Fernando Rizzello

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and Medical Management

This paper is the first in a series of two publications relating to the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn’s disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn’s disease. Surgical management as well as special situations including management of perianal Crohn’s disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016].

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohns disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohns disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.

Use of corticosteroids and immunosuppressive drugs in inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease

The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohns disease, are not curable but can be controlled by various medical therapies. The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases.

European Crohn’s and Colitis Organisation Topical Review on IBD in the Elderly

This ECCO topical review of the European Crohns and Colitis Organisation [ECCO] focuses on the epidemiology, pathophysiology, diagnosis, management and outcome of the two most common forms of inflammatory bowel disease, Crohns disease and ulcerative colitis, in elderly patients. The objective was to reach expert consensus to provide evidence-based guidance for clinical practice.

Prevalence and effectiveness of psychiatric treatments for patients with IBD: A systematic literature review

OBJECTIVESnHigher prevalence of psychiatric disorders, such as anxiety and depression, has been found in people with Crohns disease and Ulcerative Colitis compared to the general population. Nowadays, international guidelines advocate psychotherapy and psycho-pharmacological treatments as playing an important role in IBD care. The main goal of this systematic literature review was summarize the evidence on the utilization and effectiveness of treatments for depression and anxiety in persons with IBD.nnnMETHODSnA systematic literature review was conducted using three different electronic databases: MEDLINE, PsychINFO, and EMBASE to identify studies reporting the prevalence and efficacy of psycho-pharmacological and psychotherapeutic treatments for IBD. A quality appraisal was conducted using several scales as appropriate for each study design. A narrative synthesis was also performed.nnnRESULTSnForty-three studies were included. Although a high rate of psychoactive drug use was found in people with IBD, a low proportion of IBD patients have access to psychiatric referral. 1/3 of the studies found that psychotherapy was effective for improving the quality of life, perception of stress, anxiety and depression as well as disease. Antidepressants proved effective in reducing disease activity, gastrointestinal symptoms, anxiety and depression.nnnCONCLUSIONnOur results suggest that psychiatric treatment should be implemented in IBD care. However, further studies are needed to confirm the findings of our systematic review.

Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice

(Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg(−1) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg(−1) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

Training Programs on Endoscopic Scoring Systems for Inflammatory Bowel Disease Lead to a Significant Increase in Interobserver Agreement Among Community Gastroenterologists

Background and AimsnEndoscopic outcomes are increasingly used in clinical trials and in routine practice for inflammatory bowel disease [IBD] in order to reach more objective patient evaluations than possible using only clinical features. However, reproducibility of endoscopic scoring systems used to categorize endoscopic activity has been reported to be suboptimal. The aim of this study was to analyse the inter-rated agreement of non-dedicated gastroenterologists on IBD endoscopic scoring systems, and to explore the effects of a dedicated training programme on agreement.nnnMethodsnA total of 237 physicians attended training courses on IBD endoscopic scoring systems, and they independently scored a set of IBD endoscopic videos for ulcerative colitis [with Mayo endoscopic subscore], post-operative Crohns disease [with Rutgeerts score] and luminal Crohns disease (with the Simple Endoscopic Score for Crohns Disease [SESCD] and Crohns Endoscopic Index of Severity [CDEIS]). A second round of scoring was collected after discussion about determinants of discrepancy. Interobserver agreement was measured by means of the Fleiss kappa [kappa] or intraclass correlation coefficient [ICC] as appropriate.nnnResultsnThe inter-rater agreement increased from kappa 0.51 (95% confidence interval [95% CI] 0.48-0.55) to 0.76 [95% CI 0.72-0.79] for the Mayo endoscopic subscore, and from 0.45 [95% CI 0.40-0.50] to 0.79 [0.74-0.83] for the Rutgeerts score before and after the training programme, respectively, and both differences were significant [P < 0.0001]. The ICC was 0.77 [95% CI 0.56-0.96] for SESCD and 0.76 [0.54- 0.96] for CDEIS, respectively, with only one measurement.nnnDiscussionnThe basal inter-rater agreement of inexperienced gastroenterologists focused on IBD management is moderate; however, a dedicated training programme can significantly impact on inter-rater agreement, increasing it to levels expected among expert central reviewers.

