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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.

Objective: Patients with persistent eosinophilia may have many conditions ranging from relatively benign diseases such as parasitic serious infections to life-threatening serious diseases. We aimed to determine the etiological causes of hypereosinophilia in children. Material and Methods: Patients under 18 years of age who had complete blood counts in Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital’s pediatric clinics between January 2013-January 2016 were retrospectively analyzed. Hypereosinophilia was defined as having at least two peripheral blood absolute eosinophil counts greater than or equal to 1500/mm3.The results of the examinations and diagnoses when the patients were detected with hypereosinophilia were recorded from the hospital records.Results: Three hundred and forty patients who underwent complete blood count were found to have hypereosinophilia. Seventy patients whose file records could not be accessed were excluded from the study. Two-hundred seventy patients (56% male) with a median age of 5 (IQR:1-12) years were included in our study. When the diagnoses of patients were examined, 48 (17.8%) had allergic diseases, 21 (7.8%) had immunodeficiency, 14 (5.2%) had parasitic disease. 15 (5.5%) had tumor, 4 (1.5%) had leukemia, 2 (0.7%) had hypereosinophilic syndrome, 2 (0.7%) had adrenal insufficiency and 2 (0.7%) had burn. Ninety-nine (36.7%) patients were found to use medication for any disease (acute or chronic). As a result of theexaminations performed in 63 (23.3%) patients, it was found that there was no reason to explain hypereosinophilia.Conclusion: The number of eosinophils may increase in many conditions. The cause of increase in eosinophil may not always be found.Further studies are needed on the long-term prognosis of these patients., Amaç: Hipereozinofili hastaları, paraziter enfeksiyonlar gibi nispeten iyi huylu hastalıklardan yaşamı tehdit eden ciddi hastalıklara kadar pekçok duruma sahip olabilir. Çalışmamızda çocuklarda hipereozinofilinin etiyolojik nedenlerinin belirlenmesi amaçlanmıştır.Gereç ve Yöntemler: Ankara Çocuk Sağlığı ve Hastalıkları Hematoloji Onkoloji Eğitim ve Araştırma Hastanesi pediatri kliniklerinde Ocak2013 - Ocak 2016 tarihleri arasında tam kan sayımı yapılan 18 yaş altı hastalar retrospektif olarak incelendi.En az iki tam kan sayımı ölçümünde periferik kan mutlak eozinofil sayısının 1500/mm3 veya daha büyük olması hipereozinofili olaral kabuledildi. Hastane kayıtlarından hipereozinofili tespit edildiğinde yapılan tetkik ve tanıların sonuçları kaydedildi.Bulgular: Tam kan sayımı yapılan çocuk hastaların 340’ında hipereozinofili olduğu tespit edildi. Dosya kayıtlarına ulaşılamayan 70 hastaçalışma dışı bırakıldı. Çalışmamıza, yaşları ortanca 5 (1-12) [ortanca (çeyrekler arası aralık (ÇAA)] yıl olan 270 (%56’sı erkek) hasta dahiledildi. Hastalara konulan tanılar incelendiğinde: 48’ine (%17.8) alerjik hastalık, 21’ine (%7.8) immün yetmezlik, 14’üne (%5.2) paraziterhastalık, 15’ine tümör (%5.6), 4’üne (%1.5) lösemi, 2’sine (%0.7) hipereozinofilik sendrom, 2’sine (%0.7) adrenal yetmezlik, 2’sine (%0.7)yanık tanısı konulduğu tespit edildi. Doksan dokuz (%36.7) hastada ise herhangi bir hastalık için (akut veya kronik) ilaç kullanımı (antibiyotik,antiepileptik, demir şelatörü gibi) olduğu tespit edildi. Altmış üç (%23.3) hastada ise yapılan tetkikler sonucunda hipereozinofiliyi açıklayacakbir neden bulunamadığı görüldü.Sonuç: Kanda eozinofil sayısı pek çok durumda da yükselebilir. Eozinofil yüksekliğinin sebebi her zaman bulunamayabilir. Bu hastalarınuzun dönem prognozları hakkında yapılacak ileri çalışmalara ihtiyaç vardır.

