Colonic inflammatory bowel disease. Medical therapies for colonic Crohn's disease and ulcerative colitis

Advances in the treatment of inflammatory bowel disease (IBD) in the past decade include 5-aminosalicylic preparations with fewer adverse effects; new, rapidly metabolized corticosteroids; and new agents targeted at refractory or complicated IBD. Dr Tung and Dr Warner discuss the use of these and more traditional drugs in patients with colonic Crohn's disease and ulcerative colitis, stressing the need for individualized treatment.     

Composition of human colonic mucin. Selective alteration in inflammatory bowel disease.

Human colonic mucin has been isolated from mucosal scrapings of fresh surgical specimens of normal controls as well as patients with Crohn's colitis and ulcerative colitis. Following sonication and ultracentrifugation, mucin fractions were separated from other soluble colonic glycoproteins by Sepharose 4B chromatography. After nuclease digestion, cesium chloride gradient centrifugation of the excluded material yielded colonic mucin with an average buoyant density of 1.52 g/ml. Subsequent chromatography of the apparently homogeneous colonic mucin on DEAE-cellulose revealed the presence of at least six distinct mucin species (mucin I-VI). Each mucin species was found to have a distinctive hexose, hexosamine, sialic acid, and sulfate content as well as blood group substance activities. Mucin from five patients with Crohn's colitis was found to represent a mixture of at least six discrete species comparable to those isolated from normal colonic specimens. However, in mucin from eight patients with ulcerative colitis there was a marked and selective reduction of one component mucin subclass, designated species IV. Normal mucin and mucin from patients with Crohn's disease contained 48 +/- 17 and 42 +/- 12 mg of species IV/g, while mucin from patients with ulcerative colitis had 5 +/- 3 mg/g solubilized glycoprotein. The selective absence of species IV was found in preparations from both sigmoid (n = 7) and ascending (n = 4) colon and could not be accounted for by an overall decrease in total mucin content. The selective reduction of species IV was also found in mucin isolated from relatively noninflamed colonic mucosa of patients with ulcerative colitis. The carbohydrate composition and blood group activities of the remaining five mucin species were similar to their normal counterparts. Based on the results to date, there appears to be an underlying selective decrease of one colonic mucin subclass in ulcerative colitis.     

Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn's disease

Background: The colon is covered by a mucus barrier that protects the underlying mucosa and alterations in this mucus barrier have been implicated in the aetiology of inflammatory bowel disease (IBD). This study investigated the thickness and continuity of the mucus barrier in ulcerative colitis (UC) and Crohn’s disease (CD) in comparison to normal controls. Methods: Rectal biopsies were taken from 59 patients and cryostat sections stained with periodic acid‐Schiff’s/Alcian blue to visualise the mucus layer. Mucus thickness and continuity and goblet cell density were measured using light microscopy. Results: An essentially continuous adherent mucus layer was observed in normal human rectum and there was no change in the mucus barrier in quiescent UC. In active UC there was a trend for the mucus layer to become progressively thinner and significantly more discontinuous as disease severity increased. In severe active UC the mucus layer thickness and goblet cell density were significantly reduced compared with normal controls while the percentage discontinuity significantly increased. Conclusion: It is not until severe UC that there is a global change in mucosal protection as a consequence of large regions lacking mucus, a decrease in secretory potential caused by a loss of goblet cells and a thinner, less effective mucus layer even when it is present.     

T-cell immunoregulation in patients with inflammatory bowel disease. II. Enhanced suppressor T-cell activity in ulcerative colitis