Prepouch Ileitis After Ileal Pouch-anal Anastomosis: Patterns of Presentation and Risk Factors for Failure of Treatment

Background and AimsnThere is a lack in the literature about prepouch ileitis [PI], in particular regarding risk factors associated with failure of the medical treatment. Aim of the study is to analyse the characteristics of PI patients and to compare those who required surgery with those who were successfully treated with conservative therapy.nnnMethodsnAll cases presenting a diagnosis of PI were included and analysed. Patients eventually requiring surgery were compared with those who were managed conservatively, for symptoms of presentation, endoscopic characteristics, and rate of response to medical treatment. A sub-analysis of outcomes based on the final histology was performed.nnnResultsnThe overall incidence of PI among 1286 patients was 4.4% [57], after a median of 6.8 years from pouch surgery. Symptoms included increased frequency [26.4%], outlet obstruction [21%], and bleeding [15.8%]. Afferent limb stenosis affected 49.1% of patients. The comparison showed that patients requiring surgery had a higher rate of Crohns disease and indeterminate colitis [42.1 vs 0% and 15.8 vs 2.6%, p < 0.0001], outlet obstruction as main symptom [47.4 vs 7.9%, p = 0.0023], and afferent limb stenosis [73.7 vs 36.8%, p = 0.008] at endoscopy. Rate of failure of medical treatment at 5 years was 8.2% in patients with ulcerative colitis and 75% in the presence of both indeterminate colitis and Crohns disease [p < 0.0001].nnnConclusionsnCrohns disease, indeterminate colitis, and stenosis with outlet obstruction are risk factors for failure of treatment after diagnosis of PI. Early aggressive therapy and surgery should be considered in these cases.

Case-control Study on Dactylitis, Enthesitis, and Anterior Uveitis in Spondyloarthritis Associated with Inflammatory Bowel Diseases: Role of Coexistent Psoriasis

Objective. To evaluate the frequency of dactylitis, enthesitis, and anterior uveitis (AU) in spondyloarthritis (SpA) associated with inflammatory bowel disease (IBD-SpA) compared with other SpA, and to assess the role of associated psoriasis in the occurrence of dactylitis and enthesitis. Methods. In a 12-month case-control study, the frequency of dactylitis and enthesitis in 29 patients with ulcerative colitis (UC) and 59 with Crohn disease (CD) who satisfied the Spondyloarthritis international Society criteria for axial or peripheral SpA was compared with 176 controls, including 97 (55.1%) with psoriatic arthritis (PsA), 47 (26.7%) with ankylosing spondylitis (AS), and 32 (18.2%) with nonradiographic axial SpA (nr-axSpA). The occurrence of these features in IBD-SpA with and without psoriasis was also evaluated. Results. Axial, peripheral, or mixed involvement was observed in 46 (52%), 29 (33%), and 13 (15%) patients, respectively; and 14/88 (16%) had psoriasis. Dactylitis was recorded in 4/88 patients (4.5%) with IBD-SpA and in 30 controls (17.4%; p = 0.008), enthesitis in 16 cases (18.1%) and in 78/176 controls (44.3%; p < 0.001), and AU in 3 patients (3.4%) with IBD-SpA and in 26 controls (14.7%; p = 0.01). No significant differences were found between patients with UC-SpA and those with CD-SpA. Dactylitis and enthesitis were significantly more common in patients with IBD-SpA who also had psoriasis compared to those without skin disease (p = 0.009 and 0.003, respectively). Conclusion. Dactylitis, enthesitis, and AU are significantly less frequent in IBD-SpA compared with other types of SpA. Given the frequent association of psoriasis and IBD, overlooking coexistent skin disease may lead to overestimating the frequency of these features.

