Ewa Waszczuk

The Lifetime Prevalence of Anxiety Disorders Among Patients with Irritable Bowel Syndrome

BACKGROUND The prevalence of irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, ranges from 10% to 20% in the general population. It is estimated that from 40% to 90% of persons with a diagnosis of IBS suffer from mental disorders, mainly anxiety and depressive disorders. OBJECTIVES The aim of the study was to assess the lifetime prevalence of anxiety disorders in IBS patients and to compare it with the prevalence of these disorders in a control group of patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS The study included 106 patients with IBS and 53 patients with GERD. IBS was diagnosed according to the Rome II criteria after a basic evaluation to exclude an organic disease. Anxiety disorders were diagnosed using the Composite International Diagnostic Interview (CIDI) in accordance with ICD-10 diagnostic criteria. RESULTS Anxiety disorders during the patients lifetime were diagnosed in 50 IBS patients (47%). Specific phobias occurred in 23.5% of them, social phobias in 10.4%, generalized anxiety disorder in 10.4%, panic disorder in 3.8% and agoraphobia in 8.5%. In the control group with GERD, anxiety disorders during the subjects lifetime were diagnosed in 30% of the group. The difference in the prevalence of anxiety disorders between patients with IBS and GERD was statistically significant (p<0.05). CONCLUSIONS The lifetime prevalence of anxiety disorders in IBS patients was higher than in the control group with GERD (47% vs. 30%). The prevalence rate of anxiety disorders in the control group with GERD was similar to the prevalence rate in the general population.

Anorectal function and visceral hypersensitivity in celiac disease.

Objective To evaluate anorectal function and rectal sensitivity thresholds in patients with celiac disease (CD). Methods In 25 unselected patients with CD (16 female, 9 male; mean age 45, range 24 to 75 y) and 20 controls (12 female, 8 male; mean age 41, range 20 to 65 y) anorectal manometry and rectal balloon distension test were conducted using a 4 lumen water perfused catheter with a polyethylene balloon (Zinectics Manometric Catheter, Medtronic). Results In celiac patients the maximal anal resting pressure, reflecting the internal anal sphincter function, was significantly higher than that in the controls: 87.8±21.7 mm Hg versus 66.7±15.2 mm Hg (P<0.001). There were no considerable differences between both the groups neither in the maximal anal squeeze nor in the cough pressures. Celiac patients had significantly lower first sensation threshold: 25.6±10.8 mL versus 37.5±12.5 mL (P<0.05). Visceral hypersensitivity (rectal pain/discomfort threshold ≤100 mL) was observed in 36% of celiac patients and in none of the controls (P<0.01). Conclusions The increased anal resting pressure and rectal hypersensitivity are observed in CD. Disturbances in gastrointestinal motility and visceral perception in the course of CD may occur at different levels of the brain-gut axis including direct changes in the enteric nervous system.

A 'cocoon immunization strategy' among patients with inflammatory bowel disease.

Background and aims A ‘cocoon strategy’ is defined as the strategy of protecting vulnerable patients from infectious diseases by vaccinating those in close contact with them. In our study, we evaluate the vaccination status among children living with patients with inflammatory bowel disease (IBD) to determine the realization of the cocoon strategy and to identify characteristics associated with pediatric vaccine refusal. Patients and methods A self-completed survey was conducted on 136 hospitalized patients with IBD. The survey comprised questions about household child vaccination coverage, the reasons for vaccine refusal, and the history of infectious diseases among the patients. Results Fifty-six patients reported living with children. Forty percent of children were vaccinated with at least one of the recommended vaccines. Most frequently, children received pneumococcal (26%) and rotaviruses (22%) vaccines. The most common reason for nonimmunization was patients’ opinion that immunizations are not necessary for them (52%). There was a statistically significant association between the nonreimbursed vaccines coverage and the educational level of the patients (P<0.0001). Despite the fact that 28% of the patients could not definitively recall varicella infection, none of them and none of the children in their household had been vaccinated against chickenpox. Conclusion The use of nonmandatory vaccines recommended in family members of patients with IBD is insufficient. Further vaccine promotion and education of patients as well as their healthcare providers is required. A particular concern is associated with the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized and varicella-zoster virus-seronegative patients should be vaccinated, and in case of immunosuppression, vaccination of children in the household is required.

Inadequate seroprotection against hepatitis B virus and one detected case of hepatitis C virus infection among patients with inflammatory bowel disease.

