Pediatric eosinophilic esophagitis outcomes vary with co-morbid eczema and pollen food syndrome.

Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease characterized by eosinophil inflammation of the esophagus. It has been described as a component of the Allergic March and is often seen with other atopic diseases. Some atopic diseases, including asthma, are known to be heterogenous with endotypes that guide treatment. Similarly, we propose that EoE is a heterogenous disease with varying phenotypes and endotypes that might impact response to therapy. Methods: A single-center retrospective review of pediatric patients ≤18 years of age diagnosed with EoE was conducted. All gastrointestinal clinic visits and esophagogastroduodenoscopies (EGD) from disease presentation through the first three years after diagnosis were reviewed. Histologic remission rate and therapies utilized [proton pump inhibitor (PPI), topical steroid, dietary elimination] were assessed. Results: One hundred and thirty-seven patients were included, 80% of whom had at least one concurrent atopic condition at diagnosis, with food allergies being the most common (57%) followed by eczema (34%), and asthma (29%). The remission rate of the overall cohort was 65%, and by concurrent allergy, comorbid pollen food syndrome and eczema had the highest remission rates at 100% and 81%, respectively followed by asthma (62%), food allergies (62%), seasonal allergic rhinitis (60%), and history of anaphylaxis (56%). Kaplan-Meier curves for each atopic condition show that patients with eczema and pollen food syndrome achieve histologic remission faster than those without. All treatment modalities were more successful in patients with eczema than those without, and PPI was most effective treatment at inducing remission. Conclusions: In a real-world pediatric cohort, 80% of patients with EoE had an underlying atopic condition. Patients with eczema and pollen food syndrome had a swifter response and were more likely to achieve histologic remission than patients with other atopic conditions. This study suggests that EoE, like other allergic diseases, may have heterogenous phenotypes that could affect response to treatment. There is currently a knowledge gap in classifying EoE based on endotypes and phenotypes at diagnosis and correlating responses to various treatment modalities.

Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report.

Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding. Both patients underwent genetic testing given disease refractoriness and were ultimately diagnosed with cytotoxic T lymphocyte antigen 4 (CTLA4) haploinsufficiency. They are both now in complete clinical and endoscopic remission on abatacept. CTLA4 haploinsufficiency has incomplete penetrance and significant phenotypic heterogeneity but should be considered in the differential diagnosis of refractory celiac/celiac-like disease, as treatment implications are significant.

Subtyping of Eosinophilic Esophagitis Based on Disease Presentation in a pediatric Cohort.

OBJECTIVE: Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory disease characterized by eosinophilic infiltration of esophageal tissue. Subtyping of EoE patients could be useful in predicting therapeutic response. We propose clinical subtypes, apply them to our pediatric EoE population retrospectively, and assess therapy choices and remission at one year. METHODS: A retrospective chart review of pediatric patients diagnosed with EoE was conducted. Patients were grouped into proposed subtypes (severe, allergic, fibrostenotic, inflammatory, unclassified) based on presenting characteristics. The primary outcome was histologic remission, which was defined <15 eosinophils/high-powered-field (hpf) at the closest visit 1 year postdiagnosis. RESULTS: Subtyping was possible in 242 of 256 patients and follow-up histological data were available in 75 subjects. The majority had an overlap in phenotype with 17% severe, 77% allergic, 15% fibrostenotic, 60% inflammatory, and 5% unclassified, whereas 45% of the cohort were assigned to a unique subtype. At 1 year, 43/75 (57%) of patients achieved histologic remission, with an overall average decrease of 33 (IQR -47, -12) eosinophils/hpf across the entire cohort. There was no difference in remission rates among subtypes. First-line therapy review revealed higher rates of proton pump inhibitor (PPI) ± topical steroids utilization in severe patients, while topical steroids were prescribed preferentially over dietary therapy in the fibrostenotic subtype. CONCLUSION: There were no observed differences in remission rates at 1 year among clinically defined subtypes of EoE, although this could be attributed to overlapping subtypes. Most patients responded well to medical therapy. Larger scale prospective studies designed to subtype patients and protocolize treatment may help personalize the approach to EoE management.

Correlation of rapid point-of-care vs send-out fecal calprotectin monitoring in pediatric inflammatory bowel disease.

