Development of anaphylaxis upon oral food challenge and drug provocation tests in pediatric patients.

Background: The drug provocation test (DPT) and the oral food challenge (OFC) are considered as the criterion standard for the diagnosis of drug hypersensitivity reactions and food allergy. Severe allergic reactions may develop during these tests. Objective: To evaluate the frequency and features of anaphylaxis in pediatric patients undergoing OFCs and DPTs. Method: OFCs and DPTs performed in an open method in the pediatric allergy clinic of our institution between January 2014 and January 2021 were reviewed retrospectively. The characteristics of anaphylaxis that developed during these tests were evaluated. Results: A total of 3631 OFCs and/or DPTs were performed on 2588 pediatric patients. Reactions were recorded in 317 challenges (8.7%), including 42 (1.2%) in the form of anaphylaxis. Of the patients with anaphylaxis, 31 developed anaphylaxis during OFC and 11 during DPT. Anaphylaxis during OFCs was mostly triggered by yogurt (n = 8), hen's egg (n = 6), baked milk (n = 5), and baked egg (n = 4). Cases with anaphylaxis during DPT were recorded mostly with ibuprofen (54.5% [n = 6]). All patients who developed anaphylaxis during OFC had cutaneous manifestations, and 90.3% had respiratory symptoms. Gastrointestinal involvement was present in 32.3% of the patients. During DPT, cutaneous manifestations were observed in 90.9% in the patients who developed anaphylaxis and the respiratory tract was involved in 81.8%. In terms of concomitant allergic diseases, 51.6% of the patients who developed anaphylaxis during OFC had atopic dermatitis and 38.7% had asthma. All the patients with anaphylaxis triggered by nonsteroidal anti-inflammatory drug DPT had asthma. Of the anaphylaxis, 54.8% were mild, 35.7% were moderate, and 9.5% were severe. Severe anaphylaxis was recorded with baked milk (n = 2), baked egg and trimethoprim-sulfamethoxazole (n = 1, each). The patients did not require intensive care, and no death occurred. Conclusion: Anaphylaxis may develop during OFCs and DPTs. These tests should be carried out by experienced allergists in an appropriate setting where emergency equipment and medications, including epinephrine, are readily available.

Psychological Distress and Drug Provocation Test-Related Anxiety Levels of Pediatric Patients and Their Parents.

Background: Drug provocation tests (DPTs) are the gold standard for the diagnosis of drug hypersensitivity reaction (DHR). To the best of our knowledge, there is no previous study reporting DPT-related anxiety levels in children and their parents. This study aimed to determine the difference in pre- and post-DPT anxiety levels of parents and children who were informed of the possibility of another DHR during the DPT, and to evaluate the relationship between parental psychological distress and anxiety levels. Methods: The study included children who underwent DPT in our clinic between July 1, 2019, and February 29, 2020, and accompanying parents who consented to participate. Age-appropriate State-Trait Anxiety Inventory scales were used to assess levels of state and trait anxiety in the patients and parents. The Symptom Checklist-90-Revised (SCL-90-R) was used to screen for psychological symptoms in parents. Results: Data were collected from the parents of 69 children who underwent DPTs. The patients' median age was 7.28 (interquartile range: 4.52-10.06) and their parents' mean age was 35.28 ± 5.38 years. Anxiety-related data were collected from 21 pediatric patients. The children and parents had higher state anxiety scores before DPT compared to after DPT. There was a positive correlation between the parents' trait anxiety and pre-DPT state anxiety scores. In addition, parental pre-DPT state anxiety scores were positively correlated with SCL-90-R general severity index, somatization, anxiety, obsessive-compulsive, and depression subscale scores. Conclusion: The risk of allergic reaction in DPT may cause anxiety. A high level of parental anxiety before DPT, which gradually decreased after negative test results, was associated with history of drug-induced anaphylaxis in their children and high trait anxiety. Appropriate evaluation of patients and parents before DPT and providing detailed information may be important to reduce this anxiety.

