Gottfried Novacek

The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations.

Principal changes with respect to the 2004 ECCO guidelines Ileocolonoscopy is recommended within the first year after surgery where treatment decisions may be affected (Statement 8C). Thiopurines are more effective than mesalazine or imidazole antibiotics alone in post-operative prophylaxis (Statement 8F). ### 8.1 Epidemiology of post-operative Crohns disease In the natural history of CD, intestinal resection is almost unavoidable since about 80% of patients require surgery at some stage. Surgery is unfortunately not curative as the disease inexorably recurs in many patients. The post-operative recurrence rate varies according to the definition used: clinical, endoscopic, radiological, or surgical. It is lowest when the repeat resection rate is considered, intermediate when clinical indices are used and highest when endoscopy is employed as the diagnostic tool.1–10 Data from endoscopic follow-up of patients after resection of ileo-caecal disease have shown that in the absence of treatment, the post-operative recurrence rate is around 65–90% within 12 months and 80–100% within 3 years of the operation. The clinical recurrence without therapy is about 20–25%/year.1,10 It has been demonstrated that the post-operative clinical course of CD is best predicted by the severity of endoscopic lesions. Symptoms, in fact, appear only when severe lesions are present and it is not uncommon to observe patients with fairly advanced recurrent lesions at endoscopy who remain asymptomatic.1 For these reasons, clinical indices such as the CDAI have low sensitivity at discriminating between patients with or without post-operative recurrence.11 These data mandate strategies aimed at interrupting or delaying the natural course of post-operative recurrence. Several medications have been tried in an attempt to prevent post-operative recurrence, mostly with disappointing results. The aim of this Consensus was therefore critically to evaluate the optimal strategies for the management of post-operative recurrence in CD. Most, if not all, of the evidence available deals with …

Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management

### 5.1 General When deciding the appropriate treatment strategy for active ulcerative colitis one should consider the activity, distribution (proctitis, left-sided, extensive1), and pattern of disease. The disease pattern includes relapse frequency, course of disease, response to previous medications, side-effect profile of medication and extra-intestinal manifestations. The age at onset and disease duration may also be important factors. #### 5.1.1 Disease activity The principal disease activity scoring systems used in clinical trials are covered in Section 1.2 and have been comprehensively reviewed.2 However there are some practical points that are relevant for routine clinical use. For example, it is most important to distinguish patients with severe ulcerative colitis necessitating hospital admission from those with mild or moderately active disease who can generally be managed as outpatients. The simplest, best validated and most widely used index for identifying severe UC remains that of Truelove and Witts3: any patient who has a bloody stool frequency ≥ 6/day and a tachycardia (> 90 bpm), or temperature > 37.8 °C, or anaemia (haemoglobin 30 mm/h) has severe ulcerative colitis (Table 1.3). Only one additional criterion in addition to the bloody stool frequency ≥ 6/day is needed to define a severe attack.4,5 It should be standard practice to confirm the presence of active colitis by sigmoidoscopy before starting treatment. Flexible sigmoidoscopy and biopsy may exclude unexpected causes of symptoms that mimic active disease such as cytomegalovirus colitis, rectal mucosal prolapse, Crohns disease, malignancy, or even irritable bowel syndrome and haemorrhoidal bleeding. There may be a significant overlap between other diseases that mimic ulcerative colitis and the broad spectrum of UC damage.6,7 In addition, all patients with active disease require stool cultures with Clostridium difficile toxin assay to exclude enteric infection. Patients with an appropriate …

Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism

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.

Temporal Bacterial Community Dynamics Vary Among Ulcerative Colitis Patients After Fecal Microbiota Transplantation

