Faculty Bibliography

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.

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.

PURPOSE OF REVIEW/OBJECTIVE:First described in the mid 20th century, it was just in the last decade that diagnostic and treatment guidelines for food protein-induced enterocolitis syndrome (FPIES) were established. Awareness of the diagnosis is improving, and epidemiologic data are emerging. RECENT FINDINGS/RESULTS:Recent studies suggest that FPIES may affect as many as 0.5% of children worldwide. FPIES in adults is usually triggered by seafood and may be more common than previously thought. Many patients with FPIES have other allergic disorders. SUMMARY/CONCLUSIONS:With refined diagnostic criteria and improved awareness, FPIES is now diagnosed with increasing frequency, and epidemiologic data are emerging. FPIES appears to be increasing in prevalence, and the frequent association with other allergic disorders suggests a shared predisposition or immune mechanism that remains to be elucidated.

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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