Sara Anvari

Evolution of Guidelines on Peanut Allergy and Peanut Introduction in Infants: A Review

Importance The reported prevalence of peanut allergy among children in the United States has increased more than 3-fold in the last 20 years. Medical guidelines on the introduction of peanut as well as other allergenic foods have evolved with the emerging evidence that an early introduction to these foods is more beneficial than a delayed introduction. This review highlights the studies that have led to the evolving guidelines on peanut introduction in infants. Observations The prevalence of peanut allergy has increased despite the publication of guidelines from the American Academy of Pediatrics in 2000, which recommended a delayed introduction of peanut. Since the 2000 guidelines, studies have provided evidence to support an earlier rather than delayed introduction. As a result, the American Academy of Pediatrics updated their guidelines in 2008 to promote peanut introduction during infancy. Current evidence continues to support the benefits of an earlier rather than delayed introduction. Conclusions and Relevance Over the years, guidelines on the introduction of peanut have evolved, and recent literature suggests that an earlier rather than delayed introduction is beneficial to prevent peanut allergies in infants.

Peanut oral immunotherapy dose variations do not result in allergic reactions

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Improved diagnostic clarity in shrimp allergic non‐dust-mite sensitized patients

BACKGROUND Allergen specific immunoglobulin E (sIgE) levels predictive of shrimp allergy have not been identified, but these may be helpful in identifying patients at risk for shrimp-induced allergic reactions. OBJECTIVE This study sought to identify component resolved diagnostic tests useful for diagnosis of shrimp allergy in patients with or without house-dust mite (HDM) sensitization to the major allergen cysteine protease (Der p 1). METHODS Patients with positive skin-prick test (SPT) results and/or sIgE values were recruited. Shrimp allergy was classified by oral food challenge (OFC) or by a clear history of anaphylaxis after shrimp ingestion. Patients with shrimp allergy and patients who were tolerant were further classified based on HDM sensitivity (Der p 1 > 0.35 kUA/L). Testing for sIgE to total shrimp, and shrimp and HDM components was performed. The Fisher exact test, Wilcoxon sum rank test, and receiver operating characteristics analyses were used to compare sIgE levels in patients with allergy and patients who were tolerant. RESULTS Of 79 patients recruited, 12 patients with shrimp allergy (7 with positive OFC results and 5 with a history of anaphylaxis) and 18 patients who were shrimp tolerant were enrolled. Of the patients not HDM sensitized, sIgE levels to shrimp (10.5 kUA/L, p = 0.012) and Der p 10 (4.09 kUA/L, p = 0.035) were higher in patients with shrimp allergy. Shrimp sIgE of ≥3.55 kUA/L had 100% diagnostic sensitivity and 85.7% specificity (receiver operating characteristic 0.94 [0.81, 1.0] 95% CI) and Der p 10 sIgE levels of ≥3.98 kUA/L had a diagnostic sensitivity of 80% and specificity of 100% (receiver operating characteristic 0.86 [0.57, 1.0] 95% CI) for prediction of clinical reactivity. CONCLUSION HDM sensitization influences shrimp and HDM component sIgE levels and, consequently, their diagnostic accuracy in shrimp allergy. In our series, in the patients who were non-HDM sensitized, a shrimp sIgE level of >3.55 kUA/L showed 100% sensitivity and, Der p 10 sIgE of >3.98 kUA/L showed 100% specificity for the diagnosis of shrimp allergy. These levels may not be applicable to every patient and, therefore, may not obviate the need for OFC.

Utility of Shrimp and Der p 10 specific IgE for Shrimp Allergy Diagnosis in Non-House Dust Mite Sensitized Patients

