H Wenzl

Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis.

Background: In patients with ulcerative colitis (UC), alterations of the intestinal microbiota, termed dysbiosis, have been postulated to contribute to intestinal inflammation. Fecal microbiota transplantation (FMT) has been used as effective therapy for recurrent Clostridium difficile colitis also caused by dysbiosis. The aims of the present study were to investigate if patients with UC benefit from FMT and if dysbiosis can be reversed. Methods: Six patients with chronic active UC nonresponsive to standard medical therapy were treated with FMT by colonoscopic administration. Changes in the colonic microbiota were assessed by 16S rDNA–based microbial community profiling using high-throughput pyrosequencing from mucosal and stool samples. Results: All patients experienced short-term clinical improvement within the first 2 weeks after FMT. However, none of the patients achieved clinical remission. Microbiota profiling showed differences in the modification of the intestinal microbiota between individual patients after FMT. In 3 patients, the colonic microbiota changed toward the donor microbiota; however, this did not correlate with clinical response. On phylum level, there was a significant reduction of Proteobacteria and an increase in Bacteroidetes after FMT. Conclusions: FMT by a single colonoscopic donor stool application is not effective in inducing remission in chronic active therapy–refractory UC. Changes in the composition of the intestinal microbiota were significant and resulted in a partial improvement of UC-associated dysbiosis. The results suggest that dysbiosis in UC is at least in part a secondary phenomenon induced by inflammation and diarrhea rather than being causative for inflammation in this disease.

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease

Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.

Incidence of inflammatory bowel disease in the province of Styria, Austria, from 1997 to 2007: A population-based study ☆

BACKGROUND The incidence of inflammatory bowel disease (IBD) varies widely between different countries. This large variation is also observed for the incidence of its main two forms, ulcerative colitis (UC) and Crohns disease (CD). Controversy exists whether IBD incidence is increasing, especially in western countries. Currently no data are available for Austria. This study therefore aimed to evaluate for the first time the incidence of IBD over an eleven-year period in Styria, a province of Austria with a population of 1.2 million. METHODS All patients with an initial diagnosis of IBD between 1997 and 2007, who were Styrian residents, were eligible for this retrospective study. Data were acquired from electronically stored hospital discharge reports and individual reports by patients and physicians. According to population density Styria was divided into two rural and one urban area. RESULTS Throughout the study period 1527 patients with an initial diagnosis of IBD were identified. The average annual incidence was 6.7 (95% CI 6.2-7.1) per 100,000 persons per year for CD and 4.8 (95% CI 4.5-5.2) for UC. The average annual incidence increased significantly (p<0.01) for both diseases during the 11 year study period. Median age at initial diagnosis was 29 years (range 3-87) for CD and 39 years (range 3-94) for UC. At diagnosis, 8.5% of all IBD patients were <18 years of age. The incidence of both CD and UC was significantly higher in the urban area than in rural areas (CD: 8.8, 95% CI 7.8-9.8 versus 5.5, 95% CI 4.7-6.4 and 5.9, 95% CI 5.3-6.7; [p<0.001]; UC: 5.8, 95% CI 5.1-6.6 versus 4.0, 95% CI 3.4-4.7 and 4.7, 95% CI 4.1-5.4; [p=0.04]). CONCLUSION We observed an overall increase in the incidence of ulcerative colitis and Crohns disease in a part of Austria during an eleven year period. IBD was more predominant in the largest urban area than in rural areas.

Opposing Roles of Prostaglandin D2 Receptors in Ulcerative Colitis

Proresolution functions were reported for PGD2 in colitis, but the role of its two receptors, D-type prostanoid (DP) and, in particular, chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2), is less well defined. We investigated DP and CRTH2 expression and function during human and murine ulcerative colitis (UC). Expression of receptors was measured by flow cytometry on peripheral blood leukocytes and by immunohistochemistry and immunoblotting in colon biopsies of patients with active UC and healthy individuals. Receptor involvement in UC was evaluated in a mouse model of dextran sulfate sodium colitis. DP and CRTH2 expression changed in leukocytes of patients with active UC in a differential manner. In UC patients, DP showed higher expression in neutrophils but lower in monocytes as compared with control subjects. In contrast, CRTH2 was decreased in eosinophils, NK, and CD3+ T cells but not in monocytes and CD3+/CD4+ T cells. The decrease of CRTH2 on blood eosinophils clearly correlated with disease activity. DP correlated positively with disease activity in eosinophils but inversely in neutrophils. CRTH2 internalized upon treatment with PGD2 and 11-dehydro TXB2 in eosinophils of controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595 improved, whereas the DP antagonist MK0524 worsened inflammation in murine colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2 on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue, where it may contribute to inflammation, whereas DP most likely promotes anti-inflammatory actions.

A case of opportunistic skin infection with Mycobacterium marinum during adalimumab treatment in a patient with Crohn's disease

Opportunistic infections, especially reactivation with M. tuberculosis, are major complications during treatment with anti-TNF agents. Infections with atypical mycobacteria like Mycobacterium marinum are rare and tend to turn into a difficult and prolonged course due to delayed diagnosis. This is the first case of M. marinum infection during adalimumab therapy in a patient with Crohns disease. The most important diagnostic step was a detailed medical history as PCR tested for M. tuberculosis and for atypical subspecies was false negative. Up to now a discontinuation of anti-TNF therapy has been recommended, however, there is no consensus about the reintroduction of biologicals after sufficient anti-infective therapy. In this patient anti-TNF therapy had to be reintroduced because of increasing activity with no relapse of M. marinum after a follow-up of 12 months.

Diarrhea in Chronic Inflammatory Bowel Diseases

Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohns disease, focusing on diarrhea.

The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis

Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown.

C. difficile-Infektionen (CDI) bei Patienten mit chronisch entzündlichen Darmerkrankungen (CED) rezidivieren häufig und sind schwierig zu behandeln

Hintergrund:C. difficile wird bei CED-Patienten haufiger nachgewiesen als bei Personen, die nicht an einer CED erkrankt sind. Die Relevanz dieser Infektion hinsichtlich der Krankheitsaktivitat und der Symptomatik der Patienten ist jedoch unklar. Ziele dieser Studie waren: Methoden: CED-Patienten der Universitatsklinik fur Innere Medizin, Graz, die im Zeitraum von 2006 bis 2014 positiv auf C. difficile-Toxine getestet wurden, wurden in diese retrospektive Studie eingeschlossen. Relevante demographische Informationen, Risikofaktoren fur CDI (Antibiotika, Hospitalisation, PPI) und Behandlungsdetails wurden den Krankenakten entnommen. Der Fishers exakte Test wurde zur Bestimmung der statistischen Signifikanz verwendet. Resultate: Insgesamt wurden 60 CED-Patienten (25 MC, 35 CU) 93-mal positiv auf Toxin-produzierende C. difficile getestet. 23 Patienten (38%) hatten mehr als eine (2 – 5) CDI. Patienten mit einer rezidivierenden CDI wiesen zum Zeitpunkt der ersten Infektion signifikant haufiger Risikofaktoren fur eine CDI auf als Patienten mit einer C. difficile-Episode [16/23 (70%) vs. 15/37 (41%), p = 0,036]. Patienten mit mehr als einer Infektion hatten zum Zeitpunkt der ersten CDI-Episode eher eine immunsuppressive Therapie, als jene mit einer Infektion [(18/23 (78%) vs. 20/37 (54%), p = 0,097]. Bei 37 der 93 (40%) CDI-Episoden verbesserten spezifische Antibiotika die Symptomatik der Patienten, bei 19 von 93 (20%) Episoden konnte keine Verbesserung verzeichnet werden. Bei den verbleibenden 37 von 93 (40%) CDIs war es nicht moglich den Effekt der Antibiose festzustellen, was hauptsachlich auf die zusatzliche Neueinleitung von immunsuppressiven Therapien zuruckzufuhren war. Diskussion:C. difficile-Rezidive bei CED-Patienten sind mit der Prasenz von Risikofaktoren fur diese Infektion signifikant assoziiert. Spezifische Antibiotika gegen C. difficile verbessern die Symptomatik dieser Patienten nur teilweise.