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Food allergy is increasing in prevalence and the severity of allergic reactions is unpredictable. Identifying food-allergic patients at high risk of severe reactions would allow us to offer a personalized and improved management for these patients.We review the evidence for using the levels of specific IgE, the nature of the allergen, and cellular tests to identify patients at high risk of developing severe allergic reactions to foods.The evidence about whether the quantity of allergen-specific IgE reflects the severity of allergic reactions to foods is conflicting, with some positive and some negative studies. For some foods, specific IgE to individual components (e.g. Ara h 2 in peanut) can provide additional information. However, more important than the quantity of IgE is possibly the quality of IgE, which can be captured by individual measurements of affinity/avidity, diversity, and specific activity, but is best measured overall using the basophil and mast cell activation tests, which assess the function of IgE in its ability to induce cell activation, degranulation, and mediator release. Biomarkers look at a single aspect of the allergic response and should be interpreted in the broader clinical context for each individual patient assessed.

Background Omalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines. This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria (CSU). Methods CSU patients aged 12–18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study. All patients had an urticaria-activity-score (UAS7) of ≥16 or and were treated with 300 mg omalizumab every four weeks. The degree of response was classified into complete, partial and non-responders due to UAS7. Results A total of 29 patients were evaluated. The median age and symptom onset age of the patients was 15.2 (IQR, 12.8–16.5) years and 14.0 (IQR, 11.8–15.9) years, respectively. The median duration of urticaria was eight (IQR, 4–24) months at admission. Eleven (37.9%) patients had angioedema and ten (34.5%) patients had concomitant allergic diseases. The median age at the beginning of treatment with omalizumab was 15.4 (IQR, 12.9–16.9) years. The median symptom duration was 12 (IQR, 6.5–27.5) months before the omalizumab treatment. Twenty-eight (96.5%) of the patients (89.6% complete, 6.9% partial) achieved response; however, one patient was a non-responder (3.5%). The adverse effect was observed in one (3.4%) patient as angioedema after the third dose. Twenty-three patients were followed up for a median of 18 (IQR, 13–27) months. Relapse was observed in three (13%) patients. Conclusions Omalizumab is considered as an effective and safe treatment for CSU in adolescents. Relapses mostly occur within the first year after the cessation of treatment.

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

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.

Background Anaphylaxis is a sudden, severe, and potentially life-threatening allergic reaction, affecting a portion of allergic patients. Adrenaline is the first-line medication for anaphylaxis and available in many parts of the world as adrenaline autoinjectors (AAIs). Objective Aim of this study was to determine attitudes and knowledge levels of patients/parents regarding the use of AAIs, frequency, and rate of appropriate AAI use and to give a standardized and better education by improving on mistakes during administration. Method 190 patients aged 1–18 years who were prescribed AAIs for any reason between 2012 and 2017 in Hacettepe University Pediatric Allergy Unit. Demographic data were collected during face-to-face interview or by telephone. Parents completed a mini-survey regarding use, carriage, and storage of AAI. Results Some 190 patients (64.7% male) aged 7.83 (4.99–12.08) years, median (inter-quartile), were included in the study. The indications for AAI prescription were food allergy (78.9%); venom allergy (14.2%); idiopathic anaphylaxis (3.7%); mastocytosis (2.1%); and drug allergy (1.0%). One-fourth of AAI-prescribed patients experienced anaphylaxis requiring the use of AAI within the past five years. However, only 30% of the patients dared to use AAI; only three-quarters of whom had managed to use it correctly. Conclusion After prescription of AAI and initial training, patients and parents’ concerns and fears should be taken into consideration and necessary support should be provided. At every opportunity and each clinical visit, not only should training sessions be repeated but also the patients and parents should be psychologically supported.

