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.

Innate lymphoid cells: The missing part of a puzzle in food allergy.

Food allergy is an increasingly prevalent disease driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5, and IL-13 with infiltration of mast cells, eosinophils, and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. Unlike lymphocytes, ILCs lack They represent a group of lymphocytes that lack specific antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut, and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs toward inflammatory processes and regulatory mechanisms.

Subcutaneous Allergen Immunotherapy in Children: Real Life Compliance and Effect of COVID-19 Pandemic on Compliance.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment. OBJECTIVES: This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT. METHOD: Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed. RESULTS: The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT. CONCLUSIONS: Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic.

Food-induced anaphylaxis in infants, as compared to toddlers and preschool children in Turkey.

BACKGROUND: The literature includes scarce data on infants with food-induced anaphylaxis (FIA). MATERIALS AND METHODS: Medical records of the patients diagnosed with FIA aged 0-6 years between 2015 and 2020 were retrospectively analyzed. RESULTS: During the study period, there were 451 instances of FIA in 314 patients, of which 175 (38.8%) occurred in 160 infants (50.9%). The median (IQR) age of infants was 7 months (6-9 months) with a male predominance (67.5%), of which 7.5% had multiple instances (≥2) and 60% atopic dermatitis. The most common triggers were cow's milk (51.4%), tree nuts (16.6%), and hen's egg (15.4%), whereas tree nut was the most common trigger in toddlers (35.8%) and preschool children (35.2%). Skin and neurologic symptoms, and nausea-vomiting occurred more frequently (P = .003, P ≤ .001, and P = .003, respectively), whereas respiratory symptoms occurred less commonly in infants compared to toddlers and preschool children (P ≤ .001). In infants, 65 (37.1%) mild, 92 (52.6 %) moderate, and 18 (10.3%) severe episodes of anaphylaxis were detected. History of recurrent wheezing (OR: 6.837 [95% CI: 1.940-24.097], P = .003) and tree nut allergy (OR: 2.849 [95% CI: 1.056-7.688], P = .039) were found to be independent risk factors for moderate-to-severe anaphylactic reactions. 40.6% of the infants received adrenaline, which was lower than the toddlers (49.7%) and preschool children (57.6%) (P = .005). CONCLUSION: There is no doubt that food-induced anaphylaxis is a medical emergency, specifically in young children. Pediatricians should be aware of the distinct features of infant anaphylaxis, particularly gastrointestinal and neurologic symptoms to provide effective treatment as soon as possible.

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.

Spirometry in children with asthma and/or allergic rhinitis: comparison of FEF25-75% with the standard measures.

BACKGROUND: Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%), a spirometric measure of small airways, may predict the presence of airway responsiveness both in asthmatics and in allergic rhinitis (AR). We aimed to search the correlation between FEF25-75% and standard measures of spirometry (forced expiratory volume in the first second [FEV1%] and FEV1/FVC [forced vital capacity]) in different clinical conditions, that is in children with asthma, in children with asthma and AR, in children with AR and in healthy children. METHODS: Children with asthma (N.=116), asthma plus AR (N.=25), AR (N.=75) and healthy controls (N.=52) were evaluated. Clinical examinations, spirometry and bronchodilation tests were performed. RESULTS: In asthmatics there was a strong correlation between FEF25-75% and FEV1% (r=0.596, P<0.001); and between FEF25-75% and FEV1/FVC (r=0.740, P<0.001). In AR patients correlation between FEF25-75% and FEV1% (r=0.367, P=0.001); and between FEF25-75% and FEV1/FVC (r=0.534, P<0.001) were less prominent compared to asthmatics but they were still significant and strong. In children with both AR and asthma correlation between FEF25-75% and FEV1% (r=0.633, P=0.001) and between FEF25-75% and FEV1/FVC (r=0.539, P=0.005) were again significant. Pre-test FEV1% and FEF25-75% in AR patients were lower than that of the control subjects. After the bronchodilation, percentage change in the FEV1 in AR patients were significantly higher than the control subjects (P=0.010). AR patients showed significant increases in FEV1%, (P<0.001), FEF25-75%, (P<0.001) and (P=0.001) after the bronchodilation test. Within the AR patients, only 12/75 (16.0%) showed bronchodilation with salbutamol. Among the ones with a FEF25-75% <65%, FEV1% was normal in 6/43 (14%) patients in asthmatics, and FEV1% was normal in 3/9 (33%) patients in asthma +AR patients. CONCLUSIONS: Besides the FEV1% and FEV1/FVC, the FEF25-75% may be a useful and early spirometric parameter to evaluate the children with asthma and or AR.

