Alka Goyal, 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

Abstract

To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD).Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z-score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data. Specific serum cytokines were measured, hormone Z-scores were calculated based on bone age (bone age-Z), and their longitudinal associations were examined.There were 122 children with CD (63% male) who completed 594 visits. The meanSD chronological age was 11.701.79years. The meanSD height chronological age-Z-score was -0.030.99 in males and -0.490.87 in females. The meanSD height bone age-Z-score was 0.230.93 in males and 0.370.96 in females. The magnitude of the mean height Z-score difference was greater in females (-0.870.94) than males (-0.270.90; P=.005), indicating growth was better in females than males. The following negative associations were identified: in females, interleukin (IL)-8 (P<.001) and IL-12p70 (P=.035) with gonadotropin-bone age-Z-scores; IL-8 (P=.010), IL-12p70 (P=.020), and interferon- (P=.004) with sex hormone-bone age-Z-scores, and IL-8 (P=.044) and interferon- (P<.001) with insulin-like growth factor 1-bone age-Z-scores; in males, IL-1 beta (P=.019) and IL-6 (P=.025) with insulin-like growth factor 1-bone age-Z-scores.Our data suggest that sex-specific molecular pathways lead to growth impairment in children with CD (primarily growth hormone/insulin-like growth factor-1 axis in males and primarily hypothalamic-pituitary-gonadal axis in females). Mapping these sex-specific molecular pathways may help in the development of sex-specific treatment approaches targeting the underlying inflammation characteristic of CD.

View details for DOI 10.1016/j.jpeds.2022.05.041

View details for PubMedID 35649448

Abstract

Research on the utilization and effectiveness of anti-TNF biologics in children with Very Early Onset Inflammatory Bowel (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort.We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification and presence of combined immunomodulatory treatment vs. monotherapy.Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [ 50% Crohn's disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years and 45% at 5 years from diagnosis; 56 (55%) were treated between 0-6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (HR 0.17; 95% CI, 0.06-0.51; p=0.001).Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable to older children. Having Crohn's disease (compared to UC/IBD-U) is associated with greater durability.An infographic is available for this article at: http://links.lww.com/MPG/C788.

View details for DOI 10.1097/MPG.0000000000003464

View details for PubMedID 35622080

View details for DOI 10.1097/PG9.0000000000000194

View details for PubMedID 37168901

View details for PubMedCentralID PMC10158292

Abstract

Ustekinumab (UST) is a human IgG1K monoclonal antibody that binds to the p40 receptor subunit bound by cytokines IL-12 and IL-23. It is indicated in both Crohn's disease and ulcerative colitis as a second-line agent. The safety and efficacy of UST in children and young adults has not been thoroughly studied. We report a case series of six pediatric patients and young adults who developed hypersensitivity reactions during intravenous infusion with UST. These reactions ranged from mild allergic reactions to anaphylaxis, with no detectable antibodies if tested. We hypothesize the reaction could be secondary to ethylenediaminetetraacetic acid, which is present solely in the intravenous preparation. Patients who experience hypersensitivity reactions during their UST infusion may safely receive subcutaneous preparations of UST, as demonstrated by some patients who received it based on physician discretion. Further investigation is required to establish the etiology of infusion reactions.

View details for DOI 10.1097/PG9.0000000000000205

View details for PubMedID 37168900

View details for PubMedCentralID PMC10158453

Abstract

OBJECTIVES: Evidence about Specific Carbohydrate Diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD to a modified SCD (MSCD) and comparing each to the participant's baseline, usual diet (UD).METHODS: Across 19 sites, we recruited patients 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to one of two sequences of four alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets.RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response (n=11), adverse events (n=11) and not desiring to continue (n=6)). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% CrI -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD [0.77 (95% CrI 0.51, 1.10)]. Some individuals had improvement in symptoms and fecal calprotectin compared to their UD, while others did not.CONCLUSIONS: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.

View details for DOI 10.14309/ajg.0000000000001800

View details for PubMedID 35442220

View details for Web of Science ID 000784584900071

Abstract

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.

View details for DOI 10.3389/falgy.2022.981961

View details for PubMedID 36118171

View details for Web of Science ID 000717526105464

Abstract

INTRODUCTION: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown.METHODS: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted.RESULTS: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted.DISCUSSION: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children.

View details for DOI 10.14309/ajg.0000000000001350

View details for PubMedID 34140459

View details for DOI 10.1093/ibd/izab268

View details for PubMedID 34718560

Abstract

The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described.We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years.The study population included 269 children (105 [39%] Crohn's disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9-5.2). Most (94%) Crohn's disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn's disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis.Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%-15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

View details for DOI 10.1093/ibd/izaa080

View details for PubMedID 32386060

Abstract

Inflammatory bowel disease-associated liver diseases (IBD-LDs) include autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and an overlap syndrome. Prospective unbiased multicenter data regarding the frequency of IBD-LD in patients with pediatric inflammatory bowel disease (IBD) are lacking. We examined early alanine aminotransferase (ALT) and -glutamyl transpeptidase (GGT) elevations in children diagnosed as having IBD and assessed the likelihood of IBD-LD.Data collected from the prospective observational Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry enrolling children of age <16 years within 30 days of diagnosis. AIH, PSC, and overlap syndrome were diagnosed using local institutional criteria.A total of 1569 subjects had liver enzymes available. Of the total, 757 had both ALT and GGT, 800 had ALT only (no GGT), and 12 had GGT only (no ALT). Overall, 29 of 1569 patients (1.8%) had IBD-LD. IBD-LD was diagnosed in 1 of 661 (0.15%) of patients with both ALT and GGT50 IU/L compared with 21 of 42 (50%) of patients with both ALT and GGT>50 (odds ratio 660, P<0.0001). Of the 29 patients with IBD-LD, 21 had PSC, 2 had AIH, and 6 had overlap syndrome. IBD-LD was more common in patients with ulcerative colitis and IBD-unclassified (indeterminate colitis) than in those with Crohn disease (4% vs 0.8%, respectively, P<0.001).Elevation of both ALT and GGT within 90 days after the diagnosis of IBD is associated with a markedly increased likelihood of IBD-LD. Both ALT and GGT levels should be measured in all of the pediatric patients newly diagnosed as having IBD.

View details for DOI 10.1097/MPG.0000000000000409

View details for Web of Science ID 000341080700012

View details for PubMedID 24796799