Classification Of Inflammatory Bowel Disease Research Articles

Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Diagnosis and management of microscopic colitis syndrome.

Microscopic colitis syndrome consists of chronic watery diarrhea, a normal or near-normal gross appearance of the colonic mucosa, and a specific histologic picture described as either lymphocytic colitis or collagenous colitis. The cause of microscopic colitis is unknown, but recent work suggests some immunologic similarities to celiac disease, suggesting that luminal antigens may be important in its pathogenesis. Diarrhea in microscopic colitis seems to be directly related to the extent of inflammation, suggesting that inflammatory mediators are responsible for reduced water absorption by the colon. Microscopic colitis is a frequent diagnosis in patients with chronic diarrhea seen at referral centers. It is often associated with other immune-mediated conditions and frequently is complicated by fecal incontinence. The differential diagnosis is broad, comprising all causes of watery diarrhea. Evaluation is straightforward with the key aspect being review of colon biopsy specimens by an experienced pathologist. Treatment is still being defined: symptomatic management with antidiarrheal agents, 5-aminosalicylate drugs, corticosteroids, especially budesonide, bile acid-binding resins, and bismuth subsalicylate all can be effective. The prognosis is good with no evidence of conversion to classic inflammatory bowel disease or of development of neoplasia over time.

Recent advances in the diagnosis and classification of inflammatory bowel disease.

The availability of an increasing number of inflammatory bowel disease (IBD)-specific serologic antibodies, the discovery of disease-susceptibility genes, the introduction of pharmacogenetic markers, and the recent application of wireless capsule enteroscopy to the evaluation of patients with IBD are providing new types of information that must be integrated with more traditional IBD paradigms. The challenge facing researchers and clinicians is to determine how to incorporate these potentially clinically relevant insights into our understanding of disease pathogenesis and to define the spectrum of potential applications to the management of patients with IBD. The ultimate diagnostic and predictive value of these tests will likely be optimized when they are applied in combination, rather than individually. As the clinical relevance of this expanding diagnostic armamentarium is defined, it is hoped that these tests will enable clinicians not only to diagnose IBD accurately but also to determine disease patterns prospectively, suggest prognoses, and allow for individualization of therapeutic regimens.

Small bowel magnetic resonance imaging for inflammatory bowel disease.

The presented concept of hydro-magnetic resonance imaging (MRI) using a 2.5% mannitol solution as an orally applicable intraluminal contrast agent is a meaningful, reproducible, and reliable imaging method for the depiction of the small bowel. Especially in patients with Crohn's disease, hydro-MRI is the imaging method of first choice because hydro-MRI offers the advantage of a superior depiction of the inflamed bowel wall and the extramural complications of this disease without radiation exposure. In addition, hydro-MRI allows for a reliable assessment of the inflammatory activity, especially for the differentiation between an active and an inactive (scarred) stenosis. In particular, the mural enhancement, the length as well as the wall thickness of inflamed bowel segments, are considered to be significant MR parameters for the determination of the activity of Crohn's disease. Hydro-MRI of the colon is suitable for the depiction of pathologic changes in ulcerative colitis, but in contrast to Crohn's disease, the assessment of disease activity by hydro-MRI is unreliable in ulcerative colitis, probably because of the low spatial resolution (mucositis in ulcerative colitis vs. transmural inflammation in Crohn's disease). Hydro-MRI does not allow a reliable classification of inflammatory bowel diseases, but in ambiguous cases, hydro-MRI may provide helpful information for the differentiation of Crohn's disease and ulcerative colitis. There are no data of larger patient groups published regarding MR findings in inflammatory bowel diseases besides Crohn's disease and ulcerative colitis, but hydro-MRI is a promising imaging tool for these entities, which should be assessed in additional studies.

Colonic CD8 and γδ T-cell infiltration with epithelial damage in children with autism

Objectives: We have reported colitis with ileal lymphoid nodular hyperplasia (LNH) in children with regressive autism. The aims of this study were to characterize this lesion and determine whether LNH is specific for autism. Methods: Ileo-colonoscopy was performed in 21 consecutively evaluated children with autistic spectrum disorders and bowel symptoms. Blinded comparison was made with 8 children with histologically normal ileum and colon, 10 developmentally normal children with ileal LNH, 15 with Crohn’s disease, and 14 with ulcerative colitis. Immunohistochemistry was performed for cell lineage and functional markers, and histochemistry was performed for glycosaminoglycans and basement membrane thickness. Results: Histology demonstrated lymphocytic colitis in the autistic children, less severe than classical inflammatory bowel disease. However, basement membrane thickness and mucosal γδ cell density were significantly increased above those of all other groups including patients with inflammatory bowel disease. CD8+ density and intraepithelial lymphocyte numbers were higher than those in the Crohn’s disease, LNH, and normal control groups; and CD3 and plasma cell density and crypt proliferation were higher than those in normal and LNH control groups. Epithelial, but not lamina propria, glycosaminoglycans were disrupted. However, the epithelium was HLA-DR–, suggesting a predominantly TH2 response. Interpretation: Immunohistochemistry confirms a distinct lymphocytic colitis in autistic spectrum disorders in which the epithelium appears particularly affected. This is consistent with increasing evidence for gut epithelial dysfunction in autism. (J Pediatr 2001;138:366-72)

Diagnosis and classification of inflammatory bowel disease.

