Risk Factors of Challenge-Proven Beta-Lactam Allergy in Children with Immediate and Non-Immediate Mild Cutaneous Reactions.

INTRODUCTION: Beta-lactam (BL) antibiotics are the most often involved drugs in allergic reactions. Mild cutaneous reactions such as maculopapular exanthema or urticaria are the most common presenting complaints of BL allergy in the pediatric population. However, it can be challenging to distinguish BL-induced allergy from reactions due to infections or other reasons. In this study, we aimed to determine the clinical characteristics and potential risk factors of true BL allergy in children with suspected mild cutaneous reactions to BLs. METHODS: We evaluated children who were admitted to our pediatric allergy clinic with suspected BL allergy in between January 2015 and March 2020. Patients with a history suggestive of immediate and non-immediate mild cutaneous reactions were included in the study. The oral challenge test (OCT) with the culprit drug was performed on all patients to confirm the diagnosis. RESULTS: Two hundred fourteen (119 male and 95 female) patients with a median age of 4.9 years were evaluated. BL allergy was confirmed in 10.7% (23) of the patients, according to the OCT results. Most of the proven allergic reactions were of the immediate type (73.9%), and urticaria was the most common presenting complaint (60.8%) in proven BL-allergic patients. The negative predictive value of penicillin-G skin testing was 89.7% for immediate-type penicillin allergy and 93.4% for non-immediate reactions. Also, positive predictive value of penicillin-G skin testing was 50% for immediate and 25% for non-immediate reactions. In the multivariate logistic regression analysis, a history of proven drug allergy (Exp (B): 7.76, 95% CI: 1.88-31.97, p = 0.005) was found to be the risk for BL allergy. CONCLUSION: This study highlighted that OCTs should be performed to confirm the diagnosis in patients suspected of immediate and non-immediate mild cutaneous reactions to BLs and remove the overestimated "BL allergy" label. In these patients, a history of proven drug allergy might be a risk factor for true BL allergy.

Hypersensitivity to Ibuprofen: Real-Life Experience in Children with History of Suspected Immediate Reactions.

INTRODUCTION: Ibuprofen is the most common culprit drug causing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children. We aimed to evaluate the frequency, clinical characteristics, and risk factors of confirmed ibuprofen allergy in children presenting with a history of suspected immediate type ibuprofen-induced hypersensitivity reactions. METHODS: We evaluated 50 (35 M, 15 F) children with a median age of 7 years, who were referred to our clinic with suspected immediate ibuprofen hypersensitivity. Patients were subjected to a diagnostic work up including drug provocation tests (DPTs) with the culprit drug. Reactions were classified according to the European Academy of Allergy and Clinical Immunology Task Force recommendations for pediatric patients. Proven ibuprofen allergic patients underwent DPT to find a safe alternative drug. RESULTS: Ibuprofen allergy was confirmed in 34% (n: 17) of children; 9 patients were diagnosed by DPTs and 8 patients diagnosed based on their histories. Angioedema was the most common clinical manifestation (n: 30, 60%). Among patients with proven ibuprofen allergy, 7 of them were classified as cross-intolerant. Cross-intolerance reactions were further classified as NSAID-exacerbated cutaneous disease (n = 1) and NSAID-induced urticaria/angioedema/anaphylaxis (n = 6). As an alternative drug, paracetamol was safely tolerated, whereas 1 patient developed angioedema and urticaria with nimesulide. Older age and male gender were identified as independent risk factors for immediate-type ibuprofen allergy. CONCLUSION: DPTs should be performed to confirm or exclude ibuprofen allergy in children and to find safe alternative drugs. Male gender and older age are risk factors for ibuprofen allergy. NSAID-induced hypersensitivity reactions in the pediatric population cannot be well defined using the adult classification system.

Level of knowledge among healthcare professionals regarding anaphylaxis.

