[Therapy of radiation-induced esophagits by oro-dispersible budesonide]. / Therapie einer akuten Strahlenösophagitis mit orodispersiblem Budesonid.

Radiation esophagitis is a common side effect of therapeutic radiotherapy. In this case report, we describe a patient with a complete remission of the esophagitis after therapy with an oro-dispersible budesonide formulation.

Invitation to Screening Colonoscopy in the Population at Familial Risk for Colorectal Cancer.

BACKGROUND: Screening colonoscopy can lower the incidence of colorectal cancer (CRC), yet participation rates are low even in groups at high risk. The goal of this study was to double the rate of participation in screening colonoscopy among persons at familial risk and then to determine the frequency of neoplasia in this risk group. METHODS: In a nationwide, cluster-randomized, multicenter study, first-degree relatives (FDR) of patients with CRC across Germany received written informational materials concerning the familial risk of CRC, along with an invitation to undergo colonoscopy. Participants in the intervention group were additionally counseled by nurses over the telephone. The primary endpoint of the study was colonoscopy uptake within 30 days. RESULTS: The participants' mean age was 50.8 years. The colonoscopy uptake rates were 99/125 (79%) in the intervention group and 97/136 (71%) in the control group (RR = 1.11; 95% confidence interval [0.97; 1.28]). A polypectomy was performed in 72 of 196 asymptomatic persons (37%). In 13 cases (7%), an advanced neoplasia was detected; two of these persons had colon cancer (stages T0 and T1). 42% of the participants expressed barriers against colonoscopy. 22 reported mild side effects; there were no serious side effects. CONCLUSION: Additional counseling by nurses over the telephone does not increase the participation rate. Approaching patients who have CRC is an opportunity to increase the participation of their first-degree relatives in screening colonoscopy. The frequency of neoplasia that was found in this study underscores the need to screen relatives even before they reach the usual age threshold for screening.

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis.

OBJECTIVE: To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). DESIGN: Adults with active EoE (n=76) randomly received 14 days' treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm(2 )hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's preference for drug formulation. RESULTS: Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients. CONCLUSIONS: BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation. CLINICALTRIALSGOV NUMBER: NCT02280616; EudraCT number, 2009-016692-29.

Eosinophilic gastroenteritis with refractory ulcer disease and gastrointestinal bleeding as a rare manifestation of seronegative gastrointestinal food allergy.

Gastrointestinal bleeding and iron deficiency anaemia may cause severe symptoms and may require extensive diagnostics and substantial amounts of health resources.This case report focuses on the clinical presentation of a 22 year old patient with recurrent gastrointestinal bleeding from multilocular non-healing ulcers of the stomach, duodenum and jejunum over a period of four years. Extensive gastroenterological and allergological standard diagnostic procedures showed benign ulcerative lesions with tissue eosinophilia, but no conclusive diagnosis. Multiple diagnostic procedures were performed, until finally, endoscopically guided segmental gut lavage identified locally produced, intestinal IgE antibodies by fluoro-enzyme-immunoassay.IgE antibody concentrations at the intestinal level were found to be more-fold increased for total IgE and food-specific IgE against nuts, rye flour, wheat flour, pork, beef and egg yolk compared with healthy controls.Thus, a diet eliminating these allergens was introduced along with antihistamines and administration of a hypoallergenic formula, which resulted in complete healing of the multilocular ulcers with resolution of gastrointestinal bleeding. All gastrointestinal lesions disappeared and total serum IgE levels dropped to normal within 9 months. The patient has been in remission now for more than two years.Eosinophilic gastroenteritis (EG) is well known to induce refractory ulcer disease. In this case, the mechanisms for intestinal damage and gastrointestinal bleeding were identified as local gastrointestinal type I allergy. Therefore, future diagnostics in EG should also be focused on the intestinal level as identification of causative food-specific IgE antibodies proved to be effective to induce remission in this patient.

Intravenous ibandronate or sodium-fluoride--a 3.5 years study on bone density and fractures in Crohn's disease patients with osteoporosis.