OBJECTIVES:Fecal microbiota transplantation (FMT) from healthy donors, which is an effective alternative for treatment of Clostridium difficile–associated disease, is being considered for several disorders such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome. Disease remission upon FMT is thought to be facilitated by an efficient colonization of healthy donor microbiota, but knowledge of the composition and temporal stability of patient microbiota after FMT is lacking.METHODS:Five patients with moderately to severely active ulcerative colitis (Mayo score ≥6) and refractory to standard therapy received FMT via nasojejunal tube and enema. In addition to clinical activity and adverse events, the patients’ fecal bacterial communities were monitored at multiple time points for up to 12 weeks using 16S rRNA gene-targeted pyrosequencing.RESULTS:FMT elicited fever and a temporary increase of C-reactive protein. Abundant bacteria from donors established in recipients, but the efficiency and stability of donor microbiota colonization varied greatly. A positive clinical response was observed after 12 weeks in one patient whose microbiota had been effectively augmented by FMT. This augmentation was marked by successive colonization of donor-derived phylotypes including the anti-inflammatory and/or short-chain fatty acid–producing Faecalibacterium prausnitzii, Rosebura faecis, and Bacteroides ovatus. Disease severity (as measured by the Mayo score) was associated with an overrepresentation of Enterobacteriaceae and an underrepresentation of Lachnospiraceae.CONCLUSIONS:This study highlights the value of characterizing temporally resolved microbiota dynamics for a better understanding of FMT efficacy and provides potentially useful diagnostic indicators for monitoring FMT success in the treatment of ulcerative colitis.

Inflammatory Bowel Disease Is a Risk Factor for Recurrent Venous Thromboembolism

BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) are at increased risk of a first venous thromboembolism (VTE), yet their risk of recurrent VTE is unknown. We performed a cohort study to determine the risk for recurrent VTE among patients with IBD compared with subjects without IBD. METHODS We assessed 2811 patients with IBD for a history of VTE, recruited from outpatient clinics at 14 referral centers (June 2006-December 2008). Patients with VTE before a diagnosis of IBD or those not confirmed to have VTE, cancer, or a VTE other than deep vein thrombosis or pulmonary embolism, were excluded. Recurrence rates were compared with 1255 prospectively followed patients without IBD that had a first unprovoked VTE (not triggered by trauma, surgery, or pregnancy). The primary end point was symptomatic, objectively confirmed, recurrent VTE after discontinuation of anticoagulation therapy after a first VTE. RESULTS Overall, of 116 IBD patients who had a history of first VTE, 86 were unprovoked. The probability of recurrence 5 years after discontinuation of anticoagulation therapy was higher among patients with IBD than patients without IBD (33.4%; 95% confidence interval [CI]: 21.8-45.0 vs 21.7%; 95% CI: 18.8-24.6; P = .01). After adjustment for potential confounders, IBD was an independent risk factor of recurrence (hazard ratio = 2.5; 95% CI: 1.4-4.2; P = .001). CONCLUSIONS Patients with IBD are at an increased risk of recurrent VTE compared to patients without IBD.

Plummer-Vinson syndrome

Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of dysphagia, iron-deficiency anemia and esophageal webs. Exact data about epidemiology of the syndrome are not available; the syndrome is extremely rare. Most of the patients are white middle-aged women, in the fourth to seventh decade of life but the syndrome has also been described in children and adolescents. The dysphagia is usually painless and intermittent or progressive over years, limited to solids and sometimes associated with weight loss. Symptoms resulting from anemia (weakness, pallor, fatigue, tachycardia) may dominate the clinical picture. Additional features are glossitis, angular cheilitis and koilonychia. Enlargement of the spleen and thyroid may also be observed. One of the most important clinical aspects of Plummer-Vinson syndrome is the association with upper alimentary tract cancers. Etiopathogenesis of Plummer-Vinson syndrome is unknown. The most important possible etiological factor is iron deficiency. Other possible factors include malnutrition, genetic predisposition or autoimmune processes. Plummer-Vinson syndrome can be treated effectively with iron supplementation and mechanical dilation. In case of significant obstruction of the esophageal lumen by esophageal web and persistent dysphagia despite iron supplementation, rupture and dilation of the web are necessary. Since Plummer-Vinson syndrome is associated with an increased risk of squamous cell carcinoma of the pharynx and the esophagus, the patients should be followed closely.

Prevalence and clinical importance of hypertransaminasaemia in coeliac disease.

