Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy.

BACKGROUND: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow's milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5 mg to 13.9 mg cow's milk protein. We undertook a single-dose challenge study to validate a predicted ED05 for cow's milk of 0.5 mg protein. METHODS: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5 mg cow's milk protein (approximately 0.015 mL of fresh cow's milk). Children over 1 year underwent formal challenge to cow's milk to confirm clinical reactivity. RESULTS: 172 children (median age 6.0 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7%-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis that responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitization that were associated with objective reactivity to the single-dose challenge using 0.5 mg cow's milk protein. CONCLUSIONS: These data support an estimated ED05 for cow's milk of 0.5 mg protein. Values for ED05 above 0.5 mg for cow's milk protein proposed for allergen risk management need to be reviewed.

Immediate reactions with glatiramer acetate: Diagnosis of allergy and desensitization protocols.

PURPOSE OF REVIEW: Diverse adverse events have been associated with administration of glatiramer acetate (GA), mainly local reactions at the injection site. Other, less frequent generalized reactions include isolated postinjection reactions and anaphylaxis, which may lead to discontinuation of GA. RECENT FINDINGS: Close collaboration between the allergy and neurology departments is needed to study adverse reactions to GA. The allergy study should include a detailed history and skin prick and intradermal tests with GA and, if possible, determination of specific IgE levels. Furthermore, the implication of other drugs should be ruled out. SUMMARY: An accurate diagnosis of reactions to GA is essential if we are to confirm or rule out allergy to GA. When an allergy diagnosis is confirmed or firmly suspected based on clinical evidence, desensitization protocols are increasingly seen as safe methods for reintroduction of GA.

Oral Food Challenge in Food Protein-Induced Enterocolitis Syndrome by Fish: Is There Any Room for Improvement?

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow's milk or soy. Among the solid foods, rice is one of the most causative foods worldwide, but it varies depending on the geographic area. In the Mediterranean countries, fish is one of the most important triggers of FPIES. There is not a specific biological marker for the disease that allows us to confirm the diagnosis or to predict when tolerance to the offending food has been achieved, so all patients with a FPIES diagnosis undergo an oral food challenge (OFC) at least once. The OFC is a risky procedure and many patients develop severe symptoms. OBJECTIVE: We sought to evaluate the safety of a new OFC protocol in children with fish-FPIES. METHODS: A retrospective study was performed over a 22-year period (1996-2018). We compared two methodologies used in the OFC: Method 1 that consisted in giving several doses during the same day versus Method 2 that consisted in giving a unique dose per day on 2 or three non-consecutive days. RESULTS: A total of 75 positive OFC with fish done in 40 children were included. Forty-three (57.3%) OFC were performed following Method 1 and 32 (42.7%) with Method 2.The severity of the symptoms of the OFC done with Method 1 was mostly moderate (41.9%) followed by severe (39.5%) and mild (18.6%). The adverse reactions with Method 2 were mostly mild (68.8%) and only 18.8 and 12.5% presented moderate or severe symptoms, respectively. CONCLUSIONS: OFC performed in children with fish-FPIES are risky and many patients develop moderate or severe symptoms after this procedure. We propose a new protocol that has demonstrated to improve safety.

Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.

BACKGROUND: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. METHODS: Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. RESULTS: We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism. CONCLUSION: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.

Differences in the Anaphylactic Response between C3H/HeOuJ and BALB/c Mice.

BACKGROUND: Anaphylaxis is a severe and potentially lethal allergic reaction whose incidence is increasing. Murine models can elucidate the underlying mechanisms and pave the way for appropriate therapeutic options. However, differences in strains and protocols hamper comparisons of data between researchers. We performed a parallel study of clinical and immune responses with 2 strains of mice, BALB/c and C3H/HeOuJ, in an allergen-induced systemic anaphylaxis protocol. Both strains have been widely used in allergy models, although they have not been compared in an intraperitoneal systemic model. METHODS: Groups of 5-week-old female BALB/c and C3H/HeOuJ mice were intraperitoneally sensitized with peanut in the presence of adjuvants. Specific immunoglobulin (sIg) G1, sIgG2a, sIgE, total IgE, histamine release, and specific stimulated splenocyte cytokines, interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, and interferon (IFN)-γ, were assessed. At week 6, mice were intraperitoneally challenged with peanut. Anaphylaxis was evaluated by recognition of clinical symptoms and changes in body temperature. RESULTS: All peanut-sensitized mice induced sIg and developed anaphylactic symptoms upon challenge. Nonetheless, the C3H/HeOuJ strain demonstrated earlier and persistently higher sIgG1 and sIgG2a production, elevated sIgE, and more severe clinical symptoms and histamine release than the BALB/c strain. In contrast, BALB/c exhibited higher release of IL-4, IL-5, IL-10, IL-13, and IFN-γ. CONCLUSIONS: Both models are suitable for studying anaphylaxis. Consequently, they could be used in research on the pathogenesis and therapy of anaphylaxis. However, according to the type of study performed, differences in the specific clinical, humoral, and cellular responses to antigens have to be considered.