Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children.

INTRODUCTION: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. METHODS: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1-6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. RESULTS: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. CONCLUSION: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

Abbreviation of Desensitization Protocol for Pediatric Patients with Lysosomal Storage Diseases Receiving Enzyme Replacement Therapy.

INTRODUCTION: Lysosomal storage diseases (LSDs) constitute a group of metabolic disorders characterized by the accumulation of substrates within lysosomes. For their treatment, disease-specific enzyme replacement therapy (ERT) is employed. In cases of hypersensitivity reactions that may occur during these treatments, desensitization of enzyme therapy becomes necessary. Repeated desensitization procedures may result some degree of tolerance. This study presents cases of patients received abbreviated desensitization protocols following repeated desensitization procedures. METHOD: During the period between September 2019 and January 2024, pediatric patients who experienced anaphylactic reactions to ERT and whose desensitization protocols were abbreviated after receiving uneventful treatment with desensitization for at least a year were included in the study. RESULT: Six patients, four with Pompe disease, one with mucopolysaccharidosis type 2, and one with mucopolysaccharidosis type 4, had been receiving uninterrupted ERT by desensitization for at least 1 year. The mean age of the patients was 117.6 months (median: 104.5, IQR: 85.2-144). All patients experienced anaphylaxis as the initial reaction. Skin and intradermal tests were repeated on patients prior to protocol abbreviation. Premedication previously given to all patients was discontinued, and desensitization protocols were subsequently shortened by increasing the infusion rate and/or reducing the number of steps. CONCLUSION: The study investigated patients whose desensitization protocols were abbreviated. It demonstrated that some level of tolerance could be attained through repeated applications. This approach aims to identify concise, safe, and efficient protocols, thereby reducing hospitalizations, nosocomial infections, and treatment expenses.

Dog Allergy in Children: A Single-Centered Study.

INTRODUCTION: Dogs are among the most commonly allergenic pets for children. Data on risk factors for the development of dog allergy are scarce. This study aimed to evaluate the characteristics of children with dog allergy and identify predictors of symptom development with dog exposure. METHODS: The study included children with dog allergen sensitization demonstrated by skin prick test (SPT) between September 1, 2019, and December 1, 2022. Demographic, clinical, and laboratory data were collected from the patients' records and interviews with parents. RESULTS: Dog allergen sensitization was detected by SPT in 548 (5.5%) of 9,907 patients. Of these, 507 patients had complete data and were included in the analysis. The patients' median age was 11 (IQR: 8-15) years, 55.8% were male, 97.6% exhibited polysensitization (pollen 75.1%, cat 69.6%), 83.6% had allergic rhinitis, and 46.2% had asthma. Acute dog exposure caused symptoms in 164 patients (32.3%), most commonly sneezing (n = 97) and nasal symptoms (n = 80). Predictors of acute symptoms in dog-sensitized children were male sex (OR: 0.584 [CI: 0.38-0.87]), dog exposure before 1 year of age (OR: 2.35 [CI: 1.18-4.66]), close contact with a dog owner (OR: 2.93 [CI: 1.78-4.8]), and cat allergy (OR: 2.75 [CI: 1.82-4.1]). CONCLUSION: Approximately one-third of children with dog sensitization developed symptoms after exposure to the dog. Male sex, direct dog exposure before the age of one, close contact with a dog owner, and cat allergy were identified as predictors of dog allergy.

Fruit allergy and anaphylaxis in children: Culprit fruits and clinical findings.

Background: Fruit allergy usually presents with mild-to-moderate symptoms but serious systemic reactions, e.g., anaphylaxis, may also occur. Objective: This study aimed to examine the clinical and laboratory characteristics of patients with fruit allergy and fruit-induced anaphylaxis. Methods: Patients diagnosed with fruit allergy at Diskapi Hematology and Oncology Hospital and Bilkent City Hospital between January 2017 and January 2023 were included in the study. The diagnosis of anaphylaxis was made according to the European Allergy and Clinical Immunology Anaphylaxis Guideline. Results: During the study period, skin-prick tests with food allergens were performed on 9432 patients in our clinic, and fruit allergy was detected in 78 patients (0.82%). Five patients with inaccessible medical records were excluded from the study. 40 (54.8%) were boys. The median (interquartile range) age at the onset of symptoms was 72 months (12.5-144 months). Sixty-eight of the patients (93.2%) had a concomitant allergic disease, the most common of which was allergic rhinitis (n = 48 [65.8%]). The 73 patients had a history of reaction to 126 fruits. Twenty-five patients (19.8%) were allergic to multiple fruits. The most common fruit allergen was banana (22/126 [17.4%]), followed by peach (18/126 [14.2%]) and kiwi (17/126 [13.5%]). Mucocutaneous findings were observed most frequently after fruit consumption (120/126 [95.2%]). Anaphylaxis occurred in 17 patients (23.2%) with 21 fruits.The fruits most commonly associated with anaphylaxis were banana (6/21 [28.6%]) and kiwi (6/21 [28.6%]). Conclusion: Fruit allergy generally presents with mild symptoms, e.g., oral allergy syndrome, but severe systemic symptoms, e.g., anaphylaxis, can also be observed. Kiwi and banana are the fruits that most commonly cause anaphylaxis. Although more comprehensive studies are needed to comment on the development of tolerance, especially in patients with anaphylaxis, responsible fruit avoidance is still the most important strategy.