The Etiology, Clinical Features, and Severity of Anaphylaxis in Childhood by Age Groups.

INTRODUCTION: Anaphylaxis is a severe, potentially fatal systemic hypersensitivity reaction with an acute onset. Etiology, clinical presentation, risk factors, comorbidities of pediatric anaphylaxis may vary depending on the age of the child. OBJECTIVE: The aim of this study was to investigate the etiology, clinical features, management of anaphylaxis in infants, preschoolers, school-age children, and adolescents. METHODS: The patients presenting with anaphylaxis between January 2015 and December 2018 in a single pediatric tertiary hospital were evaluated retrospectively. Demographic data, the triggers, sign-symptoms, severity, and the management of anaphylaxis were recorded. RESULTS: 239 patients were included in the study, 62.3% of whom were boys. The median age was 6.7 (IQR 2.33-12.83) years. 23.8% of the patients were infants, 15.5% were preschoolers, 33.5% were school-age children, and 27.2% were adolescents. Anaphylaxis mostly occurred at home. The most common causative agents were foods (39.3%), drugs (30.1%), and venoms (15.9%) of all cases. Main food allergens were cow's milk and hen's eggs in infants, cow's milk and tree nuts in preschoolers, and tree nuts and legumes in school-age children. Cases of drug-induced anaphylaxis (DIA) were recorded mostly with antibiotics (40.3%), followed by NSAIDs (23.6%). The primary trigger of anaphylaxis was foods in infants and preschoolers and drugs in school-age children and adolescents. There was no difference between age groups in terms of the system involved and severity. Severe anaphylaxis was more common with DIA. Adrenaline was used in 69.8% of all cases with no significant difference between age groups. CONCLUSION: Etiology and symptoms of anaphylaxis may differ between age groups. Raising awareness, educating patients and their parents on anaphylaxis and its management is essential.

Evaluation of Hypersensitivity Reactions in Pediatric Patients Using Biological Drugs.

INTRODUCTION: Biological drugs are currently used for the treatment of chronic inflammatory, autoimmune, and neoplastic diseases. With their expanding indication spectrum and increasing use, hypersensitivity reactions to these drugs are also becoming more frequent. The present study aimed to report the incidence and the features of such reactions in pediatric patients using biologicals for the treatment of various diseases. METHODS: The medical records of pediatric patients treated with biological agents between October 1, 2011 and August 31, 2019 were reviewed and adverse reactions were evaluated retrospectively. RESULTS: During the study period, 211 patients (116 boys, 55%) used 21 different biological drugs for the treatment of various diseases. Their median age at the time of the first treatment was 139.9 (IQR: 92.2-187.8) months. Hematologic-oncologic diseases were the most common indication for biological therapy (97/211; 46.0%), followed by rheumatologic diseases (82/211; 38.9%). Of the 211 patients, 14 (6.64%) experienced reactions to biological drugs. The most common culprit agent was rituximab (57.1%). Most of the patients (85.7%) had a history of reactions either during the infusion or within 1 h after taking the drug. Five patients underwent desensitization to the culprit drug, while 7 other patients continued treatment with a reduced dose/infusion rate or premedication. Also 1 patient continued to take the drug without any additional treatment. CONCLUSION: It was reported that 6.64% of the patients who received biologic drug therapy for various reasons in our hospital had hypersensitivity. The most common culprit agent was rituximab, and most of the reactions were immediate reactions.

Evaluation of anaphylaxis recurrence and adrenaline autoinjector use in childhood.

