Evaluation of different protocols for classification of pediatric hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: Children with underlying allergic disease should be a separate subgroup.

Background: Different recommendations for the classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions (NSHSR) in children have been reported but a shortage still exists. Objective: The aim of the present study was to evaluate the inclusivity of two European Academy of Allergy and Clinical Immunology (EAACI) position paper classifications and to characterize the factors that underlie classification discordance in children. Methods: Patients with a history of NSHSR were evaluated with a standardized diagnostic protocol according to EAACI/ European Network for Drug Allergy (ENDA) recommendations. Children were classified and compared according to the EAACI 2013 and the pediatric EAACI/ENDA 2018 classifications. Subjects who were unclassified and those who were classified were compared. Results: Of 232 patients (median [interquartile range] age 6 years (4-11 years) with a history of NSHSR, 52 (22.4%) were confirmed with diagnostic tests. Thirty-six (69.2%) were classified as having cross-intolerance, whereas 16 patients (30.8%) were classified as selective responders. Eleven of the confirmed cases (21.2%) could not be categorized according to the 2013 EAACI classification, whereas this number was six adolescents (11.5%) when the 2018 EAACI/ENDA pediatric classification was used. Patients who were unclassified and who were all cross-intolerant were more likely to have atopic sensitization (p = 0.001) and asthma as an underlying disease (p = 0.03), higher serum eosinophil count (p = 0.022), and total immunoglobulin E levels (p = 0.007) compared with those who fit well into the classification. In multivariate regression analysis, the presence of atopic sensitization (adjusted odds ratio 20.36 [95% confidence interval, 2.14-193.48]; p = 0.009) was found to be the only significant underlying factor for an unclassified and/or blended phenotype. Conclusion: The 2013 EAACI classification resulted in a high rate of subjects who were unclassified. Despite better clinical utility, the recent pediatric EAACI/ENDA classification system still has shortcomings in terms of inclusivity for adolescents. Mostly, children with underlying allergic diseases could not be classified by the current guidelines. We propose to classify them as a separate pediatric cross-intolerance subgroup because the underlying mechanism may involve more than cyclooxygenase 1 inhibition.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

New diagnostic perspectives in the management of pediatric beta-lactam allergy.

Since overdiagnosis of beta-lactam (BL) allergy is common in the pediatric population, delabeling is a critical part of antimicrobial stewardship. Undesirable consequences of inaccurate BL allergy labeling can be handled by incorporating traditional delabeling or newer risk-based strategies into antibiotic stewardship programs. Conventional assessment of BL allergy relies upon a stepwise algorithm including a clinical history with skin testing followed by drug provocation tests (DPTs). However, a growing number of studies highlighted the suboptimal diagnostic value of skin testing in children. Recently, there has been a paradigm shift in the practice of BL allergy assessment due to recent challenging data which emphasize the safety and accuracy of direct DPTs in children with a suspicion of non-immediate mild cutaneous reactions such as maculopapular eruption, delayed urticaria, and possibly also for benign immediate reactions such as urticaria/angioedema. Identifying low-risk BL allergy patients, in whom skin tests can be skipped and proceeding directly to DPTs could be safe, has become a hot topic in recent years. New risk stratification and predictive modeling studies that have the potential to better predict BL allergy risk status have recently been introduced into the field of drug allergy, particularly in adults. However, in contrast to adults, risk assessment studies in children are rare, and optimal risk definitions are controversial. In the coming years, promising potential methods to elucidate the predictors of BL allergy in children will require multidimensional approaches that may include predictive analytics, artificial intelligence techniques, and point-of-care clinical decision tools.

An EAACI Task Force report on allergy to beta-lactams in children: Clinical entities and diagnostic procedures.

Beta-lactam (BL) allergy suspicion is common in children and constitutes a major public health problem, with an impact on patient's health and on medical costs. However, it has been found that most of these reactions are not confirmed by a complete allergic workup. The diagnostic value of the currently available allergy tests has been investigated intensively recently by different groups throughout the world. This has led to major changes in the management of children with a suspected BL allergy. Particularly, it is now well accepted that skin tests can be skipped before the drug provocation test in children with a benign non-immediate reaction to BL. However, there is still a debate on the optimal allergic workup to perform in children with a benign immediate reaction. In addition, management of children with severe cutaneous adverse drug reactions remains difficult. In this review, based on a selection of the most relevant studies found in the literature, we will review and discuss the diagnosis of different forms of BL allergy in children.