BACKGROUND AND AIM: Osteoporosis commonly afflicts Crohn's disease (CD) patients. Management remains unclear, with limited results for intravenous (i.v.) bisphosphonates and a follow-up longer than one year. Intravenous bisphosphonates bypass gastrointestinal-tract irritation offering an interesting alternative suitable for CD patients. We tested the long-term efficacy and safety of colecalciferol and calcium with sodium-fluoride or i.v. ibandronate for osteoporosis in CD. METHODS: 66 CD patients with lumbar osteoporosis (T-score<-2.5) were randomized to receive colecalciferol (1000 IU), calcium-citrate (800 mg) and intermittent sustained-release sodium-fluoride (50 mg) [groupA, n=33] or i.v. ibandronate (1 mg/3-monthly) [groupB, n=33]. Dual-energy X-ray absorptiometry of the lumbar-spine and right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading and quantitative morphometry of X-rays. RESULTS: 55 (83.3%) patients completed at least the 1st year available for intention-to-treat (ITT) analysis, 42 (63.6%) completed the 2nd and 35 (53.0%) the 3rd year available for per-protocol analysis. Lumbar T-score increased by +0.23±0.43 (95%CI: 0.057-0.407, p<0.05), +0.71±1.05 (95%CI: 0.193-1.232, p<0.001) and +0.73±0.82 (95%CI: 0.340-1.336, p<0.001) (group A), and +0.28±0.41 (95%CI: 0.132-0.459, p<0.05), +0.43±0.55 (95%CI: 0.184-0.671, p<0.01) and +0.51±0.74 (95%CI: 0.145-0.882, p<0.001) (group B) during 1.0, 2.25 and 3.5 years follow-up time. In 2.71 years of follow-up, with the ITT analysis, the lumbar T-score increased by +0.66±0.97 (group A, p<0.001) and +0.46±0.67 (group B, p<0.001). One vertebral fracture with sodium-fluoride was not enough to detect differences between groups and the study was not powered for this. Study medication was well-tolerated and safe. CONCLUSIONS: Sodium-fluoride and i.v. ibandronate improved osteoporosis. Keeping in mind bisphosphonates as a standard of osteoporosis care that reduce fracture-rate, data we do not have for sodium-fluoride, CD patients with osteoporosis can be treated safely with i.v. ibandronate.

Bones and Crohn's: no benefit of adding sodium fluoride or ibandronate to calcium and vitamin D.

AIM: To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohn's disease (CD). METHODS: Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading of X-rays and quantitative morphometry of vertebral bodies (T4-L4). RESULTS: One hundred and twenty three (83.1%) patients completed the first year for intention-to-treat (ITT) analysis. Ninety two (62.2%) patients completed the second year and 71 (47.8%) the third year available for per-protocol (PP) analysis. With a significant increase in T-score of the lumbar spine by +0.28 ± 0.35 [95% confidence interval (CI): 0.162-0.460, P < 0.01], +0.33 ± 0.49 (95% CI: 0.109-0.558, P < 0.01), +0.43 ± 0.47 (95% CI: 0.147-0.708, P < 0.01) in group A, +0.22 ± 0.33 (95% CI: 0.125-0.321, P < 0.01); +0.47 ± 0.60 (95% CI: 0.262-0.676, P < 0.01), +0.51 ± 0.44 (95% CI: 0.338-0.682, P < 0.01) in group B and +0.22 ± 0.38 (95% CI: 0.111-0.329, P < 0.01), +0.36 ± 0.53 (95% CI: 0.147-0.578, P < 0.01), +0.41 ± 0.48 (95% CI: 0.238-0.576, P < 0.01) in group C, respectively, during the 1.0, 2.25 and 3.5 year periods (PP analysis), no treatment regimen was superior in any in- or between-group analyses. In the ITT analysis, similar results in all in- and between-group analyses with a significant in-group but non-significant between-group increase in T-score of the lumbar spine by 0.38 ± 0.46 (group A, P < 0.01), 0.37 ± 0.50 (group B, P < 0.01) and 0.35 ± 0.49 (group C, P < 0.01) was observed. Follow-up in ITT analysis was still 2.65 years. One vertebral fracture in the sodium fluoride group was detected. Study medication was safe and well tolerated. CONCLUSION: Additional sodium fluoride or ibandronate had no benefit over calcium and cholecalciferol alone in managing reduced BMD in CD.

Significant differences between Crohn's disease and ulcerative colitis regarding the impact of body mass index and initial disease activity on responsiveness to azathioprine: results from a European multicenter study in 1,176 patients.