Oxidative stress in asthma: Part of the puzzle.

An imbalance between the production of reactive oxygen species and the capacity of antioxidant defense mechanisms favoring oxidants is called oxidative stress and is implicated in asthmatic inflammation and severity. Major reactive oxygen species that are formed endogenously include hydrogen peroxide, superoxide anion, hydroxyl radical, and hypohalite radical; and the major antioxidants that fight against the endogenous and environmental oxidants are superoxide dismutase, catalase, and glutathione. Despite the well-known presence of oxidative stress in asthma, studies that target oxidative burden using a variety of nutritional, pharmacological, and environmental approaches have generally been disappointing. In this review, we summarize the current knowledge on oxidative stress and antioxidant imbalance in asthma. In addition, we focus on possible biomarkers of oxidative stress in asthma and on current and future treatment strategies using the modulation of oxidative stress to treat asthma patients.

Characteristics of children with food protein-induced enterocolitis and allergic proctocolitis.

BACKGROUND: The aim of this study was to determine and compare the clinical and laboratory features of food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP), and to provide information about the short-term prognoses. METHOD: Children diagnosed with FPIES or FPIAP between 2010 and 2015 were enrolled in this study. RESULTS: Overall, 64 infants (37 FPIAP, 27 FPIES) were evaluated, with the average age at the onset of symptoms being significantly lower in the patients with FPIAP than in the patients with FPIES (2 months [1-3 months] versus 4 months [1.5-6 months]; p = 0.043). Fifteen of the patients with FPIAP (40.5%) and six of the patients with FPIES (22.2%) were exclusively breast-fed at the time of the onset of symptoms. Cow's milk was the most frequent trigger (100% FPIAP, 74% FPIES); solid foods caused FPIES more frequently. Forty-eight of the 64 patients were followed up until at least 2 years of age, with the resolution rates being 91.3% for FPIAP and 60% for FPIES. The solid food-induced cases of FPIES (27.3%) had a significantly lower rate of resolution than the liquid food-induced FPIES (83.3%) (p = 0.003). CONCLUSION: Cow's milk is the most common trigger of both FPIAP and FPIES. The symptom onset age seemed to be earlier in FPIAP. The resolution age was similar, however, the recovery in FPIES may be later if the trigger food is solid. To our knowledge, this was the first clinical study to compare the clinical and laboratory characteristics of patients with FPIAP and FPIES.

Characteristics of drug-induced anaphylaxis in children and adolescents.

