https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60750-8.pdf

Inflammatory bowel disease: cause and immunobiology

The management of inflammatory bowel disease represents a key component of clinical practice for members of the British Society of Gastroenterology (BSG). There has been considerable progress in management strategies affecting all aspects of clinical care since the publication of previous BSG guidelines in 2004, necessitating the present revision. Key components of the present document worthy of attention as having been subject to re-assessment, and revision, and having direct impact on practice include: The data generated by the nationwide audits of inflammatory bowel disease (IBD) management in the UK in 2006, and 2008. The publication of 'Quality Care: service standards for the healthcare of people with IBD' in 2009. The introduction of the Montreal classification for Crohn's disease and ulcerative colitis. The revision of recommendations for the use of immunosuppressive therapy. The detailed analysis, guidelines and recommendations for the safe and appropriate use of biological therapies in Crohn's disease and ulcerative colitis. The reassessment of the role of surgery in disease management, with emphasis on the importance of multi-disciplinary decision-making in complex cases. The availablity of new data on the role of reconstructive surgery in ulcerative colitis. The cross-referencing to revised guidelines for colonoscopic surveillance, for the management of metabolic bone disease, and for the care of children with inflammatory bowel disease. Use of the BSG discussion forum available on the BSG website to enable ongoing feedback on the published document http://www.bsg.org.uk/forum (accessed Oct 2010). The present document is intended primarily for the use of clinicians in the United Kingdom, and serves to replace the previous BSG guidelines in IBD, while complementing recent consensus statements published by the European Crohn's and Colitis Organisation (ECCO) https://www.ecco-ibd.eu/index.php (accessed Oct 2010).

https://gut.bmj.com/content/gutjnl/60/5/571.full.pdf

Guidelines for the management of inflammatory bowel disease in adults

aDepartment of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal bIBD Unit, DIMEC, University of Bologna, Bologna, Italy cDepartment of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel dGastrointestinal Unit ASST Fatebenefratelli Sacco—University of Milan—Milan, Italy eIBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita’ Cattolica del Sacro Cuore, Rome, Italy fDepartment of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain gDepartment of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark hFirst Department of Medicine, Semmelweis University, Budapest, Hungary iIBD Unit, St Mark’s Hospital, Middlesex, UK jDepartment of Gastroenterology, University Hospital of Ghent, Ghent, Belgium kInstitute of Pathology, Medical University of Graz, Graz, Austria lDepartment of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK mUnit of General Surgery, Second University of Naples, Napoli, Italy nMaria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland oDepartment of Medicine, University of Cambridge, Cambridge, UK pImperial College London; Chelsea and Westminster Hospital, London, UK qDepartment of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

/pdf/third-european-evidence-based-consensus-on-diagnosis-and-2g4pj48jlg.pdf

Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders.

BACKGROUND Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. AIM To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. METHODS A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. RESULTS Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. CONCLUSION A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.

/pdf/a-reproducible-grading-scale-for-histological-assessment-of-3yw96sc1h9.pdf

A reproducible grading scale for histological assessment of inflammation in ulcerative colitis

https://www.spg.pt/wp-content/uploads/2015/11/2013-JCC_ECCO_Endoscopy_Consensus_10_2013_inPress.pdf

European evidence based consensus for endoscopy in inflammatory bowel disease

The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and 'pouchitis' resistant to all conventional medical therapy. In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids, 5-aminosalicylic acid, and oral immunosuppressive therapy together with 1 patient with 'pouchitis' unresponsive to repeated courses of antibiotics, topical corticosteroids, and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema. Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals. Seven of 12 patients with ulcerative colitis improved. There was a strong correlation between clinical and histologic improvement (p < 0.005). Four of 12 patients showed no response. Three of these required colectomy, two of whom had more extensive disease than had previously been documented. The patient with pouchitis showed improvement in symptoms and 'pouchoscopy' appearance but not in histologic score. Cyclosporin blood concentrations were very low and side effects negligible. Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis. A controlled trial would now seem warranted.

Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'.

'Cap polyposis' is a poorly recognised condition with distinct clinical, sigmoidoscopic, and pathological features that may be confused with other inflammatory conditions of the large intestine including pseudomembranous colitis and idiopathic chronic inflammatory bowel disease. The pathogenesis is unknown but on the basis of the characteristic histological appearances, which are similar to those seen in situations where mucosal prolapse is the underlying mechanism, it has been suggested that the latter may be an important aetiological factor. Two cases are described. Histological features in the first (presence of intramucosal elastin) and clinical features in the second (rectal prolapse) support the above hypothesis.

https://gut.bmj.com/content/gutjnl/34/4/562.full.pdf

Cap polyposis--an unusual cause of diarrhoea.

