Ulcerative Colitis: Vogelsang H

Dejaco C, Haas T, Kirchgatterer A, Miehsler W, Wenzl H, Knoflach P, Petritsch W, Vogelsang H, Reinisch W, Tilg H. · Univ.-Klinik f. Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, AKH, Währinger Gürtel 18 - 20, A-1090 Wien. · Z Gastroenterol. · Pubmed #16773519 No free full text.

Abstract: 5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.

Novacek G, Haumer M, Schima W, Müller C, Miehsler W, Polterauer P, Vogelsang H. · Department of Internal Medicine IV, University of Vienna, Vienna, Austria. · Inflamm Bowel Dis. · Pubmed #15475753 No free full text.

Abstract: Thromboembolic events are a known complication in inflammatory bowel disease (IBD). We report on 2 young women with IBD and aortic mural thrombi as a source of arterioarterial embolization to the lower limbs resulting in significant morbidity. The first case was a 36-year-old woman with severe ulcerative colitis who presented with signs of microembolism into two toes of her right foot. A thrombus in the otherwise normal infrarenal aorta with occlusion of the inferior mesenteric artery was revealed by computed tomography (CT) and intrarterial angiography. The digital ischemia resolved without sequelae. The second case was a 41-year-old woman with Crohn's disease complicated by fistulas. She developed acute ischemia of her right leg. Arteriography and CT revealed infrapopliteal embolic occlusions and a thrombus in the distal otherwise normal abdominal aorta and the left iliac artery. A primarily successful thrombectomy had to be repeated 5 times because of reocclusion. Eventually the leg was exarticulated at the knee. In both patients no further thromboembolic event occurred during follow-up of 4 1/2 years and 5 1/2 years, respectively, and aortic thrombi had resolved at follow-up CT scans. Extensive work up for hypercoagulability was negative in both patients. We consider IBD as the most likely trigger for arterioarterial embolization in the absence of thrombophilia in both patients. Finally we give an overview of the literature of similar cases with aortic mural thrombi in IBD patients.

Vogelsang H, Granditsch G, Binder C, Herbst F, Moser G, Petritsch W, Knoflach P. · Univ.-Klinik für Innere Medizin IV, Wien. · Z Gastroenterol. · Pubmed #11072675 No free full text.

Abstract: Although up to 20% of patients with Crohn's disease have their first flare during childhood or adolescence, there are no or only a few randomized, controlled studies. However, big differences and uncertainty may be observed between the diagnosis and therapy of pediatricians and gastroenterologists specialized for adults. In addition, special problems result from the enormous somatic and psychological evolution during adolescence. The diagnosis is done as in adult patients by enteroclysm and ileocolonoscopy (including multiple biopsies) whereas a deep sedoanalgesia or anesthesia should be performed routinely. Corticosteroids are the gold standard for therapy of Crohn's disease in the adolescence (especially in cases with high inflammatory activity), but also enteral nutrition over 4-12 weeks--or a combination of both. A recent randomized controlled study demonstrates the positive effect of 6-mercaptopurine in newly diagnosed patients with Crohn's disease in the adolescence. 5-aminosalicylates or the probably more effective azathioprine/6-mercaptopurine could be used for prevention of recurrence in Crohn's disease. The therapy of ulcerative colitis is performed as in adults including the very effective local rectal applications. An accompanying psychosomatic therapy is recommended especially in young patients with disturbed separation from the parents and inadequate coping. The indication for surgery is similar to adults. However, a specific indication for earlier surgery is given, if severe malabsorption and delay of growth takes place in spite of adequate therapy, because this delay of growth could be only caught up before puberty. A conservative therapeutic regimen is recommended in young patients with perianal Crohn's disease.

Teml A, Schwab M, Harrer M, Miehsler W, Schaeffeler E, Dejaco C, Mantl M, Schneider B, Vogelsang H, Reinisch W. · Universitätsklinik für Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Vienna, Austria. · Scand J Gastroenterol. · Pubmed #16265777 No free full text.

