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Ozlem Cavkaytar, Mustafa Arga Department of Pediatric Allergy and Immunology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, TurkeyCorrespondence: Ozlem Cavkaytar, Department of Pediatric Allergy and Immunology, Istanbul Medeniyet University Faculty of Medicine, Prof. Dr. Suleyman Yalcin City Hospital, Kadıköy, Istanbul, Turkey, Tel +90 216 6065200, Email ozlem.bircan@gmail.comAbstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently administered drugs, mainly for their anti-pyretic, but also for pain-relieving and anti-inflammatory effects in children. NSAIDs are composed of structurally divergent subgroups of drugs with similar pharmacological and adverse effects. Aspirin originates from salicin and was the first synthesized analgesic. As a prototype of NSAIDs; aspirin-induced hypersensitivity reactions were first reported, but subsequently, other phenotypes of hypersensitivity reactions were also described with aspirin and other NSAIDs. There are certain challenging aspects of NSAID-hypersensitivity in the pediatric population that need to be further investigated. These include the effect of age on drug metabolism and the natural history of the various phenotypes of NSAID-hypersensitivity, the effect of certain co-factors (infections, exercise) on NSAID-hypersensitivity, and diagnostic clinical and laboratory biomarkers clarifying the endotypes. In recent years, a non-negligible number of case series, studies and expert panel reports have been published in this field with some novel features and diagnostic modalities in the pediatric population. With the current review; the clinical phenotypes and diagnostic and management modalities of suspected NSAID-induced hypersensitivity reactions in childhood and adolescence were explained and updated by examining past and current publications.Keywords: allergy, aspirin, child, drug, ibuprofen, paracetamol

Purpose: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease., Methods: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cT FH ) cells, and T-cell proliferation were analyzed., Results: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the T H 2-like skewing accompanied by reduced T H 17-like responses was observed in cT FH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs., Conclusions: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored., Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates., Methods: In this multicenter retrospective analysis, we gathered data from 35 patients with a diagnosis of MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes., Results: Predominant symptoms observed were pneumonia (n = 29; 82.9%), persistent diarrhea (n = 26; 74.3%), and severe infections (n = 26; 74.3%). The RFXANK gene mutation (n = 9) was the most frequent, followed by mutations in RFX5 (n = 8), CIITA (n = 4), and RFXAP (n = 2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared with those with RFX5 mutations (P =.0008 and .0006, respectively), alongside a more significant diagnostic delay (P = .020). A notable founder effect was observed in five patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n = 10), showing a significantly higher proportion in individuals with hematopoietic stem cell transplantation (n = 8; 80%). Early death and higher CD8 + T-cell counts were observed in patients with the RFX5 mutations compared with RFXANK-mutant patients (P = .006 and .009, respectively)., Conclusions: This study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Objectives: To determine the level of knowledge and practical preferences of pediatricians regarding acute urticaria (AU) management and to assess the effects of training provided in accordance with the current urticaria guideline recommendations on pediatricians who work in the pediatric emergency department (PED)., Methods: A theoretical training was provided to pediatricians regarding the diagnosis and treatment of AU in line with current urticaria guideline recommendations. Before the training, pediatricians completed a 10-item questionnaire. This prospective study assesses their treatment approaches in patients admitted to PED because of AU during the 6-month period before and the 1-year period after training., Results: Four hundred seventeen children in the pretraining and 1085 children in the posttraining periods were treated for AU in PED. Forty-eight pediatricians participated in the training. According to their questionnaire responses, 35% of them used only H1 antihistamine (AH) treatment, 50% used second-generation H1 AH (2nd-GAH) as AHs, 75% preferred the oral route of administration, and 