AIM: To assess the correlation between the send-out enzyme-linked immuno sorbent assay (ELISA) and the point-of-care (POC) calprotectin test in pediatric inflammatory bowel disease (IBD) patients. METHODS: We prospectively collected stool samples in pediatric IBD patients for concomitant send-out ELISA analysis and POC calprotectin testing using the Quantum Blue® (QB) Extended immunoassay. Continuous results between 17 to 1000 µg/g were considered for comparison. Agreement between the two tests was measured by a Bland-Altman plot and statistical significance was determined using Pitman's test. RESULTS: Forty-nine stool samples were collected from 31 pediatric IBD patients. The overall means for the rapid and ELISA tests were 580.5 and 522.87 µg/g respectively. Among the 49 samples, 18 (37.5%) had POC calprotectin levels of ≤ 250 µg/g and 31 (62.5%) had levels > 250 µg/g. Calprotectin levels ≤ 250 µg/g show good correlation between the two assays. Less correlation was observed at quantitatively higher calprotectin levels. CONCLUSION: In pediatric IBD patients, there is better correlation of between ELISA and POC calprotectin measurements at clinically meaningful, low-range levels. Future adoption of POC calprotectin testing in the United States may have utility for guiding clinical decision making in real time.

Etiology of Diarrhea, Nutritional Outcomes, and Novel Intestinal Biomarkers in Tanzanian Infants.

OBJECTIVE: Diarrheal diseases are a leading cause of morbidity and mortality worldwide, but the etiology of diarrhea and its relation to nutritional outcomes in resource-limited settings is poorly defined. We sought to determine the etiology of community-acquired diarrhea in Tanzanian infants and to assess the association with anthropometrics and novel intestinal biomarkers. METHODS: A convenience sample of infants in a trial of zinc and/or multivitamin supplementation in Tanzania was selected. Subjects were enrolled at age 6 weeks and studied for 18 months. Stool samples were obtained from children with acute diarrhea. A novel, polymerase chain reaction-based TaqMan array was used to screen stool for 15 enteropathogens. A subset of subjects had serum gastrointestinal biomarkers measured. RESULTS: One hundred twenty-three subjects with diarrhea were enrolled. The mean ± SD age at stool sample collection was 12.4 ±â€Š3.9 months. Thirty-five enteropathogens were identified in 34 (27.6%) subjects: 11 rotavirus, 9 Cryptosporidium spp, 7 Shigella spp, 3 Campylobacter jejuni/coli, 3 heat stable-enterotoxigenic Escherichia coli, and 2 enteropathogenic E coli. Subjects with any identified enteropathogen had significantly lower weight-for-length z scores (-0.55 ±â€Š1.10 vs 0.03 ±â€Š1.30, P = 0.03) at the final clinic visit than those without an identified pathogen. Fifty of the 123 subjects (40.7%) had serum analyzed for antibodies to lipopolysaccharide (LPS) and flagellin. Subjects with any identified enteropathogen had lower immunoglobulin (IgA) antibodies to LPS (0.75 ±â€Š0.27 vs 1.13 ±â€Š0.77, P = 0.01) and flagellin (0.52 ±â€Š0.16 vs 0.73 ±â€Š0.47, P = 0.02) than those without an identified pathogen. CONCLUSIONS: This quantitative polymerase chain reaction method may allow identification of enteropathogens that place children at higher risk for suboptimal growth. IgA anti-LPS and flagellin antibodies hold promise as emerging intestinal biomarkers.

Rationale for Using Social Media to Collect Patient-Reported Outcomes in Patients with Celiac Disease.

Patients with celiac disease (CD) are increasingly interconnected through social media, exchanging patient experiences and health-tracking information between individuals through various web-based platforms. Social media represents potentially unique communication interface between gastroenterologists and active social media users - especially young adults and adolescents with celiac disease-regarding adherence to the strict gluten-free diet, gastrointestinal symptoms, and meaningful discussion about disease management. Yet, various social media platforms may be underutilized for research purposes to collect patient-reported outcomes data. In this commentary, we summarize the scientific rationale and potential for future growth of social media in patient-reported outcomes research, focusing on college freshmen with celiac disease as a case study and provide overview of the methodological approach. Finally, we discuss how social media may impact patient care in the future through increasing mobile technology use.