Delayed hypersensitivity to antiepileptic drugs in children.

BACKGROUND: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening. AIM: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature. RESULTS: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. CONCLUSION: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

A combined risk modeling strategy for clinical prediction of beta-lactam allergies in children.

Background: Drug provocation test (DPT) without skin tests is increasingly recommended in the evaluation of children with low-risk beta-lactam (BL) allergies. However, risk definitions are unclear. Objective: The aim of this study was to compose a clinical predictive model that could identify the children at low risk who could safely undergo direct DPT. Methods: The clinical data of 204 children who underwent a full diagnostic algorithm for suspected BL allergy were analyzed. Clinical data were used to construct mathematical predictive model for confirmed BL allergies. A prospective new sample was used for external validation of the final model. Results: The presentations during the index reaction were anaphylaxis in 5.9% and cutaneous reactions in the majority. BL allergy was confirmed in 15.7% of suspected cases. A backward multiple logistic regression model showed that a family history of drug allergy (adjusted odds ratio [aOR], 5.52), anaphylaxis (aOR, 5.14), any atopic disease other than asthma (aOR, 4.38), and a reaction interval of 0-6 hours during the index reaction (aOR, 5.32) were significantly associated with a confirmed BL allergy. A mathematical combined model based on these factors showed a sensitivity of 77.8% and a negative predictive value (NPV) of 94.3%. The validation study replicated sensitivity and NPV values of the main cohort. Conclusion: The risk definition in BL allergies should depend on population-specific predictive models, including a combination of significant risk factors rather than empiric risk approaches. This may help to accurately determinate children at low risk who may safely proceed to direct DPT.

Diagnosis and management of drug-induced anaphylaxis in children: An EAACI position paper.

Drug hypersensitivity reactions (DHR) constitute a major and common public health problem, particularly in children. One of the most severe manifestations of DHR is anaphylaxis, which might be associated with a life-threatening risk. During those past decades, anaphylaxis has received particularly a lot of attention and international consensus guidelines have been recently published. Whilst drug-induced anaphylaxis is more commonly reported in adulthood, less is known about the role of drugs in pediatric anaphylaxis. Betalactam antibiotics and non-steroidal anti-inflammatory drugs are the most commonly involved drugs, probably related to high prescription rates. Diagnosis relies on the recognition of symptoms pattern and is based on complete allergic workup, particularly including skin tests and/or specific IgE. However, the real diagnostic value of those tests to diagnose immediate reactions in children remains not well defined for a significant number of the drugs. Generally, a drug provocation test is discussed to confirm or exclude an immediate-onset drug-induced hypersensitivity. Although avoidance of the incriminated drug (and related drug) is the rule, rapid desensitization is useful in selected subgroups of patients. There is a need for large, multicentric studies, to evaluate the real diagnostic value of the currently available skin tests. Moreover there is also a need to develop new diagnostic tests in the future to improve the management of these children.

The airway hyperresponsiveness to methacholine may be predicted by impulse oscillometry and plethysmography in children with well-controlled asthma.

