Assessment of Subclinical Atherosclerosis in Children with Atopic Dermatitis.

INTRODUCTION: Data from studies conducted to date have evaluated clinical atherosclerotic conditions in adult patients with atopic dermatitis (AD). Subclinical atherosclerotic changes that are a precursor of atherosclerotic conditions may begin in childhood. The aim of this study was to investigate the presence of subclinical atherosclerosis in pediatric patients with AD and to determine the associated risk factors. METHODS: A total of 59 patients who were referred to our department over a 6-month period and diagnosed with AD, and 53 healthy controls with a similar age and gender were included in the study. Subclinical atherosclerosis markers (carotid intima media thickness [CIMT], distensibility, stiffness, and strain) were measured using conventional echocardiography. The patients' age, SCORAD index, and duration of symptoms were recorded. Serum total immunoglobulin E, C-reactive protein (CRP), blood lipid profile, and complete blood count markers were measured. RESULTS: The median age of the patients was 61 (10-103) months, and 59.3% of them were male. The patients with AD had a higher CIMT (1.60 ± 0.35 vs. 1.30 ± 0.50 mm) and a lower distensibility (0.006 ± 0.009 vs. 0.01 ± 0.008) and strain (0.10 ± 0.14 vs. 0.19 ± 0.14) than the healthy controls (p < 0.01 for all), but there was no significant difference with regard to stiffness (10.16 ± 21.75 vs. 8.99 ± 12.66). Significant correlations between CIMT and disease duration, age, and the SCORAD index were found (p < 0.01, p < 0.01, and p < 0.05, respectively). No correlation between the subclinical atherosclerosis markers and the other laboratory results was found (p > 0.05 for all). CONCLUSION: This study demonstrates that pediatric patients with AD may express subclinical atherosclerosis markers. The evaluation of subclinical atherosclerosis in these patients revealed that CIMT may be the most important marker, as it displayed positive correlations with symptom duration, age, and disease severity.

Diagnosis and management of food allergy-associated gastroesophageal reflux disease in young children-EAACI position paper.

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.

NSAID Hypersensitivity in the Pediatric Population: Classification and Diagnostic Strategies.

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.

Experiences and attitudes of parents of children with cow's milk and other food-allergy.

INTRODUCTION AND OBJECTIVE: The attitude and behaviors of parents are important in the management of children with food allergy (FA). The aim of this study is to evaluate the experiences and attitudes of parents of children with allergy to cow's milk and other FA. MATERIALS AND METHODS: The parents of children with FA were asked to complete an 18-item questionnaire to evaluate the FA history and experiences during diagnosis, treatment, and follow up. RESULTS: The data from 558 (91.2%) survey questionnaire that were filled completely were analyzed. The mean age of the parents was 33.4+4.9. It was found that most common food allergen was cow's milk (85.3%). The mean time to diagnosis from the onset of symptoms was 10.9±18.4 months. Around 229 parents (41.6%) admitted to at least four different physicians and 68 (12.3%) parents admitted to at least five different physicians before diagnosis. The median time to diagnosis from the onset of symptoms was five (1-108) months in the patients admitted to four or more physicians, but it was one (1-48) month in the patients that admitted to less physicians (p˂0.001). The most common symptoms were dermatitis and mucus-bloody stool, the least common ones were cardiovascular symptoms. Only 21.1% of the patients were able to use hypoallergenic formulas (HAF) in accordance with the recommendation of the physician. CONCLUSIONS: Delayed diagnosis of FA is a major concern, and during this period the patients admit many physicians. A majority of the patients with CMPA experience difficulties while using HAFs, and only one-fifth of them is able to use formula regularly.

Subclinical cardiovascular dysfunction in children and adolescents with asthma.

BACKGROUND: There is close association between asthma and cardiovascular functions as both diseases share common inflammatory pathways. The current study was aimed at investigating the risk factors, associated with endothelial and cardiac functions in children with newly-diagnosed mild-persistent asthma. METHODS: A total of 33 steroid-naive asthmatic children [median(interquartile-range); 9.1 years(7.8-13.5)] and 16 healthy controls [11.5 years(9.9-13.6)] were included. Their demographic, clinical and laboratory findings were recorded. Carotid Artery intima-media thickness (CIMT), stiffness, distensibility and strain were measured as atheroclerosis markers. Conventional and tissue Doppler imaging was performed to evaluate ventricular function. RESULTS: The patients with asthma had higher CIMT and stiffness and lower strain and distensibility compared to controls (p < 0.001 for all). There was a significant correlation between the duration of asthmatic symptoms and subclinical-atherosclerosis as well as peripheral eosinophil count (p < 0.001, p < 0.05). The patients had lower tricuspid-annular-plane-systolic-excursion (TAPSE), ejection time, and higher isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and left ventricle myocardial performance index (LVMPI) than the control subjects (p < 0.001 for all). A positive correlation was also observed between the duration of asthmatic-symptoms and cardiac-function parameters. CONCLUSION: Children with mild persistent asthma had subclinical atherosclerosis and ventricular dysfunction even in the early stage of disease. Symptom duration was closely associated with both subclinical atherosclerosis and ventricular dysfunction. Myocardial performance index was abnormal in the asthmatic children when assessed by tissue Doppler Imaging even though they had normal ejection fraction in conventional echocardiography. Future prospective studies with larger sample sizes are needed to confirm these findings and to assess the possible protective effect of ICSs in the prevention of subclinical atherosclerosis.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

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.

Is Oral Food Challenge as Safe Enough as It Seems?

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.

Do Pediatric Emergency Physicians Comply With Guideline Recommendations in Management of Patients With Acute Urticaria?

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.

Revaccination following suspected vaccine-triggered hypersensitivity reactions: experience of a tertiary care centre.

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.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

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.

Preschool wheezing and asthma in children: A systematic review of guidelines and quality appraisal with the AGREE II instrument.

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.

Rare occurrence of common filaggrin mutations in Turkish children with food allergy and atopic dermatitis

Background/aim: Filaggrin is a protein complex involved in epidermal differentiation and skin barrier formation. Mutations of the filaggrin gene (FLG) are 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 FLG gene and determine the association between FLG loss-of-function (LOF) mutations and FA and/or AD in Turkish children. Materials and methods: Four FLG loss-of-function (LOF) 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. PCR-RFLP was performed for genotyping R501X, 2282del4, and R2447X mutations; S3247Xwas 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 (0.7­2.8) years] and 128 healthy controls [59% male, 2.4 (1.4­3.5) 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 FLGmutations. 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 FLG mutations were infrequent and there is no significant association with food allergy and/or atopic dermatitis in Turkish individuals.

EAACI Allergen Immunotherapy User's Guide.

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.

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

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