What is diverticular colitis?

Diverticular colitis is the term used to describe a particular pattern of active chronic inflammation in the sigmoid colon affected by diverticular disease, namely the occurrence of luminal mucosal inflammation, whether or not there is evidence of inflammation within and/or around the diverticula themselves. The pathogenesis remains uncertain but is almost certainly multifactorial. In some cases mucosal prolapse, faecal stasis and relative mucosal ischaemia have been implicated as important pathogenetic factors, whilst other cases are clearly the result of a mass effect caused by subserosal peridiverticulitis and suppuration. Symptoms and endoscopic findings are diverse. Histologically, the disease may vary from modest inflammatory changes with vascular ectasia, through classical mucosal prolapse changes, to florid active chronic inflammation, closely mimicking chronic inflammatory bowel disease, especially ulcerative colitis. Thus, accurate clinical and endoscopic correlation is vital for the attainment of the correct diagnosis. Diverticular colitis may respond well to treatment similar to that used for chronic inflammatory bowel disease, adding to the similarities of this disease, notably localised to the sigmoid colon, and ulcerative colitis. Indeed, in a few cases described in the literature, diverticular colitis may 'progress' to otherwise classical ulcerative colitis, suggesting, in some cases at least, a similar pathogenesis.     

The rectal biopsy appearances in Salmonella colitis

Rectal biopsies were examined from 22 patients with Salmonella infection of food-poisoning type and from seven patients with inflammatory bowel disease and coincidental Salmonella infection. In the former group the changes observed were mucosal oedema with acute inflammation of varying severity but with preservation of the crypt architecture. Crypt abscesses were present in a few cases but were usually localized in the crypt and mucus depletion only occurred with severe inflammation. These features are not specific and are similar to those seen in other types of infective colitis such as Shigella dysentery, gonococcal proctitis and amoebic colitis. In the majority of cases of infective colitis the appearances are usually sufficiently distinctive, however, to distinguish them from those seen in ulcerative colitis and Crohn's disease. The changes in the biopsies from the seven patients with coincidental Salmonella infection were in general those of the underlying idiopathic inflammatory bowel disease.     

Changes in neuropeptide-containing nerves in human colonic mucosa with inflammatory bowel disease

The distribution abnormality of vasoactive intestinal polypeptide-containing nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was immunohistochemically investigated in the colonic mucosa with inflammatory bowel disease (IBD) in relation to colonic glands and blood vessels In the lamina propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in severe inflammatory lesions. VIP-nerves were almost absent particularly around crypt abscesses. Even In resolving and quiescent UC, VIP-nerves still decreased, depending on the decrease of glands and blood vessels. On the other hand, both nerves Increased in some hypervascular lesions. In the uninvolved mucosa of UC, they did not change their distribution. In Crohn's disease, the distribution abnormality of both nerves resembled that of UC. These results suggest that the changes in VIP-and SP-nerve distributions in the mucosa with IBD are subsequent to mucosal inflammation and damage. However, these peptides are known to be immunoregulators, and their distribution abnormalities may induce the disorder of immunoregulation in the IBD mucosa and cause the mucosal damage and/or chronicity.     

Simple objective criteria for diagnosis of causes of acute diarrhoea on rectal biopsy.

