Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.

Development of a low allergenic product for patients with milk allergy and assessment of its specific IgE reactivity.

BACKGROUND: Milk oral immunotherapy is the riskiest and most unpredictable form of oral immunotherapy. We aimed to produce a low allergenic product than conventional once baked-cake/muffin, to develop indirect in-house ELISA to check the tolerance status with milk products and evaluate IgE reactivity of patients' sera via western blotting (WB) and indirect in-house ELISA. METHOD: A low allergenic product named biscotti-twice baked-cake was developed, and the total protein concentration was determined. The protein content was studied by SDS-PAGE and proteomics. Milk-specific IgE (sIgE) binding assays were performed by WB and indirect in-house ELISA by using patients' sera. RESULTS: Casein band intensity was observed to be lower in the biscotti-twice baked-cake than in the once baked-cake (p = .014). Proteomics analysis and αS1-casein measurement showed that the lowest intensity of casein was found in biscotti. The low binding capacity of milk sIgE to biscotti compared with once baked-cake was shown by WB (p = .0012) and by indirect in-house ELISA (p = .0001). In the ROC analysis, the area under the curve (AUC) of the in-house ELISA IgE was comparable with Uni-CAP milk and casein sIgE. The AUC of the in-house ELISA IgE for cake (0.96) and biscotti (1) was slightly better than Uni-CAP milk sIgE (0.94; 0.97) and casein sIgE (0.96; 0.97), respectively. CONCLUSION: The low allergenicity of the newly developed low allergenic product "biscotti-twice baked-cake" has been demonstrated by in vitro experiments. Biscotti could be a safe treatment option than once baked-cake/muffin in patients who are reactive to once baked-milk products.

The association of milk and multiple food avoidance with growth parameters in infants and children.

BACKGROUND: Recent studies reported that strict avoidance of milk products in cow's milk allergy (CMA) affects growth and bone turnover, causing negative calcium balance and changes in bone metabolism. OBJECTIVE: To investigate biochemical parameters to predict bone turnover and its relations with height and weight measurements and nutritional intake. METHODS: Height, weight, and body mass index z scores were plotted for age according to the World Health Organization. A 3-consecutive day food record was analyzed for nutritional values of foods. The blood levels of calcium, phosphorus, alkaline phosphatase, vitamin D, and parathyroid hormone (PTH) were determined. RESULTS: The study included 69 controls, 66 children with isolated CMA, and 59 children with multiple food allergy (FA). The z scores for weight, height, and body mass index were lower in isolated CMA and multiple FA groups than controls (P < .001, P = .004, and P = .002, respectively). The nutritional intakes of protein, fat, carbohydrates, vitamins B2 and B12, niacin, calcium, and phosphorus were significantly lower in isolated CMA and multiple FA than controls. In infants (≤2 years of age), although blood calcium level was in normal range, it was significantly lower in isolated CMA and multiple FA than in controls (P < .001). In children older than 2 years, PTH level was significantly higher in isolated CMA and multiple FA groups than in controls (P = .003). CONCLUSION: Our study revealed that children with isolated CMA and multiple FA had a high nutrition gap, growth deceleration, and unbalanced bone metabolism, as illustrated by low blood calcium and elevated PTH levels.

Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

The frequency of sleep-disordered breathing in preschool children with asthma and its effects on control of asthma.

CONCLUSION: The frequency and score of SDB were higher in patients with uncontrolled asthma. Frequency and score of SDB were significantly affected by the severity of asthma. SDB must be evaluated in preschool children with uncontrolled asthma. CONCLUSION: Sleep-disordered breathing (SDB) is more common in asthmatic patients than in non-asthmatic persons, and SDB affects negatively to control asthma. A limited number of studies are discovered on the effect of SDB in preschool asthmatic children. In this study, we aimed to investigate the prevalence of SDB and its effect on control and severity of asthma in preschool children. A pediatric sleep questionnaire was completed by parents of asthmatic children. Patients who received a score of 0.33 or higher were diagnosed with SDB. Control and severity of asthma was assessed by a pediatric allergy specialist based on the Global Initiative for Asthma (GINA) criteria. The study included 249 patients, with a mean±SD age of 4.37±1.04 (range: 2-5.9) years; 69% were boys; 56.6% children had uncontrolled asthma and 28.7% had SDB. The SDB score was significantly different between controlled and uncontrolled asthma (0.19 vs 0.28; P < 0.001). The frequency of uncontrolled asthma in patients with and without SDB was 74.3% and 49.4%, respectively (P < 0.010). Based on the severity of asthma, the frequency of SDB among patients with mild, moderate, and severe asthma was 23.4%, 35.2%, and 47.4%, respectively (P = 0.010).

