Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil‐predominant infiltration, thereby ...conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T‐helper (Th)2‐type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single‐nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen–driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.
Summary
Background
Some patients with a phenotypic appearance of eosinophilic oesophagitis (EoE) respond histologically to PPI, and are described as having PPI‐responsive oesophageal eosinophilia ...(PPI‐REE). It is unclear if PPI‐REE is a GERD‐related phenomenon, a subtype of EoE, or a completely unique entity.
Aim
To compare demographic, clinical and histological features of EoE and PPI‐REE.
Methods
Two databases were reviewed from the Walter Reed and Swiss EoE databases. Patients were stratified into two groups, EoE and PPI‐REE, based on recent EoE consensus guidelines. Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least a 6‐week course of treatment.
Results
One hundred and three patients were identified (63 EoE and 40 PPI‐REE; mean age 40.2 years, 75% male and 89% Caucasian). The two cohorts had similar dysphagia (97% vs. 100%, P = 0.520), food impaction (43% vs. 35%, P = 0.536), and heartburn (33% vs. 32%, P = 1.000) and a similar duration of symptoms (6.0 years vs. 5.8 years, P = 0.850). Endoscopic features were also similar between EoE and PPI‐REE; rings (68% vs. 68%, P = 1.000), furrows (70% vs. 70%, P = 1.000), plaques (19% vs. 10%, P = 0.272), strictures (49% vs. 30%, P = 0.066). EoE and PPI‐REE were similar in the number of proximal (39 eos/hpf vs. 38 eos/hpf, P = 0.919) and distal eosinophils (50 vs. 43 eos/hpf, P = 0.285).
Conclusions
EoE and PPI‐responsive oesophageal eosinophilia are similar in clinical, histological and endoscopic features and therefore are indistinguishable without a PPI trial. Further studies are needed to determine why a subset of patients with oesophageal eosinophilia respond to PPI.
Background
Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus with a rapidly increasing incidence. However, population‐based epidemiologic data on EoE are rare and ...limited to regions with less than 200 000 inhabitants. We evaluated the incidence and prevalence of EoE over time in Canton of Vaud, Switzerland.
Materials and methods
Canton of Vaud lies in the French‐speaking, Western part of Switzerland. As of December 2013, it had a population of 743 317 inhabitants. We contacted all pathology institutes (n = 6) in this canton to identify patients that have been diagnosed with esophageal eosinophilia between 1993 and 2013. We then performed a chart review in all adult and pediatric gastroenterology practices to identify patients with EoE.
Results
Of 263 patients with esophageal eosinophilia, a total of 179 fulfilled the diagnostic criteria for EoE. Median diagnostic delay was 4 (IQR 1–9) years. No patient was diagnosed with EoE prior to 2003. Incidence of EoE increased from 0.16/100 000 inhabitants in 2004 to 6.3/100 000 inhabitants in 2013 (P < 0.001). The cumulative EoE prevalence in 2013 was 24.1/100 000. The incidence in males was 2.8 times higher (95% CI 2.01–3.88, P < 0.001) when compared to that in females. The annual EoE incidence was 10.6 times higher (95%‐CI 7.61–14.87, P < 0.001) in the period from 2010 to 2013 when compared to that in the period from 1993 to 2009.
Conclusions
The incidence and cumulative prevalence of EoE in Canton of Vaud, Switzerland, has rapidly increased in the past 10 years.
Background
Long‐lasting food impactions requiring endoscopic bolus removal occur frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for severe esophageal injuries. We ...evaluated whether treatment with swallowed topical corticosteroids is able to reduce the risk of occurrence of this complication.
Methods
We analyzed data from the Swiss EoE Cohort Study. Patients with yearly clinic visits, during which standardized assessment of symptoms, endoscopic, histologic, and laboratory findings was carried out, were included.
Results
A total of 206 patients (157 males) were analyzed. The median follow‐up time was 5 years with a total of 703 visits (mean 3.41 visits/patient). During the follow‐up period, 33 patients (16 % of the cohort) experienced 42 impactions requiring endoscopic bolus removal. We evaluated the following factors regarding the outcome ‘bolus impaction’ by univariate logistic regression modeling: swallowed topical corticosteroid therapy (OR 0.503, 95%‐CI 0.255–0.993, P = 0.048), presence of EoE symptoms (OR 1.150, 95%‐CI 0.4668–2.835, P = 0.761), esophageal stricture (OR 2.832, 95%‐CI 1.508–5.321, P = 0.001), peak eosinophil count >10 eosinophils/HPF (OR 0.724, 95%‐CI 0.324–1.621, P = 0.433), blood eosinophilia (OR 1.532, 95%‐CI 0.569–4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%‐CI 1.034–3.755, P = 0.017). In the multivariate model, the following factors were significantly associated with bolus impaction: swallowed topical corticosteroid therapy (OR 0.411, 95%‐CI 0.203–0.835, P = 0.014) and esophageal stricture (OR 2.666, 95%‐CI 1.259–5.645, P = 0.01). Increasing frequency of use of swallowed topical steroids was associated with a lower risk for bolus impactions.
Conclusions
Treatment of EoE with swallowed topical corticosteroids significantly reduces the risk for long‐lasting bolus impactions.