Successful rapid liposomal amphotericin B desensitization in pediatric case series.

Background: Liposomal amphotericin B (LAMB) is a crucial agent in the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. In the presence of an infection caused by a fungal agent resistant to alternative antifungal drugs, desensitization may be the only option to continue treatment. However, there is insufficient information and consensus with regard to amphotericin B desensitization protocols in the pediatric age group. Objective: We present our experience with five cases of patients in whom successful desensitization protocols were applied with LAMB, along with a review of the literature on pediatric cases. We also provide a sample desensitization protocol that we successfully applied. Methods: Pediatric patients who continued their treatment with the successful rapid desensitization protocol conducted at the Paediatric Allergy and Immunology Clinic of the Ministry of Health Ankara City Hospital between September 2019 and September 2023 were examined. Desensitization protocols were applied based on Castells' desensitization protocol. Results: Five patients ages between 5 and 12 years were referred to us due to the development of anaphylaxis during their treatment with LAMB. Anaphylaxis is diagnosed clinically, according to the European Academy of Allergy and Clinical Immunology guidelines: anaphylaxis (2021 update). A 16-step desensitization protocol was prepared by using LAMB solutions at four different dilutions (0.001, 0.01, 0.1, and 1 mg/mL). Each solution consisted of four steps, with a 15-minute infusion for each step. The patients were premedicated with 1 mg/kg/dose methylprednisolone and an antihistamine. Conclusion: The data we present on the successful application of a sample protocol to five cases, particularly in a pediatric setting, are noteworthy valuable contributions to the field, which demonstrates the feasibility and success of rapid desensitization with LAMB in pediatric patients. This can provide important insights and potentially serve as a reference for medical professionals working with similar cases in the future.

Clinical utility of serum tryptase levels in pediatric anaphylaxis.

Introduction: This study aimed to evaluate the preliminary diagnosis, demographic characteristics, and outcomes of patients whose serum total tryptase levels were measured while in a tertiary pediatric hospital and to ascertain the role of serum tryptase levels in the etiology, diagnosis, severity, and course of systemic anaphylaxis. Methods: Patients ages between 1 month and 17 years who were followed up in the pediatric emergency department or as inpatients and with a diagnosis of immediate-type reactions between September 1, 2019, and August 31, 2021, were included in the study. Patient data were obtained retrospectively by examination of medical records and patient observation forms. Results: It was determined that serum tryptase levels were measured in a total of 310 patients during the study period. One hundred and fifty-five patients who met the defined diagnostic criteria were named as the anaphylaxis group and their data were detailed. The serum tryptase elevation was detected in 15.5% of the patients among the samples that met the anaphylaxis diagnostic criteria. No relationship was found between the serum total tryptase levels, the triggering factor, and the severity of anaphylaxis. Discussion: Anaphylaxis is a complex syndrome that involves different phenotypes that develop with various triggers in which different immunologic pathways, cell types, and mediators play a role. Serial measurements, including the basal value measured at least 24 hours after the symptoms disappear, are useful to confirm the diagnosis and guide the diagnostic tests during the follow-up, especially allergy evaluation.

Characteristics of Patients Who Underwent a Diagnostic Test for Hereditary Angioedema Admitted Due to Angioedema.

OBJECTIVE: Hereditary angioedema (HAE) is clinically characterized by recurrent attacks of angioedema. This study evaluated the clinical findings and examination results of patients admitted due to angioedema who then underwent a diagnostic test for HAE. The study aimed to assess the contribution of laboratory findings to the diagnostic process and to determine clinicians' level of awareness regarding the differential diagnosis of angioedema and the appropriate laboratory tests. METHODS: Pediatric patients suspected to have HAE based on the presence of angioedema and screened for C1 esterase inhibitor levels and/or function were included in the study. RESULTS: A total of 136 patients were evaluated for a preliminary diagnosis of HAE in the presence of angioedema. Angioedema was accompanied by urticaria in 65 patients (47.7%) and itching in 24 patients (17.6%). Patients were evaluated using laboratory tests, C4 levels were studied in 124 patients (91.1%) and were found to be within normal reference limits. C1 esterase inhibitor levels were studied in all patients and were found to be within normal limits. C1 esterase inhibitor function was also studied in 101 patients (74.2%) and was found to be within normal limits. DISCUSSION: It was concluded that clinicians keep HAE in mind when encountering angioedema, but that increasing their knowledge of clinical findings that assist in differential diagnosis among angioedema types would be useful. The study authors would like to emphasize that this topic should be included in the specialty training curriculum to raise the awareness of clinicians, especially pediatricians, about clinical HAE findings and the algorithmic approach to the differential diagnosis of angioedema.