Abstract: OBJECTIVE: 6-thioguanine (6-TG) has emerged as a promising therapeutic alternative in patients with Crohn's disease intolerant or resistant to azathioprine (AZA) and/or 6-mercaptopurine (6-MP). The aim of the present study was to evaluate the safety and efficacy of 6-TG in patients with ulcerative colitis (UC) or indeterminate colitis (IC) intolerant or resistant to AZA/6-MP. MATERIAL AND METHODS: Twenty patients with an acute flare, steroid-dependent or steroid-refractory disease attending our outpatient department were included in the study. Measurement of 6-TG nucleotide levels was done to check compliance. Complete, partial and non-response were defined by means of the clinical activity index and the daily steroid demand. Secondary outcome parameters included changes in cumulative steroid doses, C-reactive protein (CRP) levels, and an endoscopic score. RESULTS: Out of 20 patients 4 were excluded owing to noncompliance; 2/16 compliant patients (13%) had to be prematurely withdrawn because of adverse events, which ceased upon drug discontinuation. By per-protocol analysis, 5/14 patients (36%) were complete, 6/14 (43%) partial and 3/14 (21%) non-responders. In addition to the reduction of the cumulative steroid dose over 3 months, CRP decreased in the study population and the endoscopic score decreased in treatment responders. CONCLUSIONS: Treatment with 6-TG was effective in patients with UC or IC previously intolerant or resistant to AZA/6-MP. Future work is needed to define a subpopulation of patients at low risk for its potential hepatotoxicity, which we assume will benefit from 6-TG.

Brunner M, Vogelsang H, Greinwald R, Kletter K, Kvaternik H, Schrolnberger C, Eichler HG, Brunner H, Dudczak R, Müller M. · Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria. · Aliment Pharmacol Ther. · Pubmed #16128685 links to  free full text

Abstract: BACKGROUND: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. AIMS: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. METHODS: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously. RESULTS: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. CONCLUSIONS: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Tilg H, Vogelsang H, Ludwiczek O, Lochs H, Kaser A, Colombel JF, Ulmer H, Rutgeerts P, Krüger S, Cortot A, D'Haens G, Harrer M, Gasche C, Wrba F, Kuhn I, Reinisch W. · Department of Gastroenterology and Hepatology and Biostatistics, University Hospital Innsbruck, Austria. · Gut. · Pubmed #14633951 links to  free full text

Abstract: BACKGROUND: Pilot studies of interferon alpha (IFN-alpha) suggest a high remission rate in the treatment of active ulcerative colitis. We evaluated the safety of pegylated interferon alpha (PegIFN) and its role in induction of remission in patients with active ulcerative colitis, in a multicentre placebo controlled trial. METHODS: Sixty patients with a clinical activity score (CAI) of >6 were randomised to receive placebo (n=20), PegIFN 0.5 microg/kg (n=19), or PegIFN 1.0 microg/kg body weight (n=21) once weekly (PegIntron; Schering-Plough, USA) over 12 weeks. Patients receiving 5-aminosalicylates, steroids, and/or azathioprine in stable dosages were included. RESULTS: Serious adverse events were seen in none of the placebo patients, in 3/19 patients in the PegIFN 0.5 microg/kg group (hospitalisation due to disease flare up n=3), and in 3/21 in the PegIFN 1.0 microg/kg group (hospitalisation due to disease flare up n=1; thrombosis n=1; grand mal seizure n=1). Otherwise, we observed only minor IFN-alpha side effects. Clinical remission rates at week 12 (CAI < or =4) were 7/20 (35%) in the placebo, 9/19 (47%) in the PegIFN 0.5 microg/kg group, and 7/21 (33%) in the PegIFN 1.0 microg/kg group (NS). Early withdrawal from the study was observed in 11/20 placebo patients, in 6/19 in the PegIFN 0.5 microg/kg group, and in 10/21 in the PegIFN 1.0 microg/kg group, mainly due to lack of efficacy. The higher PegIFN dose was associated with a significant decrease in levels of C reactive protein (p=0.003, day 0 v 85). CONCLUSIONS: PegIFN is safe but not effective, at the dosages used, in patients with ulcerative colitis.

Teml A, Kratzer V, Schneider B, Lochs H, Norman GL, Gangl A, Vogelsang H, Reinisch W. · Universitätsklinik für Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, and Institut für Medizinische Statistik, Universtität Wien, Vienna, Austria. · Am J Gastroenterol. · Pubmed #14572572 No free full text.

