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Clinical and Pathological Aspects of Inflammatory Bowel Disease

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Clinical and Pathological Aspects of Inflammatory Bowel Disease Inflammatory Bowel Diseases: B.R. Bistrian; J.A. Walker-Smith (eds), Nestlé Nutrition Workshop Series Clinical & Performance Programme, Vol. 2, pp. 83–92, Nestec Ltd.; Vevey/S. Karger AG, Basel, © 1999. Clinical and Pathological Aspects of Inflammatory Bowel Disease Ph. Marteau Gastroenterology Department, European Hospital Georges Pompidou, Paris, France The term “inflammatory bowel disease” applies to bowel diseases of unknown etiology characterized by chronic and often relapsing inflammation. They include ulcerative colitis, Crohn’s disease, indeterminate colitis, pouchitis, and micro- scopic colitides. Although these diseases share a number of epidemiological, pathological, and clinical features, they differ sufficiently to be classified as dis- tinct entities. The term “indeterminate colitis” is used for colitides which do not present enough criteria to be classified as ulcerative colitis or Crohn’s disease. Ulcerative Colitis Pathology Ulcerative colitis is a mucosal disease, which always affects the rectum and often also involves a variable contiguous proximal segment of colonic mucosa [1]. The lesions are continuous, and their upper limit is sharply demarcated from the normal mucosa above. They are limited to the rectum in about 25% of the patients (proctitis); reach the sigmoid colon in another 25% (proctosigmoiditis); spread to the splenic flexure in another 25% (left-sided colitis), and affect the whole colon in about 15% (pancolitis). The small intestine is usually normal but may be occasionally involved by superficial inflammation (“backwash ileitis”) in some patients with pancolitis. Macroscopic lesions can be evaluated during endoscopic examination [2]. Active lesions consist of edema, erythema, lack of the normal vascular pattern, bleeding, exudation of mucus or pus, and ulceration (Table 1). The pathologic findings are in most cases limited to the mucosa and submucosa. Ulceration reaches the deeper layers of the colonic wall only in the severe forms of the dis- 83 Clinical and Pathological Aspects of Inflammatory Bowel Disease Table 1. Ulcerative Colitis Disease Activity Index 1. Stool frequency (qualitative rating scale 0 = Normal with four subscales) 1 = 1–2 stools/day 1 normal [adapted from 31] 2 = 3–4 stools/day 1 normal 3 = 14 stools/day 1 normal 2. Rectal bleeding 0 = None 1 = Streaks of blood 2 = Obvious blood 3 = Mostly blood 3. Mucosal appearance 0 = Normal 1 = Mild friability 2 = Moderate friability 3 = Exsudation, spontaneous bleeding 4. Physician’s rating of disease activity 1 = Normal 2 = Mild 3 = Moderate 4 = Severe Maximum score = 13. ease. Structural abnormalities may be seen at the same time or after the acute lesions. They include pseudopolyps, loss of interhaustral folds, narrowing of the colonic lumen which develops a tubular shape, and sometimes stricture forma- tion. Pseudopolyps are common and correspond to hypertrophic islands of granu- lation tissue which usually appear during healing of ulceration. When examined microscopically (on biopsy samples), active lesions are char- acterized by a polymorphonuclear infiltrate confined to the mucosa with crypt abscesses, edema, vascular congestion, branching of the crypts, and mucus deple- tion from the goblet cells. Rectocolonic Symptoms The symptoms depend in part on the spread of the lesions and on their severity [1]. The main symptoms of active ulcerative colitis are the presence of blood and/ or mucus in stools and frequent bowel movements. When the disease is mild only those signs may be present, sometimes associated with extradigestive symptoms (see below). When the lesions are only located in the distal part of the colon, patients complain of frequent bowel movements because of rectal irritation, but the fecal volume is normal. Rectal pain (tenesmus) may be present. When lesions are extensive, diarrhea is often present (but constipation is reported in some cases). The presence of many bowel movements, large number of bloody stools, 84 Clinical and Pathological Aspects of Inflammatory Bowel Disease Table 2. Truelove and Witts’ Classification of Ulcerative Colitis [adapted from 3] Severe Diarrhea: six or more motions per day, with blood Fever: mean evening temperature over 37.5 °C on at least 2 of 4 days Tachycardia: mean pulse rate over 90 beats/min Anemia: hemoglobin of 75 mg/dl or less compared with normal values, allowing for recent transfusions Sedimentation rate: 130 mm/h Mild Mild diarrhea: less than four motions per day, with only small amounts of blood No fever No tachycardia Mild anemia Sedimentation rate: !30 mm/h Moderately severe Intermediate between mild and severe fever, severe abdominal pain, tachycardia, and