Faculty Bibliography

Eczema is a complex chronic inflammatory skin disease impacted by environmental factors, infections, immune disorders, and deficiencies in skin barrier function. Shi Zhen Tea (SZT), derived from traditional Chinese medicine Xiao-Feng-San, has shown to be an effective integrative therapy for treating skin lesions, itching, and sleeping loss, and it facilitates reduction of topical steroid and antihistamine use in pediatric and adult patients with severe eczema. Yet, its active compounds and therapeutic mechanisms have not been elucidated. In this study, we sought to investigate the active compounds and molecular mechanisms of SZT in treating eczema using systems pharmacology and in silico docking analysis. SZT is composed of 4 medicinal herbs, Baizhu (Atractylodis macrocephalae rhizome), Jingjie (Schizonepetae herba), Kushen (Sophorae flavescentis radix), and Niubangzi (Arctii fructus). We first identified 51 active compounds from SZT and their 81 potential molecular targets by high-throughput computational analysis, from which we identified 4 major pathways including Th17 cell differentiation, metabolic pathways, pathways in cancer, and the PI3K-Akt signaling pathway. Through network analysis of the compound-target pathway, we identified hub molecular targets within these pathways including carbonic anhydrase II (CA2), peroxisome proliferator activated receptor γ (PPAR γ), retinoid X receptor α (RXRA), and vitamin D receptor (VDR). We further identified top 5 compounds including cynarine, stigmasterin, kushenol, β-sitosterol, and (24S)-24-propylcholesta-5-ene-3β-ol as putative key active compounds on the basis of their molecular docking scores with identified hub target proteins. Our study provides an insight into the therapeutic mechanism underlying multiscale benefits of SZT for eczema and paves the way for developing new and potentially more effective eczema therapies.

PURPOSE OF REVIEW/OBJECTIVE:Food oral immunotherapy (OIT) has emerged as way to mitigate serious allergic reactions including life-threatening anaphylaxis related to accidental ingestion. However, gastrointestinal-related adverse effects of OIT have been reported and are often cited as reasons for discontinuation of therapy. We summarize recent research on the prevalence of eosinophilic esophagitis (EoE) in patients undergoing OIT. RECENT FINDINGS/RESULTS:We examined 12 recent studies on OIT for peanut, milk, walnut, egg, and wheat, which enrolled a total of 620 patients. Gastrointestinal symptoms were common during OIT, and while generally mild, 24 (3.9%) patients from the reviewed studies reported gastrointestinal symptoms that were significant enough to prompt discontinuation of OIT. Of these, two (0.3% of the total 620 patients or 8.3% of those with gastrointestinal symptoms) patients had biopsy-confirmed EoE. One of these patients was subsequently found to also have ulcerative colitis that had been previously undiagnosed. SUMMARY/CONCLUSIONS:EoE is a rare but concerning side effect of OIT. More research is needed to better elucidate both the OIT-related and patient-related factors that may predispose individuals to develop EoE. The presence of comorbid conditions and/or preexisting subclinical esophageal eosinophilia may account for some of cases of EoE identified during OIT.

INTRODUCTION AND OBJECTIVES/OBJECTIVE:Although food allergy is recognized as a growing worldwide public health problem, there continues to be limited data on prevalence rates in developing and emerging countries. Most prevalence estimates are based on self-reports, with only few studies using objective assessments. The aim was to analyze the frequency of sensitization to food allergens by serum specific IgE in a large group of unselected allergic patients in Mexico. MATERIALS AND METHODS/METHODS:We analyzed data registries from patients of all ages with suspected food allergy referred to a specialized laboratory in Mexico City from January 2016 to April 2018. A descriptive analysis, and an age/food-group comparison were made. RESULTS:A total of 2633 subjects tested for food allergy were identified during the study period; 1795 subjects fulfilled the inclusion criteria. The overall positivity (sIgE≥0.35kUA/L) to at least one food was 24%. The most frequently positive foods were hazelnut, apple, shrimp, peanut, egg white, egg yolk, peach, almond, tomato, bean, milk, strawberry, kiwi, maize and wheat. Positivity for some foods was more frequent across different age groups, in young children (≤5 years) milk; in older children (6-17 years): peanut, almond, wheat, soy and maize; in adults: apple. We also found other foods with high positivity but less than 50 samples: rye 60%, mango 42.9%, carrot 37.5%, cashew 27.3%, banana 21.1% and oat 20.6%. CONCLUSION/CONCLUSIONS:Our study reported the presence of a differential regional IgE sensitization pattern as compared with the internationally reported one, highlighting the importance of local staple foods.