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

Risk factors predisposing children to food allergies.

BACKGROUND: Food allergies are the most common cause of anaphylaxis in children, and their incidence is increasing globally. The aim of this study was to determine the risk factors leading to food allergies in childhood. METHODS: Children with food allergies and non-atopic healthy children were compared using a questionnaire that included prenatal, neonatal, and postnatal risk factors. RESULTS: A total of 314 subjects, 155 patients and 159 healthy children for the control group, were enrolled in the study. The median age of patients with a food allergy at diagnosis was 6 months (1-156 months), and 71 patients (45.8%) were males. The median age of the control group was 12 months (1-61 months), and 67.0% were males. Older maternal age (P = 0.023), birth by caesarean section (P = 0.001), birth in the summer or autumn (P = 0.011), crowded housing (P = 0.001), damp houses (P = 0.001), being fed with breast milk and complementary food (P = 0.001), use of synthetic bedding (P = 0.024), and being the oldest child in the family (P = 0.001) were the considered risk factors for an immunoglobulin-E (IgE)-mediated food allergy. A low frequency of yoghurt consumption by mother (P = 0.001) and use of wool bedding (P = 0.018) were identified as risk factors for non-IgE-mediated food allergies. Low socioeconomic status (P = 0.001) played a protective role against both IgE- and non-IgE-mediated food allergies whereas breastfeeding played a protective role against IgE-mediated food allergies (P = 0.030). CONCLUSION: The most important aspect of this study was that it separately identified prenatal, neonatal, and postnatal risk factors for IgE- and non-IgE-mediated food allergies.

IgE-mediated Anisakis allergy in children.

Anisakids are nematodes responsible for different clinical patterns in humans. The well-known human-infecting Anisakis species include members of the Anisakis simplex (AS) complex. Humans usually contract anisakiasis through ingestion of raw or undercooked seafood containing Anisakis larvae. Once Anisakis has been ingested, patients may develop disease driven directly by Anisakis larvae and/or by allergic reaction due to this nematode. The capability of inducing allergic reactions depends on the expression of specific antigens by nematodes and host factors. This study aims to resume actual knowledge about AS and Anisakiasis with regard to epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment. Particular attention is paid to Anisakis allergens and their cross-reactivity on available diagnostic methods, and defining a diagnostic pathway for Anisakis allergy. Because only a few data are available in the literature about pediatric population, we focus on this group of patients specifically.

The common triggers of urticaria in children admitted to the pediatric emergency room.

BACKGROUND: Urticaria frequently causes pediatric emergency department (PED) admissions. Children with urticaria may unnecessarily avoid suspected allergens. We aimed to investigate the possible and exact triggers of urticaria in children admitted to the PED. METHODS: Medical records of children admitted to the PED within a 1-year period were evaluated for the International Classification of Diseases 10 (ICD-10) L50 urticaria code, noting symptoms, and possible triggers of urticaria. We performed telephone interviews to complete the missing data and further diagnostic tests for IgE-mediated allergies to identify the exact triggers of urticaria. RESULTS: Among 60,142 children, 462 (0.8%) with the L50 code were evaluated. Possible triggers based on the history and physical examination could be identified in 46%: infections (18%), drugs (11%), foods (8%), infections and drugs (3%), insects (3%), pollen (1%), blood products (0.4%), and vaccines (0.4%). The most frequent infections related to urticaria were upper respiratory tract infections (74.5%), urinary tract infections (13.2%), gastroenteritis (8.2%), and otitis media (4.1%). After a diagnostic workup, IgE-mediated allergic diseases were diagnosed in 6% of patients. Twenty-two percent of the patients had multiple PED admission for the same urticaria flare. Urticaria severity was found to be the most important risk factor for readmissions to the PED (odds ratio: 3.86; 95% confidence interval: 2.39-6.23; p < .001). No relationship between urticaria severity, duration, and the triggers was present. CONCLUSIONS: Despite detailed diagnostic tests, IgE-mediated allergic triggers were rarely the cause of urticaria in children admitted to the PED. Infections are the most frequent trigger. Severe urticaria causes more frequent readmissions to the PED.