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.

Evaluation of the frequency and characteristics of drug hypersensitivity reactions in hospitalized children: Real life-cohort study.

Introduction: There are limited data regarding the characteristics and management of drug hypersensitivity reactions (DHR) in hospitalized children. This study aims to determine the prevalence, clinical features, and management of DHRs in pediatric inpatients. Methods: Children who had pediatric allergy consultation for suspected DHR during hospitalization in Ankara Bilkent City Hospital between August 1, 2020, and July 30, 2021, were included. Patient and reaction characteristics, culprit drugs, and management strategies were recorded. When possible, diagnostic tests (skin or provocation tests) were performed after discharge. Results: Among the 14,090 hospitalized children, 165 (72% male, median age: 106 months) underwent consultation for 192 suspected DHRs with 246 drugs. Cutaneous eruptions were the most common (94.3%). There was anaphylaxis in 40 patients and severe cutaneous adverse drug reaction in 4 patients (drug rash with eosinophilia and systemic symptoms in 3, acute generalized exanthematous pustulosis in 1). Antimicrobials were the leading cause (78.4%, n = 193/246). In 48 reactions, 60 (24%) culprit drugs could be readministered with close follow-up or desensitization (n = 12). In total, 186 suspected drugs were discontinued, and 115 were replaced with alternative drugs. After discharge, 38 provocation tests (2 positives) and 36 skin tests (1 positive prick test, 1 positive intradermal test, and 1 positive patch test) were performed. Discussion/conclusions: The incidence of suspected DHR among pediatric inpatients was approximately 1.1%. Skin symptoms were the most common manifestation. Twenty-four percent of suspected drugs could be continued during hospitalization. Patients with DHR during hospitalization should be evaluated with a drug allergy work-up unless there are contraindications to testing.

Evaluation of emotional, Behavioral, and clinical characteristics of children aged 1-5 with a history of food-related anaphylaxis.

BACKGROUND: Our study aimed to investigate emotional, behavioral, and social characteristics assessed with internationally validated psychometric scales and their relationship with demographic, clinical, and laboratory data in children with a history of food-related anaphylaxis. METHOD: The study included patients aged 1-5 who were followed up in the pediatric allergy outpatient clinic with a diagnosis of food-related anaphylaxis. All participants were evaluated during admission to the clinic using a study questionnaire, which was prepared by the authors, consisting of three parts: a sociodemographic information form, a clinical evaluation form, and the Aberrant Behavior Checklist (ABC) for psychiatric evaluation. Parents answered the questionnaires regarding the patients' emotional and behavioral health. RESULTS: Thirty patients aged between 12 and 62 months were included in the study. The data were compared with 30 healthy controls with similar age and gender distribution. The total ABC score (p = 0.015), and the stereotypic behavior (p = 0.003) and hyperactivity (p = 0.002) subscale scores were significantly higher in patients with anaphylaxis history compared to the controls. CONCLUSION: Emotional and behavioral status assessments and the clinical follow-up of food allergies of patients who experienced anaphylaxis in early childhood are useful for the holistic management and early recognition of possible pathologies.

Evaluation of Frequency and Characteristics of Drug Allergy in Pediatric Patients with Cystic Fibrosis.

Background: Previous studies reported that the prevalence of drug allergy is higher in patients with cystic fibrosis (CF) than in the general population. It is important to exclude or confirm the drug allergy diagnosis with detailed allergic evaluation for preventing drug allergy overdiagnosis. Our study aims to determine the actual frequency of drug allergy proven by diagnostic tests in children with CF and to compare it with the control group. Methods: Patients diagnosed with CF who were followed up in the Pediatric Pulmonology Clinic were included in the study group. Children with similar gender and age characteristics who did not have any chronic diseases and who applied to the Pediatric Polyclinics were included in the control group. We reviewed the medical data of patients with CF. Also, we evaluated the parents of the patients via phone conversation and/or during the control of the outpatient clinic and questioned them in terms of drug allergy. In addition, we assessed those with suspected drug allergies in the pediatric allergy clinic for diagnostic tests and compared it to the control group. Results: CF patients (n = 44) and control group (n = 100) were included in the study. Only 1 patient (2.2%) out of the 44 patients in the study group had a suspicion of drug-related hypersensitivity history. In the control group, 1 patient had a history of rash, provocation test was performed to rule out drug hypersensitivity reaction, and it was evaluated as a negative result. Conclusions: The result of our study showed that the frequency of drug allergy in children diagnosed with CF was not different from the control group. However, it will be useful to confirm the data of pediatric patients with CF in larger groups. In the presence of suspicion of drug allergy, a diagnostic evaluation can prevent unnecessary drug allergy diagnoses.