The term inflammatory bowel (IBD) refers mainly to two idiopathic diseases of the gastrointestinal system that are char-acterized by acute and chronic inflammation: ulcerative colitis and Crohn's disease. Ulcerative colitis is characterized by in-flammatory changes involving the colonic mucosa and submu-cosa in a continuous fashion, starting at the rectum and ex-tending proximally. Depending on the extent of the disease, ul-cerative colitis can be divided into proctitis (rectum only), proctosigmoiditis, left-sided colitis (extending to the splenic
flexure), or universal colitis (pancolitis). Such classification is important for therapeutic and prognostic reasons. Crohn's dis-ease, on the other hand, can involve any segment of the gas-trointestinal system, usually in a discontinuous fashion (skip lesions), and the inflammation is frequently transmural.
Etiology
The immune system has separate compartments, includ-ing the systemic compartment, represented by the peripheral blood lyphocytes, and the gastrointestinal mucosa, in which numerous intraepithelial lymphocytes and lamina propria lym-phocytes are found. Patients with IBD have an abnormality in the expression and activation in the gastrointestinal mucosal compartment.
The gastrointestinal system is normally in a"contmlled state of inflammation. " To regulate immune and inflammatory functions, constant cell-to-cell communication is mediated through cytokines, Cytokines are small pepties that regulate immune function and include interleukins (IL), inteferons, monokines, and lymphokines. Some cytokines are primarily proinflammatory (tumor necrosis factor-s, IL-1 ), whereas others have immunoregulatory or anti-inflammatory actions (IL-2, IL-4, IL-10, transforming growth factor-). In a sim-plistic way, hoeostasis is disrupted with IBD because of over-expression of proinflammatory cytokines, underexpression of regulatory or anti-inflammatory cytokines, or both.
Evidence also suggests that genetic factors play a role in IBD, and the disease is most likely polygenic. Firstdegree rela-tives of patients with ulcerative colitis or Crohn's disease have a 10 to 15 fold increased risk of developing IBD, usually with the same disease as the patient. Furthermore, about 10% of patients with IBD have a first-degree relative with the disease. Infectious agents have been implicated, but none have fulfilled Koch's criteria. Environmental factors are suspected because the disease is more common in industrialized countries, and the frequency is increasing in countries that are becoming industri-alized. However, to date, the only environmental factor clear-ly associated with IBD is cigarette smoking. Cigarette smoking seems to be protective for ulcerative colitis; some patients de-velop symptoms when they stop smoking cigarettes, whereas smokers with Crohn' s disease have more aggressive disease than do nonsmokers with Crohn's disease.
Incidence and Epidemiology
Whereas the incidence of ulcerative colitis has remained stable, the incidence of Crohn's disease is increasing world-wide. Both diseases are more common in the northern parts of the Western world, among whites, and particularly in Ashke-nazi Jews living in Europe or
Ulcerative Colitis: Clinical Features
Patients with ulcerative colitis usually present with bloody diarrhea, which has a chronic intermittent course, with episodes of remissions and exacerbations. The symptoms, severity, and prognosis of the disease are often dertermined by the extent of the disease. At presentation, nearly 50 % of pa- tients have proctitis or proctosigmoiditis; however, after 13 years, the disease extends to involve the entire colon in more than 30 % of patients. Patients with proctitis have urgency and frequent trips to the toilet to pass small amounts of mucus and blood. Patients with more extensive disease have bloody diar-rhea, predefecational cramps, and, if they have severe of ful-minant disease,signs and symptoms of dehydration, abdominal pain, and fever. Not infrequently, patients present with ex-traintestinal manifestations such as erythema nodosum, arthri-tis, or pyodermagangrenosum before they develop intestinal symptoms.