OBJECTIVE: Airway hyperresponsiveness (AHR) is a hallmark of asthma. Methacholine challenge test which is mostly used to confirm AHR is not routinely available. The aim of this study was to investigate the predictive values of fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and plethysmography for the assessment of AHR in children with well-controlled asthma. METHODS: 60 children with controlled allergic asthma aged 6-18 years participated in the study. FeNO measurement, spirometry, IOS, and plethysmography were performed. Methacholine challenge test was done to assess AHR. PC20 and dose response slope (DRS) of methacholine was calculated. RESULTS: Mild to severe AHR with PC20 < 4 mg/ml was confirmed in 31 (51.7%) patients. Baseline FeNO and total specific airway resistance (SRtot)%pred and residual volume (RV)%pred levels in plethysmography were significantly higher and FEV1%pred, FEV1/FVC%pred, MMEF%pred values were lower in the group with PC20 < 4 mg/ml. FeNO, SRtot%pred, and RV%pred levels were found to be positively correlated with DRS methacholine. The higher baseline FeNO, frequency dependence of resistance (R5-R20) in IOS and SRtot%pred in plethysmography were found to be significantly related to DRS methacholine in linear regression analysis (ß: 1.35, p = 0.046, ß: 4.58, p = 0.002, and ß: 0.78, p = 0.035, respectively). The cut-off points for FeNO and SRtot% for differentiating asthmatic children with PC20 < 4 mg/ml from those with PC20 ≥ 4 mg/ml were 28 ppb (sensitivity: 67.7%, specificity: 72.4%, p < 0.001) and 294.9% (sensitivity: 35.5%, specificity: 96.6%, p = 0.013), respectively. CONCLUSION: IOS and plethysmography may serve as reliable and practical tools for prediction of mild to severe methacholine induced AHR in otherwise "seemingly well-controlled'' asthma.

Seasonal variation of asthma control, lung function tests and allergic inflammation in relation to vitamin D levels: a prospective annual study.

INTRODUCTION: There are scarce data about the role of vitamin D (vitD) in asthma control related to seasons and other confounders. AIM: To investigate the seasonal relationship between vitD levels and asthma control, lung function tests (LFTs) and cytokines during a 1-year period, among 7-17-year-old asthmatic children. MATERIAL AND METHODS: Thirty patients with asthma with house dust mite monosensitization were evaluated 3 monthly about the previous month's health and vitD related lifestyle factors and asthma control test (ACT), spirometry and bronchial provocation test for a year. Serum vitD, vitD binding protein (VDBP), total IgE levels, absolute eosinophil and Treg counts and cytokine levels were simultaneously measured. The seasonal changes of vitD and other parameters and the relationship between 120 pooled data sets of vitD and major outcomes were evaluated. RESULTS: Mean vitD levels, forced expiratory volume in 1 s (FEV1%) and ACT score were lowest in winter and highest in summer. Pooled vitD levels were positively correlated with pooled ACT scores, Treg counts, FEV1% values and VDBP levels and negatively with total immunoglobulin E (IgE) and interleukin-4 (IL-4) levels and bronchodilator response. VitD levels were positively associated with ACT score, and FEV1% value and negatively with serum IgE level and bronchodilator response after adjusting for confounders. CONCLUSIONS: This study revealed that asthma control measures, LFTs and IgE levels were significantly related to serum vitD levels, independent from age, body mass index, inhaled corticosteroid use, sun exposure and season among asthmatic children. Vitamin D levels showed a positive correlation with Treg counts and a negative correlation with Th2 type cytokines.

Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children.

BACKGROUND: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently encountered in daily clinical practice. The aim of this study was to determine the confirmation rates, risk factors of NSAID hypersensitivity in children and to try to classify them with a standardized diagnostic protocol. METHODS: All patients with a suspicion of NSAID-induced hypersensitivity were evaluated with European Network for drug Allergy (ENDA) recommendations. The children were classified as selective responders (SRs) or cross-intolerant (CI) depending on the drug provocation test (DPT) results. RESULTS: We evaluated 106 children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and 27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could not be categorized according to ENDA/GA2LEN classification; one CI patient could not be classified based on pathomechanisms, seven CIs could not be categorized based on the underlying disease and clinical manifestations. A reaction within an hour of drug intake (aOR:3.0, 95% confidence interval: 1.18-7.67, p = 0.021), a history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval: 1.16-7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence interval: 1.50-10.82, p = 0.006) were found as the independent risk factors related to confirmed NSAID hypersensitivity. CONCLUSIONS: This study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity.

Impulse oscillometry in acute and stable asthmatic children: a comparison with spirometry.