BACKGROUND/AIMS: Regional differences in the biology of the colonic epithelium may determine the extent of involvement by ulcerative colitis. Novel monoclonal antibodies (MAbs) were used in this study to investigate regional heterogeneity in the colonic mucosa. METHODS: MAbs generated using a method of tolerisation against common antigens in the proximal colon and distal colon were used for immunoperoxidase staining, comparative histochemistry, immunoblotting, and slot-blot analysis. RESULTS: The colon specific MAbs 5F1 (IgG3) and 6G4 (IgM) stained goblet cell contents throughout the normal distal colon but staining was markedly reduced in the proximal colon (p < 0.0001). In the distal colon of patients with ulcerative colitis, whether quiescent or actively inflamed, reactivity was reduced compared with controls (p < 0.05, p < 0.001 respectively). By contrast, an overall increase in staining was seen in the uninflamed proximal colon in ulcerative colitis compared with controls (p < 0.02). Comparative staining with high iron diamine and biochemical analyses indicated that MAb 6G4 was reactive with mucin bearing sulphate or O-acetylated sialic acid groups, or both. CONCLUSIONS: Regional differences in the staining characteristics of normal colonic mucin have been shown using novel monoclonal antibodies. The pattern of mucin expression throughout the colon in ulcerative colitis is altered even in the absence of histological changes.

https://gut.bmj.com/content/gutjnl/40/2/234.full.pdf

Altered expression of mucins throughout the colon in ulcerative colitis.

Background: Expression of adhesion molecules is increased in inflamed colonic mucosa, but little is known about their functional activity in vascular endothelium.Method: We studied in situ nitroblue tetrazolium reducing activity and expression of E-selectin, ICAM-1, CD31, and VCAM-1 by immunohistochemistry in the same biopsy specimen in controls and patients with ulcerative colitis (UC).Results: VCAM-1 expression was negative in mucosal vessels. E-selectin-positive vessels were significantly increased in endoscopically active colitis compared with normal mucosa. ICAh4-1-positive vessels were consistently found in normal, quiescent UC and active UC. 031-positive vessels were not significantly increased in quiescent UC and active UC compared with control. Only E-selectin significantly correlated with the histologic grade of inflammation. Nitroblue tetrazolium reducing vessels were increased in inflamed mucosa, and these vessels expressed ICAM-1 and CD31. E-selectin positivity in association with nitroblue t...

Adhesion Molecule Expression on Vascular Endothelium and Nitroblue Tetrazolium Reducing Activity in Human Colonic Mucosa

Cytomegalovirus (CMV) colitis may cause symptoms and signs identical to those of idiopathic inflammatory bowel disease. Although difficult to diagnose with certainty, the histological finding of cytomegalovirus inclusions in tissue from a case of suspected inflammatory bowel disease is strongly suggestive. CMV colitis is an entity almost entirely confined to cases of severe immunosuppression. The case of a 79 year old widower who was admitted to hospital with symptoms suggestive of inflammatory bowel disease is presented. Despite medical treatment his condition worsened and he developed toxic dilatation of the colon requiring colectomy. Histological examination showed a mild superficial pancolitis, with focal severe inflammation, deep fissuring ulceration, and pseudopolyposis. Abundant CMV inclusions were seen in cells associated with the ulcerating inflammatory tissue. A diagnosis of indeterminate colitis with CMV was made. The patient's condition worsened after surgery and he died a few days later despite intensive treatment, including antiviral chemotherapy directed against CMV. After death HIV serology was found to be positive. Regardless of the age and perceived lifestyle of the patient, a diagnosis of CMV colitis in someone not known to be immunosuppressed raises the possibility of HIV infection.

https://gut.bmj.com/content/gutjnl/37/1/148.full.pdf

A P Campbell

Papers

Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'.

Cap polyposis--an unusual cause of diarrhoea.

Altered expression of mucins throughout the colon in ulcerative colitis.

Adhesion Molecule Expression on Vascular Endothelium and Nitroblue Tetrazolium Reducing Activity in Human Colonic Mucosa

HIV associated cytomegalovirus colitis as a mimic of inflammatory bowel disease.