Crohn' s Disease: Clinical Features
Crohn's disease is a heterogeneous disease with the clini-cal manifestations depending on the site of involvement and the behavior of disease. Patients can have mostly inflammatory symptoms, characterized by abdominal pain in the right lower quadrant, fever, weight loss, and a palpable inflammatory mass. They may have obstructive symptoms, characterized by postprandial abdominal pain, bloating, nausea, and vomiting; or they may have fistulous disease, characterized by en-terovaginal fistula, enterocutaneous fistulas, or other internal fistula or abscess. However, the three patterns of disease can occur in the same patient. Not infrequently, patients present with perianal disease including anal fissures abscess fistula, or skin tags. These manifestations should not be confused with "hemorrhoids. " The most common site of involvement is ileo-colonic disease; such patients usually have inflammatory dis-ease that, over time, becomes stricturing disease. Patients with disease confined to the colon have nonbloody diarrhea, abdominal pain, fever, and weight loss. Patients with gastro-duodenal Crohn's disease have dyspeptic symptoms, whereas patients with jejuoileal disease have obstruction or symptoms related to fistulae.
Extraintestinal Manifestations
IBD is a systemic disease that affects primarily the gas-trointestinal system and has numerous extraintetinal manifesta-tions, including musculoskeletal, skin, hepatic,ocular, renal, and other features. The most frequent musculoskeletal compli-cation is seronegative "arthritis". This pauciarticular, asym-metric, nondeforming arthritis involves large ioints more com-monly. It occurs in 15 % to 45 % of patients with colonic dis-ease, either Crohn's disease or ulcerative colitis. The other maior usculoskeletal manifestations are sacroiliitis and ankylos-ing spondylitis, which are axial arthroathies. These disorders are more common in patients with ulcerative colitis, have a close association with the histocompatibility antigen HLA-B27, and run a course independent of disease activity. To date, more than 40 skin manifestations of IBD have been de-scribed; the 3 most commonly seen are aphthous ulcerations of the oral mucosa, erythema nodosum, and pyoderma gangreno-sum. Erythema nodosum occurs in 15% of patients with Cmhn's disease and in 4% of patients with ulcerati'ae colitis. It is characterized by red, tender subcutaneous, usually on the anterior tibial surface. Pyoderma gangrenosum does not have a clear association with disease activity. It occurs in 0 % -2% d patients with IBD, and it usually presents at sites of trauma. It usually occurs over the shins or on the face and is character. ized by large ulcers of the skin, with a necrotic center and an advancing border that is undermined or rolled.
Ocular manifestations occur in approximately 6% of pa-tients with IBD. The most common manifestation is episcleri-tis, which occurs more commonly in patients with Crohn's colitis. A less frequent, but more serious manifestation is uveitis, which usually presents with a sudden-onset headache and blurred vision and is an ophthalmologic emergency. Hema-tologic features are multiple. Some are complications of the in-testinal .disease such as iron deficiency anemia or vitamin B12 malabsorption, whereas others are extraintestinal manifesta-tions such as a hypercoagulable state leading to venous and ar-terial thrombosis that can have fatal complications.
Hepatic complications occur in approximately 5% of pa-tients with IBD. The most common finding is asymptomatic elevation of hepatic transaminases with fatty infiltration of the liver, either resulting from nutritional factors or secondary to medications used to treat IBD. A more significant hepatobil-iary complication is primary sclerosing cholangitis, which is characterized by progressive inflammation of the intrahepatic and extrahepatic biliary tree, leading to strictures, with sep-sis, cirrhoisis, and cholangiocarcinoma as possible compiica-tions. Primary sclerosing cholangitis occurs more commonly in patients with ulcerative colitis than in those with Crohn's dis-ease, and it follows a course that is independent of disease ac-tivity.
Other Complications
Patients with Crohn' s disease can develop multiple metabolic abnormalities. They have increased absorption of ox-alate that leads to kidney stones and a disrupted enterohepatic circulation with increased frequency of gallstones. Metabolic bone disease is a complication of IBD, either because of vita-min D malabsorption or as a side effect of steroid use. Other rare complications include acute pancreatitis, pleuroperi-carditis, fibrosing alveolitis, bronchiolitis obliterans, club-bing, hypertrophic osteoarthropathy, and amyloidosis.
