Faculty Bibliography

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.
Copyright

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.
Copyright

Rationale: Oral food challenges (OFC) are recommended for introducing peanut to infants at high risk of developing peanut allergy. We examined peanut-OFC safety, utility of pre-challenge risk assessment and rates of peanut tolerance at follow-up.
Method(s): his is a single-center, retrospective review of infant peanut-OFC per LEAP protocol performed between 01/2015-01/2019. Pre-challenge skin prick test (SPT) wheal size, serum whole and component peanut-sIgE were analyzed via area under the ROC curve (MedCalc Statistical Software).
Result(s): We analyzed 87 peanut-OFCs; 55.8% were male infants, median age at OFC 8 months (IQR 7-10). Indications for OFC were: eczema, egg allergy or both (n=71); sibling with food allergy (n=7); adverse reaction to peanut-containing food (n=6) or adverse reaction to other food (n=3). OFC outcome was negative in 70 (80.5%), positive in 17 (19.5%). Of those who reacted, 16 (94.1%) received oral antihistamine therapy alone; one (5.9%) received epinephrine. Post-OFC follow up was available in 45 who passed peanut-OFC. Of those, 35 (77.7%) consumed peanut regularly, whereas 10 (22.3%) avoided peanut, including 6 (13.3%) who reported allergic symptoms attributed to peanut. Arah2-sIgE testing outperformed whole peanut-sIgE and SPT in predicting positive challenge outcome by ROC analysis (cutoff >0.56 kU/L, AUC 0.78; p=0.003 vs. sIgE AUC 0.63; p=0.23 and SPT AUC 0.69; p=0.007).
Conclusion(s): Infant peanut-OFC and early introduction are safe in select patients. The majority of infants passing peanut-OFC continue to consume peanut, however a subset avoids peanuts due to potential mild allergic reactions at home. Arah2-sIgE testing has superior diagnostic capacity in our cohort.
Copyright

Rationale: Peanut OIT induces desensitization in peanut-allergic participants after 1-3 years of treatment; tolerance induction has not been evaluated in young children.
Method(s): A multi-center study was conducted in peanut-allergic children (ages 1-3 years), reactive to <500mg peanut protein during baseline double-blind, placebo-controlled food challenge (

Rationale: Pathophysiology of non-IgE-mediated gastrointestinal food hypersensitivity, including food protein-induced enterocolitis syndrome (FPIES) remains poorly understood. Increased TNF-alpha and IL-8 have been detected in FPIES reactions. We sought to determine the effect of natural plant-derived products E-B-FAHF-2 (ethyl acetate and butanol purified food allergy herbal formula-2) and 7,4'-Dihydroxyflavone (DHF) on TNF-alpha and IL-8 production, respectively using in vitro cell lines.
Method(s): RAW 264.7 mouse macrophage cells that produce TNF-alpha were treated with E-B-FAHF-2 ranging 0-120 mug/mL and stimulated with lipopolysaccharides (LPS,1 mug/mL). Human epithelial cell line, CACO2 that produces IL-8 was treated with DHF (0-40 mug/mL) for 24 hours followed by IL1-beta (10 ng/ml) stimulation for 24 hours. TNF-alpha and IL-8 levels in supernatants were measured by ELISA. Cytotoxic effect was evaluated by trypan blue exclusion or MTT assay. Quality control of compounds was monitored by HPLC.
Result(s): E-B-FAHF-2 treatment significantly reduced TNF-alpha levels in a dose-dependent manner in RAW 264.7 cells (p<0.001 vs vehicle). It essentially eliminated TNF-alpha production at a dose of 120 mug/ml. No cytotoxicity was observed at any tested doses. DHF treatment significantly reduced IL-8 production by CACO2 cells (p<0.001 vs vehicle) without cytotoxicity at any tested doses. These effects were associated with reduction of phosphorylated IkappaBalpha.
Conclusion(s): E-B-FAHF-2 and DHF either alone or in combination may be a potential intervention for non-IgE mediated food hypersensitivity. Studies on inhibitory effects of cross-treatment or combined treatment of E-B-FAHF2 and DHF in RAW 264.7 and CACO2 cells on TNF-alpha and IL-8 are underway.
Copyright