85.4% did not administer systemic corticosteroid (sCS) to all patients. Comparing the practice approaches of the pediatricians in the pretraining and posttraining periods, first-generation H1 antihistamine (1st-GAH) preference rate decreased from 68.4% to 30.3% and the sCS preference rate decreased from 58.5% to 25.7%, while the 2nd-GAH preference rate increased from 31.7% to 69.7% (P < 0.001 for all). No treatments were prescribed for 10.8% of patients before the training and 3% after the training during discharge at home (P < 0.05). Comparing the home treatment choices of the pediatricians in the pretraining and posttraining periods, 1st-GAH preference rate decreased from 11.5% to 5%, while the 2nd-GAH preference rate increased from 78.7% to 91.5% (for both parameters, P < 0.001)., Conclusions: Practical treatment preferences of pediatricians in the treatment of children with AU differ considerably from both current guideline recommendations and their own theoretical knowledge, and training can enhance pediatricians' compliance with current guideline recommendations., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Oral food challenges (OFCs) assist in the diagnosis of food allergies and are essential to determine whether an allergy has been outgrown. During the OFC, a medical procedure e introduces foods suspected to be allergenic orally in increasing doses. Mild skin reactions such as urticaria or rarely serious life-threatening reactions such as anaphylaxis may develop., Objective: In this study, we aimed to retrospectively evaluate the clinical and laboratory characteristics of patients who experienced anaphylaxis during open OFCs in a tertiary care children's hospital., Methods: Patients who underwent OFCs to confirm the presence of a food allergy or to assess tolerance status at the University of Health Sciences, Ankara, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Pediatric Allergy and Immunology Outpatient Clinic between 1 January 2013 and 1 February 2016, were included in the study. Patients' data were obtained retrospectively from electronic medical records and challenge chart reviews., Results: A total of 623 OFCs were performed during the period studied. Nine patients (1.4%) between 13 and 67 months of age (mean age: 38.3 months) developed anaphylaxis during their OFC., Conclusion: OFCs should be performed in a hospital or outpatient office under medical supervision that is adequate for anaphylaxis intervention by an allergy specialist. Close observation of objective and subjective symptoms is essential during the challenge because there are no laboratory tests that can predict an anaphylactic diagnosis or the severity of the reaction., (© The Author(s) [2021]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction and Objectives: Suspected hypersensitivity reactions (HRs) associated with vaccines are frequently reported, but confirmed cases of vaccine-triggered HRs are rare. Suspected HRs should be distinguished from actual HRs. The aims of this study are to identify the rate of actual vaccine-triggered hypersensitivity in patients who were referred to the paediatric allergy clinic due to a suspected HR and to explore the rate of revaccination in a real clinical setting., Materials and Methods: A retrospective study was performed with a group of preschool children who were evaluated by skin and/or provocation tests (PTs) for the suspected HRs following vaccination., Results: A total of 26 paediatric patients (61.5% male; median age 9 months) with a previous history of suspected vaccine-triggered HR were included. In this group, 69.2% and 38.5% of the patients had a pre-existing atopic disease and an immediate reaction (emerging <1 hour after vaccine administration), respectively. Skin rash was the most frequent clinical presentation (96.1%). Vaccine-triggered anaphylaxis was reported in six patients (23.1%). Measles-mumps-rubella was the most frequently suspected vaccine causing HRs. The skin test positivity with the suspected vaccine was 4%, whereas PTs revealed no reaction after reimmunisation in 76.9% (20/26) of the study participants tested., Conclusions: Most incidents of skin rashes after immunisation are not suggestive of actual HRs. The results in the current study showed that the majority of the patients presenting with suspected HRs tolerated revaccination, including those with a previous history of suspected anaphylaxis. Revaccination of these patients is safe with adequate precautions. It is absolutely essential to be equipped for the management of anaphylaxis., Competing Interests: All authors declare that they have no conflicts of interest.