BACKGROUND: Although data on anaphylaxis in the general population exist for different allergens, there is still lack of detailed etiologic data on drug-induced anaphylaxis (DIA), particularly in children. OBJECTIVE: To define the etiology of DIA, to determine the accuracy of drug-related anaphylaxis histories, along with the severity and culprit drug associations among individuals <18 years old. METHODS: Patients with a history of drug hypersensitivity reaction (DHR) referred to our center between January 2012 and February 2016 were included. After the collection of European Network for Drug Allergy questionnaire results, initial skin tests and/or provocation tests were performed for the offending drug. RESULTS: Among 561 children and adolescents referred due to a suspected DHR, 113 (19%) (median age [interquartile range], 9.6 years [5.4-13.8 years]; 55% boys) had anaphylaxis in their history. At the end of diagnostic evaluation of the patients, 84 (74% of the patients with a history of DIA) were actually hypersensitive to the offending drug. Major drugs that resulted in DIA were antibiotics (33%), nonsteroidal anti-inflammatory drugs (25%), and chemotherapeutics (19%). The majority of patients reported grade 2 (moderate) (45%) and grade 3 (severe) (33%) anaphylactic reactions. A history of systemic illness (41.7 versus 7.1%; p = 0.001), concomitant intake of other drugs regularly (36.9 versus 10.3%; p = 0.007), and the use of chemotherapeutics as the culprit drug (19 versus 0%; p = 0.011) were more frequent, whereas the use of antibiotics was less frequent (34.5 versus 75.9%; p < 0.001) among patients with actual DIA compared to drug tolerant patients. CONCLUSION: Three-fourths of the children and adolescents referred due to a suspected history of DIA were found to actually be drug hypersensitive. Prediagnosed systemic illness and different types of drugs would have an impact on the risk of DIA; however, atopic disease or a family history of drug hypersensitivity did not have an impact on actual DIA.

Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages.

BACKGROUND: Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. OBJECTIVE: We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. METHODS: Interactions between sex and polymorphisms on childhood asthma risk were evaluated in the Multicentre Asthma Genetics in Childhood Study (MAGICS)/Phase II International Study of Asthma and Allergies in Childhood (ISAAC II) population on a genome-wide level, and findings were validated in independent populations. Genetic fine mapping of sex-specific asthma association signals was performed, and putatively causal polymorphisms were characterized in vitro by using electrophoretic mobility shift and luciferase activity assays. Gene and protein expression of the identified gene doublesex and mab-3 related transcription factor 1 (DMRT1) were measured in different human tissues by using quantitative real-time PCR and immunohistochemistry. RESULTS: Polymorphisms in the testis-associated gene DMRT1 displayed interactions with sex on asthma status in a population of primarily clinically defined asthmatic children and nonasthmatic control subjects (lowest P = 5.21 × 10(-6)). Replication of this interaction was successful in 2 childhood populations clinically assessed for asthma but showed heterogeneous results in other population-based samples. Polymorphism rs3812523 located in the putative DMRT1 promoter was associated with allele-specific changes in transcription factor binding and promoter activity in vitro. DMRT1 expression was observed not only in the testis but also in lung macrophages. CONCLUSION: DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation.

Basal serum tryptase is not a risk factor for immediate-type drug hypersensitivity during childhood.

BACKGROUND: High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age- and sex-matched controls without any history of DHRs. METHOD: Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. RESULTS: Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) µg/l vs. 2.8 (1.6-4.3) µg/l vs. 2.6 (1.8-3.6) µg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) µg/l, mild anaphylaxis 3.0 (1.9-4.9) µg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) µg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. CONCLUSION: The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom.

Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use.

The possible risk of adverse effects due to regular use of inhaled corticosteroids (ICS) is a real concern. Our aim was to describe the factors that have an impact on hypothalamic-pituitary-adrenal axis suppression (HPA-AS) in children and adolescents taking ICS regularly. The HPA axis status of patients who were on moderate-to-high-dose ICS [>176 and >264 µg/day fluticasone propionate-hydrofluoroalkane (FP-HFA) for patients 0-11 and ≥12 years, respectively] was investigated. Various types of ICS were converted to FP-HFA equivalent according to National Asthma Education and Prevention Program (NAEPP) guidelines. Participants with a baseline (8 a.m.) serum cortisol <15 µg/dL underwent a low-dose ACTH stimulation test (LDAT) to diagnose HPA-AS. Among 91 patients, 60 (75.9 %) participants underwent LDAT, and seven (7.7, 95 % CI 3.5-15.3 %) were diagnosed with HPA-AS. Ciclesonide was more frequently used by the participants with HPA-AS compared to patients with a normal HPA axis (42.9 vs. 4.8 %, p = 0.009). Use of ICS at moderate-to-high doses for at least 7 months distinguished participants with HPA-AS from those with a normal HPA axis. Among the duration, type, and dose of ICS, solely the use of ICS with a body mass index (BMI)-adjusted daily dose of ≥22 µg FP was found to increase the risk for HPA-AS (odds ratio (OR) 7.22, 95 % confidence interval (CI) 1.23-42.26, p = 0.028). The receiver operating characteristics (ROC) curve analysis revealed a cutoff value of 291 µg/day FP (area under the curve (AUC) = 0.840, p = 0.003) for predicting HPA-AS Conclusion: The prevalence of HPA-AS was found to be 7.7 % in children taking not only high-dose ICS but also moderate-dose ICS. Dose alone was found to be an actual risk factor for HPA-AS.