WOS: 000504849100004 Objective: Children with food allergy need special care. Therefore, parents of food allergic children usually seek information on the internet to improve their knowledge. However, the quality and accuracy of internet-based information may vary and misdirect parents in their daily practices. Materials and Methods: We aimed to investigate the habits of internet usage in the families reporting cow's milk protein allergy or multiple food allergy in their children. This study was conducted by using a web-based questionnaire that can be completed on the Internet in Facebook groups of families who stated that their children had diagnosis of food allergy. Results: A total of 458 (96% female) individuals with a mean age of 32.03 +/- 4.49 years participated in our survey. Three hundred forty three (74.9%) participants reported that they have preferred the internet to get information associated with the complaints of their children before seeing a physician. Two hundred ninty five (64.4%) participants reported that the information obtained on the internet and the information provided by the physicians were sometimes contradictory. As regards the contradicting information, 147 (49.8%) participants reported that they relied on the information provided by the physicians, whereas, 43 (14.9%) reported that they relied on the information on the internet. In addition, 44.3% stated that they always or most of the time gave advice to other patients and their families on the internet. Conclusion: Considering that social media use is an unpreventable habit, online sources should include correct information for information-seeking parents and should possibly be supervised or be certified by health institutions and organizations.

Background: Tree nut (TN) allergies are the most common cause of fatal anaphylaxis and generally are ongoing food allergies throughout life. Objective: To investigate the predicting factors for TN anaphylaxis in children. Methods: Children with TN allergy were divided into anaphylactic and nonanaphylactic groups, those who had an anaphylactic reaction with at least one type of TN and those with any type of reaction other than anaphylaxis with TNs, respectively. Children with TN allergies were evaluated for the predictors of anaphylaxis by using multivariate logistic regression analysis. Results: A total of 184 children (ages 4.9 years; 3.2‐6.9 years) with TN allergy were included in the study. Of these, 90 experienced an anaphylactic type of reaction on exposure to at least one type of TNs. Comparisons of the two groups showed that concomitant asthma, skin-prick test, specific immunoglobulin E, total immunoglobulin E, and serum basal tryptase (sBT) levels were significantly higher in the anaphylactic group compared with the nonanaphylactic group. In multivariate analysis, female gender (odds ratio [OR] 4.905 [95% confidence interval {CI}, 1.266‐19.001], p = 0.021), sBT levels (OR 2.287 [95% CI, 1.431‐3.654], p < 0.001), concomitant egg white allergy (OR 4.135 [95% CI, 1.016‐16.481], p = 0.048), and concomitant asthma (OR 3.874 [95% CI, 1.109‐13.526], p = 0.034) were risk factors for anaphylaxis. The optimal cutoff value for sBT was 2.06 ng/mL, with a sensitivity of 85.9% and a specificity of 69%, as well as an area under the curve 0.810 (95% CI, 0.717‐0.903, p < 0.001). The sBT levels of 1.94 ng/mL and 5.30 ng/mL predicted clinical reactivity at 50% and 95% probabilities. Conclusion: Different aspects, including gender, higher mast cell load and/or activation, and a stronger atopic background (e.g., coexisting egg allergy, asthma), contributed to the development of anaphylactic reactions to TNs in children.

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.

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.

Background: Skin prick tests (SPTs) are the gold standard for the diagnosis of IgE-mediated allergic diseases. Newly introduced devices have different results in performance. This study aimed to provide data for sensitivity, reproducibility, and acceptability of a new SPT device by using different techniques. Methods: The study was conducted in 4 sections. Different application techniques were evaluated. In the first section, a drop of histamine/saline was put by vial (V). In the second section, it was taken from a well via the test device (W). ALK® Lancet served as a reference in both sections. The techniques were as follows; 1) apply vertical pressure (VP/WP), 2) apply vertical pressure and rotate 90° clockwise (VC/WC), 3) apply vertical pressure and rotate 90° clockwise and then counter-clockwise (VCC/WCC). Pain assessment was performed by using the Wong-Baker FACES Pain Rating Scale. Different histamine concentrations were transferred from the well by the Oryum device and applied as WC in section 3. Lancet and Oryum-WP were compared in terms of time and allergen adequacy in section 4. Results: In the first section the sensitivity of all techniques for Oryum and lancet were 100%. The false positivity of Oryum-VP, WP and lancet were found 0%. The Oryum-VP technique was found the best for intrapatient coefficient of variation (CV) (10.72%) (p

