Colites microscopiques--quoi de neuf ? [Microscopic colitis: update 2014].

Microscopic colitis, which includes lymphocytic colitis and collagenous colitis, represents a frequent cause of chronic watery diarrhea especially in the elderly population. Several medications, such as nonsteroidal antiinflammatory drugs, proton pump inhibitors or antidepressants, as well as cigarette smoking have been recognized as risk factors for microscopic colitis. The diagnosis of microscopic colitis is based on a macroscopically normal ileo-colonoscopy and several biopsies from the entire colon, which demonstrate the pathognomonic histopathologic findings. Therapy is mainly based on the use of budesonide. Other medications, such as mesalazine, cholestyramine and bismuth, have been evaluated as well but the evidence is less solid.

Chronic colitis associated with HIV infection can be related to intraepithelial infiltration of the colon by CD8+T lymphocytes

Gastrointestinal complications in AIDS patients with diarrhoea are common clinical manifestations, frequently diagnosed by colonoscopy as non-specific colitis. We retrospectively study colon biopsies diagnosed as chronic colitis associated with HIV (CCH). Biopsies were sorted as patients with AIDS (serum CD4 < 200 cell/mm(3)) but without any clear infectious process (n = 12) and patients without HIV infection (n = 24). There are low numbers of CD4+ T lymphocytes in lamina propria of AIDS patients, but CD8+ T populations in this area appear to be similar in all studied groups, regardless of HIV infection or laboratory evidence of a specific agent. We found the clear evidence of CD8+ T cells infiltration in colonic mucosa in HIV patients with microscopic colitis. An imbalance of lymphocyte subpopulations in the colon, both in the lamina propria and epithelium, could result in an intraepithelial CD8 infiltration, involved in the pathogenesis of CCH in AIDS patients.

Le Coliti Microscopiche nei soggetti con diarrea non ematica: uno studio prospettico

Introduzione: le Coliti Microscopiche, altrimenti note come Colite Collagena e Colite Linfocitica, sono disordini infiammatori cronici del colon che causano diarrea e colpiscono più frequentemente donne in età avanzata e soggetti in terapia farmacologica. Negli ultimi anni la loro incidenza sembra aumentata in diversi paesi occidentali ma la prevalenza in Italia è ancora incerta. Scopo: il presente studio prospettico e multicentrico è stato disegnato per valutare la prevalenza delle CM in pazienti sottoposti a colonscopia per diarrea cronica non ematica. Pazienti e metodi: dal Maggio 2010 al Settembre 2010 sono stati arruolati consecutivamente tutti i soggetti adulti afferenti in due strutture dell’area metropolitana milanese per eseguire una pancolonscopia. Nei soggetti con diarrea cronica non ematica sono state eseguite biopsie multiple nel colon ascendente, sigma e retto nonché in presenza di lesioni macroscopiche. Risultati: delle 8008 colonscopie esaminate 265 sono state eseguite per diarrea cronica; tra queste, 8 presentavano informazioni incomplete, 52 riscontri endoscopici consistenti con altri disordini intestinali (i.e. IBD, tumori, diverticoliti). 205 colonscopie sono risultate sostanzialmente negative, 175 dotate di adeguato campionamento microscopico (M:F=70:105; età mediana 61 anni). L’analisi istologica ha permesso di documentare 38 nuovi casi di CM (M:F=14:24; età mediana 67.5 anni): 27 CC (M:F=10:17; età mediana 69 anni) e 11 CL (M:F=4:7; età mediana 66 anni). In altri 25 casi sono state osservate alterazioni microscopiche prive dei sufficienti requisiti per la diagnosi di CM. Conclusioni: nel presente studio l’analisi microscopica del colon ha identificato la presenza di CM nel 21,7% dei soggetti con diarrea cronica non ematica ed indagine pancolonscopica negativa. Lo studio microscopico del colon è pertanto un passo diagnostico fondamentale per il corretto inquadramento diagnostico delle diarree croniche, specialmente dopo i 60 anni di età. Ampi studi prospettici e multicentrici dovranno chiarire ruolo e peso dei fattori di rischio associati a questi disordini.

Inhibition Of Tumor Necrosis Factor-alpha And Cyclooxigenase-2 By Isatin: A Molecular Mechanism Of Protection Against Tnbs-induced Colitis In Rats.

Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and anti-inflammatory effects. Due to its findings, we evaluated whether this alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH rats, aged 8 weeks old) were induced colitis through a rectal administration of 2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the rectum of the animals. The rats were divided into two major groups: non-colitic and colitic. The colitic group was sub-divided into 6 groups (10 animals per group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of avoiding the increase in TNF-α, COX-2 and PGE₂ levels when compared to the colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were also capable of preventing the decrease in IL-10 levels comparing with the colitic non-treated group. The levels of MPO, (an indirect indicator of neutrophil presence), were also maintained lower than those of the colitic non-treated group. Isatin also prevented the decrease of SOD activity and increase of GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion, both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa against the injury caused by TNBS, through the combination of antioxidant and anti-inflammatory properties, which, together, showed a protective activity of the indole alkaloid Isatin.

Quality of life in patients with ileal pouch for ulcerative colitis

INTRODUCTION:proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical procedure for the treatment of ulcerative colitis (UC) and is associated with the prospect of cure. Experience gained over the years has demonstrated the occurrence of a high number of complications as well as bowel disorders that can compromise quality of life (QoL).OBJECTIVE:evaluate QoL in patients with IPAA for ulcerative colitis.PATIENTS AND METHODS:the Inflammatory Bowel Disease Questionnaire (IBDQ) was used to assess QoL in patients with IPAA after its validation in Portuguese.RESULTS:thirty-one patients submitted to IPAA by the same group of professionals were evaluated. QoL was classified as regular in all domains evaluated (intestinal and systemic symptoms and emotional and social aspects). There were no differences in relation to gender, type of pouch or postoperative time. However, elderly patients showed a tendency toward lower scores. Having a professional activity was associated with higher scores in systemic symptoms and social aspects (p < 0.05). Patients with ileostomy showed lower values in the domains of systemic symptoms, emotional and social aspects (p <0.05).CONCLUSION:in all domains assessed, patients with IPAA for UC had QoL classified as regular. Ileostomy and lack of professional activity negatively influenced QoL.

Intestinal Anti-Inflammatory Activity of Baccharis dracunculifolia in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Baccharis dracunculifolia DC (Asteraceae) is a Brazilian medicinal plant popularly used for its antiulcer and anti-inflammatory properties. This plant is the main botanical source of Brazilian green propolis, a natural product incorporated into food and beverages to improve health. The present study aimed to investigate the chemical profile and intestinal anti-inflammatory activity of B. dracunculifolia extract on experimental ulcerative colitis induced by trinitrobenzenosulfonic acid (TNBS). Colonic damage was evaluated macroscopically and biochemically through its evaluation of glutathione content and its myeloperoxidase (MPO) and alkaline phosphatase activities. Additional in vitro experiments were performed in order to test the antioxidant activity by inhibition of induced lipid peroxidation in the rat brain membrane. Phytochemical analysis was performed by HPLC using authentic standards. The administration of plant extract (5 and 50 mgkg(-1)) significantly attenuated the colonic damage induced by TNBS as evidenced both macroscopically and biochemically. This beneficial effect can be associated with an improvement in the colonic oxidative status, since plant extract prevented glutathione depletion, inhibited lipid peroxidation and reduced MPO activity. Caffeic acid, p-coumaric acid, aromadendrin-4-O-methyl ether, 3-prenyl-p-coumaric acid, 3,5-diprenyl-p-coumaric acid and baccharin were detected in the plant extract.

Intestinal mucosa-associated microflora in ulcerative colitis patients before and after restorative proctocolectomy with an ileoanal pouch

PURPOSE: This study was designed to identify the mucosa-associated microflora in patients with severe ulcerative colitis before and after restorative proctocolectomy with ileoanal pouch construction in comparison with historic controls. METHODS: Ten patients with a diagnosis of ulcerative colitis were evaluated. Mucus was collected during colonoscopy from all segments of the colon and terminal ileum before surgery, and from the ileal pouch two and eight months after ileostomy closure. The prevalence and mean concentration of the mucosa-associated microflora were compared over time and with historic controls. RESULTS: Veillonella sp was the most prevalent bacterium in patients and controls. Klebsiella sp was significantly more prevalent in the ileum of controls, was not found in patients with ulcerative colitis, and after proctocolectomy returned to values found in controls. Some bacteria such as Enterobacter sp, Staphylococcus sp (coag-), Bacteroides sp (npg), Lactobacillus sp, and Veillonella sp had higher mean concentrations in the ileal pouch of patients after surgery than in controls. CONCLUSION: No bacterium was identified that could be exclusively responsible for the maintenance of the inflammatory process. The mucosa-associated microflora of patients with ulcerative colitis underwent significant changes after proctocolectomy with ileal pouch construction and returned to almost normal values for some bacteria.

Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease

Background and aims: Recent studies on appendicectomy rates in ulcerative colitis and Crohn's disease have generally not addressed the effect of appendicectomy on disease characteristics. The aims of this study were to compare appendicectomy rates in Australian inflammatory bowel disease patients and matched controls, and to evaluate the effect of prior appendicectomy on disease characteristics. Methods: Patients were ascertained from the Brisbane Inflammatory Bowel Disease database. Controls matched for age and sex were randomly selected from the Australian Twin Registry. Disease characteristics included age at diagnosis, disease site, need for immunosuppression, and intestinal resection. Results: The study confirmed the significant negative association between appendicectomy and ulcerative colitis (odds ratio (OR) 0.23, 95% confidence interval (Cl) 0.14-0.38; p

IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis

Objective - We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis. Patients and methods - A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes. Results - Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03), but a higher likelihood of responding to AZT (P=0.05). A significant synergism was observed between IL23R C2370A and EIMs with respect to nonresponse to 5-ASA (P=0.03). Conclusion - Besides extent of disease and age at disease onset, the presence of EIMs may be a marker of refractoriness to 5-ASA, corticosteroids, and AZT. IL23R SNPs are associated both with EIMs and with nonresponse to 5-ASA and corticosteroids.

Development of TNBS-induced colitis: animal model to test new pharmacological approaches

IBD is a gastro-intestinal disorder marked with chronic inflammation of intestinal epithelium, damaging mucosal tissue and manifests into several intestinal and extra-intestinal symptoms. Currently used medical therapy is able to induce and maintain the patient in remission, however no modifies or reverses the underlying pathogenic mechanism. The research of other medical approaches is crucial to the treatment of IBD and, for this, it´s important to use animal models to mimic the characteristics of disease in real life. The aim of the study is to develop an animal model of TNBS-induced colitis to test new pharmacological approaches. TNBS was instilled intracolonic single dose as described by Morris et al. It was administered 2,5% TNBS in 50% ethanol through a catheter carefully inserted into the colon. Mice were kept in a Tredelenburg position to avoid reflux. On day 4 and 7, the animals were sacrificed by cervical dislocation. The induction was confirmed based on clinical symptoms/signs, ALP determination and histopathological analysis. At day 4, TNBS group presented a decreased body weight and an alteration of intestinal motility characterized by diarrhea, severe edema of the anus and moderate morbidity, while in the two control groups weren’t identified any alteration on the clinical symptoms/signs with an increase of the body weight. TNBS group presented the highest concentrations of ALP comparing with control groups. The histopathology analysis revealed severe necrosis of the mucosa with widespread necrosis of the intestinal glands. Severe hemorrhagic and purulent exsudates were observed in the submucosa, muscular and serosa. TNBS group presented clinical symptoms/signs and histopathological features compatible with a correct induction of UC. The peak of manifestations became maximal at day 4 after induction. This study allows concluding that it’s possible to develop a TNBS induced colitis 4 days after instillation.

Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis

Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.

Pyoderma Gangrenosum Associated with Sclerosing Cholangitis, Type 1 Diabetes Mellitus and Ulcerative Colitis

We describe the case of a 22-year-old black female with type 1 diabetes mellitus diagnosed when she was 12 years old. She first presented (March 1994) with pustules and ulcerations on the upper and lower limbs, trunk and scalp at the age 17. The diagnosis of pyoderma gangrenosum was made. Since presentation, changes in liver function were detected and subsequent study led to the diagnosis of sclerosing cholangitis. The diagnosis of ulcerative colitis was made after colonoscopy. Partial response was obtained with minocycline and clofazimine, but treatment with 5-aminosalicylic acid achieved no improvement of the ulcerations. Liver transplantation, followed by immunosuppressive therapy led to complete regression of the cutaneous lesions.

Pyoderma gangrenosum and ulcerative colitis in the tropics

Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.