The genetic variants of thymic stromal lymphopoietin protein in children with asthma and allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is expressed by airway epithelial cells and plays a key role in immunological events in asthma. Data on the genetic variants of TSLP and its association with asthma and allergic rhinitis are scarce. We aimed to investigate the effects of the genetic variants of TSLP in children with asthma and allergic rhinitis. METHODS: The genetic variants of the TSLP gene were determined by sequencing 25 asthmatic and 25 healthy children. In an association study, a population of 506 asthmatics and 157 healthy controls was screened for the following single-nucleotide polymorphisms (SNPs): rs3806933 and rs2289276 in the promoter region; rs11466741, rs11466742, and rs2289278 in intron 2; rs10073816, rs11466749, and rs11466750 in exon 4, and rs11466754 in 3'-UTR. RESULTS: In Multifactor Dimensionality Reduction analysis, presence of the rs11466749 AA genotype with atopy was significantly associated with a diagnosis of asthma (testing set accuracy: 0.720 and cross validation: 9/10). Two functional SNPs showed a gender-specific association with allergy, i.e. the rs3806933 CC genotype with asthma in boys (p = 0.032, nonsignificant after multiple testing) and the rs2289276 CC genotype with higher eosinophil numbers in asthmatic girls (p = 0.003). The presence of allergic rhinitis in asthmatic children strengthened the association of the rs11466749 GG genotype with asthma (p = 0.001), and rs2289276 was significantly associated with lower FEV1 levels in asthmatics without allergic rhinitis (p = 0.003). CONCLUSION: Variants in the gene encoding the TSLP protein may have differential effects on asthma phenotypes depending on gender, atopy, and the presence of allergic rhinitis.

Challenges in identifying asthma subgroups using unsupervised statistical learning techniques.

RATIONALE: Unsupervised statistical learning techniques, such as exploratory factor analysis (EFA) and hierarchical clustering (HC), have been used to identify asthma phenotypes, with partly consistent results. Some of the inconsistency is caused by the variable selection and demographic and clinical differences among study populations. OBJECTIVES: To investigate the effects of the choice of statistical method and different preparations of data on the clustering results; and to relate these to disease severity. METHODS: Several variants of EFA and HC were applied and compared using various sets of variables and different encodings and transformations within a dataset of 383 children with asthma. Variables included lung function, inflammatory and allergy markers, family history, environmental exposures, and medications. Clusters and original variables were related to asthma severity (logistic regression and Bayesian network analysis). MEASUREMENTS AND MAIN RESULTS: EFA identified five components (eigenvalues ≥ 1) explaining 35% of the overall variance. Variations of the HC (as linkage-distance functions) did not affect the cluster inference; however, using different variable encodings and transformations did. The derived clusters predicted asthma severity less than the original variables. Prognostic factors of severity were medication usage, current symptoms, lung function, paternal asthma, body mass index, and age of asthma onset. Bayesian networks indicated conditional dependence among variables. CONCLUSIONS: The use of different unsupervised statistical learning methods and different variable sets and encodings can lead to multiple and inconsistent subgroupings of asthma, not necessarily correlated with severity. The search for asthma phenotypes needs more careful selection of markers, consistent across different study populations, and more cautious interpretation of results from unsupervised learning.