COmparisoN of TastES of Available NutriTional integrated or non-integrated formulas for infants older than 1 year of age with cow's milk allergy: A multicenter, prospective, single blind, cross-sectional observational clinical study (CONTEST Study).

Palatability of the infant formulas lacking cow milk protein formulas is reported by parents to be an important drawback. The purpose of this study is to examine decisions made by mothers of infants having cow milk protein allergy, and physicians concerning the palatability of unflavored extensively hydrolyzed formulas and amino acid-based formulas. We conducted a multi-center, randomized, single-blinded, observational taste study involving 149 pediatricians from gastroenterology and allergy subspecialties at 14 tertiary healthcare units from different regions of Turkey and involving 94 mothers of infants with cow milk protein allergy. Blinding was performed for seven formulas available in the market, which were the most commonly prescribed for feeding: four AAFs (Neocate-Numil®, Aptamil Pregomin AS-Numil®, Alfamino-Nestle®, Comidagen-Mamma®), one AAF specifically designed to address the growing nutritional and lifestyle needs of children >1 year (Neocate Junior-Numil®), 2 eHFs (Bebelac Pepti Junior-Numil®, Similac Alimentum-Abott®). Considering all three formula characteristics, Neocate junior-Numil® ranked as the number 1 product among seven products by mothers (63.8%) and physicians (69.8%). The ratings of mothers were significantly higher than the physicians (8.1 points and 6.1 points, respectively; p < 0.001). No difference was found in terms of taste, smell, and appearance for Neocate junior-Numil® between the mothers' and physicians' ratings. Since caregivers have responsibility for careful selection of replacement products for infants with cow milk protein allergy, it is noteworthy that increased awareness and confidence in the palatability characteristics of these products should motivate mothers and physicians to comply with replacement treatment in the long term.

Can serum periostin, YKL-40, and osteopontin levels in pre-school children with recurrent wheezing predict later development of asthma?

BACKGROUND: Currently, there are no reliable clinical tools available for predicting asthma in pre-school-aged children with recurrent wheezing. The aim of this study was to evaluate the usefulness of serum periostin, YKL-40, and osteopontin biomarkers in wheezy pre-school-aged children for predicting the development of asthma in school ages. METHODS: The study was prospectively conducted between 2011 and 2017. The clinical features of the pre-school-aged children with recurrent wheezing and the levels of serum periostin, YKL-40, and osteopontin were measured. The same participants were reevaluated in school-age period, and participants with asthma were identified. Relative risk (RR) for the development of asthma was analyzed. RESULTS: Of the 197 pre-school-aged children with recurrent wheezing who were reevaluated in school-age years, 32% of them had asthma. Serum periostin, YKL-40, and osteopontin levels at admission could not predict participants who would have asthma symptoms in school-age years. The RR for continuing of asthma symptoms was higher in participants who had their first wheezing episode before 1 year of age, preterm birth, cesarean section delivery, prenatal smoking exposure, multi-trigger wheezing, parental asthma, modified asthma predictive index positivity, prophylactic vitamin D intake ≤ 12 months, breastfeeding time ≤ 12 month, and aeroallergen sensitivity [RR (95% CI) and P value: 2.813 (1.299-6.091), 0.002; 1.972 (1.274-3.052), 0.009; 1.929 (1.195-3.114), 0.004; 2.232 (1.463-3.406), <0.001; 3.152 (1.949-5.097), <0.001; 1.730 (1.144-2.615), 0.016; 2.427 (1.559-3.777), <0.001; 2.955 (1.558-5.604), <0.001; 1.767 (1.084-2.881), 0.016; 0.765 (0.556-1.053), 0.016; respectively]. CONCLUSION: Results have shown that clinical features were more valuable than biomarkers in predicting having asthma in school-age years in participants who had recurrent wheezing in pre-school-age period.

Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study.

Background: Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. Objective: To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. Methods: This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Results: Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non-IgE mediated in 15.5%, and mixed IgE/non-IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0-2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13-18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non-IgE-mediated FA in multivariate regression analysis. Conclusion: This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.

Pistachio and cashew nut allergy in childhood: Predictive factors towards development of a decision tree.

BACKGROUND: Pistachio and cashew nut, which belong to the same botanical family, are tree nuts that induce serious allergic reactions. OBJECTIVE: We aimed to determine the predictive factors for pistachio and cashew nut reactivity during oral food challenge (OFC). METHODS: A total of 112 pistachio and/or cashew nut sensitized children, aged 58.45 (IQR:40.38-88.32) months, were included. Cutoff values and probability curves for skin prick test (SPT), sIgE, sIgE/Total IgE that predict reactivity were determined for pistachio and cashew nut. Additionally, a diagram was created that can be useful while making a decision for OFC based on SPT and sIgE values. RESULTS: A total of 73 patients underwent OFC with pistachio and/or cashew nut. Twelve children with current anaphylaxis history were not challenged and accepted as allergic. SPT was the only predictive factor for positive pistachio/ cashew nut OFC. According to area under curve (AUC) analysis, SPT was more predictive than sIgE and sIgE/Total IgE both for pistachio and cashew nut. Optimal cutoff values according to "Youden index" for pistachio SPT, sIgE, and sIgE/ Total IgE were 7.25 mm, 4.14 kUA/L, and 1.32%, respectively. And those values for cashew nut SPT, sIgE, and sIgE/Total IgE were 6.25 mm, 1.125 kUA/L, and 3.30%, respectively. The diagram showed that SPT predicted the reactivity together with sIgE better than only the SPT values. CONCLUSION: SPT was the best predictor for reactivity both for pistachio and cashew nut. Combined use of SPT and sIgE may improve the prediction of reactivity at pistachio and cashew nut OFCs in children.

IgE-Mediated Fish Allergy in Children.

Fish allergy constitutes a severe problem worldwide. Its prevalence has been calculated as high as 7% in paediatric populations, and in many cases, it persists into adulthood with life-threatening signs and symptoms. The following review focuses on the epidemiology of Immunoglobulin E (IgE)-mediated fish allergy, its pathogenesis, clinical manifestations, and a thorough approach to diagnosis and management in the paediatric population. The traditional approach for managing fish allergy is avoidance and rescue medication for accidental exposures. Food avoidance poses many obstacles and is not easily maintained. In the specific case of fish, food is also not the only source of allergens; aerosolisation of fish proteins when cooking is a common source of highly allergenic parvalbumin, and elimination diets cannot prevent these contacts. Novel management approaches based on immunomodulation are a promising strategy for the future of these patients.

IgE and IgG4 binding to lentil epitopes in children with red and green lentil allergy.

BACKGROUND: The consumption of lentil is common in the Mediterranean area and is one of the causes of IgE-mediated food allergy in many countries. Len c 1 is a well-defined allergen of lentil and approximately 80% of the patients with lentil allergy recognize the purified Len c 1 protein. We sought to identify IgE and IgG4 sequential epitopes of Len c 1 in patients with red and/or green lentil allergy. We also aimed to determine IgE and IgG4 binding differences between those patients who had outgrown or remained reactive to lentil. METHODS: Children with IgE-mediated lentil allergy were included in the study. We applied a microarray immunoassay to determine the characterization of positive IgE and IgG4 binding to Len c 1 epitopes in the patients' sera. RESULTS: The peptides specifically recognized by IgE and IgG4 antibodies were mainly detected between peptides 107 and 135 of Len c 1. The signal intensities of positive epitopes were significantly greater in reactive patients than tolerant ones (P = .008 for IgE and P = .002 for IgG4). Moreover, IgE and IgG4 antibodies bound largely the same sequential epitopes in patients who remained reactive or outgrew their allergy. CONCLUSION: IgG4-binding epitopes in lentil allergy were identified and IgE and IgG4 binding to epitopes in both red and green lentils was compared. Our data regarding signal intensity differences between reactive and outgrown patients and overlap binding of IgE and IgG4 antibodies may be important for the development of more accurate diagnostic tests and understanding of natural tolerance development.

Desensitisation overcomes rituximab- and tocilizumab-related immediate hypersensitivity in childhood.