Auriculotemporal or Frey syndrome in children is rare and often misdiagnosed as food allergy. Here, we report a case of Frey syndrome and coincidental cutaneous mastocytoma in a 6-month-old boy. In view of the benign nature of this syndrome, no therapy is recommended. This rare disease should be kept in mind in order to prevent unnecessary diagnostic tests and elimination diets.

Aim We aimed to identify the frequency, magnitude and risk factors of salbutamol-induced hypoxia in children with acute asthma. Methods This study was conducted at Hacettepe University on children who presented to the paediatric allergy clinic or the paediatric emergency room with acute asthma between July 2014 and June 2015. Vital signs, pulse oximetry-defined oxygen saturation and modified pulmonary index scores were evaluated before and after the first, second and third doses of nebulised salbutamol and repeated one and 10 days later. Results We included 304 patients (65.7% male) from median age of 5.3 years (range 1-18 years). Salbutamol-induced hypoxia was detected in 14.7%, 3.9% and 1.3%, respectively, after the first, second and third doses of salbutamol. The risk factors for hypoxia were younger age and a higher modified pulmonary index score, but the risk factors for salbutamol-induced hypoxia were the number of salbutamol doses given in the last six hours and the presence of aeroallergen sensitisation. The maximum decrease in oxygen saturation after salbutamol was %5. Conclusion Although bronchodilators are the first-line treatment for acute asthma, they caused modest hypoxaemia, especially at repeated doses and, or, in patients with aeroallergen sensitisation.

Background Beta-lactam antibiotics (BLA) are the most commonly prescribed antibiotics and are responsible for the majority of immediate hypersensitivity reactions to drugs in children. Cross-reactivity is important in hypersensitivity to BLAs because these drugs all share a common beta-lactam structure and some share similar side chains. Objective The aim of this study was to evaluate the clinical characteristics of patients who are diagnosed with immediate-type BLA hypersensitivity and frequency of patients with side chain hypersensitivity, "selective responders." Methods The study included patients who were diagnosed with immediate-type BLA hypersensitivity between January 2011 and May 2016 in a pediatric allergy outpatient clinic. The patients who had negative penicillin test (minor determinant mixture, benzylpenicilloylpoly-L-lysine, penicillin G) results and could tolerate penicillin V and/or BLAs with dissimilar side chains but had positive skin and/or provocation test results with the suspected drug were diagnosed as selective responders. Results During the study period, 357 patients (55.2% girls) were admitted to our clinic with suspected immediate-type BLA hypersensitivity. Parents of 11 patients did not give consent for an allergy workup with the suspected drug. Forty-five of the patients were diagnosed (45/346 [13%]) based on skin test or drug provocation test results. The most common susceptible agent was amoxicillin-clavulanate. Of the patients, 71.4% with a reaction to sulbactam-ampicillin /or amoxicillin-clavulanate and 93.7% with a reaction to cephalosporin were classified as selective responders. Conclusion Among children with immediate BLA hypersensitivity, selective responders constituted an important group. Most of the patients with reactions to aminopenicillin and cephalosporins safely tolerated penicillin V and BLAs with dissimilar side chains after negative allergy workup results.