Methylene tetrahydrofolate reductase polymorphisms and homocysteine level in heart defects.

BACKGROUND: While several single nucleotide polymorphisms are known to influence the metabolism of folate, the methylene tetrahydrofolate reductase (MTHFR) gene has been the most extensively studied. The aim of this study was to investigate the relationship between the MTHFR polymorphisms 1298A>C and 677C>T and congenital heart disease. In addition, the relationship between these gene polymorphisms and homocysteine level was determined in Turkish subjects. METHODS: Patients with non-syndromic congenital heart defects who were admitted to the Pediatric Cardiology Unit at Hacettepe University Ihsan Dogramaci Children's Hospital, Ankara, Turkey between June 2002 and June 2003 were recruited for the study. A total of 163 children with congenital heart defects (mean age, 7.63 ± 6.03 years; M/F, 93/70) and 93 healthy controls were analyzed. RESULTS: When evaluated either separately or together, there were no differences in the frequency of MTHFR 677C>T or 1298A>C polymorphisms between the children with congenital heart defects and the control group. The results were the same when considering only conotruncal defects. Those with the 677C>T polymorphism had significantly lower homocysteine level (P = 0.004), but the 1298A>C polymorphism was not related to homocysteine level. CONCLUSION: No relationship was found between congenital heart defects and 1298A>C or 677C>T polymorphisms. The 677C>T polymorphism was related to low homocysteine level. Because there is often much heterogeneity between populations, this study should be conducted in different populations and with larger numbers of participants.

Clinical features of children with venom allergy and risk factors for severe systemic reactions.

BACKGROUND: Severe systemic reactions (SRs) to insect venom are rare in childhood and there are few data on this study population. The aim of our study is to analyze the clinical features and to document the risk factors for severe SRs in children with insect venom allergy. METHODS: Children with SRs after Hymenoptera sting were analyzed. The diagnosis was based on medical history, skin tests and/or specific IgE testing. RESULTS: Seventy-six children were included [57 boys (75%), mean age 9.8 ± 3.4 years]. The mean age of children at the time of SR was 8.3 ± 3.4 years. Reactions were accounted for Vespula (wasp) venom in 58 (76%) and Apis mellifera (bee) venom in 18 (24%) patients. Twenty-six percent of patients had aeroallergen sensitization and 33% had atopic disease, whereas 66% had experienced previous stings. The upper limb was the most frequent area of sting (43%), and the cutaneous system (99%) was the most frequent involved system. SRs occurred in 59% of patients. Multivariate logistic regression analysis revealed eosinophilia (>5%) [odds ratio (OR) 12.6; confidence interval (CI) 1.5-109.7; p = 0.022], female sex (OR 6.4; CI 1.5-26.9; p = 0.011) and accompanying atopic disease (OR 3.4; CI 1.2-12.3; p = 0.016) as significant risk factors for severe SRs. Ninety-seven percent of patients were admitted to the emergency department; however, epinephrine was used in only 46% of patients. CONCLUSIONS: There was a high frequency of hypersensitivity to wasp venom among the study population, and severe reactions were related to mild eosinophilia, female sex and concomitant atopic diseases. A better understanding of the risk factors may lead to effective utilization of health care sources in the future.

Role of specific IgE in predicting the clinical course of lentil allergy in children.