In a recent study, we have shown that peripheral blood B cells from patients with ulcerative colitis (UC) synthesized less immunoglobulin (Ig) in co-culture with autologous T cells than normal adults' B cells. When UC patients' T cells were co-cultured with normal adults' B cells, Ig synthesis was significantly decreased as compared with normal controls. In contrast, Crohn's disease (CD) patients' B and T cells functioned normally. In the present study, the activity of suppressor T cells in patients with UC and CD was determined. Peripheral blood B and T cells with monocytes were obtained from patients and normal adults of the same age and sex, and co-cultured for 10 days with pokeweed mitogen (PWM). Suppressor T-cell function was measured in mixed co-culture assays in which graded numbers of normal or patient's T cells were added to normal adults' B and T cells with PWM. Immunoglobulins (Ig) M, G and A were measured in culture supernatants using a sensitive enzyme-linked immunosorbent assay. The quantity of Ig present in the culture supernatants was determined from a standard curve. T cells from UC patients significantly decreased immunoglobulin production by control B and T cells (IgM and IgA, p = 0.02; IgG, p = 0.01). In contrast, addition of T cells from CD patients produced no significant differences. Complement mediated, monoclonal OKT8 antibody directed cell lysis revealed that the inhibition observed with UC patients' T cells in co-culture was due to a T8+ suppressor T cell. The degree of inhibition of immunoglobulin synthesis did not correlate with disease activity, duration of illness, location of disease, or corticosteroid treatment. Thus, patients with ulcerative colitis display enhanced suppressor T-cell activity in peripheral blood while patients with CD show normal helper and suppressor T-cell functions. These results provide evidence supporting a role for altered immunoregulatory activity in the pathogenesis of ulcerative colitis.     

The value of rectal biopsy in distinguishing self-limited colitis from early inflammatory bowel disease

When a patient presents for the first time with acute diarrhoea, it can be difficult to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease. This study was designed to determine whether detailed interpretation of rectal histology can enable this distinction to be made early in the course of the illness. Seventy-two rectal biopsies, taken at the time of presentation from patients with undiagnosed colitis, were reviewed independently by two observers without access to clinical information. Distorted crypt architecture, crypt atrophy, basal lymphoid aggregates and dense lymphocytic infiltrates each emerged as features with a 76 to 86 per cent probability of predicting idiopathic inflammatory bowel disease, but their discriminant value was limited by inter-observer disagreement (16-29 per cent). Isolated basal giant cells, epithelial surface erosions and epithelioid granulomas were found to be the most reliable histological features in the early diagnosis of idiopathic inflammatory bowel disease, and their interpretation was associated with the lowest inter-observer disagreement (6 per cent).     

Diagnosis of acute ulcerative colitis and colonic Crohn's disease by colonic sonography

By instilling water into the large intestine, sonographic visualization of the whole length of the colon from the rectosigmoid to the cecum can be achieved. Furthermore, using this method, it is possible to evaluate the lumen, the intestinal wall, and the surrounding connective tissue in detail. In our study, severe, active colonic Crohn's disease and ulcerative colitis could be detected by diagnostic sonography of the colon with a sensitivity of 91% and 89%, respectively. Pathological changes were subsequently confirmed by colonoscopy. Differing echo patterns made differentiation of these two diseases possible. Our results thus show that colonic sonography is a diagnostic procedure that promises to greatly facilitate the evaluation and differentiation of inflammatory large bowel diseases.     

T-cell immunoregulation in patients with inflammatory bowel disease. I. Differential helper T-cell function in ulcerative colitis and Crohn's disease

The role of helper T-cells in patients with ulcerative colitis (UC) and Crohn's disease (CD) was investigated. Peripheral blood B- and T-cells with or without monocytes were obtained from patients and normal adults of the same age and sex, and co-cultured for 10 days with pokeweed mitogen (PWM). Immunoglobulins (Ig) M, G and A were measured in the culture supernatants using a sensitive enzyme-linked immunosorbent assay. The quantity of Ig present in the culture supernatants was determined from a standard curve. Immunoglobulins M, G and A synthesis and secretion by B-cells in the presence of T-cells required monocytes and PWM. The data indicate that co-cultures of heterologous normal adult T-cells and B-cells with PWM did not significantly affect Ig synthesis as compared with autologous cultures. Autologous cultures of CD patients' B- and T-cells were found not to be significantly different from normals in their capacity to synthesize Ig. In contrast, autologous UC patients' B- and T-cells were found to be significantly less effective as compared with normal adults' co-cultures in the synthesis Ig. When CD patients' T-cells were in co-culture with normal adults' B-cells, Ig synthesis was maintained. However, a marked diminution in Ig synthesis was seen when UC patients' T-cells were used in co-culture with normal adults' B-cells. The degree of inhibition of immunoglobulin synthesis did not correlate with disease activity, duration of illness, location of disease, or corticosteroid treatment. These results suggest that patients with ulcerative colitis have an altered helper T-cell population while CD patients' T-cells are either normal or hyperactive in the capacity to provide helper function in PWM-induced immunoglobulin secretion by peripheral blood B-cells.     

Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin.

Increased binding of the lectin peanut agglutinin is a common feature in epithelial malignancy and hyperplasia. This may have considerable functional importance in the intestine by allowing interaction between the epithelium and mitogenic lectins of dietary or microbial origin. Peanut agglutinin binds the disaccharide Thomsen-Friedenreich (TF, T or core 1) blood group antigen, Gal beta (1-3) GalNAc alpha-, but is not totally specific for this site. Consequently, there has been controversy about the presence of this structure in colon cancer; studies with anti-TF monoclonal antibodies have failed to detect it. We have examined the presence of TF antigen in colonic mucus glycoprotein (mucin) using endo-alpha-N-acetylgalactosaminidase (O-Glycanase), which specifically catalyzes the hydrolysis of TF antigen from glycoconjugates. Samples of adenocarcinoma, inflammatory bowel disease (ulcerative colitis), and normal mucin were treated with O-glycanase, the liberated disaccharide was separated from the glycoprotein and analyzed using dual CarboPac PA-100 column high performance anion-exchange chromatography coupled with pulsed amperometric detection. O-Glycanase treatment released increased amounts of TF antigen from both colonic adenocarcinoma (8.0 +/- 3.9 ng/micrograms protein, n = 11; P < 0.0001 ANOVA) and ulcerative colitis mucin (3.3 +/- 0.3 ng/micrograms protein, n = 5; P = 0.04) compared with mucin samples from histologically normal mucosa distant from carcinoma (1.5 +/- 1.1 ng/micrograms protein, n = 9). However, after mild acid treatment to remove sialic acids and fucose, releasable TF antigen was increased in all nine of these histologically normal mucin samples (5.5 +/- 2.6 ng/micrograms protein, P < 0.0002). We conclude that TF antigen is an oncofetal antigen which is expressed in colon cancer, but is concealed by further glycosylation (sialylation and/or fucosylation) in the normal colonic mucosa.     

Inflammatory bowel disease: primary health care management of ulcerative colitis and Crohn's disease

Inflammatory bowel disease encompasses both ulcerative colitis and Crohn's disease, two conditions so alike clinically that they are frequently indistinguishable from one another. Inflammatory bowel disease occurs at a rate of approximately five per 100,000 people. It tends to cluster in families and is seen four to five times more often in Jewish Caucasians than in other Caucasians. The etiology is unknown. Increasing attention is being paid to autoimmune factors, genetic factors and food allergies, and the notion that inflammatory bowel disease has its roots in a psychological disorder continues to pale for want of empirically sound evidence. Disease pattern is one of remission and exacerbation. The aim of therapy is to maintain an optimal lifestyle in remission through an individually tailored protocol of medications. Sulfasalazine remains the medication of choice; corticosteroids have short-term utility in exacerbation; and immunosuppressants, though controversial, are thought to have some steroid-sparing benefits during acute flare-ups. Indications for surgery vary, depending on whether or not a clear differential diagnosis has been made between ulcerative colitis and Crohn's disease. There is no cure for inflammatory bowel disease except for total colectomy in clearly diagnosed ulcerative colitis. Current research endeavors seek a cause or causes for inflammatory bowel disease, but the literature does not solidly support any one possibility above other rival etiologies.     