AIM: To identify simple, objective, accurate histological criteria for distinguishing acute infective-type colitis, chronic idiopathic inflammatory bowel disease, and irritable bowel syndrome on rectal biopsy in patients with acute onset diarrhoea at first presentation, one to 10 weeks after onset. METHODS: Cell counts and measurements of mucosal architecture were made on initial rectal biopsies from 18 patients with acute infective-type colitis, 17 patients with first acute presentation of chronic idiopathic inflammatory bowel disease, and 23 patients with irritable bowel syndrome. The data were analysed by ANOVA and discriminant analysis. RESULTS: Lamina propria cells were mainly in the upper third in irritable bowel syndrome patients. Increased lamina propria cellularity, mainly in the middle third, and numbers of crypt intraepithelial neutrophils distinguished acute infective-type colitis from irritable bowel syndrome in 93% of cases. Chronic idiopathic inflammatory bowel disease differed from irritable bowel syndrome and acute infective-type colitis in a decreased number of crypts and altered crypt architecture. Chronic idiopathic inflammatory bowel disease showed higher lamina propria cellularity, especially in the basal third, with an increased number of lamina propria neutrophils. On discriminant analysis, crypt numbers distinguished 86% of the cases of chronic idiopathic inflammatory bowel disease from the other groups. CONCLUSION: At one week or more from onset, acute infective-type colitis is characterised by a superficial increase in lamina propria cellularity, with only a slight increase in the number of polymorphs. At this stage, chronic idiopathic inflammatory bowel disease is characterised by a transmucosal increase in cellularity together with crypt loss and architectural abnormality. Thus, measurement of mucosal architecture establishes simple, accurate, objective criteria for routine biopsy diagnosis of chronic idiopathic inflammatory bowel disease from acute infective-type colitis and irritable bowel syndrome at initial presentation, one to 10 weeks after onset.     

Met-enkephalins in patients with inflammatory bowel diseases

PurposeOpioid peptides provide a link between the neuroendocrine and immune systems. They modify the inflammatory process through their effect on the synthesis and secretion of cytokines and on the proliferation of leukocytes to the inflammatory lesion. The evaluation analyzed changes in free met-enkephalin concentration values in the serum and colon mucosal biopsy specimens of patients with inflammatory bowel disease (IBD).Material and MethodsIn serum and colon mucosal biopsy specimens, free met-enkephalin levels were determined in 43 patients with ulcerative colitis (UC) and 38 individuals with Crohn's disease (CD). The evaluation analyzed the effect of disease activity, inflammatory lesions of the colon and laboratory parameters, on the level of the investigated marker. The control group consisted of 45 healthy volunteers.ResultsSerum free met-enkephalin levels were depressed in patients with CD (85.4pg/ml) and UC (101.5pg/ml) as compared to the controls (119.4pg/ml). Met-enkephalin levels in colonic biopsies collected from inflammatory lesions in IBD patients were significantly higher as compared to sections without inflammatory lesions (6.59pg/mg vs. 2.89pg/mg, p < 0.01 in the CD group and 6.12pg/mg vs. 3.47pg/mg, p < 0.05 in the UC group) and their level correlated with disease activity.ConclusionsThe present investigation is the first study that demonstrates changes in free met-enkephalin levels in IBD that may play a role in the pathogenesis and course of the disease. Further studies are necessary to assess the anti-inflammatory effect of opioid peptides.     

A new approach using tissue alkaline phosphatase histochemistry to identify Crohn's disease

In the present study, we investigate intestinal alkaline phosphatase activity in mucosal biopsies in patients with inflammatory bowel disease. Crohn's disease influences the alkaline phosphatase activity in the intestine, increasing its activity. We present a histochemistry-based method for alkaline phosphatase that is useful for the identification of Crohn's disease and the differentiation of ulcerative colitis.     

Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease.