Background There are no set specific IgE (sIgE) to predict shrimp allergy as cross-reactivity with other arthropods play a role in shrimp sensitization. Objective This study identifies the allergens associated with shrimp allergy in house dust mite (HDM) and non-HDM sensitized patients. Methods Patients with shrimp sensitization (positive skin prick test [SPT] and/or sIgE) with/without history of clinical reaction were recruited. Allergy was confirmed by oral food challenge (OFC) except for patients with history of anaphylaxis. Shrimp allergic (SA) and shrimp tolerant (ST) patients were further classified based on HDM sensitivity. The sIgE to shrimp, shrimp and HDM components were performed. Fisher’s exact test, Wilcoxon sum rank test and receiver operating characteristics analyses were done. Results Of 79 patients recruited, 12 SA (7 positive OFC and 5 with history of anaphylaxis), 18 ST and 10 non-shrimp sensitized controls (NC) were enrolled. In non-HDM sensitized patients, sIgE to shrimp (10.5 kUA/L, p=0.012) and Der p 10 (4.09 kUA/L, p=0.035) were higher in SA patients. Shrimp sIgE ≥3.55 kUA/L had 100% sensitivity and 85.71% specificity (ROC=0.94[0.81, 1.0]). Der p 10 sIgE ≥3.98 kUA/L had sensitivity of 80% and specificity of 100% (ROC=0.86[0.57, 1.0]). rPen a 1 ≥1.1 kUA/L had sensitivity of 80% and specificity of 85.7% (ROC=0.80[0.47,1.0]). Conclusions In non-HDM sensitized patients, shrimp sIgE ≥3.55 kUA/L and Der p 10 sIgE≥3.98 kUA/L give 100% sensitivity and specificity, respectively, to diagnose shrimp allergy. HDM sensitivity can influence sIgE levels to shrimp and shrimp/HDM components due to cross-reactivity.

Protein transport inhibitors downregulate the expression of LAG-3 on regulatory T cells

Modern immunologic studies demand increasing complexity because of a need to improve our understanding of the relationship between a cells phenotype and its function. Regulatory T cells (Tregs) have been defined by a narrow set of phenotypic markers, however their actual functional capacity has not been determined at the single-cell level. Although the lymphocyte activation gene 3 (LAG-3; CD223) is a key marker for the identification of exhausted T cells, it may be useful also in resolving Treg subpopulations by indicating distinct functional breadths. Here we define the experimental conditions necessary for the optimal detection by flow cytometry of LAG-3 expression on activated Tregs. We stimulated human PBMCs with either PMA/ionomycin or Staphylococcal Enterotoxin B (SEB) and analyzed CD4+CD25+FoxP3+ Tregs for LAG-3 expression in concert with other Treg phenotypic markers. We prescribe a 24-hour stimulation period for the optimal detection of LAG-3 on Tregs. Furthermore, we determine LAG-3 protein expression on Tregs is compromised when the cells are treated with brefeldin A (BFA) and monensin. Therefore, the simultaneous assessment of Treg phenotype and function is complicated by the use of protein transport inhibitors.

The role of intravenous access during oral food challenges in food protein‐induced enterocolitis syndrome

BACKGROUND Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E mediated food hypersensitivity syndrome characterized by profuse vomiting and diarrhea, which leads to lethargy, dehydration, and hypotension. Given the potential severity of reactions, resolution of FPIES is confirmed via oral food challenge (OFC) during which intravenous (IV) access is recommended to facilitate IV fluids (IVF) and steroid therapy. Risk factors for IV treatment are not well characterized. OBJECTIVES The objectives of this study were to analyze predictors for IV treatment during OFC in patients with FPIES. METHODS A retrospective chart review was conducted of patients with The International Classification of Diseases, Ninth Revision codes 558.3 and 558.9, and with OFC who were seen in an allergy and immunology clinic from January 2000 to October 2015. OFC reaction severity was scored (1, mild; 2, moderate; 3, severe), and demographics, IV treatment frequency, and OFC outcomes were evaluated. The Fisher exact test and Wilcoxon rank sum test statistical analyses were performed. RESULTS Of 184 patients, 28 met inclusion criteria, with 39 OFCs performed. The median age of onset of FPIES was 6 months. The median age at OFC was 2.6 years. This was 2.2 years (range, 0.3-8.5 years) from symptom onset. Of 39 OFCs, IV treatment, including IVF and/or steroids, was required in only 7.7%. Thirty-eight OFCs (97.4%) were of equal or lesser severity than historical reactions. The median severity of presenting reaction (3[IV+]:1[IV-]; p = 0.05) was greater in those who required IV treatment. OFCs with IV treatment were in younger patients (15 months [IV+]:32 months [IV-]; p = 0.039) who underwent OFCs earlier relative to the time of diagnosis (8 months [IV+]:28 months [IV-]); p = 0.018). CONCLUSION Although FPIES can potentially elicit severe symptomatology, the patients most commonly experienced only vomiting and diarrhea, which often resolved with minimal treatment. Reactions generally did not worsen over time. Fewer than 10% of the patients challenged required IV treatment, all were young and with severe FPIES. It is reasonable to consider age and length of time from historical reactions when evaluating the necessity of IV placement in patients undergoing FPIES OFC.