BACKGROUND: Legumes, and particularly lentils, are frequently consumed in Mediterranean, Middle Eastern, and some Asian countries. The aim of this study was to document the demographic features of children with lentil allergy and to determine the role of specific IgE (sIgE) in predicting the risk of clinical reactivity and disease persistence. METHODS: Thirty children were enrolled. The diagnosis of lentil allergy was based on convincing history of symptoms or anaphylaxis after the ingestion of lentils, with positive skin tests and/or sIgE to lentils. To determine the diagnosis and prognosis of lentil allergy, 24 children were evaluated with food challenges. RESULTS: The median age at the onset of symptoms was 1.5 yr (0.9-2.3) (inter-quartile range). The most frequent symptoms were immediate cutaneous (97%) and respiratory (30%) reactions, whereas eight patients (27%) reported anaphylactic reactions. The median level of lentil sIgE at the time of diagnosis was 3 kU/l (1.2-9.6). Of the 24 challenges, 12 were positive. Fifteen patients (50%) outgrew the lentil allergy by the age of 3.5 (2.5-11) years. Children with an initial lentil sIgE < 4.9 kU/l had a significantly higher likelihood (68.4% vs. 18.2%) of outgrowing the lentil allergy than children with an initial lentil sIgE ≥ 4.9 k/l (p = 0.008). CONCLUSIONS: Our results suggest that sIgE levels may be important for predicting clinical reactivity and persistence of lentil allergy.

Factors that predict the clinical reactivity and tolerance in children with cow's milk allergy.

BACKGROUND: Specific IgE (sIgE) may be used for the diagnosis of cow's milk allergy (CMA) and as a guide to perform food challenge tests in patients with CMA. The effect of genetic variants on the prognosis of food allergy is largely unknown. OBJECTIVE: To examine the performance of sIgE analysis and the utility of the genetic variants of CD14, STAT6, IL13, IL10, SPINK5, and TSLP in predicting the clinical course in children with CMA. METHODS: Serum sIgE levels of 94 children who underwent open food challenges and 54 children with anaphylaxis due to cow's milk (CM) were retrospectively analyzed between January 2002 and May 2009. The genetic polymorphisms were determined in 72 children. RESULTS: A total of 148 children were followed up for a median of 3.5 years, and 42 of the 94 challenge results were positive. The probability curves with 95% decision points were 2.8 kU/L for younger than 1 year, 11.1 for younger than 2 years, 11.7 for younger than 4 years, and 13.7 for younger than 6 years. Sixty-six children outgrew CMA during follow-up. Children with initial an CM sIgE level less than 6 kU/L outgrew CMA earlier than children with an initial CM sIgE level of 6 kU/L or higher (P < .001). The age of tolerance development for CM was significantly higher in children with the GG genotype at rs324015 of the STAT6 gene compared with those with the AA+AG genotype (2 years [range, 1.5-3.9 years] vs 1.2 years [range, 1.0-2.2 years]) (P = .02). CONCLUSION: The decision points of sIgE obtained in different age groups may help to determine the likelihood of clinical reactivity more precisely. The results suggest that sIgE levels and STAT6 gene variants may be important determinants to predict longer persistence of CMA.

Validation of the Turkish version of "Test for Respiratory and Asthma Control in Kids (TRACK)" questionnaire.

BACKGROUND: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire is the first to measure both the risk and impairment domains of the current guidelines in preschool children. We aimed to measure the reliability, validity and responsiveness of the Turkish version of the TRACK. METHODS: A total of 268 children (69.8% boys) were included in the study. Caregivers responded to three individual TRACK questionnaires, at each clinical visit (baseline, 1st month, and 3rd month). At each visit, physicians determined the control level and the treatment strategy based on the GINA guideline recommendations. RESULTS: The internal consistency reliability of the Turkish version of the TRACK questionnaire was found to be 0.74, 0.74, and 0.76 at each of the three visits, respectively (reliability statistics, Cronbach's alpha). There was a significant difference between the mean TRACK scores of the patients in different asthma control status categories (p < 0.001). The test-retest reliability in stable patients was 0.90. The optimal cut-off scores according to the Youden index were 80 and 60 points for uncontrolled and very poorly controlled children, respectively. CONCLUSION: The Turkish version of the TRACK is an accurate and reliable tool for evaluating asthma control status among preschool Turkish children. Its widespread use may help physicians correctly assess control levels among children and may improve the quality of life for both patients and their caregivers.

Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions.