Nasha Khavari, MD

Abstract

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.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 one year post-diagnosis.Subtyping was possible in 242/256 patients and follow-up histological data was 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 one 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 fibrostenotic subtype.There were no observed differences in remission rates at one 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.

View details for DOI 10.1097/MPG.0000000000003580

View details for PubMedID 35897130

View details for Web of Science ID 000784584900071

Abstract

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.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 g/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.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 g/g respectively. Among the 49 samples, 18 (37.5%) had POC calprotectin levels of 250 g/g and 31 (62.5%) had levels > 250 g/g. Calprotectin levels 250 g/g show good correlation between the two assays. Less correlation was observed at quantitatively higher calprotectin levels.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.

View details for DOI 10.4292/wjgpt.v8.i2.127

View details for PubMedID 28533922

Abstract

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.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.One hundred twenty-three subjects with diarrhea were enrolled. The mean SD age at stool sample collection was 12.43.9 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 (-0.551.10 vs 0.031.30, 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 (0.750.27 vs 1.130.77, P=0.01) and flagellin (0.520.16 vs 0.730.47, P=0.02) than those without an identified pathogen.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.

View details for DOI 10.1097/MPG.0000000000001323

View details for Web of Science ID 000391346100018

View details for PubMedID 27347720

View details for PubMedCentralID PMC5183517

Abstract

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.In total, 1078 HIV-infected pregnant woman were enrolled in a double-blind, 22 factorial, randomised, placebo-controlled trial in Tanzania. Data were collected for 874 children at monthly clinic visits through a median age of 51 months.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).Maternal vitamin supplementation during pregnancy and lactation may be associated with long-lasting affects in HIV-exposed children [ClinicalTrials.gov Identifier: NCT00197743].

View details for PubMedID 25173342

View details for PubMedCentralID PMC4311151

Abstract

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 1year 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.

View details for DOI 10.1111/pde.12402

View details for PubMedID 25382799

Abstract

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 1year 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.

View details for DOI 10.1111/pde.12402

View details for Web of Science ID 000345694100008

View details for PubMedID 25382799

Abstract

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.

View details for PubMedID 25392743

Abstract

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.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.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.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.

View details for DOI 10.1016/j.cgh.2012.12.037

View details for PubMedID 23357490

View details for DOI 10.1177/0148607109346276

View details for Web of Science ID 000271393400001

View details for PubMedID 19892900

Abstract

Mutations in alpha6 or beta4 integrins (ITGA6, ITGB4) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB-PA), often lethal in infancy through skin desquamation. There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease, of unknown molecular basis.We report 2 Kuwaiti siblings with pyloric atresia and life-threatening intestinal desquamation without significant skin abnormality. The older sibling died of intractable diarrhoea, and the younger sibling suffered episodes of massive protein-losing enteropathy, triggered by viral infections, in addition to obstructive uropathy. Mutation analysis was performed for ITGA6 and ITGB4 and expression of ITGA6 and ITGB4 protein was examined in skin and intestinal biopsies. Her serum also was incubated with normal intestine.We identified a novel mutation in ITGB4, with homozygous deletion of a single residue (isoleucine 1314) within the intracellular plectin-binding domain. Expression of ITGA6 and ITGB4 within skin, duodenal, and colonic epithelium was normal or minimally reduced, in contrast to previous reports. Biopsies taken during relapse showed accumulation of immunoglobulin G and C1q within intestinal basement membrane, whereas immunoglobulin G from her serum bound to basement membrane of normal small intestine. Immunomodulatory therapy induced significant improvement following relapses.ITGB4 mutation may induce a desquamative enteropathy in infancy without significant skin disease. A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB-PA associated mutations. Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial.

View details for Web of Science ID 000260519400009

View details for PubMedID 18955862

Abstract

The purpose of this work was to evaluate the use of serologic testing as a screening test for inflammatory bowel disease compared with erythrocyte sedimentation rate and hemoglobin in a referred patient population with suspected inflammatory bowel disease.A retrospective study was performed, reviewing medical charts of patients who had inflammatory bowel disease serology performed at Prometheus Laboratories from September 2002 to September 2004. Patients were divided into 4 categories: ulcerative colitis, Crohn disease, indeterminate colitis, and noninflammatory bowel disease groups. Patients were categorized based on clinical evaluation by board-certified pediatric gastroenterologists.A total of 227 patients seen at the Lucile Packard Children's Hospital Gastroenterology Clinic had inflammatory bowel disease serology performed at or before the time of diagnosis. Seventeen charts were excluded secondary to inadequate information. Forty children were found to have inflammatory bowel disease, a prevalence of 19%. Overall, serologic testing for inflammatory bowel disease had 60% sensitivity and 92% specificity. A positive laboratory test for anemia or an elevated erythrocyte sedimentation rate had 83% sensitivity, whereas the combination of anemia and elevated erythrocyte sedimentation rate had 96% specificity. The positive predictive value of serologic testing was 60% compared with 79% in patients with anemia and elevated erythrocyte sedimentation rate. The positive predictive value of serologic testing in the subgroup of subjects without rectal bleeding (139 subjects) was only 35% compared with 60% using routine tests. Almost one third of all positive serologic tests were in patients with no demonstrable inflammatory bowel disease.As a pediatric inflammatory bowel disease screening strategy for the general pediatrician or gastroenterologist, the measurement of the combination of erythrocyte sedimentation rate and hemoglobin has a higher positive predictive value and is more sensitive, more specific, and less costly than commercial serologic testing.

View details for DOI 10.1542/peds.2006-1361

View details for PubMedID 17158948