Summary
Background
While rifaximin was able to improve symptoms in patients with irritable bowel syndrome (IBS) in phase III trials, these results are yet to be repeated in phase IV studies.
Aim
To ...evaluate the treatment response to rifaximin in IBS patients in a phase IV trial.
Methods
IBS patients underwent lactulose hydrogen breath testing (LHBT). LHBT‐positive patients were treated with rifaximin for 14 days. Prior to treatment as well as at week 4 and 14 following the start of rifaximin treatment, patients completed a questionnaire assessing symptom severity on a Likert scale from 0 to 10.
Results
One hundred and six of 150 IBS patients (71%) were LHBT‐positive and treated with rifaximin. As assessed at week 4 following commencement of the therapy, rifaximin provided significant improvement of the following IBS‐associated symptoms: bloating (5.5±2.6 before the start of the treatment vs. 3.6±2.7 at week 4, P<0.001), flatulence (5.0±2.7 vs. 4.0±2.7, P=0.015), diarrhoea (2.9±2.4 vs. 2.0±2.4, P=0.005) and abdominal pain (4.8±2.7 vs. 3.3±2.5, P<0.001). Overall well‐being also significantly improved (3.9 ± 2.4 vs. 2.7 ± 2.3, P < 0.001). Similar improvements in IBS symptoms were obtained at week 14. Eighty‐six per cent of patients undergoing repetitive LHBT (55/64) tested negative at week 4.
Conclusions
We found a high percentage of LHBT‐positive IBS patients. IBS‐associated symptoms (bloating, flatulence, diarrhoea, pain) were improved for a period of 3 months following 2 weeks of treatment with rifaximin. We conclude that rifaximin treatment alleviates symptoms in LHBT‐positive IBS patients.
One of the several possible causes of irritable bowel syndrome (IBS) is thought to be low‐grade mucosal inflammation. Flagellin, the primary structural component of bacterial flagellae, was shown in ...inflammatory bowel disease patients to activate the innate and adaptive immunity. It has not yet been conclusively established if IBS patients show reactivity to luminal antigens. In 266 patients 112 IBS, 61 Crohn’s disease (CD), 50 ulcerative colitis (UC) and 43 healthy controls (HC), we measured antibodies to flagellin (FAB, types A4‐Fla2 and Fla‐X), anti‐Saccharomyces cerevisiae antibodies (ASCA) (both ELISA), antipancreas antibodies (PAB) and perinuclear antineutrophil cytoplasmatic antibodies (p‐ANCA) (both IF). All IBS patients had normal fecal calprotectin (mean 21 μg mL−1, SD 6.6) and fulfilled the ROME II criteria. Frequencies of antibodies in patients with IBS, CD, UC and HC, respectively, are as follows (in per cent): antibodies against A4‐Fla2: 29/48/8/7; antibodies against Fla‐X: 26/52/10/7; ASCA: 6/59/0/2; p‐ANCA: 0/10/52/0; and PAB: 0/28/0/0. Antibodies against A4‐Fla2 and Fla‐X were significantly more frequent in IBS patients than in HC (P = 0.004 and P = 0.009). Antibodies to A4‐Fla2 and Fla‐X were significantly more frequent in IBS patients with antecedent gastroenteritis compared to non‐postinfectious IBS patients (P = 0.002 and P = 0.012). In contrast to ASCA, PAB and p‐ANCA, antibodies against A4‐Fla2 and Fla‐X were found significantly more often in IBS patients, particularly in those with postinfectious IBS, compared to HC. This observation supports the concept that immune reactivity to luminal antigens has a putative role in the development of IBS, at least in a subset of patients.
Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet ...been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.
Summary
Background
There is uncertain evidence of effectiveness of 5‐aminosalicylates (5‐ASA) to induce and maintain response and remission of active Crohn's disease (CD), and weak evidence to ...support their use in post‐operative CD.
Aim
To assess the frequency and determinants of 5‐ASA use in CD patients and to evaluate the physicians' perception of clinical response and side effects to 5‐ASA.
Methods
Data from the Swiss Inflammatory Bowel Disease Cohort, which collects data since 2006 on a large sample of IBD patients, were analysed. Information from questionnaires regarding utilisation of treatments and perception of response to 5‐ASA were evaluated. Logistic regression modelling was performed to identify factors associated with 5‐ASA use.
Results
Of 1420 CD patients, 835 (59%) were ever treated with 5‐ASA from diagnosis to latest follow‐up. Disease duration >10 years and colonic location were both significantly associated with 5‐ASA use. 5‐ASA treatment was judged to be successful in 46% (378/825) of treatment episodes (physician global assessment). Side effects prompting stop of therapy were found in 12% (98/825) episodes in which 5‐ASA had been stopped.
Conclusions
5‐Aminosalicylates were frequently prescribed in patients with Crohn's disease in the Swiss IBD cohort. This observation stands in contrast to the scientific evidence demonstrating a very limited role of 5‐ASA compounds in the treatment of Crohn's disease.
Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is ...commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction.
•Repeated, intermittent, low-dose ketamine induces locomotor sensitization at a lower dose in female rats than males.•Ketamine sensitization was associated with increased dendritic spine density in the nucleus accumbens of males and females.•Ketamine sensitization was associated with increased protein expression in the nucleus accumbens of male and female rats.
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