In a survey comprising 1,176 patients with inflammatory bowel disease (IBD) we recently showed that azathioprine (AZA) beyond 4 years is beneficial in ulcerative colitis (UC) patients and in a subset of Crohn's disease (CD) patients. Here, we show for the first time that azathioprine responsiveness depends on body mass index (BMI). The relationship is reciprocal in UC and CD, with a better outcome in UC patients with a BMI<25 and in CD patients with a BMI>25. These observations are particularly interesting considering the evolving concept of a relationship between fatty metabolism and immune regulation. Additionally, we show that CD patients, but not UC patients, respond better to AZA when it is started in clinical remission. This observation may support data favouring a "hit hard and early" regime in CD. Finally, we were able to demonstrate a decrease in the incidence of CD-related complications requiring surgery through treatment with AZA.

Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients. METHODS: One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT). RESULTS: Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO. CONCLUSION: SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors.

Osteoporosis in inflammatory bowel disease.

Half of all patients with inflammatory bowel disease show a significant reduction of their bone mass during the course of their chronic inflammatory disease. In contrast to women with postmenopausal osteoporosis these patients are much younger and a significant subgroup develops vertebral fractures which are mostly asymptomatic. The activity of the chronic inflammatory disease and the steroid treatment leads to bone loss predominantly through the TNFα-driven osteoprotegerin system. Clinical useful genetic markers to identify patients at risk for fractures have not been developed so far. Long-term clinical remission leads in most patients to normalisation of the bone density. Patients with reduced bone density should be substituted with calcium and vitamin D. Patients with vertebral fractures should receive bisphosphonates.

6-thioguanine nucleotide-adapted azathioprine therapy does not lead to higher remission rates than standard therapy in chronic active crohn disease: results from a randomized, controlled, open trial.

BACKGROUND: A prospective randomized trial in patients with Crohn disease studied whether 6-thioguanine nucleotide (6-TGN) concentration-adapted azathioprine (AZA) therapy is clinically superior to a standard dose of 2.5 mg/kg/day AZA. METHODS: After 2 weeks of standard therapy, patients (n = 71) were randomized into standard (n = 32) or adapted-dose (n = 25) groups; 14 patients dropped out before randomization. In the adapted group, the AZA dose was adjusted to maintain 6-TGN concentrations between 250 and 400 pmol/8 x 10(8) erythrocytes (Ery). Response criteria were the number of patients in remission after 16 weeks without steroids (primary) and remission after 24 weeks, frequency of side effects, and quality of life (secondary). RESULTS: After 16 weeks, 14 of 32 (43.8%) patients in the standard group vs 11 of 25 (44%) in the adapted group were in remission without steroids (intent-to-treat analysis). After 24 weeks, 43.8% vs 40% were in remission. No significant differences were found concerning quality of life, disease activity, 6-TGN concentrations, AZA dose, or dropouts due to side effects. Sixty-six patients had a wild-type thiopurine S-methyltransferase (TPMT) genotype, with TPMT activities of 8 to 20 nmol/(mL Ery x h). Five patients (dropouts after randomization) were heterozygous, with TPMT activities <8 nmol/(mL Ery x h). 6-Methyl mercaptopurine (6-MMP) concentrations >5700 pmol/8 x 10(8) Ery were not associated with hepatotoxicity. CONCLUSION: Standard and adapted dosing with the provided dosing scheme led to identical 6-TGN concentrations and remission rates. Adapted dosing had no apparent clinical benefit for patients with TPMT activity between 8 and 20 nmol/(mL Ery x h). Additionally, 6-MMP monitoring had no predictive value for hepatotoxicity.

Long-term effectiveness of azathioprine in IBD beyond 4 years: a European multicenter study in 1176 patients.

In Crohn's disease the optimal duration of azathioprine treatment is still controversial and for ulcerative colitis only limited data are available to support its efficacy. Charts of 1176 patients with IBD from 16 European centers were analyzed. Flare incidences and steroid dosages were assessed for the time before and during treatment and after discontinuation. Within the first 4 years, azathioprine suppressed flare incidence and steroid consumption in both diseases (P < 0.001). While in CD discontinuation after 3-4 years did not lead to reactivation, this was the case in UC. However, continuation beyond 4 years further improved clinical activity in CD and steroid requirement in both diseases (P < 0.001). Discontinuation of azathioprine may thus be considered after 3-4 years in CD patients in complete remission without steroid requirement. In all other CD patients and for UC patients in general, continuation seems beneficial. These results support a novel differential algorithm for long-term azathioprine therapy in IBD.