Previous studies have demonstrated the presence of much more marked macrophage heterogeneity in colonic mucosa affected by the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn's disease) than in normal mucosa. This study examines the morphology, distribution and phenotypic expression of mucosal macrophage-like cells in biopsies from patients with idiopathic inflammatory bowel disease in comparison with disease control samples from patients with colonic infection or ischaemia. Approximately 80% of macrophage-like cells in histologically normal mucosa co-express the antigens recognized by the monoclonal antibodies RFD1 (an interdigitating cell marker) and RFD7 (a marker for mature tissue macrophages). In idiopathic inflammatory bowel disease, the normal colonic macrophage population is partly replaced by cells staining positively with RFD7 alone, and, to a lesser extent, with RFD1+ dendritic cells. Sections from patients with infections and ischaemia exhibited epithelial HLA-DR positivity and infiltration of the lamina propria by a more heterogeneous population of macrophages than that seen in histologically normal mucosa. However, the displacement of the normal colonic macrophage phenotype by RFD7+ tissue macrophages occurred to a significantly greater extent in idiopathic inflammatory bowel disease than in disease control mucosa. A pathognomonic feature of the ulcerative colitis and Crohn's colitis sections was the clustering of RFD9+ epithelioid cells at the bases of disrupted crypts and adjacent to areas of mucosal damage. It is concluded that a degree of macrophage heterogeneity and macrophage infiltration can occur as a non-specific response to colonic mucosal damage. The distinctive feature of idiopathic inflammatory bowel disease mucosa is the almost complete replacement of the normal colonic mucosal macrophage population by tissue macrophages and epithelioid cells, and this phenomenon may be important in promoting the development of a chronic inflammatory state.     

Diamond-shaped'' crypts and mucosal elastin: elpful diagnostic features in biopsies of rectal prolapse

The biopsy diagnosis of prolapsing rectal mucosa syndrome can be difficult. We present two newly described features--'diamond-shaped' crypts and mucosal elastin--which appear to be helpful in histological diagnosis. Of 32 biopsies of prolapsing rectal mucosa syndrome, all showed diamond-shaped crypts or mucosal elastin, and 28 contained both. Control biopsies comprised cases of normal or irritable bowel syndrome (46), irradiation colitis and ischaemic colitis (16), inflammatory bowel disease (26), and adenomas (30). Mucosal elastin and 'diamond-shaped' crypts with distinctive scalloped edges, which were never seen in prolapse, were observed in half the cases of irradiation and ischaemic colitis. Diamond-shaped crypts were seen in one case of inflammatory bowel disease. Diamond-shaped crypts and elastin were seen in the base of adenomas large enough to cause localized prolapse, and in four biopsies from patients with irritable bowel syndrome, all of whom had given a history of straining at stool.     

How to Diagnose Chronic Rejection. A Study in Porcine Intestinal Allografts

Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.     

Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease

Previous studies on the frequency of intestinal mast cells and eosinophils in patients with inflammatory bowel disease yielded conflicting results. In the present morphometric study, we quantified mast cells and eosinophils in the lamina propria by histological and immunohistochemical methods in 64 patients suffering from Crohn's disease (33 cases) or ulcerative colitis (31 cases), and in 29 controls. Histological data from 206 biopsies were related to the presence of mucosal inflammation and clinical parameters. The number of eosinophils was increased in patients with inflammatory bowel conditions (mean ±  SE : 331 ± 44/mm²) as compared to controls (258 ± 27/mm²), and was dependent on disease activity and drug treatment. Mean mast cell numbers did not differ between patients and controls. However, a reduced mast cell number was found in toluidine blue-stained sections of actively inflamed tissue areas (143 ± 16/mm², versus 206 ± 18/mm² in non-inflamed tissue). Immunohistochemical studies using antibodies against the granule proteins tryptase and chymase suggest that this decrease in mast cell numbers is due to mast cell degranulation. The present data show that the number of intestinal mast cells and eosinophils is altered in patients with inflammatory bowel diseases, suggesting that both cell types are involved in the pathogenesis of chronic intestinal inflammation.     