Background The severe cutaneous adverse drug reactions (SCARs) are rare but could be life-threatening. These include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis. Objective The purpose of this study was the evaluation of the clinical characteristics of patients with the diagnosis of SCARs. Methods Patients who were diagnosed with SCARs between January 2011 and May 2016 by pediatric allergy clinics in the provinces of Ankara, Trabzon, Izmir, Adana, and Bolu were included in this multicenter study. Clinical and laboratory findings, the time between suspected drug intake and development of clinical findings, treatments they have received, and length of recovery time were recorded. Results Fifty-eight patients with SCARs were included in this study. The median age of the patients was 8.2 years (interquartile range, 5.25-13 years) and 50% (n = 29) were males. Diagnosis was Stevens-Johnson syndrome/TEN in 60.4% (n = 35), DRESS in 27.6% (n = 16), and acute generalized exanthematous pustulosis in 12% (n = 7) of the patients. In 93.1% of the patients, drugs were the cause of the reactions. Antibiotics ranked first among the drugs (51.7%) and antiepileptic drugs were the second (31%) most common. A patient who was diagnosed with TEN developed lagophthalmos and a patient who was diagnosed with DRESS developed secondary diabetes mellitus. Only 1 patient with the diagnosis of TEN died. Conclusions SCARs in children are not common but potentially serious. Early diagnosis and appropriate treatment of SCARs will reduce the incidence of morbidity and mortality.

Background/aim: filaggrin is a protein complex involved in epidermal differentiation and skin barrier formation. Mutations of the filaggrin gene (FLG) arc associated with allergen sensitization and allergic diseases like atopic dermatitis (AD), allergic rhinitis, food allergy (FA), and asthma. The aim of the study is to reveal the frequency of change in the FIG gene and determine the association between FIG loss-of-function (LOF) mutations and FA and/or AD in Turkish children. Materials and methods: four PLC loss-of-function (WO mutations known to be common in European populations were analyzed in 128 healthy children, 405 food-allergic children with or without atopic dermatitis, and 61 children with atopic dermatitis. PCRRFLP was performed for genotyping R501X, 2282del14, and R2447X mutations; 53247X was genotyped using a TaqMan-based allelic discrimination assay. Results were confirmed by DNA sequence analysis in 50 randomly chosen patients for all mutations. Results: a total of 466 patients [(67% male, 1 (0.7-2.8) years] and 128 healthy controls [59% male, 2.4 (1.4-3.5) years)] were included in this study. Two patients were heterozygous carriers of wild-type R501X, but none of the controls carried this mutation. Three patients and one healthy control were heterozygous carriers of wild-type 2282del4. Neither patients nor controls carried R2447X or S3247X PLC mutations. There were no combined mutations determined in heterozygous mutation carriers. Conclusions: although R501X, 2282del4, R2447X, and S3247X mutations are very common in European populations, we found that FIG mutations were infrequent and there is no significant association with food allergy and/or atopic dermatitis in Turkish individuals., Hacettepe University Scientific Research Coordination Unit

WOS: 000486613600003, This review addresses the current strategies of inducing tolerance development in infant and childhood cow's milk protein allergy (CMPA). The change in prevention strategies for CMPA has been emphasized based on the lack of evidence to support the efficacy of food allergen avoidance in infancy and the concept of the dual-allergen-exposure hypothesis, which suggests that allergen exposure through the skin leads to sensitization, whereas early oral consumption of allergenic food protein induces oral tolerance. The new approach is based on the likelihood of early introduction of allergenic foods to the infant's diet to reduce the development of food allergies through oral tolerance induction. The latest treatment guidelines recommend the continuation of breast feeding and the elimination of cow's milk and products from the maternal diet in exclusively breast-fed infants with CMPA, the use of an extensively hydrolyzed infant formula (eHF) with proven efficacy in CMPA as the first elimination diet in formula-fed infants with CMPA and the use of amino acid-based formula (AAF) in severe cases, such as anaphylaxis, enteropathy, eosinophilic esophagitis, and food protein-induced enterocolitis syndrome (FPIES), as well as cases of multiple system involvement, multiple food allergies, and intolerance to extensively hydrolyzed formula (eHF). In conclusion, this paper presents the current knowledge on tolerance development in infants and children with CMPA to increase the awareness of the clinicians concerning the new approaches in CMPA treatment Tolerance development is considered a relatively new concept in CMPA, inducing a shift in interventions in CMPA from a passive (avoidance of responsible allergen) toward a proactive (tolerance induction) strategy., Abbot Nutrition Turkey, We thank Cagla Ayhan, MD and Prof. Sule Oktay, MD, PhD. from the KAPPA Consultancy Training Research Ltd., Istanbul, who provided editorial support funded by Abbot Nutrition Turkey. We also thank Saglik Bahcesi Design & Communication-Learning & Development-Digital Solutions, Istanbul, Turkey, for providing scientific background support and moderation for the panel meeting.