Abstract: OBJECTIVES: An increased prevalence of elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with Crohn's disease (CD) has been described. The aim of the present work was to investigate serum ASCA levels during the courses of prednisolone and mesalamine therapy in CD patients. METHODS: Serum samples of 25 patients with active CD were studied for ASCA levels before as well as 2 and 9 wk after initiation of a prednisolone tapering regimen. The influence of mesalamine (4 g o.d.) on serum ASCA levels compared to that of placebo was tested over 1 yr in 38 patients (20 mesalamine and 18 placebo) participating in a postoperative prophylaxis study. Serum IgG and IgA ASCA levels were measured by ELISA. Sera of 91 CD and 40 ulcerative colitis (UC) patients as well as 334 healthy donors were tested for ASCA to recalculate new cut-off values. RESULTS: For IgG ASCA cut-off values were determined to be 17.0 U and 25.0 U, and for IgA ASCA 9.3 U and 14.0 U. At baseline visit, 73.0% (46/63) of patients displayed serum ASCA positivity. During prednisolone therapy, a decrease in serum IgG and IgA ASCA levels from baseline to wk 2 (p < 0.0001 and p < 0.001, respectively) as well as to wk 9 (p < 0.001 and p = 0.01, respectively) was observed. A trend toward an association of ASCA positivity and steroid responsiveness was calculated (p = 0.07). During mesalamine treatment, no differences in changes of ASCA levels were observed compared to placebo at any time point. CONCLUSIONS: ASCA are stable markers during steroid and mesalamine treatment, highlighting their reliability for use in diagnosis of CD.

Tilg H, Feichtenschlager T, Knoflach P, Petritsch W, Schöfl R, Vogelsang H, Reinisch W. · Die Institutsangaben sind am Ende des Beitrags gelistet. · Z Gastroenterol. · Pubmed #17701864 No free full text.

Abstract: Infliximab, a chimeric monoclonal anti-tumour necrosis factor alpha (TNF) antibody has dramatically changed the management of various chronic inflammatory disorders such as Crohn's disease (CD), rheumatoid arthritis, ankylosing spondylitis or psoriasis. This drug is well established for the treatment of CD in case of steroid-refractoriness, failure to respond to an immunosuppressant agent or fistulizing disease. The immunological concept that ulcerative colitis (UC) reflects primarily a T-helper cell type-2 mediated disease prevented the earlier use of anti-TNF agents in this disease. Promising initial pilot studies in steroid-refractory UC patients led to two large placebo-controlled trials in patients with moderate to severe UC. These studies clearly showed a benefit for infliximab treatment in UC with mucosal healing and improved life quality. Infliximab therefore can be used in patients not responding adequately to steroids and/or immunosuppressants. Furthermore, one study showed evidence that infliximab might also be effective in severe, intravenous steroid-refractory UC. Therefore, infliximab might be used alternatively to cyclosporine A or tacrolimus in this patient group. Infliximab has now been established as an additional treatment option in patients with chronic-active UC not responding to an immunosuppressive agent and/or in case of severe acute UC. Experienced gastroenterologists should be involved in the decision making for such a therapy to balance thoroughly the benefit/risk ratio for our patients.

Petritsch W, Tillinger W, Vogelsang H, Reinisch W, Knoflach P, Tilg H. · Universitätsklinik für Innere Medizin, Klinische Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Graz. · Z Gastroenterol. · Pubmed #17115362 No free full text.

Abstract: Ileocolonoscopy including biopsies is the first line investigation in suspected inflammatory bowel disease (IBD). In up to 90 % of the cases ulcerative colitis and Crohn's disease are differentiated on endoscopic presentation. Standardised reporting of endoscopic results increases the validity and comparability of IBD findings. When there is a firm diagnosis of IBD, colonoscopy should only be performed for specific questions. An upper gastrointestinal endoscopy is only indicated in patients with upper gastrointestinal symptoms. Push and capsule endoscopy should also be limited to specific questions and situations. IBD with extended colitis is associated with an increased risk for colorectal cancer. Endoscopic surveillance with accurate biopsy sampling is a valuable tool for the prevention of colorectal cancer.