OBJECTIVES: Biologic drugs (BD) have been game-changers in rheumatic diseases; however, severe hypersensitivity reactions concerning anaphylaxis may limit their use. Desensitisation is a crucial option that is safe and effective to maintain patients on the preferred drug. Herein we report 84 Rapid Drug Desensitisation (RDD) procedures with rituximab and tocilizumab in children with rheumatic diseases. METHODS: The study was conducted as a retrospective chart review of patients who received tocilizumab or rituximab therapy between January 2010 and December 2018. The results of RDD with tocilizumab and rituximab were documented. RESULTS: The study group consisted of 53 patients (11.6±4.5 years, 67.9% female) with rheumatic disease who had used tocilizumab (64.1%, 1007 infusions) or rituximab (35.8%, 73 infusions). Five patients (14.7%) had experienced anaphylaxis with tocilizumab and two patients (10.5%) with rituximab. Anaphylaxis was grade II in four cases whereas it was grade III in the remaining three children. Skin testing with the culprit BD performed in five children yielded positive results. We performed 65 RDDs with tocilizumab in 3 patients and 19 RDDs with rituximab in two patients. No reactions were recorded in 97.6% of the procedures. We observed one anaphylaxis during the 5th RDD of tocilizumab. After modifying the protocol, this patient continued tocilizumab RDD uneventfully. CONCLUSIONS: RDD is a groundbreaking innovation which ensures giving the full target doses while protecting the patient against severe hypersensitivity reactions (HSRs) and anaphylaxis. As BD use increases in childhood, management of HSRs to BD will become more complicated, necessitating an increased need for RDD in clinical practice.

Risk Factors Influencing Tolerance and Clinical Features of Food Protein-induced Allergic Proctocolitis.

OBJECTIVE: Continued progress in our understanding of the food protein-induced allergic proctocolitis (FPIAP) will provide the development of diagnostic tests and treatments. We aimed to identify precisely the clinical features and natural course of the disease in a large group of patients. Also, we investigated the predicting risk factors for persistent course since influencing parameters has not yet been established. METHODS: Infants who were admitted with rectal bleeding and had a diagnosis of food protein-induced allergic proctocolitis in 5 different allergy or gastroenterology outpatient clinics were enrolled. Clinical features, laboratory tests, and prognosis were evaluated. Risk factors for persistent course were determined by logistic regression analyses. RESULTS: Among the 257 infants, 50.2% (n = 129) were girls and cow's milk (99.2%) was the most common trigger. Twenty-four percent of the patients had multiple food allergies and had more common antibiotic use (41.9% vs 11.8%), atopic dermatitis (21% vs 10.2%), wheezing (11.3% vs 1.5%), colic (33.8% vs 11.2%), and IgE sensitization (50% vs 13.5%) compared to the single-food allergic group (P < 0.001, P = 0.025, P = 0.003, P < 0.001, respectively). In multivariate logistic regression analysis, presence of colic (odds ratio [OR]: 5.128, 95% confidence interval [CI]: 1.926-13.655, P = 0.001), IgE sensitization (OR: 3.964, 95% CI: 1.424-11.034, P = 0.008), and having allergy to multiple foods (OR: 3.679, 95% CI: 1.278-10.593, P = 0.001] were found to be risk factors for continuing disease after 1 year of age. CONCLUSION: Although most children achieve tolerance at 1 year of age, IgE sensitization, allergy to multiple foods, and presence of colic were risk factors for persistent course and late tolerance. In this context, these children may require more close and extended follow-up.

Phenotypical characterization of tree nuts and peanut allergies in east Mediterranean children.