Background/aim: The aim of this study was to compare the effect of salbutamol delivered to children by jet nebulizer (JN) and mesh nebulizer (MN). Materials and methods: Children admitted with acute asthma were treated with 3 doses of nebulized salbutamol, 1 given by MN. The patients' vital signs, lung function measurements, modified pulmonary index score (MPIS), and whole body plethysmography (WBP) measurements were evaluated before and 20 min after each dose of salbutamol.Results: Thirty-onechildren [9.5 (6.4-17.2) years, 67.7% male, 32.3% female] with mild (67.7%) and moderate (32.3%) asthma attacks were included in the study. The improvements with MN were comparable with JN in terms of changes in pretreatment and posttreatment forced expiratory volume in the first second (FEV1) (2.57 ± 4.57, 3.65 ± 5.44; P = 0.44), forced vital capacity (FVC) (2.52 ± 5.29, 4.17 ± 7.54; P = 0.28), heart rate (7.33 ± 10.21, 4.14 ± 9.32; P = 0.24), peripheral capillary oxygen saturation (SpO2) (0.38 ± 0.23, 0.43 ± 0.15; P = 0.83), and modified pulmonary index score (MPIS) (-6.30 ± 22.70, -8.77 ± 25.46; P = 0.70). The pre- and posttreatment values of total lung capacity (TLC), residual volume (RV), specific conductance (sGaw), and RV/TLC were similar for the JN and MN groups. Adverse effects were not different: however, complaints of palpitation were significantly higher in the posttreatment MN group than the pretreatment MN group (32.3% vs 9.7%, respectively, P = 0.016).Conclusions: These findings support the previous evidence found in studies of adults that MN is as effective as and as safe as JN in the treatment of acute asthma in children.

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.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.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.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.

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.

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. David H. and Julia Koch Research Program in Food Allergy Therapeutics This study was supported in part by the David H. and Julia Koch Research Program in Food Allergy Therapeutics. WOS:000493798700001 31598994 Q1

Background Pollen-food syndrome (PFS) is an allergic reaction to fresh fruits, vegetables and/or nuts that can occur in patients who are allergic to pollen. The prevalence of PFS in children is not clearly known. Objective The objective of this study was to determine the frequency and clinical features of PFS in pediatric patients with pollen-induced allergic rhinitis (AR). Method This study was conducted in the pediatric allergy outpatient clinic of our hospital. Pollen-induced seasonal AR patients who were evaluated for any symptoms appearing after consuming any fresh fruits and vegetables. Results Six hundred and seventy-two pollen-sensitized patients were included in this study. The symptoms related to PFS were reported in 22 (3.3%) patients. The median age of the patients was 12.3 years and 59% (n = 13) were female. Peach was the most common culprit (22%). There were isolated oropharyngeal symptoms in 20 (91%) patients and anaphylaxis in two (9%) patients with the suspected food. The multiple logistic regression analysis revealed that female gender, history of atopic dermatitis and allergic diseases in the family were the potential risk factors for PFS [Odds ratio 95%CI: 3.367 (1.344–8.435), 5.120 (1.935–13.550), 3.046 (1.239–7.492), respectively]. Conclusion PFS can be seen in children who are followed up for pollen-induced AR. The symptoms of PFS are usually mild and transient. However, comprehensive evaluation of patients is important since serious systemic reactions such as anaphylaxis can also be observed.