Real-time elastography for the detection of fibrotic and inflammatory tissue in patients with stricturing Crohn’s disease

PurposeThe distinction between active inflammation and fibrosis of the bowel wall is essential for therapeutic decisions in stricturing Crohn’s disease. We aimed to assess whether real-time elastography (RTE) with strain ratio measurement could be useful in differentiating fibrotic from inflamed bowel strictures and to evaluate the possible relationship between US techniques and the histology of the stenotic bowel wall.Materials and methodsBowel ultrasonography (including RTE, color-Doppler and CEUS examination) was prospectively evaluated in 26 patients with symptomatic stricturing Crohn’s disease, before surgery. RTE was adopted to evaluate bowel stiffness: five loops of 20 RTE frames were recorded for each stenotic segment and the mean strain ratio (MSR) was obtained. Histology scoring systems both for inflammation and fibrosis were established for surgical specimens.ResultsNo significant correlation was found between MSR and fibrosis score (Pxa0=xa00.877). Color-Doppler score was significantly related to gut wall and submucosal thicknesses (Pxa0=xa00.006 and Pxa0=xa00.032, respectively). There was no significant correlation between the number of vessels counted at histology and color-Doppler and CEUS examinations (Pxa0=xa00.170 and Pxa0=xa00.302, respectively).ConclusionMSR detection was not able to distinguish fibrotic from inflammatory tissue in our selected population. This result could be influenced by the presence of the superimposed inflammation. Larger cohort of patients, further analysis with shear wave elastography, and validated histopathology classification systems for fibrosis and inflammation are necessary to assess if intestinal fibrosis could be reliably detected on the basis of bowel elastic properties.SommarioObiettivola distinzione tra infiammazione attiva e fibrosi nella parete intestinale è essenziale nel proceso decisionale della terapia nella malattia di Crohn stenosante. Lo scopo del nostro studio era di stabilire se l’elastografia real-time (RTE) con la misurazione dello strain ratio potesse essere utile nel differenziare il tessuto fibrotico da quello infiammatorio nella parete intestinale stenotica, e di valutare la presenza di correlazioni tra le tecniche ecografiche di studio delle anse intestinali e le caratteristiche istologiche dei segmenti analizzati.Materiali e metodiLo studio ecografico delle anse intestinali che comprendeva anche RTE, valutazione color-Doppler e CEUS, è stato eseguito in maniera prospettica in 26 pazienti con malattia di Crohn stenosante sintomatica, prima dell’ intervento chirurgico resettivo. La RTE è stata utilizzata per valutare la rigidità della parete intestinale: 5 filmati di 20 frames di elastografia sono stati registrati per ogni segmento stenotico, per ogni frame è stato calcolato lo strain ratio e quindi ne è stata ottenuta la media (MSR). E’ stato poi stabilito uno score istologico per l’ infiammazione e la fibrosi per i pezzi operatori analizzati.Risultatinon è stata rilevata alcuna correlazione significativa tra MSR e score istologico della fibrosi (Pxa0=xa00877). Il Color-doppler correlava significativamente con lo spessore di parete e l’ispessimento della sottomucosa (Pxa0=xa00006 e Pxa0=xa00032, rispettivamente). Non è stata trovata una correlazione significativa tra il numero di vasi rilevato sul pezzo istologico e gli score color-Doppler e CEUS (Pxa0=xa00170 e Pxa0=xa00302, rispettivamente).Conclusioniil calcolo del MSR non si è rivelato un parametro efficace nel distinguere tra tessuto fibrotico ed infiammatorio nella nostra popolazione. Questo risultato è influenzato da vari fattori, tra cui probabilmente la compresenza di infiammazione. Coorti di pazienti più ampie, ulteriori analisi con l’ausilio eventualmente dell’ elastografia shear-wave, e sistemi di classificazione istopatologici validati sia per la fibrosi che per l’infiammazione, risultano necessari per stabilire se la fibrosi intestinale possa essere rilevata in maniera affidabile sulla base delle proprietà elastiche della parete intestinale.