OBJECTIVE: Lung function tests have attracted interest for the diagnosis and follow-up of childhood asthma in recent years. For patients who cannot perform forced expiratory maneuvers, impulse oscillometry (IOS), performed during spontaneous breathing, may be an alternative tool. METHODS: Thirty-five acute, 107 stable asthmatic and 103 healthy children who presented to our clinic performed IOS followed by spirometry before and after salbutamol inhalation. The mean baseline and reversibility of IOS and spirometry parameters were compared between the groups. Correlation analyses were undertaken within the asthmatics, and the healthy controls separately. To distinguish the three groups, the sensitivity and specificity of baseline and reversibility values of IOS and spirometry were computed. When spirometry was taken as the gold standard, the discriminating performance of IOS to detect the airway obstruction and reversibility was investigated. RESULTS: The mean absolute values of Zrs, R5, R5-R20, X5, X10, X15, Fres, AX, and all spirometric parameters, and the mean reversibility values of R5, R10, Fres, AX and forced expiratory volume in one second were different between the groups and the highest area under curve values to discriminate the groups was obtained from area of reactance (AX) and ΔAX. Zrs, all resistance (including R5-R20) and reactance parameters, Fres and AX were correlated with at least one spirometric parameter. Spirometric reversibility was detected by ≤-22.34 and ≤-39.05 cut-off values of ΔR5 and ΔAX, respectively. CONCLUSIONS: IOS has shown a highly significant association with spirometric indices and reversibility testing. It may be a substitute for spirometry in children who fail to perform forced expiratory maneuvers.

The characteristics of indoor and outdoor fungi and their relation with allergic respiratory diseases in the southern region of Turkey.

Indoor and outdoor fungal exposure has been shown to be associated with the development of allergic respiratory diseases. The aim of the study was to investigate the types and concentrations of airborne fungi inside and outside homes and evaluate the association between fungal levels and allergic diseases in the southern region of Turkey. A total of 61 children admitted with respiratory complaints to the pediatric allergy clinic between September 2007 and November 2008 were included in this study. The air samples were obtained using the Air IDEAL volumetric air sampler longitudinally for 1 year. A comprehensive questionnaire was used for medical history and housing conditions. Skin prick test was performed to determine fungal sensitivity and spirometric indices were employed. The predominant indoor fungal species were Cladosporium (69.3 %), Penicillium (18.9 %), Aspergillus (6.5 %), and Alternaria (3.1 %). A strong correlation between indoor and outdoor fungal levels was detected for the Cladosporium species (p < 0.001, r = 0.72) throughout the year. Living in a detached home (p = 0.036) and the presence of cockroaches (p = 0.005) were associated with total indoor fungal levels. The presence of cockroaches (aOR 3.5; 95 % CI 0.95-13.10, p = 0.059) was also associated with fungal sensitization at the edge of significance. The statistical cutoff values of indoor and outdoor Cladosporium levels to predict symptomatic asthma were found to be >176 CFU/m(3) (p = 0.003, AUC 0.696; sensitivity 65.5 %; specificity 68.7 %) and >327 CFU/m(3) (p = 0.038; AUC 0.713; sensitivity 66.6 %; specificity 76.9 %), respectively. Children with respiratory symptoms are exposed to a considerable level of fungi inside and outside their homes. The prevention of fungal exposure may provide valuable intervention for respiratory diseases.

A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia and variable bone marrow phenotype can also be part of this syndrome.

Glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency is a newly described syndrome characterized by severe congenital neutropenia associated with multiple organ abnormalities including cardiac and urogenital malformations. The underlying pathophysiology of increased apoptosis of myeloid cells and of neutrophil dysfunction in G6PC3 deficiency involves disturbed glucose metabolism, increased endoplasmic reticulum stress and deficient protein folding. Here, we report a new case of G6PC3 deficiency caused by a novel homozygous G6PC3 gene mutation p.Trp59Arg. The patient showed pancytopenia and a variable bone marrow phenotype with maturation arrest and vacuolization in myeloid lineage cells and a normocellular marrow, respectively. She also showed persistent lymphopenia with low CD4 T- and CD19 B-cell counts. Lymphopenia and even pancytopenia as well as a variable bone marrow phenotype can be part of this syndrome. These clinical findings in a patient with chronic neutropenia should alert the clinician to consider a diagnosis of G6PC3 deficiency.

