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.

BACKGROUND:Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear. OBJECTIVE:Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood. METHODS:Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry. RESULTS:17 cells. CONCLUSIONS:These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES.

PURPOSE OF REVIEW/OBJECTIVE:The prevalence of food allergy is increasing on a global scale, and therefore increased attention is being paid to specific food allergy epidemiology and management. There has been a large amount of progress made in the last decade on human trials of wheat oral immunotherapy (WOIT). RECENT FINDINGS/RESULTS:To date, there has been one multicenter, double-blind, randomized controlled trial of WOIT, one randomized, noncontrolled trial of WOIT, and several smaller, nonrandomized clinical trials of WOIT. WOIT trials are generally limited by smaller sample sizes, affecting the demographic skew of evaluated patients. In addition, there is minimal standardization of efficacy and safety outcomes between trial protocols, making head-to-head comparison challenging. However, some common themes emerge. The majority of WOIT regimens result in successful desensitization, and success is more likely with higher maintenance dosing for longer periods of time. Limited studies have looked at sustained unresponsiveness in WOIT. WOIT can induce allergic reactions, including anaphylaxis, but more severe reactions often have an associated augmenting factor, such as exercise. Lower maintenance doses likely are associated with less severe reactions, and food modification and/or adjunct therapeutics may also decrease the risk of reactions. SUMMARY/CONCLUSIONS:WOIT trials are ongoing and will optimize updosing protocols and maintenance doses to improve efficacy and safety.

BACKGROUND:Understanding about patient-reported biphasic food-related allergic reactions currently remains sparse. OBJECTIVE:To characterize patient-reported biphasic food-related allergic reactions among a national food allergy registry. METHODS:We utilized two Patient Registry surveys established by Food Allergy Research & Education (FARE). Variables were described with proportions and 95% confidence intervals; unadjusted results were stratified by respondent type. Multivariable logistic regression evaluated the adjusted odds of reporting a biphasic reaction. RESULTS:The incidence of reported biphasic reactions was 16.4% (CI: 15.3-17.7). 12.8% (CI: 12.5-14.3) of parent/guardian respondents and 21.8% (CI: 19.7-23.8) of self-respondents indicated a biphasic reaction during their most recent food-allergic reaction. Among respondents with a mild initial reaction, 7.4% reported a biphasic reaction compared with 30% with a very severe initial reaction. When the initial reaction was mild, 69.6% of parent/guardian respondents (CI: 47.2 - 85.4) and 52.0% of self-respondents (CI: 38.0 - 35.7) with a biphasic reaction reported a mild secondary reaction. When the initial reaction was very severe, 36.3% of parent/guardian respondents (CI: 26.4 - 47.5) and 42.9% of self-respondents (CI: 31.1 - 55.5) with a biphasic reaction reported a very severe secondary reaction. Female gender, Black/African-American race, reaction age 5-12 and 26-66 years, initial moderate, severe, or very severe reaction, and one or more annual reactions were associated with increased odds of a biphasic reaction. CONCLUSION/CONCLUSIONS:This study characterizes the incidence of patient-reported biphasic reactions and provides valuable information on probable severity of a biphasic food-related allergic reaction. Further research is necessary to understand the epidemiology of food-related biphasic reactions.

Background and aims/UNASSIGNED:The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. Methods/UNASSIGNED:We undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed. Results/UNASSIGNED:We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate. Conclusions/UNASSIGNED:There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy. Systematic review registration/UNASSIGNED:A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.york.ac.uk/prospero/#recordDetails).

OBJECTIVE:Food protein-induced enterocolitis syndrome (FPIES) is typically diagnosed based on a characteristic clinical history; however, an oral food challenge (OFC) may be necessary to confirm the diagnosis or evaluate for the development of tolerance. FPIES OFC methods vary globally, and there is no universally agreed upon protocol. The objective of this review is to summarize reported FPIES OFC approaches and consider unmet needs in diagnosing and managing FPIES. DATA SOURCES:PubMed database was searched using the keywords food protein-induced enterocolitis syndrome, oral food challenge, cow milk allergy, food allergy, non-immunoglobulin E-mediated food allergy and FPIES. STUDY SELECTIONS:Primary and review articles were selected based on relevance to the diagnosis of FPIES and the FPIES OFC. RESULTS:We reviewed the history of FPIES and the evolution and variations in the FPIES OFC. A summary of current literature suggests that most patients with FPIES will react with 25% to 33% of a standard serving of the challenged food, there is little benefit to offering a divided dose challenge unless there is suspicion of specific immunoglobulin E to the food being challenged, reactions typically appear within 1 to 4 hours of ingestion, and reactions during OFC rarely result in emergency department or intensive care unit admission. CONCLUSION:International standardization in the FPIES OFC approach is necessary with particular attention to specific dose administration across challenged foods, timing between the patient's reaction and offered OFC to verify tolerance, patient safety considerations before the OFC, and identification of characteristics that would indicate home reintroduction is appropriate.

Purpose of Review/UNASSIGNED:Management of anaphylaxis during the SARS-CoV-2 pandemic should consider local infection rates so as to not burden local ED at times of pandemic, while also protecting patients from infection risks and progression of anaphylaxis. In this review, we identify a treatment strategy for anaphylaxis that balances the risks versus benefits of ED versus home management in this unprecedented time. Recent Findings/UNASSIGNED:Physicians and patients have had to adapt new approaches to medical care during the SARS-CoV-2 pandemic due to restricted access to health care facilities. Telemedicine has substituted in-person visits, and such a drastic change in the patient care paradigm presents a need to revise the acute management of anaphylaxis. Summary/UNASSIGNED:Physicians should utilize telemedicine during this time to engage in shared decision-making with patients and their families to devise an anaphylaxis plan of management that emphasizes home care when symptoms are mild with an exception for ED care if a patient has had severe, near-fatal anaphylaxis episodes in the past. Previous anaphylaxis recommendations should remain in place despite the pandemic, including prompt use of epinephrine when needed, avoidance of known allergens, training of patients and their caregivers, and carrying of epinephrine autoinjector devices at all times to remain prepared in the event of an anaphylaxis episode. Supplementary Information/UNASSIGNED:The online version contains supplementary material available at 10.1007/s40521-021-00284-0.