Collagenase activity in colonic mucosa during inflammatory bowel disease

A simple test for collagenase activity was performed on colonic mucosa specimens of 35 patients with inflammatory bowel disease, 7 patients with carcinoma of the colon, 3 with benign polyps, and 34 normal subjects. Increased collagenase activity was present in 94.2% of the specimens taken from the inflamed mucosa and 71.4% of those obtained from colonic carcinoma, as compared to 8.8% of the control group.     

Studies of rectal mucosal catecholamines in ulcerative colitis.

Rectal mucosal biopsies from six patients suffering from ulcerative colitis were studied by estimating the catecholamine (CA) content and by fluorescence microscopy. Adrenergic nerve fibres were relatively scanty both in diseased and control patients. The adrenergic structures seem well preserved in the affected areas of the colon, although the nonspecific collagenous autofluorescence makes interpretation difficult. There was a significant rise in the noradrenaline (NA) content compared with the seven control patients (p smaller than 0.01). This may be a compensatory phenomenon to inhibit increased intestinal motility. The increased NA level may be due to the intense perivascular adrenergic plexus typical for ulcerative colitis. In both groups there were varying amounts of fluorescing enterochromaffin cells probably without relation to the diagnosis.     

Atopic disease in ulcerative colitis and Crohn's disease.

Three hundred patients with ulcerative colitis, 200 with Crohn's disease and matched control subjects completed questionnaires about atopic disease. They were asked whether they had ever suffered from asthma, hay fever, allergic rhinitis or eczema; in ulcerative colitis all of these features occurred with twice the frequency, but in Crohn's disease only eczema was more common than in controls.     

Phospholipase A2 in serum and colonic mucosa in ulcerative colitis.

Group II phospholipase A2 is involved in the pathogenesis of various inflammatory diseases and in the host defence against bacteria. The enzyme is expressed in the epithelial cells of colonic mucosa in ulcerative colitis. In this study, we measured the concentration of group II phospholipase A2 in serum and colonic mucosa of patients with ulcerative colitis of different severity and of control patients without any inflammatory disease. The activity of ulcerative colitis was assessed by endoscopy. The concentration of group II phospholipase A2 was measured with an immunoassay. The concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher in patients with active and inactive ulcerative colitis than in controls. However, the group II phospholipase A2 levels did not separate patients with different disease activity. The concentration of group II phospholipase A2 in colonic mucosa corresponded with the mucosal inflammatory activity (higher in active colonic areas) intra-individually, but not between different patients with ulcerative colitis. Serum group II phospholipase A2 values were above the normal reference range more often than the values of 11 standard laboratory blood tests widely used for the follow-up of inflammatory activity in ulcerative colitis. These results indicate that the concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with ulcerative colitis. The clinical value of the measurement of group II phospholipase A2 in the follow-up of ulcerative colitis remains to be clarified.     

炎症性肠病回盲部溃疡内镜下特征性表现与鉴别诊断

目的观察回盲部溃疡性病变黏膜特征性改变,初步诊断和鉴别诊断,为临床诊断提供有力依据。方法收集该院自2008年1月-2014年12月行结肠镜检查诊断为炎症性肠病性溃疡43例,观察溃疡特点及黏膜特征性改变。结果回盲部溃疡性病变内镜下特征性表现主要分为3种:溃疡表浅斑片地图状、溃疡较深不规则,沟槽状和回盲瓣瓣口受累变形伴假息肉形成。结果显示以上3种内镜下特征性改变,在单项及两组构成比方面,溃疡性结肠炎(UC)患者和克罗恩病(CD)患者比较,差异有统计学意义(P0.01),可以作为根据其作出初步的鉴别诊断。结论 CD、UC均缺乏诊断的金标准,诊断需结合临床、内镜和组织病理学表现进行综合分析并随访观察,但有一定的特征性表现及规律可循。所以在组织病理学没有充分证据的情况下,观察病变的内镜下特征性表现就显得尤为重要,可能会对临床诊断提供有力的依据。降低此类病变在诊断上的盲目性,提高回盲部溃疡性病变病因确诊率。