Faculty Bibliography

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.

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.

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.

PURPOSE OF REVIEW/OBJECTIVE:The aim of the article is to critically appraise the most relevant studies in the rapidly advancing field of food allergy prevention. RECENT FINDINGS/RESULTS:Epidemiologic studies identified atopic dermatitis as a strong risk factor for food allergy, with mounting evidence for impaired skin barrier and cutaneous inflammation in the pathogenesis. Additional risk factors include a family history of atopy, the timing of allergenic food introduction into the infant's diet, dietary diversity, vitamin D, and environmental factors, such as dog ownership. Early introduction of allergenic foods (such as peanut) into the infant diet was shown to significantly reduce the risk of food allergy in infants with risk factors, whereas studies targeting skin barrier function have produced conflicting results. Cumulative evidence supports dietary diversity during pregnancy, breastfeeding, infancy, and early childhood. SUMMARY/CONCLUSIONS:A variety of interventions have been evaluated for the prevention of atopic dermatitis and food allergy, often producing conflicting results. At present, official guidelines encourage breastfeeding and early allergenic food introduction for infants at risk for food allergy, with an emphasis on dietary diversity, fruits, vegetables, fish, and food sources of vitamin D during pregnancy, lactation, and early life for all infants.

Rationale: Gut microbiota play an important role in food allergy. We previously showed that the natural compound berberine (BBR) reduces IgE and others have reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. We evaluated an orally available BBR-containing natural medicine (BCNM) for efficacy as food allergy treatment and explored whether treatment-induced changes in gut microbiota correlated with therapeutic outcomes Methods: C3H/HeJ mice were orally sensitized with peanut and cholera toxin. Allergic mice were orally treated with BCNM or its individual components. Allergic mice given no treatment and naive mice were controls. Mice received periodic post-therapy peanut exposures. Anaphylaxis was assessed by symptom visualization and measurement of body temperature. Histamine and serum peanut-specific IgE were measured by ELISA. IgE+B cells in spleen were assessed by flow cytometry. Fecal pellets were used for sequencing bacterial 16S rDNA by Illumina MISeq. Microbiota data were analyzed using microbiomeanalyst.ca.
Result(s): BCNM-treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE. Symptom scores, plasma histamine, body temperatures, IgE levels and number of IgE+ B cells (P<0.05-P<0.001 vs Sham). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups (P<0.05-0.01). Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae and Hydrogenanaerobacterium (R²= 0.82 to 0.36, P<0.05-0.0001) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae and Bacteroidales, were negatively correlated (R²= -0.73 to -0.43, P<0.05-0.0001)
Conclusion(s): BCNM is effective as food allergy treatment and its benefits are associated with a distinct microbiota signature.
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Rationale: Following completion of clinical trials for food allergy (FA) therapies, many patients/families wish to maintain desensitization. We describe the results of follow-up of participants transitioned to real food equivalents following epicutaneous (EPIT) and oral immunotherapy (OIT) clinical trials.
Method(s): Post-study participants were offered the option to transition to daily ingestion of real food equivalents based upon their OFC outcomes upon study completion. Charts of those who transitioned to ingestion of daily doses of real food equivalents from January 2016-May 2019 were reviewed. Participants without recent follow-up were contacted by telephone. This study was IRB approved.
Result(s): Thirty-seven patients (65% male; median age 8.8 years, range 4-24 years) from 8 studies (milk and peanut EPIT; egg, wheat, and peanut OIT; multi-food OIT+omalizumab) underwent transition to ingestion of daily doses of real food equivalents for milk, baked/lightly-cooked egg, wheat, peanut, tree nuts, sesame, and/or shrimp; 35 patients had follow-up. Thirty-one patients continued dosing for at least one year or were confirmed to be actively dosing if transitioned in the past year, with 22 patients contacted in the prior 4 months confirmed to be actively dosing (median of 2.6 years). Five patients discontinued dosing after a median of 0.2 years, with reasons including dosing-related side effects (gastrointestinal, hives, wheezing; n=3), eosinophilic esophagitis (n=1), or unknown (n=1).
Conclusion(s): Most post-study participants (88.6%) who transitioned to real food equivalents continued dosing long-term. This suggests that transitioning to real food equivalents may be a desirable and sustainable option for patients/families wishing to maintain desensitization achieved during FA therapeutic studies.
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