anemia are often (although not invariably) associated with severity [3]. Patients with severe forms of ulcerative colitis (“fulminant colitis”) have a high spontaneous risk of colonic perforation and death. Clinical classifications, especially the classification derived from that first proposed by Truelove & Witts (Table 2), are widely used to determine treat- ment, including colectomy [3, 4]. However, specialists increasingly base their therapeutic decisions not only on the symptoms and the results of simple labora- tory tests (hemoglobin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasma albumin) but also on the severity of the colonic lesions (which do not always fully reflect the symptoms) [5–8]. The diagnosis of severe colitis on endoscopy is made by the presence of at least one of the following signs in any segment of the colon: extensive deep ulcerations, mucosal detachment on the edge of these ulcerations, well-like ulcerations, and large mucosal abrasions [6]. Extradigestive Symptoms Manifestations in organs other than in the digestive tract occur in up to 15% of patients with inflammatory bowel disease [9]. Peripheral arthritis, isolated sacroiliitis, erythema nodosum, pyoderma gangrenosum, oral aphthae, perichol- angitis, chronic active hepatitis, uveitis, and episcleritis usually occur in conjunc- tion with active intestinal inflammation and respond to its treatment. In contrast, ankylosing spondylitis and sclerosing cholangitis (the prevalence of which is increased in patients with inflammatory bowel disease) usually run an indepen- dent course from the intestinal inflammation. Patients with inflammatory bowel disease are at increased risk of thromboem- bolic events, especially during acute phases of the disease [10]. Weight loss and 85 Clinical and Pathological Aspects of Inflammatory Bowel Disease growth failure may be present in patients with ulcerative colitis, but less often than in Crohn’s disease. Sixty to seventy percent of patients with ulcerative colitis have serum perinuclear antineutrophil cytoplasmic antibodies (P-ANCA). Complications Complications of ulcerative colitis include fulminant colitis, severe hemor- rhage, toxic megacolon, and colonic cancer. Toxic Megacolon and Perforation Toxic megacolon is a severe complication resulting from paralysis of colonic motility which occurs in some patients with deep ulcerations [11]. Dilatation of the colon is often associated with fever, prostration, severe pain, dehydration, and tachycardia. The risk of perforation and death is high. Perforation can also occur in patients with fulminant colitis without toxic megacolon. Colonic Cancer Patients with extensive colitis have a higher risk of developing colonic adeno- carcinoma than the general population [12]. Risk factors include the extent of mucosal involvement, the duration of disease, the presence of sclerosing cholangi- tis, and the presence of colonic strictures or mass lesions. The risk becomes appre- ciable 8–10 years after the initial diagnosis of ulcerative colitis. Certain macro- scopic lesions (strictures and masses) and dysplasia on colonic biopsy remote from severely inflamed areas are warning signals of cancer development. Surveil- lance of the colonic mucosa with regular endoscopic and histologic examination of biopsies taken every 10 cm throughout the colon is recommended for patients with extensive colitis diagnosed more than 8 years earlier. Evolution More than 90% of the patients with a first attack of ulcerative colitis will devel- op chronic disease [13]. Most of these will experience recurrent attacks (“chronic intermittent form”), and less than 10% have continuous symptoms, which are sometimes even refractory to treatment (“chronic continuous form”). Resistance to treatment seems to be associated with a greater likelihood of having P-ANCA in the blood [14]. The frequency of recurrence varies between subjects and is higher in patients who have already experienced many episodes. The lesions may either remain in the same colonic segments or they may spread progressively [15]. The probability that proctitis will spread to involve the sigmoid colon after 10 years is about 30%. The risk for a patient with ulcerative colitis of having a severe episode (“fulminant colitis”) is about 15%, and about one third of the cases of fulminant colitis occur as the first presentation of ulcerative colitis. The life expectancy of patients with ulcerative colitis is similar to that of the general popu- lation, and the mortality of fulminant colitis has changed from 30% 30 years ago to about 1% in the most recent series (largely because of the development of inten- 86 Clinical and Pathological Aspects of Inflammatory Bowel Disease sive medical treatment and the establishment of criteria for early colectomy) [3, 4, 6–8]. In a retrospective study of 130 cases of pancolitis,
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