The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children.

BACKGROUND: Recent evidence about the various effects of vitamin D (vit D) on innate and adaptive immunity has led to a search for the role of vit D in asthma. It is postulated that a decrease in cathelicidin, a multifunctional host defense molecule, production due to low vit D status may predispose to infectious complications in children with asthma. OBJECTIVE: The aim of this study was to determine the association of vit D, vit D-binding protein (VDBP) and cathelicidin with acute asthma attacks among children with allergic asthma. METHODS: This prospective study included 35 patients with acute asthma attack and 32 children with controlled asthma, and all were matched by sampling season, sensitization to mites, and previous severity of asthma. A comprehensive questionnaire about risk factors, blood sampling for 25-hydroxyvitamin D vit D, VDBP, and cathelicidin levels; spirometric indices were used. Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis. RESULTS: The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group (p < 0.001). The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma (p = 0.002). There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels. Risk factors that may influence vit D levels revealed that body mass index (BMI) (p = 0.038), duration of sun exposure (p < 0.001), and amount of dietary vit D (p < 0.001) independently affected serum vit D levels. Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks (p < 0.001, adjusted odds ratio 16.11). Cathelicidin levels showed a significant positive association with asthma attacks and BMI. CONCLUSIONS: Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma.

Hypersensitivity reactions to non-betalactam antibiotics in children: an extensive review.

In contrast to hypersensitivity reactions (HSRs) to ß-lactam antibiotics in children, studies about HSR to non-ß-lactam antibiotics (NBLAs) such as sulfonamides, macrolides, quinolones, and antituberculosis agents are scarce, and information is generally limited to case reports. The aim of this extensive review was to summarize our present knowledge on clinical characteristics, evaluation, and management of HSR to NBLAs in children based on the literature published between 1980 and 2013. NBLAs have been reported to induce a wide spectrum of HSRs from mild eruptions to severe, and sometimes fatal, systemic drug reactions, especially in some high-risk groups. The diagnosis relied upon history and remained unconfirmed by allergological tests in most of the cases. Obtaining a detailed history is valuable in the diagnosis of suspected reactions to NBLAs. Diagnostic in vivo and in vitro tests for NBLAs lack validation, which makes the diagnosis challenging. The definitive diagnosis of NBLA hypersensitivity frequently depends upon drug provocation tests. Studies including children showed that only 7.8 to 36% of suspected immediate and delayed HSRs to NBLAs could be confirmed by skin and/or provocation tests. Therefore, a standardized diagnostic approach and management strategy should be developed and employed for pediatric patients in the evaluation of suspected HSRs to NBLAs, some of which may be critical and unreplaceable in certain clinical situations.

A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence. Methods: We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study. Results: CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS. Conclusion: Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.

Diagnostic evaluation of hypersensitivity reactions to arylpropionic acid derivatives: a descriptive observational study focusing on clinical characteristics and potential risk factors in children.

BACKGROUND: Arylpropionic acid derivatives (APs) are the main triggers of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Data on clinical patterns and risk factors for AP hypersensitivity in children are quite limited. AIM: To assess the clinical characteristics and potential risk factors for proven AP hypersensitivity in children. METHOD: Patients with a history of AP hypersensitivity were retrospectively assessed using a standardized diagnostic algorithm. Children with confirmed hypersensitivity were defined as selective responders or cross-intolerants based on the result of drug provocation tests and further categorized according to the EAACI/ENDA classification. A multivariable logistic regression analysis was performed to analyze the potential risk factors for proven AP hypersensitivity. RESULTS: A total of 166 patients (51.2% male, median age of six years) with a history of AP hypersensitivity were included. Ibuprofen (89.2%) was the most frequently reported AP in the patients' histories. The reported hypersensitivity of 40 (22.4%) patients was confirmed by diagnostic testing: eight (13.6%) patients with a history of reaction only to APs and 32 (29.9%) patients with a history of reactions to multiple NSAIDs, including chemically unrelated NSAIDs in addition to APs. Five (12.5%) patients were classified as selective responders and 35 (87.5%) were cross-intolerants. Overall, five (12.5%) of the confirmed cases could not be categorized according to the EAACI/ENDA classification. Older age (aOR: 1.11, 95% CI 1.02-1.21, p = 0.015), chronic urticaria as an underlying disease (aOR: 2.87, 95% CI 1.09-7.54, p = 0.033) and a history of anaphylaxis (aOR: 7.84, 95% CI 1.86-33.04, p = 0.005) were related to confirmed AP hypersensitivity. CONCLUSION: Almost a quarter of children and adolescents were confirmed to have AP hypersensitivity. Older age, the presence of chronic urticaria and a history of anaphylaxis were potential risk factors for proven AP hypersensitivity.

Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature.

Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2-17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens-Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.

Management of Anaphylaxis in Pediatric Population.

Although an increase in the incidence of childhood anaphylaxis has been reported, it remains underdiagnosed. Foods are the most common triggers for anaphylaxis, particularly cow's milk, hen's egg, and nuts. Other common causes of anaphylaxis in children and adolescents include venom and drugs. The skin is the most commonly affected organ, but approximately 10% of patients with anaphylaxis may present without skin symptoms, which can lead to misdiagnosis. Recognition of anaphylaxis is a great challenge in children, possibly due to a lack of vigilance among patients, caregivers, and healthcare professionals, but also in part due to discrepancies in the clinical definition of anaphylaxis. In addition, anaphylaxis in infants often poses a distinct challenge because the wide spectrum of clinical manifestations and the inability of infants to describe their symptoms may hinder prompt diagnosis and treatment. Given the rapid onset of anaphylaxis and its unpredictable severity, rapid assessment and appropriate treatment are critical. Although the morbidity and mortality associated with anaphylaxis are potentially preventable with the timely administration of life-saving epinephrine, anaphylaxis is still undertreated worldwide. Long-term management of pediatric anaphylaxis is a patientcentered, multidimensional approach that focuses on the recognition of anaphylaxis, the use of epinephrine auto- injectors, and prevention of recurrences. Therefore, close communication and collaboration between the child, caregivers, healthcare professionals, and schools are the cornerstone of long-term care. This paper is designed to provide a comprehensive overview of current perspectives and concepts related to anaphylaxis in the pediatric population in light of recent guidelines and literature.

Perceptions of parents and physicians concerning the Childhood Asthma Control Test.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) has been proposed to be a simple, patient-based test that is able to reflect the multidimensional nature of asthma control. In this analysis, the aim was to evaluate the perceptions of physicians and caregivers concerning C-ACT and its predictive value for future asthma-related events. METHOD: In a multicenter prospective design, 368 children aged 4-11 years with asthma who were either well- or not well-controlled were included in the study. The study participants were evaluated during three visits made at 2-month intervals and the Turkish version of C-ACT was completed each month. Parents completed questionnaires concerning their perception of asthma (before and after the study) and the C-ACT (after the study). Physicians completed a survey about their perception of a control-based approach and the C-ACT. RESULTS: The C-ACT scores increased from visit 1 to visit 3, with improvement seen in all domains of the test. At the end of the study period, the parents more strongly agreed that asthma could be controlled completely and that asthma attacks and nocturnal awakenings due to asthma were preventable (p < .05). Most of the parents reported that the C-ACT helped them to determine asthma treatment goals for their children and also that the C-ACT improved communication with their physicians. The physicians indicated that a control-centered approach was more convenient (95%) and simpler (94.5%) than a severity-centered approach and provided better disease control (93.4%). A higher C-ACT score was associated with a decreased risk of asthma attack and emergency department admittance in the 2 months following the administration of C-ACT. Conclusion. Our findings indicated that the C-ACT improved both parental outlook on asthma control and the communication between the physician and parents. There was a good correlation between the C-ACT score and the level of asthma control achieved, as described by the physician. Additionally the C-ACT score was predictive of future asthma-related events. These findings suggest that the C-ACT may have an important role in asthma management in the future.