Endoscopic and bioptic study of the upper gastrointestinal tract in Crohn's disease patients

In the present study, virtually all of 225 patients suffering from Crohn's disease of the lower gastrointestinal tract (small and/or large bowel) were subjected to endoscopic examination of the upper gastrointestinal tract (esophagus, stomach, duodenum); while histologic examination of the upper gastrointestinal tract was performed in a portion of the patients (54 initial esophageal, 221 initial gastric and 210 initial duodenal examinations). Statistical evaluation of the findings from the upper gastrointestinal tract revealed that: Endoscopic lesions were observed in the esophagus of 15%, the stomach of 49%, and the duodenum of 34% of the 225 Crohn's disease patients. Of the 54 patients from which esophageal biopsies were taken, 31 (57%) revealed histopathologic alterations. Of the 221 patients from which gastric biopsies were obtained, 60% revealed histopathologic alterations; the rate was 53% in the 210 patients from which duodenal biopsies were taken. Calculated from the present data, noncaseating granulomas, i.e., Crohn's disease, were present only in the stomach of 29.4% of the patients, only in the duodenum in 3.4% of patients, and in both the stomach and duodenum in 4.9% of patients. Gastric granulomas were confined to the region of the stomach body and fundus in 3.4% of the patients from which gastric biopsies were obtained and to the antrum in 15.6% of the respective patients. Both gastric regions were involved in 8.3% of the respective patients. The incidence of gastric granulomas was significantly increased in young patients, patients with enterocolic manifestations of Crohn's disease, and those with brief duration of disease. Patient sex or previous drug therapy had no effect on the incidence of granulomas. The most frequent endoscopic findings in the stomach of patients with Crohn's disease were mucosal edema, mucosal redness, and acute or chronic erosions. Only chronic erosions were of significant predictive value for the presence of granulomas, i.e., diagnosis of Crohn's disease. The most frequent endoscopic lesion in the duodenum was mucosal redness, followed by mucosal edema and aphthous lesions. Ulcers, stenosis, and mucosal redness had significant predictive values for the presence of granulomas.     

Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease

Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by prominent cellular infiltrates in the bowel wall. Chemokines are chemotactic cytokines that are able to promote leukocyte migration to areas of inflammation and are also able to initiate cell activation events. They have recently been implicated in the pathophysiology of many disease states. The aim of this study was to detail the degree and distribution of specific chemokines, interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, -2, and -3, and macrophage inflammatory protein (MIP)-1alpha and -1beta, in IBD mucosa. Thirty-nine patients were included, ten controls, 20 ulcerative colitis (UC), and nine Crohn's disease (CD), with a range of disease activity. Colonic mucosal biopsies were collected from UC, CD, and control patients and embedded in glycol methacrylate. Two-micrometre-thick sections were cut and stained using immunohistochemistry for chemokine protein expression. Sections were analysed using a light microscope. Expression of all types of chemokine protein was detected in colonic mucosa from both control and IBD patients. Patterns of staining between IBD patients and controls differed significantly, but CD and UC patients demonstrated similar patterns of staining. Individual chemokine expression was found to be significantly up-regulated in IBD when patients were compared with the non-diseased group in all areas of the mucosal sections. Up-regulated chemokine expression correlated with increasing activity of the disease. It is concluded that human colonic chemokine expression is non-selectively up-regulated in IBD. The results supported the hypothesis that the degree of local inflammation and tissue damage in UC and CD is dependent on local expression of specific chemokines within IBD tissues.     

Intercellular adhesion molecule-1 (ICAM-1) deficiency protects mice against severe forms of experimentally induced colitis

ICAM-1 (CD54), the ligand for LFA-1 and Mac-1, is up-regulated during inflammatory reaction on the activated vascular endothelium. To determine its role in intestinal inflammation, we induced acute experimental colitis in mice with a deleted ICAM-1 gene, by feeding them with 3% dextran sodium sulphate (DSS) in drinking water for 7 days. Chronic colitis was elicited by DSS similarly, followed by 2 weeks with water. In the acute phase of inflammation, ICAM-1-deficient mice exhibited a significantly lower mortality rate (5%) than control C57Bl/6J mice (35%). Control animals, but not the ICAM-1-deficient mice, exhibited diarrhoea and rectal bleeding. Histological examination of large-bowel samples evaluated the intensity of inflammatory changes, and type and extent of mucosal lesions. In the acute phase, 33.3% of samples from ICAM-1-deficient mice exhibited mucosal defects (flat and fissural ulcers), predominantly mild to moderate inflammatory infiltrate within the lamina propria mucosae and lower grades of mucosal lesions. Much stronger inflammatory changes were present in control animals, flat ulcers (sometimes multiple) and fissural ulcers being observed in 62.5% of samples. Mucosal inflammatory infiltrate was moderate to severe, typically with higher grades of mucosal lesions. In chronic colitis, smaller inflammatory changes were found in the large bowel. The two mouse strains differed, the chronic colitis being accompanied by an increased serum level of anti-epithelial IgA autoantibodies in C57Bl/6 control mice but not in ICAM-1-deficient mice. These findings provide direct evidence of the participation of ICAM-1 molecule in the development of experimentally induced intestinal inflammation.     