Reinisch W, Dejaco C, Knoflach P, Petritsch W, Vogelsang H, Tilg H. · Univ.-Klinik f. Innere Medizin IV, Abteilung Gastroenterologie und Hepatologie, AKH Wien, Austria. · Z Gastroenterol. · Pubmed #15455280 No free full text.

Abstract: Azathioprine (AZA) or 6-mercaptopurine (6-MP) are the immunosuppressive drugs of choice in the treatment of inflammatory bowel disorders (IBD). Optimal dosage for AZA is around 2.5 mg/kg body weight and induction of remission by these drugs may take 6 - 7 months. Intramuscularly applied Methotrexate (MTX) is the second choice, while its efficacy starts earlier than that of AZA; studies assessing oral low-dose MTX treatment are lacking. Cyclosporin is the standard treatment in case of steroid-refractory severe ulcerative colitis. This drug may also be used in patients with severe extraintestinal manifestations of IBD. Regarding other immunosuppressive drugs such as mycophenolic acid or 6-thioguanine respective controlled clinical study data are not available. The risk of malignancy using immunosuppressive drugs such as AZA is low and furthermore, especially AZA and 6-MP can be used rather safely during pregnancy.

Miehsler W, Reinisch W, Valic E, Osterode W, Tillinger W, Feichtenschlager T, Grisar J, Machold K, Scholz S, Vogelsang H, Novacek G. · Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, University of Vienna, Vienna, Austria. · Gut. · Pubmed #15016749 links to  free full text

Abstract: BACKGROUND: Patients with inflammatory bowel disease (IBD) are thought to be at increased risk of venous thromboembolism (TE). However, the extent of this risk is not known. Furthermore, it is not known if this risk is specific for IBD or if it is shared by other chronic inflammatory diseases or other chronic bowel diseases. AIMS: To compare the risk of TE in patients with IBD, rheumatoid arthritis, and coeliac disease with matched control subjects. PATIENTS AND METHODS: Study subjects answered a questionnaire assessing the history of TE, any cases of which had to be confirmed radiologically. A total of 618 patients with IBD, 243 with rheumatoid arthritis, 207 with coeliac disease, and 707 control subjects were consecutively included. All three patient groups were compared with control subjects matched to the respective group by age and sex. RESULTS: Thirty eight IBD patients (6.2%) had suffered TE. This was significantly higher compared with the matched control population with only 10 cases reported (1.6%) (p<0.001; odds ratio (OR) 3.6 (95% confidence interval (CI) 1.7-7.8)). Five patients with rheumatoid arthritis (2.1%) had suffered TE compared with six subjects (2.5%) in the control population matched to patients with rheumatoid arthritis (NS; OR 0.7 (95% CI 0.2-2.9)). TE had occurred in two patients with coeliac disease (1%) compared with four subjects (1.9%) in the control population matched to the coeliac disease group (NS; OR 0.4 (95% CI 0.1-2.5)). In 60% of TE cases in the IBD group, at least one IBD specific factor (active disease, stenosis, fistula, abscess) was present at the time TE occurred. CONCLUSIONS: IBD is a risk factor for TE. It seems that TE is a specific feature of IBD as neither rheumatoid arthritis, another chronic inflammatory disease, nor coeliac disease, another chronic bowel disease, had an increased risk of TE.

Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D, Peeters M, Geboes K, Bossuyt X, Vandewalle P, Oberhuber G, Vogelsang H, Rutgeerts P, Colombel JF. · Gastroenterology Unit, Department of Pathology, U.Z. Gasthuisberg, Leuven, Belgium. · Gastroenterology. · Pubmed #11984510 No free full text.

