Sveta Shah

Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease

Background:Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD. Methods:A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities. Results:In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25). Conclusions:Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

Patient Perception of Treatment Burden Is High in Celiac Disease Compared With Other Common Conditions

OBJECTIVES:The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of CD, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares with other medical treatments, and there are limited data on the socioeconomic factors influencing treatment adherence. In this study, we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence.METHODS:Survey was mailed to participants with CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome, inflammatory bowel disease, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, and end-stage renal disease (ESRD) on dialysis. Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific health status, and overall health status.RESULTS:We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education, and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment.CONCLUSIONS:Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for CD argues for the need for safe adjuvant treatment, as well as interventions designed to lower the perceived burden of the GFD.

The Role of Mucosal Healing in the Treatment of Patients With Inflammatory Bowel Disease

Opinion statementMucosal healing is a promising therapeutic endpoint in the treatment of inflammatory bowel disease. Currently, the treatment of IBD focuses predominantly on clinical remission, without requiring a demonstration of mucosal healing. However, recent studies suggest that achieving mucosal healing engenders better outcomes. In this review, we will examine the concept of mucosal healing, including its definitions and assessment techniques, and will evaluate the data regarding the potential benefits of achieving mucosal healing in the treatment of IBD. Furthermore, we will discuss how often mucosal healing can be expected with each of the therapies for IBD. While achieving mucosal healing is an ideal outcome, it may not be practical or feasible in any given patient. Although we suggest that mucosal healing be discussed with all patients, the practicing physician should realize that this goal may not be possible and should manage the patient accordingly.

Changes in Body Mass Index on the Gluten Free Diet: Risk of Obesity

Background and Aims: The association between selective complete IgA deficiency (SIgAD) and celiac disease (CD) is well recognized. However, most data come from European pediatric populations. Given that the prevalence of immunoglobulin deficiency syndromes including SIgAD varies markedly in different populations, available data may not be representative of the adult celiac population in the United States. Our objective was to determine the distribution of SIgAD in an adult U.S. celiac population compared to controls. While, SIgAD precludes use of IgA serology, the effect of partial IgA deficiency (PIgAD) on IgA tTG test performance is unknown. Thus, our secondary aim is to assess the effect of PIgAD on serologic testing for untreated CD. Methods: In adults SIgAD is defined as a serum IgA concentration of less than 7mg/dl in the presence of normal levels of other immunoglobulins. PIgAD describes a low serum IgA of less than 70 but greater than 7mg/dlis. Total IgA was measured in patients undergoing tTG testing including patients with biopsy proven CD and an equal number of tTG negative disease controls with various GI disorders. Patients were classified as having CD if duodenal pathology showed a Marsh 2 or 3 lesion and there was either positive serology or histologic response to GFD, in the absence of negative CD genetic testing (DQ2/DQ8). Controls consisted of patients on a normal diet with negative IgA-tTG or IgGDGP, and without other diagnostic criteria for CD. Results: IgA data were available for 135 CD patients and 168 disease controls. 1.5% (2 of 135) CD patients had SIgAD compared to 0.6% (1 of 168) of controls (P=0.5). A further 3.7% of CD patients and 5.9% of disease controls had PIgAD. The median age at diagnosis for IgAD CD patients was 59 yr compared to 42 yr for CD patients with a normal IgA (p= 0.05). Pre-treatment tTG serology was negative in 100% (2 of 2) SIgAD CD patients. Of note, 40% (2 of 5) of the PIgAD CD group compared to 1.7% (2 of 117) of the non IgA deficient CD group had a negative tTG at diagnosis. Interestingly, all IgAD CD patients with an IgA level >50 mg/dl had positive IgA tTG results compared to 0 of 4 with IgA levels < 50 mg/dl. Conclusions: The incidence of SIgAD was 1.5% in our CD patients which is consistent with the European literature. IgA deficient patients were older, possibly representing an association between advancing age and IgA deficiency. The high prevalence of partial IgA deficiency in non-CD gastroenterology patients (5.9%) is novel, suggesting that IgA deficiency may be a risk factor for GI symptoms, via small intestinal bacterial overgrowth or other mechanisms. This finding warrants further study. IgG-based celiac serology testing should be considered for all patients with a total serum IgA level of less than 50 mg/dl.

394 Celiac Disease Has Higher Treatment Burden Than Common Medical Conditions

and 1 patient had 4 previous EGDs. The median time from the first EGD until the diagnostic EGD was 39 months (range: 1 month to 13 years). The same endoscopist performed the non-diagnostic and the diagnostic EGD in 10/17 patients (59%). During the prior nondiagnostic EGD, a duodenal biopsy was performed in only 41% of the patients, and ≥4 specimens (the recommended number) were submitted in 29% of the patients. On the diagnostic EGD, ≥4 specimens were submitted in 94%. CD serologies were obtained in 3/ 17 (18%) prior to the non-diagnostic EGD but were obtained in 10/17 (59%) prior to the diagnostic EGD. During the non-diagnostic EGDs, the indications were dyspepsia/abdominal pain (n=5), reflux or Barretts esophagus (n=4), diarrhea (n=2), dysphagia (n=2), and other (n=4). During the diagnostic EGD, the indications were diarrhea (n=6), positive CD serologies (n=5), abdominal pain/dyspepsia (n=3), dysphagia (n=2), and reflux (n=1). The mean age of diagnosis of those with missed/incident CD was 53.1 years, slightly older than those diagnosed with CD on their first EGD (46.8 years, p=0.11). Both groups were predominantly female (missed/incident CD: 65% vs. 66%, p=0.94). Conclusions: Among patients with CD who had previously undergone a non-diagnostic EGD, most did not have duodenal biopsies taken on a prior EGD. Dyspepsia and reflux were the predominant symptoms among these patients, and most did not initially have CD serologies checked. Routine performance of duodenal biopsy during EGD for the indications of dyspepsia and reflux may improve the under-diagnosis rates, and shorten the time for diagnosis, of patients with CD in the United States.