[Show abstract][Hide abstract] ABSTRACT: Background and aims:
Azathioprine (AZA) is recommended for maintenance of steroid-free remission in IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors.
We studied 510 IBD patients (338 Crohn's disease, 157 ulcerative colitis, 15 indeterminate colitis) with initiation of AZA treatment in a prospective multicenter registry study. Acute pancreatitis was diagnosed in accordance with international guidelines.
AZA was continued by 324 (63.5%) and stopped by 186 (36.5%) patients. The most common cause of discontinuation was nausea (12.2%). AZA-induced pancreatitis occurred in 37 patients (7.3%). Of these, 43% were hospitalized with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections, 24% had to vomit and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis (p<0.0002) in univariate and multivariate analyses CONCLUSIONS: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but had a mild course in all patients. Smoking is the most important risk factor.
Full-text · Article · Oct 2015 · Journal of Crohn s and Colitis
[Show abstract][Hide abstract] ABSTRACT: Diverticulosis, diverticular disease and diverticulitis have come into focus again because new aspects concerning diagnosis, risk factors and treatment arose only recently which prompted a new Guideline released by the DGVS and DGAV summarising the current evidence.Along with the guideline's essentials for medical practice a diagnosis of diverticulitis is considered unsatisfactory unless a cross-sectional imaging method (either ultrasonography [US] or computed tomography [CT] ) has proven that the clinical findings and inflammation (CRP considered superior to WBC and temperature) are due to diverticular inflammation. For reasons of practicability and considering relevant legislation for radiation exposure protection, US is the primary - and usually effectual - diagnostic method of choice as it is equipotent to CT. While US offers better resolution and enables precise imaging exactly at the location of pain as well as reiterative application, the latter implies advantages in the case of a deep abscess or diverticulitis in difficult locations (e. g. the small pelvis).Clinical evidence and laboratory and imaging findings allow for distinguishing a large number of differential diagnoses and also form the basis of a new classification (classification of diverticular disease, CDD) which comprises all forms of diverticular disease, from diverticulosis to bleeding and to the different facettes of diverticulitis. This classification -which should be applied in any patient with the diagnosis of diverticular disease- is independent of specific diagnostic preferences and applicable both to conservative and operative treatment options.While the number of recurrent episodes is no longer a significant indicator for surgery in diverticulitis, severity and / or complications determine treatment options along with the patients preferences. According to first data, conservative treatment may waive antibiotics under certain circumstances, however they are indispensible in complicated disease or patients bearing risk factors. Spasmoanalgetics and supportive fluid supply are individually necessary, and avoidance of potentially aggravating medications (e. g. NSAIDS) appears advisable, but many suggestions (nil by mouth, bed rest, laxatives) come along without an adaequate body of evidence. Similarly medical advice concerning prevention and secondary prophylaxis relies mainly on epidemiological plausibility. Because minor perforations (CDD type 2 a) as well as recurrent episodes of uncomplicated diverticulitis and even some abscesses > 1 cm (CDD type 2 b) respond favourably to medical treatment, the timely indication for surgery in these cases requires precise classification along with a close surveillance in trustful cooperation between the gastroenterologist and the surgeon.
No preview · Article · Sep 2015 · DMW - Deutsche Medizinische Wochenschrift
[Show abstract][Hide abstract] ABSTRACT: Diverticular disease is a common condition in Western countries and the incidence and prevalence of the disease is increasing. The pathogenetic factors involved include structural changes in the gut that increase with age, a diet low in fibre and rich in meat, changes in intestinal motility, the concept of enteric neuropathy and an underlying genetic background. Current treatment strategies are hampered by insufficient options to stratify patients according to individual risk. One of the main reasons is the lack of an all-encompassing classification system of diverticular disease. In response, the German Society for Gastroenterology and Digestive Diseases (DGVS) has proposed a classification system as part of its new guideline for the diagnosis and management of diverticular disease. The classification system includes five main types of disease: asymptomatic diverticulosis, acute uncomplicated and complicated diverticulitis, as well as chronic diverticular disease and diverticular bleeding. Here, we review prevention and treatment strategies stratified by these five main types of disease, from prevention of the first attack of diverticulitis to the management of chronic complications and diverticular bleeding.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Obesity is a risk factor for inflammatory diseases such as nonalcoholic steatohepatitis, pancreatitis, and Crohn's disease. The effect of being overweight or obese on the severity and clinical course of ulcerative colitis (UC) was assessed in a retrospective analysis of data from 2000-2006.
Two hundred and two consecutive UC patients were categorized according to body mass index (BMI). Patient and disease characteristics were compared between BMI categories using chi-square or Kruskal-Wallis tests. The percentage of patients with active UC, complications, steroid therapy, or immunosuppressive therapy was calculated for each group, and matched pair analyses were performed.
Ten patients (5%) were underweight, 111 (55%) were normal weight, 54 (26.7%) were overweight, and 27 (13.4%) were obese. Pancolitis was inversely related to weight. BMI was also inversely correlated to disease severity, with a significantly smaller proportion of years with chronic active disease among overweight subjects versus normal-weight subjects (17.6 versus 23.9%, p = 0.05). More overweight than normal-weight patients had no chronic active disease in any year (66 versus 49%, p = 0.06), and the proportion of years with disease complications was higher in normal weight than in overweight subjects (1.8 versus 0.4%, p = 0.08). Disease activity during 2000-2006 was higher for underweight versus normal-weight patients, and only 20% of underweight subjects had no hospital admission compared to 80% of normal-weight patients (p = 0.07).
This first study to explore the influence of obesity on UC showed that high BMI had rather a favorable effect on the prognosis, whereas low BMI pointed to a more severe course of the disease.
No preview · Article · Nov 2014 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix®, nor MMX 5-ASA, nor Pentasa® granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk®, and Pentasa® employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT).
A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy.
In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can determine the need for an immunosuppressive drug therapy or if a "watch and wait" approach is reasonable already early in the treatment course of UC.
Using six simple clinical parameters, we can estimate the patients individual risk of developing a progressive disease course.
Full-text · Article · Sep 2014 · World Journal of Gastroenterology