Abstract: BACKGROUND & AIMS: In the absence of pathognomonic markers for Crohn's disease (CD) and ulcerative colitis (UC), the diagnosis of inflammatory bowel disease depends on a compendium of clinical, radiographic, endoscopic, and histologic criteria that bears imperfect specificity to the individual disorders. In 10% of cases of colitis, no differentiation can be made between CD and UC; these patients are diagnosed with indeterminate colitis (IC). We evaluated the value of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) to increase diagnostic accuracy in categorizing IC. METHODS: Since 1996, 97 patients with IC from 3 centers (Leuven, Lille, and Vienna) were enrolled, analyzed for pANCA and ASCA, and followed up prospectively. RESULTS: A definitive diagnosis has been reached for 31 of 97 patients (32%). In these patients, ASCA+/pANCA- correlated with CD in 8 of 10 patients, whereas ASCA-/pANCA+ correlated with UC in 7 of 11 patients. The remaining 4 cases became CD, clinically behaving as UC-like CD. Almost half of the patients (47 of 97 [48.5%]) were negative for ASCA and pANCA, and 40 remain diagnosed with IC to date. Only 7 seronegative cases (14.9%) became CD or UC compared with 48% (24 of 50) of seropositive patients (P < 0.001). CONCLUSIONS: Results so far show that ASCA+/pANCA- predicts CD in 80% of patients with IC and ASCA-/pANCA+ predicts UC in 63.6%. Interestingly, 48.5% of patients do not show antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC during their further clinical course, perhaps reflecting a distinct clinicoserological entity.

Oberhuber G, Püspök A, Peck-Radosavlevic M, Kutilek M, Lamprecht A, Chott A, Vogelsang H, Stolte M. · Department of Clinical Pathology, University of Vienna, Medical School, Austria. · Am J Surg Pathol. · Pubmed #10435568 No free full text.

Abstract: Esophageal histology is not well studied in patients with Crohn's disease (CD). We, therefore, analyzed the histologic and immunohistologic appearance of esophageal mucosa in CD. Biopsy specimens taken from the esophagus of 57 consecutive patients with known CD of the large and/or small bowel, of 200 Crohn's-free controls, of 15 cases with ulcerative colitis, and of 5 cases with viral esophagitis were evaluated. In controls, most patients had either HLA-DR negative esophageal epithelium or showed focal or diffuse basal staining. HLA-DR expression of all epithelial layers (transepithelial staining) was observed in only four (2%) control subjects, in one case with herpes esophagitis, but not in patients with ulcerative colitis. In contrast, transepithelial HLA-DR expression was found in 19 (33%) patients with CD (p < 0.0001). In CD patients, it was associated with a significantly increased epithelial content in T-cells (CD3+, TIA-1+, granzyme B+), B-cells (CD79a+), natural killer cells (CD57+), and macrophages (CD68+). There was no correlation with either histological findings elsewhere in the upper gastrointestinal tract or with laboratory findings, symptoms, CDAI, or medication. Transepithelial esophageal HLA-DR expression is common in CD. Immunohistochemistry may prove useful in supporting the histologic diagnosis of CD in staging procedures, for initial diagnosis as well as in doubtful cases.

Novacek G, Miehsler W, Kapiotis S, Katzenschlager R, Speiser W, Vogelsang H. · Department of Internal Medicine IV, Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria. · Am J Gastroenterol. · Pubmed #10086652 No free full text.

Abstract: OBJECTIVE: Thromboembolic events are serious complications in patients with inflammatory bowel disease (IBD). Resistance of factor V to degradation by activated protein C (APC) is a major cause for venous thrombosis and is found in approximately 30% of patients with thromboembolism. The aim of the present study was to assess the prevalence of APC resistance and clinical risk factors in patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38 men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with ulcerative colitis) and 102 gender- and age-matched healthy control subjects were investigated prospectively for the presence of APC resistance. None of the healthy controls but 16 patients with IBD had a history of thromboembolism. RESULTS: Patients with IBD and thromboembolism were young, with a median age of 37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more common than in patients with IBD without thromboembolism (7%) and in controls (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13 each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most common thromboembolic complications (84.2%). Active disease, fistula, or bowel stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%) cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is not associated with IBD but, when present, increases the risk of thromboembolism. Patients with IBD and thromboembolism are mostly young and clinical risk factors can be found in one-half of cases.

Haumer M, Teml A, Dirisamer A, Vogelsang H, Koppensteiner R, Novacek G. · No affiliation provided · Inflamm Bowel Dis. · Pubmed #17278129 links to  free full text

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Palkovits J, Häfner M, Rand T, Vogelsang H, Kutilek M, Gangl A, Novacek G. · No affiliation provided · Inflamm Bowel Dis. · Pubmed #17206707 links to  free full text

This publication has no abstract.