Background: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy., Objective: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood., Methods: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study., Results: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002)., Conclusion: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria., (© 2021 S. Karger AG, Basel.)

Background: Asthma-like symptoms in preschool children, such as wheezing and dyspnea, are common time- and resource-consuming diagnostic and management challenges. Quality of wheezing and asthma recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma., Methods: The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool., Results: We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%., Conclusion: Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non-asthmatic preschool wheeze., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence)., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are available as over-the-counter drugs, and they are commonly used in children for their antipyretic, analgesic, and anti-inflammatory effects. NSAIDs are among the most frequently reported drugs associated with hypersensitivity reactions and even with anaphylaxis. A complete evaluation of the patients based on reported clinical manifestations, timing of the reaction, the presence of underlying disease, and reactions to other NSAIDs allows clinicians to stratify children with a history of reaction to NSAIDs. Although NSAID-induced hypersensitivity reactions have mainly been investigated in adults, recent studies have aimed to explore their epidemiology in the pediatric population. This review will cover the current understanding of clinical manifestations, the risk factors, and the different phenotypes of NSAID-induced hypersensitivity reactions with a comprehensive overview of the epidemiologic data from past to present and the practical approach to the management of NSAID hypersensitivity in children and adolescents., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

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., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Severe cutaneous drug hypersensitivity reactions involve of different mechanisms , some of which are life-threatening, such as Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, generalized bullous fixed drug eruptions, serum sickness and serum sickness-like reaction and drug-induced vasculitis. These reactions may have substantial morbidity and mortality. In the past years, successive studies have provided new evidence regarding the pathogenesis of some of these severe reactions and revealed that underlying mechanisms are highly variable. Since these reactions have unique presentations and distinct pathomechanisms, the treatment methods and response rates might be different among various entities. Although supportive and local therapies are sufficient in some of these reactions, targeted immunosuppressive treatments and even mechanistic therapies such as plasmapheresis may be required in severe ones. However, there is still insufficient evidence to support the best treatment options for these patients since number of patients and large-scale studies are limited. In this review, conventional and new treatment options for severe cutaneous drug hypersensitivity reactions are presented in detail in order to provide the contemporary approaches to lessen the morbidity and mortality relevant to these severe iatrogenic diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Food allergy (FA) affects the daily lives of children and parents in varying degrees. The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a valid and reliable instrument to assess the quality of life (QoL) of children from parents' perception. The aim of this study was to validate and determine the reliability of the Turkish FAQLQ-PF and to assess QoL in food-allergic children., Methods: Children aged between 0 and 12 years and diagnosed with immunoglobulin E (IgE)-mediated FA for at least 1 month were enrolled. The English FAQLQ-PF was translated into Turkish according to the World Health Organization guidelines. The Food Allergy Independent Measure and the Turkish Child Health Questionnaire-Parent Form 50 were used for construct validity., Results: One hundred and fifty-seven patients participated. The median age of patients and FA duration were 2.4 years (1.2-5.2 years, interquartile-ranges) and 2 years (0.8-5.1), respectively. Ninety-six (61.1%) patients had anaphylaxis. The Cronbach's alpha coefficient and intra-class correlation coefficient for test-retest reliability was good for all age groups of children (<4, 4-6, and 7-12 years). Patients with either asthma or anaphylaxis had worse scores than others. Total scores of FAQLQ-PF tended to increase with age. Patients aged 7-12 had the highest total scores among all patients (2.2±0.1, 3.0±0.2, and 3.3±0.3 for <4, 4-6, and 7-12 years, respectively, P<0.001, P for trend <0.001). Other factors causing the poor QoL were cow's milk allergy, sibling allergy, mother's age over 30 years, mother's high education level and lower number of persons in household., Conclusions: The Turkish FAQLQ-PF is a valid and reliable scale. FA-related QoL was significantly worse with age. Coexistent asthma, anaphylaxis regardless of its severity, cow's milk allergy, sibling allergy and the older and educated mothers seem to poorly affect QoL., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

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.

Background: There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma., Objectives: To undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma., Methods: We searched nine electronic databases from inception to October 31, 2015. Systematic reviews were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme quality assessment tool for systematic reviews. Data were descriptively and thematically synthesized., Results: We identified nine eligible systematic reviews; these focused on delivery of AIT through the following routes: subcutaneous (SCIT; n = 3); sublingual (SLIT; n = 4); and both SCIT and SLIT (n = 2). This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity. The impact on measures of lung function or asthma control was however less clear. We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT. SLIT had a favorable safety profile when compared to SCIT, particularly in relation to the risk of systemic reactions., Conclusions: AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved. Bearing in mind the limitations of synthesizing evidence from systematic reviews and the fact that these reviews include mainly dated studies, a systematic review of current primary studies is now needed to update this evidence base, estimate the effectiveness of AIT on asthma outcomes and to investigate the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT.

Background: Musculoskeletal complaints (MSCs) are one of the leading causes of outpatient admissions. However, analytical and epidemiological data are limited. The aim of this study is to identify the etiology of MSCs (excluding acute traumatic conditions) in children and adolescents, and to identify clues for the differential diagnosis., Methods: Children and adolescents presenting with musculoskeletal pain, swelling or limitation of movement were enrolled in a prospective design. Demographic, clinical and laboratory features were recorded., Results: Four hundred and twenty-two children (48.2% female) with a mean age of 7.90±3.95 years were enrolled. Etiology was identified in 97.2% of the cases: non-inflammatory and mechanical conditions (NIMC; 42.2%), rheumatic diseases (RD; 31%), infection-related disorders (IRD; 21.6%) and malignancy (M; 2.4%). NIMC was characterized by longer duration of complaints, a higher rate of non-articular complaints, a lower rate of joint involvement and limping and lower levels of leukocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The prevalence of RD was higher in the age group of >12 years; younger age was associated with higher prevalence of IRD. Small-joint involvement was highest in the RD group. Median ESR in RD and M groups was higher; compared to the other groups; the frequency of patients with ESR ≥ 60 mm/hr was higher in the M group; compared to the RD group. In the RD group familial Mediterranean fever (9.7%), juvenile idiopathic arthritis (8.3%) and Henoch-Schönlein purpura (5.7%) were the leading causes of MSCs., Conclusions: RD accounted for one-third of the etiologies for MSCs. Age, duration of complaints, pattern of joint involvement and acute phase reactants are practical tools that may guide the pediatrician for diagnosis.

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.

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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)