BACKGROUND Increased numbers of mast cells that contain tryptase are found in lesional atopic dermatitis (AD) skin. The association of serum basal tryptase (sBT) with anaphylactic reactions and mast cell diseases has recently been shown in children with venom and food allergy. OBJECTIVE We aimed to identify the risk factors that predict the severity of AD and the association of sBT levels with AD and disease severity. METHOD AD diagnosis was made according to Hanifin and Rajka criteria. Disease severity was scored by the objective scoring atopic dermatitis (SCORAD) index. The sBT levels were measured. Skin-prick testing, total immunoglobulin E, eosinophil percentages and counts, and a questionnaire concerning the history of atopic diseases and the risk factors of AD were applied. RESULTS The children, ages 0.5 to 3.0 years, with AD (n = 85) were analyzed in two groups according to the presence (AD+/atopy+ [n = 55]) or absence (AD+/atopy- [n = 30]) of skin-prick test positivity. The comparisons were made with an age- and sex-matched control group (n = 82). The median (interquartile range) sBT in the AD+/atopy+, AD+/atopy-, and control groups were 5.01 ng/mL (2.75-6.79 ng/mL), 3.02 ng/mL (1.67-4.44 ng/mL), and 2.63 ng/mL (1.31-4.49 ng/mL), respectively (p = 0.003). The median (interquartile range) sBT levels were higher in patients with moderate-severe objective SCORAD index scores compared with the those with mild disease (3.85 ng/mL [2.04-5.91 ng/mL] versus 2.80 ng/mL [1.83-3.48 ng/mL]; p = 0.038). Multivariate logistic regression analysis showed that an sBT level of ≥3.9 ng/mL (odds ratio 8.77 [95% confidence interval, 1.87-41.18]; p = 0.006) was independently associated with an increased risk of moderate-severe AD (objective SCORAD index). CONCLUSION To our knowledge, this was the first study that indicated that sBT levels may be important in the AD disease process and associated with the disease severity and atopy.

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

Background: Although non-steroidal anti-inflammatory drug hypersensitivity (NSAID-H) has been widely studied in adults, there is still a lack of data regarding the features and phenotypes of NSAID-H in children. Our aim was to define risk factors and different phenotypes according to clinical patterns. Methods: Patients with a history of reaction to any NSAIDs referred between January 2012 and October 2014 were included. After completing a European Network for Drug Allergy (ENDA) questionnaire, initial skin and/or oral provocation tests (OPTs) were performed for the offending drug. Additional OPTs were done with aspirin in case of NSAID-H to determine cross-reactivity. NSAID-hypersensitive patients were defined as being either a selective responder (SR) or cross-intolerant (CI) and further categorized according to either the ENDA/GA2LEN classification or an alternative scheme by Caimmi et al. [Int Arch Allergy Immunol 2012;159:306-312]. Results: Among 121 patients [58.7% male, average age 7.8 years (4.7-10.8)] with 161 NSAID-related reactions, 110 patients with 148 reactions were assessed. NSAID-H was diagnosed in 30 (27%) patients with 37 (25%) reactions. Multivariate regression analysis revealed that an immediate-type reaction and respiratory symptoms during the reaction increased the risk of a reproducible NSAID-related reaction (OR 3.508, 95% CI 1.42-8.7, p = 0.007; OR 3.951, 95% CI 1.33-11.77, p = 0.014, respectively). Additional OPTs revealed 13 SRs and 14 CIs. A family history of allergic disease was more frequent in CIs compared to SRs (57.1 vs. 15.4%, p = 0.031). Reactions belonging to CIs were more frequently characterized by angioedema compared to those of SRs (81.3 vs. 46.2%, p = 0.019). SRs and CIs were further classified as single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 13), NSAID-induced urticaria/angioedema (n = 7), NSAID-exacerbated cutaneous disease (n = 2) and NSAID-exacerbated respiratory disease (n = 1). Four CIs could not be categorized according to either classification system. One SR could not be categorized according to ENDA/GA2LEN. Conclusion: During childhood, NSAID-H exhibits different phenotypes and the majority of them can be categorized with current classification systems; however, classifications based on adult data may not exactly fit NSAID-H in paediatric patients.

