Semanur Kuyucu

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but severe cutaneous adverse drug reaction encountered in both adults and children with a significant mortality rate. A number of guidelines or consensus reports have been published for optimal diagnosis and treatment of DRESS in adults, but none specifically for children. It is increasingly evident that there are significant differences in drug pharmacokinetics, metabolism, co‐occurring infections, comorbidities, clinical manifestations, and severity of drug allergies between children and adults, as well as across different pediatric age groups. Aim: This position paper aimed to evaluate and compare all the available data related to clinical features, diagnosis, and treatment of DRESS in adults and children in an attempt to identify the differences and gaps, and produce recommendations on diagnosis and treatment of this fatal disorder in children. Materials and Methods: A search of MEDLINE (via PubMed) and Web of Science from 2000 to 2024, including studies that assessed children with DRESS syndrome, was performed. In the absence of pediatric‐specific data, studies involving adults or mixed populations (both adults and children) were also analyzed. Among a total of retrieved 5264 records, following duplicate removal and full‐text assessment, a total of 493 manuscripts related to DRESS were included in the report and recommendation generation. The recommendations for the clinical diagnosis and treatment of DRESS in children were formulated in accordance with the directionality and strength guidelines suggested by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group and related research. Results: Among retrieved records, there was only one randomized controlled trial, one meta‐analysis, one systematic review, six retrospective comparative studies on treatment, and one systematic review on the accuracy of skin tests in DRESS. All of these studies were conducted in adults, rarely involving children, and none were exclusively performed in pediatric populations. Comparison of systematic case reviews revealed that some aspects of clinical features, prognosis, and mortality in children differed from those in adults. The diagnosis of DRESS is based on several clinical and laboratory criteria, which have been developed for adult patients but have not been validated for children. Causality assessment tools, in vivo skin tests, and in vitro tests have been used widely in adults to identify the culprit drugs in DRESS, while these tools are more rarely employed or reported in children. Adult guidelines or consensus reports recommend a severity‐based, stepwise treatment approach for DRESS, whereas no such severity classification or treatment algorithms exist exclusively for children, leading to inconsistent management with numerous instances of overtreatment and undertreatment. Conclusion: There is very limited evidence‐based data on the diagnosis and management of DRESS both in adults and in children. Until more evidence becomes available, we propose a diagnostic algorithm, a DRESS severity classification, and a severity‐based tailored treatment approach, all adapted to pediatric needs together with issued recommendations to enable physicians to provide better care and reduce morbidity and mortality in pediatric patients.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare but severe cutaneous adverse drug reaction (SCAR) which presents by both skin and systemic symptoms and a significant mortality rate. The clinical features and prognosis in children differ markedly from those in adults. The diagnosis of DRESS is based on several clinical and laboratory criteria, which have been developed for adult patients but have not been validated for children. Differential diagnosis is both important and challenging in children due to the potential mimicry of a wide range of diseases, particularly viral infections. Causality assessment tools, in vivo skin tests, and in vitro tests have been used to identify the culprit drugs in DRESS, with low to moderate sensitivity in adults. However, these tools are more rarely employed or reported in children. Adult guidelines or consensus reports recommend a severity-based, stepwise treatment approach for DRESS, whereas no such severity classification or treatment algorithms exist for children, leading to inconsistent management with numerous instances of overtreatment and undertreatment. This EAACI Task Force on paediatric SCARs has developed a severity classification and a treatment strategy based on this classification, along with recommendations for the diagnosis and treatment of DRESS in children.

The aim of the study is to elucidate demographic characteristics, risk factors, clinical presentations, causative agents, and management approaches pertaining to drug-related anaphylaxis in the paediatric population. This study is a multicenter retrospective study that included paediatric patients aged between 1 month and 18 years, who were admitted to the Pediatric Allergy and Immunology outpatient clinics of 11 participating centres with a presumptive diagnosis of drug-induced anaphylaxis, that fulfilled the standardised criteria for anaphylaxis, between January 2017 and December 2022. A total of 293 anaphylactic episodes presented among 265 patients, of which 48.1% (n 141) were female, were included. The median age of patients during the index episode was 107 months (IQR 56.5–161.5). Anaphylaxis occurred most frequently within hospital settings (62.1%, n 182) compared to home environments (34.1%, n 100). The administration were peroral in 40.3% (n 118), parenteral in 59.7% (n 175) of the cases. While antibiotics (56.7%), non-steroidal anti-inflammatory drugs (25.7%), and chemotherapeutics (3.4%) were the most commonly suspected drug groups, the cephalosporin group, and especially ceftriaxone (27.5% [n 80]) were the leading culprits among antibiotics. The anaphylaxis severity was severe in 39.6% (n 116), and moderate in 54.9% (n 161) of episodes. A biphasic reaction occurred in five patients. Only 72% (n 213) of patients were given adrenaline treatment. There were no fatalities. Diagnostic tests (n 64), including skin prick, intradermal, and drug provocation tests, which were performed between 1 and 120 months after the index reaction, yielded positive results in 23.4% (n 15), 17.2% (n 11), and 20.3% (n 13) of cases respectively, giving a total confirmation of 39 patients. Four patients underwent suspected drug desensitisation protocols. There were no fatalities. Conclusions: Antibiotics, particularly ceftriaxone, were the most commonly implicated agents in paediatric drug-induced anaphylaxis. Non-steroidal anti-inflammatory drugs, particularly ibuprofen, constituted the second most frequently implicated drug group. Paediatric patients experiencing drug-related anaphylaxis warrant algorithmic evaluation to ensure accurate diagnosis, prevent recurrence, and identify safe alternative treatments. What is Known: • Antibiotics, particularly ceftriaxone were the most frequently implicated culprit drugs, followed by NSAIDs, with ibuprofen being the most common within this group. What is New: • To the best of our knowledge, this is the largest multicenter paediatric drug-related anaphylaxis study, involving a large number of patients who evaluated by paediatric allergist. • We propose paediatric patients who experience drug induced anaphylaxis should undergo evaluation at specialized centres, to ensure accurate diagnosis, to prevent recurrence and identify safe alternative treatments.

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.

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.

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.

!969 yılında Ankara’da doğan Elvan Çağlar Çıtak liseyi Ankara Fen Lisesinde, tıp fakültesini Ankara Üniversitesi’nde okumuştur. Çocuk Sağlığı ve Hastalıkları uzmanlığını 2000 yılında Gazi Üniversitesi’nden alan Dr Çıtak daha sonra aynı üniversitenin Çocuk Onkolojisi bölümünde Çocuk Onkolojisi Yan Dal uzmanlığı eğitimini tamamlamıştır. 2009 yılında Çocuk Onkolojisi Doçentlik ünvanını aldıktan sonra 2010 yılından itibaren Mersin Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı’nda öğretim üyesi olarak çalışmaya başlamıştır. Dr Çıtak 2014 yılında profesörlük ünvanını almaya hak kazanmıştır.Çocuk Onkoloji departmanında tek öğretim üyesi olarak görev yaptığı 11 yıl boyunca gerek kanserli çocuklar ve onların ailelerinin sağaltımı için, gerekse tıp öğrencileri ve araştırma görevlilerinin eğitimi için titizlikle ve fedakarca çalışmış, büyük emekler vermiş ve onların kalbinde yer etmiştir. 15 Ağustos 2021’de elim bir hastalık sonucu kaybettiğimiz hocamızı rahmet, minnet ve saygıyla anıyoruz.

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 patient-centered, 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 is 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.