Food allergy is increasingly prevalent and poses a life-threatening risk to those afflicted. The health care costs associated with food allergies are also increasing. Current and emerging treatments for food allergies aim at protecting against reactions caused by accidental ingestion and increasing the food allergen reaction threshold, although this protection is often temporary. In the future, ideal biologic therapies would target key mediators of the type II immune pathway, essential in development of the atopic march to prevent development of food allergies. Biologics offering long-term protection against allergic reactions to food are needed, and several agents are already in development.

BACKGROUND:We previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT™) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250μg) in a 12-month randomized controlled study (PEPITES) of peanut-allergic children aged 4-11 years. OBJECTIVE:To assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) open-label extension PEOPLE study. METHODS:Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250μg, subjects who had received DBV712 250μg in PEPITES underwent Month-36 double-blind, placebo-controlled, food challenge (DBPCFC) with an optional Month-38 sustained unresponsiveness (SU) assessment. RESULTS:198 (93%) of 213 eligible subjects who had received DBV712 250μg in PEPITES entered PEOPLE, of whom 141 (71%) had assessable DBPCFC at Month 36. At Month 36, 51.8% (73/141) of subjects reached an eliciting dose (ED) of ≥1000 mg, compared with 40.4% (57/141) at Month 12. 75.9% (107/141) demonstrated increased ED compared to baseline. 13.5% (19/141) tolerated the full DBPCFC of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. 18 subjects underwent an optional SU assessment; 14/18 (77.8%) maintained an ED of ≥1000 mg at Month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events low (1%). CONCLUSION/CONCLUSIONS:These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Professor Hugh A. Sampson, MD is a Canadian- born American clinician and translational researcher, whose evidence-based approach validated food allergy as a legitimate allergic disorder. He single-handedly transformed the management of patients with food allergies and initiated investigations that led to novel diagnostic tests and therapies giving hope to millions of individuals and their families worldwide. Hugh Sampson's immense impact on the rapidly developing field of food allergy makes him a true legend in allergy/immunology.

Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in the esophagus.

BACKGROUND:Sesame is an allergen of increasing importance. OBJECTIVE:We sought to characterize the outcomes of oral food challenges (OFCs) to sesame and evaluate the diagnostic accuracy of skin prick testing (SPT), sesame, and Ses i 1-specific IgE (sIgE). METHODS:We reviewed sesame OFCs performed at the Mount Sinai pediatric allergy clinic between January 2010 and April 2018. We assessed the accuracy of diagnostic tests by calculating the area under the curve (AUC) of the receiver operating characteristic curves. The association between OFC outcome and sesame sensitization was analyzed using a logistic regression, which was then used to estimate the 95% positive predictive value (PPV) of these tests. RESULTS:We identified 341 patients (69% male, mean age 7.7 years) who underwent sesame OFC. Among 106 (31%) positive OFCs, the median cumulative eliciting dose was 500 mg sesame protein (1/2 teaspoon tahini). Sesame SPT wheal ≥6 mm had sensitivity 54.1% and specificity 87.8%; AUC 0.756 (95% confidence interval [CI], 0.699-0.814). SPT wheal size ≥14 mm had 95% PPV. Sesame-sIgE level did not correlate with OFC outcome. Ses i-sIgE levels were analyzed in 30 patients using the Immuno Solid-phase Allergen Chip (ISAC) microarray and were significantly associated with OFC outcome (AUC: 0.715 [95% CI, 0.541-0.890]). Ses i 1-sIgE ≥0.3 ISAC Standardized Units had sensitivity 58.3% and specificity 83.3%. CONCLUSIONS:This is the largest study of sesame allergy to date. Sesame SPT is a more accurate predictor of sesame allergy compared with sesame sIgE. Ses i 1-sIgE appears promising but requires further study regarding diagnostic accuracy.