OBJECTIVE To assess the prevalence and potential pathogenetic factors of hypertransaminasaemia in patients with coeliac disease prior to initiation of a gluten-free diet (GFD) and to assess the course of transaminases on a GFD. PATIENTS A retrospective study was made of 178 patients with coeliac disease (130 women, 48 men; median age 36 years; range 17-84 years) at the gastroenterological department of a university hospital. METHODS Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured prior to initiation of a GFD and at 3, 6 and 12 months of GFD. Intestinal permeability, a test for functional integrity of the small bowel, was investigated before starting a GFD in 116 patients by an oral test using lactulose and mannitol. RESULTS In 72 patients (40.4%) AST and/or ALT were increased prior to initiation of a GFD. Within 1 year on a GFD ALT and AST normalized except in eight cases (4.6%). The intestinal permeability index (% lactulose/% mannitol in 5 h urine) was higher in patients with elevated (median 0.34; range 0.03-1.43) than in patients with normal transaminases (0.11; 0.02-1.28) (P < 0.0001) and correlated with AST (tau = 0.34; P < 0.0001) and ALT (tau = 0.32; P < 0.0001). In five cases with hypertransaminasaemia a liver biopsy was performed prior to initiation of a GFD. Two patients had mild to moderate hepatitis with septal fibrosis. The other three had minimal lymphocytic infiltrates of the portal tracts. Inflammatory alterations of the bile ducts were not found. CONCLUSION Hypertransaminasaemia before GFD is frequent in coeliac patients, correlates with intestinal permeability and normalizes on a GFD in most patients. In cases of persistently elevated liver function tests of unknown origin underlying coeliac disease should be considered.

Dental and periodontal disease in patients with cirrhosis - role of etiology of liver disease

BACKGROUND/AIMS Bacterial infections are frequent complications in patients with cirrhosis, especially in alcoholics. A potential source of infection may be dental foci. The aim of the study was to assess the role of cirrhosis and chronic alcoholism in the development of dental or periodontal disease. METHODS Dental and periodontal examinations were performed prospectively in 97 patients with cirrhosis (alcoholic: 64, nonalcoholic: 33), in 68 alcoholics without cirrhosis and in 71 healthy subjects (subdivided into age groups: 21-30, 31-40, 41-50, and 51-60 years). RESULTS Measures of oral hygiene (p < 0.01), dental care (p < 0.001), and periodontal parameters were worse and the number of teeth requiring treatment (p < 0.001) was higher in alcoholics with or without cirrhosis than in healthy subjects and nonalcoholic patients with cirrhosis. Alcoholics had a lower total number of teeth than patients without alcohol abuse and healthy controls (p < 0.05). The dental and periodontal status of patients with nonalcoholic cirrhosis did not differ from the control group. The severity and duration of liver disease had no influence on dental and peridontal disease. CONCLUSION The presence of cirrhosis itself, therefore, is not a predisposing factor for dental and periodontal diseases. In alcoholics, these diseases appear to be caused primarily by bad oral hygiene and poor dental care.

Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding ☆

BACKGROUND Recommendations on breastfeeding under thiopurines are inconsistent due to limited data. AIM To assess the risk of infections in offspring breastfed by mothers receiving azathioprine (AZA) for inflammatory bowel disease (IBD). METHODS Babies, who were breastfed from their mothers treated either with or without AZA were included from a local pregnancy-registry. Women were asked by structured personal interview on general development, infections, hospitalisations and vaccinations of their offspring. RESULTS A group of 11 mothers taking AZA (median 150 mg/d) during pregnancy and lactation and another of 12 patients without using any immunosuppressive therapy breastfed 15 babies each for median 6 months and 8 months, respectively. Median age of children at time of interview was 3.3 and 4.7 years, respectively. All offspring showed age-appropriate mental and physical development. Infections were commonly seen childhood diseases. Similar rates were observed for most of the various infections between offspring with and without azathioprine exposure during breastfeeding. However, common cold more than two episodes/year and conjunctivitis were numerically more often reported in the group without AZA exposure. In an exploratory analysis no difference in the rate of hospitalisations was seen between exposed (0.06 hospitalisations/patient year) versus non-exposed children (0.12 hospitalisations/patient year, p=0.8) CONCLUSION Our study which reports the largest number of babies breastfed with exposure to AZA suggests that breastfeeding does not increase the risk of infections.

Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease.

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.