Cytokines and growth factor modulators in intestinal inflammation and repair

Breakdown in gastrointestinal mucosal integrity may be due to increased aggressive factors, including an excessive inflammatory response, decreased mucosal defence or a combination of the two. Our understanding of the control processes underlying these changes has rapidly expanded over the last decade and it is becoming clear that rather than being distinct elements, inflammation and repair are interrelated processes mediated by common cytokines and growth factors, with the division of factors as being a cytokine or a growth factor being somewhat artificial. The use of biological therapies, such as antibodies that cause receptor blockade or administering recombinant growth factors, has now progressed from the laboratory to the clinical arena. This review summarizes current thoughts on the use of these factors in general, but with particular emphasis on inflammatory bowel disease.     

What is the significance of muciphages in colorectal biopsies?

Muciphages (mucin‐containing macrophages), first described in 1966 by Azzopardi & Evans, are a common feature of biopsies of large intestinal mucosa, even in the absence of other abnormalities such as active inflammation or evidence of chronic inflammatory bowel disease. Should they be mentioned in diagnostic reports? Do muciphages reliably indicate previous mucosal disease, now quiescent? In the following articles, Salto‐Tellez & Price review what is known about muciphages and conclude that they reflect previous occult and clinically unimportant mucosal damage and that, in an otherwise normal colorectal mucosa, they have no diagnostic significance; and Shepherd draws attention to a wide range of clinically much more significant mucosal infiltrates that could be mistakenly regarded as muciphages and thus overlooked.     

What is the significance of muciphages in colorectal biopsies?

Muciphages (mucin‐containing macrophages), first described in 1966 by Azzopardi & Evans, are a common feature of biopsies of large intestinal mucosa, even in the absence of other abnormalities such as active inflammation or evidence of chronic inflammatory bowel disease. Should they be mentioned in diagnostic reports? Do muciphages reliably indicate previous mucosal disease, now quiescent? In the following articles, Salto‐Tellez & Price review what is known about muciphages and conclude that they reflect previous occult and clinically unimportant mucosal damage and that, in an otherwise normal colorectal mucosa, they have no diagnostic significance; and Shepherd draws attention to a wide range of clinically much more significant mucosal infiltrates that could be mistakenly regarded as muciphages and thus overlooked.     

Expression of T cell receptors alpha beta and gamma delta in the ileal mucosa of patients with Crohn''s disease and with spondylarthropathy.

The expression of the alpha beta and gamma delta heterodimer of the T cell receptor (TCR) was studied in normal human ileal mucosa or in ileal biopsies featuring Crohn's disease or acute and chronic spondylarthropathy-related gut inflammation. With an immunohistochemical technique we demonstrated that the increase of mucosal lymphocytes per mm mucosa in Crohn's disease and spondylarthropathy-related ileitis is exclusively due to expansion of the alpha beta + T cell compartment. In Crohn's disease and chronic ileitis observed in some spondylarthropathy patients the alpha beta + T cells were increased amongst intraepithelial lymphocytes (IEL). The lamina propria lymphocytes (LPL) were augmented in all studied inflammatory conditions. The gamma delta + T cells showed no changes in IEL or LPL and their proportions were not altered. They were evenly dispersed throughout the ileal mucosa and did not seem to participate in the inflammatory process. This study confirms that gamma delta T cells are a distinct subset in the intestinal mucosa. The increase in alpha beta + T cells suggests augmented mucosal antigen handling and involvement of the major histocompatibility complex in the pathogenesis of spondylarthropathy-related gut inflammation and Crohn's disease.     

Validation of 16S rDNA sequencing in microdissected bowel biopsies from Crohn's disease patients to assess bacterial flora diversity

The bowel flora is implicated in Crohn's disease (CD) pathogenesis but its precise role is still unclear. Several non-mutually exclusive hypotheses have been proposed: an unidentified persistent pathogen; excessive bacterial translocation; an immune system abnormality in response to normal bacteria; or a breakdown in the balance between protective and harmful bacteria. These hypotheses can be tested by identifying bacteria in specific microscopic bowel structures or lesions. The present paper describes a novel technique to assess bacterial flora diversity in bowel biopsies, by combining laser capture microdissection with broad-range 16S rDNA sequencing. Fifty-four samples comprising histologically normal and pathological mucosa, MALT, ulcers, submucosal lymphangiectasias, epithelioid granulomas, and lymph nodes were microdissected out of 30 bowel biopsies from five CD patients. Bacterial 16S rDNA was successfully amplified by PCR in all samples, and PCR products from 15 samples were selected for cloning and sequence analysis. A total of 729 bacterial DNA sequences were analysed, which could be attributed to six different phyla (Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, and Planctomycetes). DNA from typical bowel bacteria (Enterobacteriaceae, Clostridiales, Bacteroidetes, Fusobacteria) was detected in all microdissected areas. It was thus convincingly demonstrated that 16S rDNA sequencing can be combined with microdissection to study the bowel flora. However, no specific persistent pathogen causal for CD was identified. The results suggest that Enterobacteriaceae may initiate or colonize ulcers in CD. Translocation of bacteria through established mucosal lesions or as a result of increased permeability may be involved in the evolution towards chronic inflammation and in the establishment of persistent lesions. Further study is needed to confirm these preliminary findings.     

Elevated Serum Anti-Saccharomyces cerevisiae, Anti-I2 and Anti-OmpW Antibody Levels in Patients with Suspicion of Celiac Disease

OBJECTIVES: Expression of anti-Saccharomyces cerevisiae antibodies (ASCA) identifies patients and individuals at risk for Crohn's disease and has also been reported in 40-60% of celiac disease (CD) cases, suggesting a role of host response to enteric microbiota in the development of inflammatory lesions. In this prospective study in patients with suspicion of CD, we evaluate the frequency and association of ASCA to serological responses for other host microbial targets formally associated with Crohn's disease, including the Pseudomonas fluorescens associated sequence I2 and a Bacteroides caccae TonB-linked outer membrane protein, OmpW. METHODS: Small bowel mucosal biopsies were taken from 242 patients with suspicion of CD, their sera were tested for antibodies to tissue transglutaminase (tTG), ASCA, I2, and OmpW. Eighty adult healthy blood donors were used as controls. RESULTS: The diagnosis of CD was confirmed on biopsy in 134 cases. The occurrence of ASCA and I2 positivity was significantly higher in adult CD patients than in patients with non-CD disease. Anti-I2 levels in the sera were significantly higher in adult CD patients than in non-CD disease or the controls and anti-OmpW levels in CD and non-CD patients when compared to controls. Positive seroreactivity to OmpW seemed to increase with age. Of the CD patients, 90% were seropositive for at least one microbial antigen tested. CONCLUSIONS: This study demonstrates a mosaic of disease-related serological responses to microbial antigens in patients with CD. Immune responses to commensal enteric bacteria may play a role in the small intestine mucosal damage in CD.