Association between lichen sclerosus and celiac disease: a report of three pediatric cases.

The prevalence of celiac disease (CD) is increasing and may be as high as 1% of the US population. The typical presentation of CD generally includes gastrointestinal symptoms, but more individuals are presenting with extraintestinal manifestations. A wide variety of dermatologic associations have been described with CD, including alopecia, dermatitis herpetiformis, and enamel hypoplasia. In this report we describe three girls with CD who presented with hypopigmented skin lesions and pruritus in the perivaginal and perianal areas, consistent with the diagnosis of lichen sclerosus (LS). All three presented within 1 year to the same practitioner. To our knowledge, this association has not previously been explored in the literature. These cases elucidate a possible relationship between CD and LS.

Maternal multivitamin supplementation reduces the risk of diarrhoea among HIV-exposed children through age 5 years.

BACKGROUND: The aim of this study was to determine whether maternal vitamin supplementation affects long-term mortality and morbidity of children born to HIV-infected mothers. METHODS: In total, 1078 HIV-infected pregnant woman were enrolled in a double-blind, 2×2 factorial, randomised, placebo-controlled trial in Tanzania. Data were collected for 874 children at monthly clinic visits through a median age of 51 months. RESULTS: Maternal receipt of multivitamins (HR=0.93; 95% CI: 0.70-1.22) or vitamin A (HR=1.00; 95% CI: 0.76-1.32) did not affect all-cause child mortality through age 5 years. Among HIV-negative children, maternal multivitamin supplementation was associated with a lower mortality rate up to 5 years (HR=0.60; 95% CI: 0.38-0.95), primarily in children <2 years of age. Maternal vitamin A supplementation did not significantly affect child mortality up to 5 years (HR=0.76; 95% CI: 0.48-1.20). Children born to mothers who received multivitamins had a lower risk of all types of diarrhoea (RR=0.86; 95% CI: 0.75-0.98) through 5 years of age. The reduced risk of watery diarrhoea persisted in children from 2-5 years of age (RR=0.71; 95% CI: 0.54-0.95). CONCLUSIONS: Maternal vitamin supplementation during pregnancy and lactation may be associated with long-lasting affects in HIV-exposed children [ClinicalTrials.gov Identifier: NCT00197743].

Cost-effectiveness of universal serologic screening to prevent nontraumatic hip and vertebral fractures in patients with celiac disease.

BACKGROUND & AIMS: Patients with asymptomatic or poorly managed celiac disease can experience bone loss, placing them at risk for hip and vertebral fractures. We analyzed the cost-effectiveness of universal serologic screening (USS) vs symptomatic at-risk screening (SAS) strategies for celiac disease because of the risk of nontraumatic hip and vertebral fractures if untreated or undiagnosed. METHODS: We developed a lifetime Markov model of the screening strategies, each with male or female cohorts of 1000 patients who were 12 years old when screening began. We screened serum samples for levels of immunoglobulin A, compared with tissue transglutaminase and total immunoglobulin A, and findings were confirmed by mucosal biopsy. Transition probabilities and quality of life estimates were obtained from the literature. We used generalizable cost estimates and Medicare reimbursement rates and ran deterministic and probabilistic sensitivity analyses. RESULTS: For men, the average lifetime costs were $8532 and $8472 for USS and SAS strategies, respectively, corresponding to average quality-adjusted life year gains of 25.511 and 25.515. Similarly for women, costs were $11,383 and $11,328 for USS and SAS strategies, respectively, corresponding to quality-adjusted life year gains of 25.74 and 25.75. Compared with the current standard of care (SAS), USS produced higher average lifetime costs and lower quality of life for each sex. Deterministic and probabilistic sensitivity analyses showed that the model was robust to realistic changes in all the variables, making USS cost-ineffective on the basis of these outcomes. CONCLUSIONS: USS and SAS are similar in lifetime costs and quality of life, although the current SAS strategy was overall more cost-effective in preventing bone loss and fractures among patients with undiagnosed or subclinical disease. On the basis of best available supportive evidence, it is more cost-effective to maintain the standard celiac screening practices, although future robust population-based evidence in other health outcomes could be leveraged to reevaluate current screening guidelines.