosa and inflammatory pseudopolyps (tags of damaged mucosa and granulation tissue) characterize chronic phases of the disease. One should culture the stool for Entamoeba histolytica, Campylobacter, Shigella, Salmonella, Escherichia coli 0157, Yersinia, and Neisseria gonorrhoeae and test for Clostridium difficile toxin(s) (see Chapters 64 and 66). Rectal biopsy helps to confirm the diagnosis and exclude conditions such as Crohn disease of the rectosigmoid, amoebic colitis, pseudomembranous colitis, cytomegalovirus infection, and herpetic pancolitis. Barium enema or colonoscopy can be used to provide supportive evidence when the diagnosis is in doubt and helps to document the extent of disease. There is a small risk of perforation when the procedure is performed on an acutely and severely inflamed bowel; under such circumstances, it is safer to limit the exam to the rectum and delay full colonoscopic exam for determining the extent of disease until there has been clinical improvement.

Estimating Disease Activity and Severity

The appearance of the bowel mucosa on colonoscopy remains the mainstay of assessment of disease activity. Scoring systems based on clinical parameters are sometimes used in research settings but have little utility in clinical practice. Disease severity is defined more clinically. Mild disease is defined as fewer than four bowel movements a day and no signs of toxicity (i.e., fever, tachycardia, anemia, or elevation of sedimentation rate). Moderate disease is characterized by four to six bowel movements a day plus minimal toxicity. Severe disease is manifested by six or more bloody bowel movements a day and/or signs of toxicity.

Crohn Disease

Diagnosis

Crohn disease of the colon may mimic ulcerative colitis clinically. Differentiating features include skip areas in the colon, significant small-bowel involvement, fistulas, strictures, perianal disease, oral
aphthous ulcers, and granulomas on biopsy. The diagnosis is suggested by a history of recurrent lower abdominal pain and diarrhea, especially with nocturnal bowel movements; it is reinforced by finding on physical examination a mass or tenderness in the right lower quadrant.

Small-bowel involvement can be demonstrated by both noninvasive and invasive study. Upper gastrointestinal series with small-bowel follow-through (SBFT) may show segmental narrowing, areas with loss of the normal mucosal pattern interspersed with areas of normal mucosa, fistula formation, and the string sign (a narrow band of barium flowing through an inflamed or scarred area) in the terminal ileum. The advent of video capsule endoscopy, magnetic resonance (MR), and computed tomographic (CT) enterography provides improved noninvasive imaging compared to SBFT and a noninvasive alternative to colonoscopy, which requires terminal ileum intubation for the detection of small-bowel involvement. CT enterography also enables the detection of other intraabdominal abnormalities, such as mesenteric adenopathy and intestinal fistulas. MR enterography avoids radiation exposure but requires significant cost and patient cooperation. One risk of video capsule endoscopy is capsule impaction, which necessitates surgical removal.

Colonic disease may be documented noninvasively by aircontrast barium enema, with asymmetric segmental changes distinguishing Crohn disease of the large bowel from ulcerative colitis. Disease of the terminal ileum can often be detected on barium enema; however, involvement of the terminal ileum is not unique to Crohn disease; some ulcerative colitis patients also demonstrate inflammatory changes in the terminal ileum (backwash ileitis), but they lack the skip pattern characteristic of Crohn disease.

Endoscopy helps determine the extent and severity of disease, especially documenting the presence or absence of disease in the terminal ileum. Biopsy should always be done as part of the endoscopic examination; findings of chronic inflammation help to confirm IBD and differentiate it from acute intestinal inflammatory conditions.

Estimating Disease Activity and Severity

Disease activity in the colon is best assessed by colonoscopy and in the small bowel by colonoscopy with ileal intubation and/or barium enema or MR or CT enterography. Disease severity is categorized clinically. Mild to moderate disease is defined as having symptoms but functioning adequately on an ambulatory basis, maintaining oral intake of food and fluids, and showing no signs of toxicity or complications. In moderate to severe disease, symptoms are more severe, sometimes interfering with daily activity and not responding fully to treatment. In severe disease, there may be toxicity, complications, and failure to respond to full doses of oral corticosteroids.

Differentiation Between Crohn Disease and Ulcerative Colitis

It is not always possible to distinguish these two entities. In the instances of indeterminate colitis, it may be helpful to test for presence of perinuclear antineutrophil cytoplasmic antibodies (found in about half of patients with ulcerative colitis) and anti-Saccharomyces cerevisiae antibodies (associated with Crohn disease). However, the sensitivity and specificity of such antibody testing are too limited for these studies to be useful in differentiating between IBD and other colonic conditions. Use should be limited to distinguishing between Crohn disease and ulcerative colitis and only in conjunction with a consideration of all other clinical findings.