Objectives The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with inflammatory bowel disease (IBD) from central and eastern European countries is unknown. Postvaccination HBV immunity in an immunocompromised host may wane. The aims of the study were as follows: to assess the immune status for HBV and HCV among IBD patients, the level of HBV seroprotection, and to compare the immune status of patients who received mandatory versus recommended HBV vaccination. Materials and methods Serological markers of HBV and HCV (anti-HBs, anti-HBc, HBsAg, and anti-HCV) were determined in 147 consecutive IBD patients. An anti-HBs of 10 IU/l or more was considered as immunity to HBV infection. Results HBV infection was detected in 21 patients, whereas 11 of them recalled previous HBV vaccination. Sixty-eight noninfected patients had a level of anti-HBs 10 IU/l or more and only 29% reached the cut-off level of 100 IU/l. Among patients vaccinated obligatorily, two patients had previous HBV infection and 15% did not have an adequate seroprotection against HBV. Patients who received a mandatory HBV vaccine more frequently had a protective anti-HBs level than those vaccinated voluntarily (P<0.001). One positive anti-HCV result was found. Conclusion A mandatory HBV vaccination significantly increased the number of patients effectively protected against HBV; however, a remarkable number of vaccinated IBD patients had inadequate HBV seroprotection. All IBD patients should be screened for HBV and HCV infections and monitored for anti-HBs titers.

Genetic polymorphism of ABCB1 gene (C3435T) in patients with inflammatory bowel diseases. Is there any gender dependency

BACKGROUND In recent years, an increasing incidence of inflammatory bowel disease (IBD) has been reported, mainly as Crohns disease (CD) and ulcerative colitis (UC). The individual susceptibility, the diseases course and response to the applied therapy is likely due to genetic factors such as ABCB1 gene mutations, exemplified by C3435T polymorphism. The aim of the study was to evaluate the distribution of C3435T polymorphism regarding the gender in IBD patients and control subjects from Lower Silesia region and its possible association with IBD susceptibility. METHODS The research was conducted in groups of 61 IBD patients and 101 healthy subjects from the Lower Silesia region. Polymorphism of C3435T was determined using PCR-RFLP method. RESULTS Frequency distributions of C3435T genotype and of 3435T or 3435C gene alleles of IBD, CD or UC patients were compared to control group; each treated as a whole or split further by gender. The statistically significant correlation was discovered between gender and C3435T genotype both for IBD and CD patients, with 3435CT heterozygote prevailing in IBD and CD males. Odds ratio calculations revealed statistically significant difference for the 3435CT genotype between control and: IBD group considered as a whole; IBD males; CD males; and for 3435TT variant between control and IBD males. Conclusions. The 3435CT genotype could be a risk factor for IBD and CD in men. The 3435TT genotype in males seems to be associated with the lower chance of IBD presence.

Mo2040 Association of Polymorphisms in 5-HT2A and 5-HT2C Receptors Genes With Depressive and Anxiety Disorders in Patients With Irritable Bowel Syndrome

BACKGROUND: Subgroups of patients with irritable bowel syndrome (IBS) may have low grade mucosal immune activity. Fecal calprotectin (f-calprotectin) levels are considered a marker for mucosal neutrophil inflammation and may be used as a biomarker for disease activity in inflammatory diseases. IBS patients are reported to have normal levels of calprotectin, but the levels may vary within the patient group, and it is not known whether this variation within or slightly above the normal range may reflect pathology or symptoms of the patients. AIM: To determine if levels of f-calprotectin may reflect the clinical and pathophysiological phenotype of IBS patients. METHODS: Analyses of f-calprotectin in stool samples of 98 IBS patients and 35 healthy controls were performed with Buhlmann ELISA (lower detection limit 10 ug/g). All IBS subjects completed the Bristol stool form (BSF) scale and the IBS symptom severity scale (IBS-SSS) questionnaire to assess gastrointestinal symptom severity. Patients also underwent a rectal barostat test with ballon distentions and colonic transit time measurement with ingestion of radiopaque rings. RESULTS: IBS patients had comparable levels of f-calprotectin to controls (17.5 (10-47.0) vs. 11(10-44.0) (median (2575%) percentiles) ug/g; p=0.21)). Among IBS patients, 13 subjects (13.2%) had f-calprotectin levels above the 90th percentile in the controls (98.8ug/g). There was no difference in IBS subgroup according to Rome III (IBS-C, IBS-D, IBS-M, IBS-U) in patients with high as compared to normal f-calprotectin. Also the disease duration was comparable in the two groups (9.5 (2-15) vs. 10 (5-15.3) years; p=0.46). There was no difference between IBS patients with high vs. normal levels of f-calprotectin regarding intensity or frequency of pain, bloating severity, bowel habit dissatisfaction, or daily life as estimated by IBS-SSS (Table 1). Also, total IBS-SSS score was comparable in the two groups (Table 1). The average stool form according to BSF (3.7 (2.9-4.4) vs. 4.1 (3.3-4.9); p=0.2) and stool frequency (1.5 (0.75-1.9) vs. 1.6 (1.2-2.3); p=0.29) were also similar in patients with high respective normal calprotectin levels. The pain threshold in rectal barostat test was comparable in IBS patients with high respective normal levels of f-calprotectin (24 (24-28) vs. 24 (20-32) mmHg; p=0.65). Moreover, oroanal transit time (OATT) was comparable in the two groups (1.5 (0.5-1.9) vs. 1.2(0.7-1.9) days; p=0.95) CONCLUSION: Fecal calprotectin within the normal range is not associated with the severity of IBS symptoms or key pathophysiological factors. Our data do not support that mucosal neutrophil inflammation is of major importance for symptom generation in IBS. Table 1. Symptom severity assessed by -IBS-SSS in IBS patients with high respective normal levels of fecal calprotectin.