Introduction: Limited data are available on recurrent anaphylaxis in childhood. Delayed adrenaline administration is the major cause of deaths due to anaphylaxis. As well as prescribing the adrenaline autoinjector (AAI), it is important to make sure that the patient carries the device at all times and uses it correctly for the appropriate indication. Objective: The aim of our study was to evaluate the recurrence of anaphylaxis and AAI use in childhood. Methods: Pediatric patients who were evaluated for anaphylaxis and prescribed AAI between January 2015 and December 2018, in the pediatric allergy and immunology clinic of our hospital were screened retrospectively. A telephone-based survey was conducted with the parents of the patients to investigate the recurrence of anaphylaxis in patients and the use of AAI by their parents for the management of anaphylaxis. Results: A total of 148 patients (64.9% boys) were prescribed an AAI for anaphylaxis. The telephone survey could be conducted with 111 parents (75%) with an AAI prescription. Of these patients, 23.4% (n = 26) of the parents reported that their children experienced recurrent episodes of anaphylaxis. In the recurrent anaphylaxis cases, the triggers were foods in 77%, venoms in 11.5%, drugs in 3.8%, and idiopathic anaphylaxis in 7.7% of the patients. AAI use at the time of anaphylaxis was reported by 42.3% of the parents. The reasons cited by the parents for not using AAI during an episode of anaphylaxis included the preference to have adrenaline administered at a health care facility because of its proximity (60%), fear of using the device (13.3%), hesitation (6.7%), not having the device with them (13.3%), and unavailability of the device (6.7%). Conclusion: Educating the patients and families about the importance of using AAI is crucial, and training on how to use the device should be repeated at each clinic visit and every opportunity.

Evaluation of drug patch tests in children.

Background: Patch tests are used to diagnose nonimmediate T-cell-mediated drug hypersensitivity reactions. The aim of this study was to evaluate the results of patch tests performed with suspect drugs in children. Methods: Patients < 18 years of age who had a drug patch test at the pediatric allergy outpatient clinic of our hospital between January 2014 and January 2020 were included in the study. Age, sex, culprit drug(s), reaction characteristics, and patch test results were recorded from the patients' files. Results: A total of 105 drug patch tests were performed on 71 patients during the study period. The patients' median age was 7 years (interquartile range, 4-11 years), and 57.7% (n = 41) were boys. Twenty-three patients (32.3%) had severe cutaneous adverse reaction (Stevens-Johnson syndrome in 11, drug reaction with eosinophilia and systemic symptoms in 9, and acute generalized exanthematous pustulosis in 3 patients), 45 (63.3%) had maculopapular rashes, and 3 (4.2%) had fixed drug eruption. A total of 20 patch test results (28%) were positive: 18 of 44 patch tests (40.9%) with antiepileptic drugs and 2 of 48 patch tests (4.1%) with antibiotics. Positive results were obtained in 23% of the patch tests (6/26) in 20 patients with severe cutaneous adverse reactions and in 17.7% of the patch tests (14/79) in 51 patients with mild cutaneous reactions. No adverse reactions occurred during or after the patch tests. Conclusion: In our study, patch test positivity was more common with antiepileptic drugs and in patients with severe cutaneous drug reaction.

Evaluation of Clinical Properties and Diagnostic Test Results of Cephalosporin Allergy in Children.

INTRODUCTION: Beta-lactams (BLs) are one of the most frequent causes of drug hypersensitivity reactions (HRs), and cephalosporins are a widely used subclass of BLs, especially in children. The aim of this study was to evaluate the clinical features and diagnostic test results of pediatric patients evaluated for suspected cephalosporin allergy. METHODS: This study included patients who presented to our pediatric allergy clinic with a history of reactions attributed to cephalosporins between January 1, 2011, and December 31, 2019, and whose diagnostic tests were completed for the diagnosis. RESULTS: This study included 120 pediatric patients and 69 (57.5%) of them were girls. The median age was 38.63 (interquartile range 10.5-85.7) months. Reactions occurring within 1 h of drug intake were reported in 33 patients (27.5%). Reactions were maculopapular rash in 55 (45.8%) patients, urticaria and/or angioedema in 49 (40.8%), anaphylaxis in 11 (9.2%), severe cutaneous drug reaction in 4 (3.3%), and fixed drug reaction in 1 patient (0.83%). The most frequently suspected agent was cefixime in 41 patients (34.2%). In total, 30 (25%) patients were diagnosed as having cephalosporin hypersensitivity. Confirmation of HRs was also significantly more frequent among patients who were older (p: 0.000), who had taken the drug parenterally (p: 0.000) and with immediate reactions (p: 0.000). CONCLUSION: Cephalosporin allergy has been confirmed in approximately one-fourth of the patients evaluated for suspected cephalosporin allergy. Confirmation of HRs was significantly more common among patients who were older, had immediate reactions, and had taken the drug parenterally.