INTRODUCTION/OBJECTIVES: The characteristics of tree nuts (TNs) and peanut (PN) allergies vary in different regions of the world. We aim to identify the characteristics of TNs/PN allergies in Turkish children. PATIENTS AND METHODS: A total of 227 children [4.8 (3.2-6.8) years] with TN and/or PN allergies were included. The phenotypical features of TNs/PN allergic children and the risk factors for multiple TNs/PN allergies were evaluated. RESULTS: Allergy to TNs/PN developed at a median age of 12.0 (10.0-18.0) months. The most common TNs/PN responsible for food allergies were the hazelnut (63.9%) and the pistachio (54.6%). Of TNs/PN allergic children, 54.2% experienced reactions with at least two types of . Current ages 6-10 years [OR:2.455, 95% CI:1.255-4.852, p=0.009] and family history of atopy [OR:2.156, 95% CI:1.182-3.932, p=0.012] were the risk factors for multiple TNs/PN allergies. Most of the patients with cashew nut and pistachio allergies exhibited co-sensitization and co-allergy to both of these TNs/PN. Although the rarest TNs/PN allergy was seen with almond, the possibility of allergy to other TNs or PN was highly increased in the patients with almond allergy compared to other TNs/PN. CONCLUSIONS: Children with TNs/PN allergy living in an East Mediterranean region differ from the counterparts living in Western countries by an earlier age of onset of the TNs/PN allergy symptoms, increasing possibility to have multiple TNs/PN allergy at older ages, and different spectrum of TN/PN allergies (hazelnut followed by pistachio/cashew) that all indicate the consumption habits which are important determinants of TN/PN allergy development.

A new Luminex-based peptide assay to identify reactivity to baked, fermented, and whole milk.

BACKGROUND: The majority of children with cow's milk allergy (CMA) tolerate baked milk. However, reactivity to fermented milk products such as yogurt/cheese has not been previously evaluated. We sought to determine whether children with CMA could tolerate yogurt/cheese and whether a patient's IgE and IgG4-binding pattern to milk protein epitopes could distinguish clinical reactivity. METHODS: Four groups of reactivity were identified by Oral food challenge: baked milk reactive, fermented milk reactive, whole milk reactive, and outgrown. sIgE and sIgG4 binding to milk protein epitopes were assessed with a novel Luminex-based peptide assay (LPA). Using machine learning techniques, a model was developed to predict different degrees of CMA. RESULTS: The baked milk reactive patients demonstrated the highest degree of IgE epitope binding, which was followed sequentially by fermented milk reactive, whole milk reactive, and outgrown. Data were randomly divided into two groups with 75% of the data utilized for model development (n = 68) and 25% for testing (n = 21). All 68 children used for training were correctly classified with models using IgE and IgG4 epitopes. The average cross-validation accuracy was much higher for models using IgE plus IgG4 epitopes by LPA (84.8%), twice the performance of the serum component proteins assayed by UniCAP (41.9%). The performance of the model on "unseen data" was tested using the 21 withheld patients, and the accuracy of IgE was 86% (AUC = 0.89) while of IgE+IgG4 model was 81% (AUC = 0.94). CONCLUSION: Using a novel high-throughput LPA, we were able to distinguish the diversity of IgE/IgG4 binding to epitopes in the varying CMA phenotypes. LPA is a promising tool to predict correctly different degrees of CMA.

Proven immunologically-mediated drug hypersensitivity in children with a history of multiple drug intolerances.

BACKGROUND: Children may be referred to pediatric allergy clinics for reactions to multiple drugs. Multiple drug hypersensitivity (MDH) is defined as immunologically-mediated hypersensitivity to 2 or more chemically different drugs. OBJECTIVE: The aim of this study is to report the allergy workup results of children who had a history of potential hypersensitivity reactions to 2 or more unrelated drugs. METHODS: This study was conducted in the Pediatric Allergy and Immunology department of our hospital. Children who described hypersensitivity reactions to 2 or more drugs were included and were evaluated by allergy workup (skin and/or provocation tests) between January 2011 and July 2016. RESULTS: During the study period, 886 children were evaluated for a history of drug intolerance. Of these children, 73 (8.2%) had a history of drug reactions to 2 or more chemically different drugs. The median age of the children who had a history of reactions to 2 or more drugs was 7.8 (min-max: 2.5-16.4) years, and 59% (n = 43) were male. Among the suspected drugs, antibiotics (65.9%) ranked first, and nonsteroid anti-inflammatory drugs (34.1%) were the second. All 73 children were evaluated with skin or provocation tests with the suspected drugs, and MDH was confirmed in only 2 (2.7%) children. CONCLUSION: Multiple drug hypersensitivity is uncommon in children. The incidence and prevalence of MDH may vary with the specific population studied. Evaluating children with a history of MDH, by performing drug hypersensitivity testing, will help avoid the morbidity associated with unnecessary drug avoidance.