Gluten, Dysbiosis, and Genetics in Celiac Disease: All Are Important

We have read with a great interest the article ‘‘Gut microbiota and celiac disease’’ by Marasco et al. which provides the latest advances in understanding the role of the dysbiosis in the pathogenesis of celiac disease (CD) and the influence of a gluten-free diet (GFD) on gut microbiota. However, we disagree with their statement that the period of gluten introduction into the infant diet increases the prevalence of CD. It is against the current knowledge, especially regarding healthy children, without increased risk of CD. Recent studies (CELIPREV and Prevent CD) have shown that early (at 4 or 6 months of age) exposition to gluten does not influence the absolute risk of CD during the childhood [1, 2]. Furthermore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPHAGAN) has changed previous recommendations and now gluten may be introduced into the infant diet from 4 to 12 months completed [3]. Of particular concern are children who have a first-degree relative with CD, because they have a 10–15 % of risk to be homozygous for HLA-DQ2. In this case, early gluten exposition may provoke an immunologic response. It is still under debate if it is beneficial for them to delay the gluten exposure, but the data are conflicting and timing of gluten introduction seems to play a minor role in onset of symptoms. It was a great value of the Marasco et al.’s paper to mention the impact of environmental conditions influencing a microbiota composition, i.e., the mode of delivery, breastfeeding, early infections, and antibiotic use. We would like to emphasize that also other drugs, such as PPI or NSAIDs (both commonly overused), change the balance between bacteria and may cause dysbiosis [4, 5]. Every physician should be aware of the complex impact of prescribed therapy, especially in a patient with a chronic condition like CD. Gut microbiota fluctuates over the first 2–3 years of life, in young group of patients there is a high interindividual variability, and the outcomes may vary depending on different environmental factors. In studies from Collado et al. and Sanz et al. cited by Marasco the mean age of participants was 2.2 and 3 years of age, respectively, so the drawn conclusions may not be repetitive and the issue should be investigated in further studies. Generally, we support the statement that on GFD there is no complete restoration of gut microbiota. However, in contrary to the authors, we can conclude that on GFD often remains unbalanced microbial composition with predominance of potential harmful bacteria species, i.e., increase in Enterobacteriaceae and Staphylococcus spp. and decreased levels of Lactobacillus and Bifidobacterium [6, 7]. In consequence, patients may suffer from persisting gastrointestinal symptoms despite the GFD. Finally, we would like to correct that Staphylococcus spp. neither are Gram (-) bacteria nor belong to Proteobacteria. & Ewa Waszczuk ewawaszcz@interia.pl

Women with inflammatory bowel diseases have a suboptimal cervical cancer screening rate and are not aware of the recommended human papilloma virus vaccine

Abstract The aim of the study was to assess the self-reported cervical cancer screening rate among patients with inflammatory bowel diseases (IBD) and patient attitude towards human papilloma virus (HPV) vaccination. A self-designed survey was conducted in hospitalized IBD patients. The survey comprised demographic data, questions regarding cervical smear test frequency and vaccinations recommended for an IBD patient. Randomly, patients completed the survey with a physician present to determine question comprehension. In order to provide test–retest reliability a group of 10 patients completed it twice. Survey data from 150 IBD patients (mean age: 36 years, SD ± 13; mean IBD duration: 10 years, SD ± 6.5) were analyzed. Fifteen percent of the patients reported irregular cervical testing and 15% do not remember when having had a previous cervical testing performed. Only 69% of the patients undergo testing regularly; 30% annually, 32% every 2–3 years; 7% every 5 years. The mean age of patients tested regularly was 22 years, vs. 32 years tested irregularly (p < .001). Only 10% of women claimed that HPV vaccine is recommended for an IBD patient. There is a low adherence to the recommendations regarding cervical cancer screening and prophylaxis. Better multi-disciplinary cooperation between patients and physicians is required to improve patient education and outcomes.

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders

Aim To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). Methods The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. Results IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. Conclusions Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.