The risk of colon cancer is increased in patients with IBD, particularly in those with ulcerative colitis. The risk is related to the extent and duration of disease, and it is increased in pa-tients with primary sclerosing cholangitis. In patients with pancolitis, the risk increases after 10 years and is estimated to increase by 0.5 % to 1% per year, to reach an absolute risk of 30% after 35 years of disease. Patients with extensive Crohn' s colitis and those with left-sided ulcerative colitis also have an increased risk of colorectal cancer, but the risk is lower than in patients with ulcerative pancolitis. Proctitis is not associated with a cancer risk. Because of the evolution from diseased mu-cosa to dysplasia to cancer, different regimens with colonscopy and multiple biopsies throughout the colon are recommended, and whenever dysplasia is found, colectomy is recommended.
Diagnosis
The diagnosis of IBD is based on clinical features, labora. tory,tests, and endoscopic and histologic features. Laboratory tests are not specific and usually reflect inflammation and/or anemia. The only specific feature is perinuclear antineutmphil cytoplasmic antibody (pANCA), which is positive in up to 70 % of patients with ulcerative colitis but rarely positive in pa-tients with Crohn's disease. During colonosc0py in patients with ulcerative colitis, the mucosa has a granular appearance, decreased vessel marking and mucosal shine, and superficial ul-cerations, and in more severe cases, the mucosa is friable, with deeper ulcerations and an exudate. Patients with long-standing disease have "pseudopolyps. " Histologically, crypt architecture is distorted, with crypt abscesses and inflamma-tion consisting of plasma cells, neutrophils, lymphocytes, and eosinophils.
Stool cultures for ova and parasite identification and stool testing for Clostridium difficile toxin, are helpful, because these infections can mimic IBD. In Crohn' s disease, small bowel radiography remains the best study with which to inves-tigate the jejunum and ileum. Involved areas have edema and thickening of the wall that lead to bowel loop separation and can also show ulcerations of the mucosa, fistulas, or stric-tures. A tight, long stricture in the terminal ileum is common-ly called the "string sign" On endoscopic examination, the in-volved mucosa shows aphthoid ulcerations, deep linear or stel-late ulcers, edema, erythema, exudate, and friability with in-tervening areas of normal mucosa (skip lesions). Linear ulcers with segments of edematous or uninvolved mucosa lead to the characteristic pattern called "cobblestoning. " Patients with a suspected abscess should have a computed tomographic exami-nation before other radiologic or endoscopic studies are per-formed(Table 24).
Differential Diagnosis
The differetial diagnosis of IBD includes infectious coli-tits, ischemic colitis, radiation enteritis, enterocolitis induced by nonsteroidal anti-inflammatory drugs, diverticulitis, appen-dicitis, colon cancer, and lymphoma. Among the infectious cases. Yersinia enterocolitica infection can mimic Crohn's dis-ease because the pathogen causes ileitis, mesenteric adenitis, fever, diarrhea, and abdominal pain in the right lower quad-rant, all of which are features of Crohn's disease. Tuberculo-sis, strongyloidiasis, and amebiasis must be excluded in popu-lations at high risk because these diseases can mimic IBD, and treatment with corticosteroids can lead to death.
Treatment
As part of the initial management of patients with IBD, the clinician must determine the extent and severity of the pa-tient's disease. Patients with mild or moderate disease can be managed as outpatients, whereas patients with severe or fulmi-nant disease require hospital admission and multidisciplinary management with a colorectal surgeon. Patients with severe disease arefebrile, tachycardic, and anemic, and they have leukocytosis and abdominal pain. Because IBD is a chronic re-current illness, treatment is divided first into management of the acute attack, next into treatment to induce remission, and finally into maintenance of remission.
Nutrition
Nutritional support is an important aspect of supportive treatment in patients with IBD. However, as primary treat-ment it has a role only in small bowel Crohn's disease, because these patients may achieve remission when they are treated with total parenteral nutrition or elemental diets for prolonged periods (at least 4 weeks). Vitamins and minerals should be supplemented; patients with extensive ileal disease cannot ab-sorb vitamin B12 orally, whereas patients taking corticosteroids require supplemental calcium and vitamin D. Patients with ex-tensive small bowel involvement develop malabsorption of fat-soluble vitamins (A, D, E, and K), iron deficiency, folate deficiency, and, if diarrhea is significant, zinc deficiency.
Antidiarrheal Medications
Antidiarrheal agents should be used cautiously during ex-acerbations because they can precipitate toxic colitis or mega-colon. Their main role is in controlling postoperative diarrhea. When less than