Diagnostic value and safety of penicillin skin tests in children with immediate penicillin allergy.

Background: The first-line method in the diagnosis of patients who describe an immediate reaction after penicillin intake is a skin test (ST) with penicillin reagents. Objectives: We aimed to determine the safety and diagnostic value of penicillin STs in the diagnosis of immediate reactions to penicillins in pediatric patients. Methods: The study included pediatric patients with suspected immediate reaction to penicillin who were subjected to STs by using a standard penicillin test kit as well as suspected penicillin and the drug provocation tests (DPT) with the suspected penicillin at our clinic. Results: A total of 191 patients (53.9% boys) with a median age of 6.83 years (interquartile range, 4.2-12 years) were included in the study. The time from drug intake to the onset of reaction was ≤1 hour in 138 patients (72.3%) and 1 to 6 hours in 53 patients (27.7%). Penicillin allergy (PA) was confirmed by diagnostic tests in 36 of the 191 patients (18.8%). In multivariate logistic regression analysis, the history of both urticaria and angioedema (odds ratio [OR] 27.683 [95% confidence interval {CI}, 3.143-243.837]; p = 0.003) and anaphylaxis (OR 56.246 [95% CI, 6.598-479.489]; p < 0.001) were the main predictors of a PA diagnosis. Although ST results were positive in 23 patients (63.8%), 13 patients (26.2%) had positive DPT results despite negative ST results. The negative predictive value (NPV) of STs was calculated 92.2% (155/168). None of our patients experienced immediate or delayed systemic and/or local reactions in relation to the STs. Conclusion: A history of urticaria with angioedema and anaphylaxis were the main predictors of true PA in children with suspected immediate reactions. STs with penicillin reagents are safe for use in children. Although STs have a high NPV, DPT is the gold standard for diagnosis. DPTs should be performed as the final step of the diagnostic evaluation of PA in patients with negative ST results.

Results of NSAID provocation tests and difficulties in the classification of children with nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in children and can frequently cause hypersensitivity reactions. Rates of confirmed NSAID hypersensitivity (NSAID-H) in children are low. OBJECTIVE: To evaluate the results of drug provocation tests (DPTs) with NSAIDs and to evaluate the difficulties encountered in the classification of NSAID-H in children. METHODS: The study included patients with suspected NSAID-H who were examined in our clinic between January 1, 2015, and December 31, 2018. Oral provocation tests with NSAIDs were performed and reactions were classified according to the European Academy of Allergy and Clinical Immunology position paper on NSAID-H. RESULTS: A total of 243 patients (57.2% male patients) presented with suspected NSAID-H during the study period. Of these, 168 patients (69.1%) had a history of reaction to ibuprofen. Isolated skin involvement was the most frequent symptom (86%). A total of 238 DPTs were performed with the suspected agents and 34 had positive results. The families of 12 patients refused provocation testing with the suspected agent or aspirin and these patients could not be diagnosed. Of the 231 patients, 47 patients (20.3%) received a diagnosis of NSAID-H. Twenty patients with NSAID-H could not be classified because their guardians did not consent to further testing with aspirin. CONCLUSION: Performing diagnostic tests is important in patients with no contraindications. Characterizing these reactions in children can be difficult because of the coexistence of indistinguishable symptoms in their history and DPTs, as well as the need for multiple provocation tests. Therefore, further research is needed on this subject.