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.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the second-most frequent drug type to cause hypersensitivity reactions in children. Asthma is one of the risk factors for NSAID hypersensitivity (NSAID-H) in adult patients. There are limited number of studies evaluating NSAID-H among children with asthma. Our aim was to assess the frequency of confirmed NSAID-H and evaluate the classification of NSAID-H in children with asthma. Methods: Patients followed with a diagnosis of asthma in our Pediatric Allergy Clinic were evaluated for NSAID-H. Patients were questioned whether they had used NSAIDs, and if they experienced any reaction with these drugs. A control group was also questioned for reactions to NSAID use. Results: 976 children with asthma and 2,000 healthy children as a control group were included in this study. The mean age of the patients with asthma was 10.61 ± 4.21 years and 59.5% were male. Ten (1%) had a reaction history to NSAIDs. NSAID-H was confirmed in 9 (0.9%) who were tested with the suspected drugs. Six of these were classified as “single NSAID-induced urticaria/angioedema or anaphylaxis” and 3 were classified as “NSAIDs-exacerbated respiratory disease.” In the control group, only 1 subject had a reaction history to acetylsalicylic acid and no reaction developed in the provocation test. Conclusions: In our study, NSAID-H was found more frequent in children with asthma than in the control group. Children with asthma should be evaluated for reactions to NSAIDs during hospital visits.

Background During the recent pandemic, Influenza A/H1N1 vaccine uptake remained far below the targeted rates. Associated factors regarding vaccine refusal in the general population have been reported in many studies, however the reasons behind refusals for asthmatic children have not yet been identified. We aimed to investigate Influenza A/H1N1 virus vaccine acceptance for children with asthma, to determine the attitudes and beliefs of parents concerning Influenza A/H1N1 disease and vaccine and to identify the association of asthma control parameters with vaccination. Methods The parents of asthmatic children aged 6–18 years participated in a cross-sectional survey study in three pediatric allergy outpatient clinics. The survey measured demographic factors, asthma control parameters, vaccination rates, and beliefs and attitudes regarding Influenza A/H1N1 vaccine. Results Of the 625 asthmatic children, 16.8% (n = 105) were immunized with Influenza A/H1N1 and 45.7% (n = 286) with seasonal influenza vaccine. Educational background of parents (p

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.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.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.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.

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

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.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.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.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).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.

Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare and recently described immunodeficiency, which is characterized with cutaneous viral and sinopulmonary infections, eczema, and high IgE levels. A DOCK8 deficient patient who had been followed up for severe atopic dermatitis, multiple food allergies, and asthma for several years is reported and clues are given for the diagnosis of DOCK8 deficiency. A 7-year-old girl was referred due to refractory eosinophilia and eczema. She had angioedema of the lips and increase in eczematous lesions during infancy after milk and egg ingestion and during childhood after fish, hazelnut, and wheat-containing food ingestion. She had episodic wheezing attacks since she was 1-year-old, and she had recurrent pneumonia and acute otitis media in the following years. She was hospitalized for pyoderma after a zona zoster infection. Laboratory findings suggested DOCK8 deficiency and mutational analysis verified. She had stem cell transplantation from a matched unrelated donor ...

In recent years, allergy skin testing has increasingly become an area of interest and is being widely performed by physicians other than allergists and immunologists. In this article, the indications, necessity, selection of allergens to be used, risks and adverse events, essential precautions during application, evaluation methods, and disadvantages of evaluation mistakes of allergy skin tests and why they should be performed by an allergist or immunologist are reviewed.