Diagnosis and classification of inflammatory bowel disease.

MUCOSAL T-CELL REACTIVITY IN CHILDREN WITH INTESTINAL INFLAMMATION PREDICTS DIAGNOSIS OF CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS (UC)

A firm diagnosis CD or UC is difficult to establish in children during the initial stages of disease. Some are classified as inflammatory bowel disease (IBD) (indeterminate for CD or UC) or non-specific chronic inflammation (NSCI). T-cells are pivotal to all forms of chronic inflammation but each form may be associated with unique T-cell reactivity. If so, such reactivity may help predict which IBD or NSCI children have CD or UC. Aims: 1) Characterize mucosal T-cell reactivity from normal, CD, and UC mucosa; 2) Determine its diagnostic value in patients with IBD and NSCI for CD and UC. 29 children with CD, 11 UC and 9 control were studied to develop standards; 14 IBD, and 18 NSCI children were used as test groups. Endoscopic colonic biopsies were cultured with IL-2 (20 U/ml) to generate T-cell lines, and T-cell numbers were counted at 2, 3 and 4 weeks. Results: At 3 weeks, CD T-cell growth was higher (p<0.001) than that of UC and normal; UC T-cell growth was lower (p<0.01) than that of normal. When mean ± ISD of cell count was used as a cut off, the following results were obtained: Table In the combined CD plus UC group, 78% of patients agreed, while only 2% disagreed with established diagnoses. When test groups were evaluated, of 14 IBD patients 9 were predicted to be CD and 1 UC; of 18 NSCI patients 3 were predicted to be CD, and 6 UC; this allowed reclassification in 60% of patients. Conclusions: 1) Mucosal T-cell reactivity significantly differs among CD, UC and normal 2) In the absence of typical clinical and pathological features, individual T-cell growth patterns help establishing the true nature of gut inflammation and allow early classification of IBD and NSCI patients into CD or UC.

Studies on the enteropathy associated with primary hypogammaglobulinaemia.

Twelve patients with primary hypogammaglobulinaemia with diarrhoea not associated with known microbial pathogens were investigated. Histological evidence of inflammation was common in the stomach and jejunum. Moreover, eight of 10 patients undergoing colonoscopy had low grade 'microscopic colitis' with raised intraepithelial lymphocytes and an intact crypt architecture. Five of 12 patients had small intestinal inflammation on 111indium leucocyte scintigrams and all had increased faecal excretion (normal < 1%) of 111indium (over four days), which varied in intensity from mild (faecal excretion of 111indium = 1-3%) to that comparable with moderately active (7-14.5%) Crohn's disease. Three patients had small intestinal strictures superficially resembling Crohn's disease. Histologically, however, these lacked characteristic diagnostic features of Crohn's disease in two and the third patient had non-steroidal anti-inflammatory drug induced diaphragm like strictures. Six of seven who were most severely symptomatic were successfully treated with an elemental diet with rapid improvement of symptoms. The faecal excretion of 111indium was repeated in five and all improved but histologically the colitis remained unchanged. These studies show that some patients with primary hypogammaglobulinaemia have intestinal inflammation unlike that found in classic inflammatory bowel disease. Elemental diet is a useful temporary measure in the treatment of these patients.

Colitis caused by food allergy in infants.

Thirteen infants with eosinophilic colitis caused by food allergy were reviewed after five to 10 years. By the age of 5 years most foods were tolerated. The colon was normal in the one child re-examined. There was an atopic association, but no family history of classical inflammatory bowel disease. Allergic colitis is a temporary disorder of early childhood.

An Investigation into the Validity of the Present Classification of Inflammatory Bowel Disease

To assess the validity of the present subdivision of patients with inflammatory bowel disease into those with Crohn's disease of the small bowel or of the colon and those with ulcerative colitis, 252 patients with inflammatory bowel disease have been studied by questionnaire and case note review. One hundred and seventy-two variables concerning the nature and frequency of symptoms in remission and relapse, the incidence of complications and results of investigation have been analysed by computer. As expected, there were many highly significant variables between patients with ulcerative colitis and those with Crohn's disease of the small bowel. The latter showed evidence of a more severe disease course with more complications. There were similar, although less marked, differences between patients with Crohn's disease of the colon and those with Crohn's disease of the small bowel. There were very few differences in disease course between patients with Crohn's disease of the colon and those with ulcerative colitis. The results suggest that while separate classification of patients with Crohn's disease of the small bowel is justified on clinical grounds, the present separation of patients with disease confined to the colon into groups labelled ulcerative colitis or Crohn's disease of the colon is not. Alternative methods of classification should therefore be investigated.

Management of inflammatory bowel disease: an effective and concise approach.

Experience in treating 100 patients with inflammatory bowel disease, for periods ranging from one to 15 years, is reviewed. A concise clinical classification of inflammatory bowel disease, correlated with a method of management, is presented. Relative rates of operation appear to be reduced over previously reported series: among chronic ulcerative colitis patients, 11 per cent had major precedures; for Crohn's disease, 36 per cent.

Crohn's Colitis: A Diagnostic Dilemma

Considerable confusion surrounds the condition of Crohn's disease of the colon, and delay in diagnosis is frequent. In this paper the classification of colitis is considered, and the reasons for this delay and the frequency of misdiagnosis are discussed.