Background: Anaphylaxis is defined as a severe, life-threatening systemic hypersensitivity reaction. Healthcare professionals must recognize the symptoms, apply correct treatment immediately, and provide epinephrine auto-injectors (EAI) to patients who experience anaphylaxis. Objective: In this study, we aimed to investigate the knowledge of healthcare professionals regarding anaphylaxis. Methods: This cross-sectional study, which was conducted between February 2022 and March 2022, included healthcare professionals working in various hospitals in Turkey. A survey consisting of 21 questions which concerned with the demographic data, personal experience and level of knowledge about anaphylaxis was applied to healthcare professionals. Results: The study included a total of 301 participants, comprising 160 specialist physicians (53.16%), 86 resident physicians (28.57%), 31 family physicians (10.3%), and 24 allied health personnel (7.97%). Most of the healthcare professionals (93%) chose epinephrine as the first-line treatment for anaphylaxis. Two hundred ten participants (69.77%) knew the correct dose of epinephrine in the treatment of anaphylaxis, and allied healthcare professionals had least knowledge (p = 0.009). The participants who received anaphylaxis training and had experience with anaphylaxis had a higher knowledge about epinephrine dosing (p < 0.001 and p = 0.003, respectively). Only 49.17% of the participants knew the epinephrine doses of EAIs, and only 19% of participants had prescribed an EAI. Conclusion: Our results showed that healthcare professionals' knowledge about epinephrine doses in the treatment of anaphylaxis was not sufficient. Furthermore, the prescribing rate of EAIs was still inadequate. There is a need for national training programs to increase and update the knowledge of healthcare professionals to reduce anaphylaxis mortality.

Clarithromycin hypersensitivity in children: Is there a link with ß-lactam hypersensitivity?

BACKGROUND: Clarithromycin hypersensitivity is reported as the most common cause of non-ß-lactam antibiotic allergy in children. Clarithromycin is frequently prescribed in cases of suspected ß-lactam hypersensitivity. Oral provocation tests stand as the gold standard to confirm drug hypersensitivity as diagnostic value of skin tests is variable. We analyzed the frequency of true clarithromycin hypersensitivity ratio and its relationship with ß-lactam allergy among children with suspected clarithromycin hypersensitivity and evaluated the diagnostic value of skin tests. METHODS: The study included 160 children referred with suspected clarithromycin hypersensitivity. Clinical history and allergy workups including skin tests or/and oral provocation tests were retrieved from medical records. RESULTS: Oral provocation test confirmed clarithromycin hypersensitivity rate was 5.6% (n = 9/160). Skin tests with clarithromycin showed positivity in 32.6% (n = 29/89) of the tested patients. The sensitivity of clarithromycin skin tests was negligible, and specificity was 73.9% (95% confidence interval [CI], 64.7-81.8). Eighty-eight of the patients (55%) reported that they had previously tolerated a ß-lactam antibiotic. ß-lactam hypersensitivity was suspected in 40% (n = 64/160) of the patients (simultaneous [n = 10], sequential [n = 19], distant form [n = 35]) in relation with clarithromycin usage. ß-lactam hypersensitivity (95% CI, 2.1-70.6, p = .005) and sequential usage of clarithromycin after the development of a rash with amoxicillin-clavulanic acid (95% CI, 2.0-96.4, p = .007) were found as risk factors for confirmed clarithromycin hypersensitivity. CONCLUSION: The frequency of confirmed clarithromycin hypersensitivity was found low among suspected patients. Oral provocation test is crucial for definite diagnosis. Confirmed ß-lactam allergy may be attributed as a risk factor for clarithromycin hypersensitivity, particularly clarithromycin treatment after a developing rash with amoxicillin-clavulanic acid in sequential usage.

Behind the scene: Paracetamol hypersensitivity in children.

BACKGROUND: Paracetamol, a non-steroidal anti-inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity. METHODS: Sixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX-1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross-intolerance hypersensitivity. A subsequent OCT with a selective COX-2 inhibitor was performed in those cross-intolerant patients to find out a safe alternative drug. RESULTS: Sixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross-intolerant after OCT with a COX-1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross-intolerant patients, a safe alternative non-steroidal anti-inflammatory drug was identified after an OCT with a selective COX-2 inhibitor. CONCLUSION: OCT stands as the gold-standard procedure in verifying the diagnosis of patients with paracetamol-induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.

Venom allergy and knowledge about anaphylaxis among beekeepers and their families.

BACKGROUND: Beekeepers and their families are at an increased risk of life-threatening anaphylaxis due to recurrent bee-sting exposures. OBJECTIVE: The aim of this study is to evaluate the demographic features, previous history of anaphylaxis among beekeepers and their family members, and their knowledge about the symptoms and management of anaphylaxis. METHODS: A standardized questionnaire was administered to beekeepers during the 6th International Beekeeping and Pine Honey Congress held in 2018, in Mugla, Turkey. Additionally, food-service staff from restaurants were surveyed as an occupational control group about their knowledge about anaphylaxis. RESULTS: Sixty-nine beekeepers (82.6% male, mean age 48.4±12.0 years) and 52 restaurant staff (46.2% male, mean age 40.5±10.0 years) completed the questionnaire. Awareness of the terms 'anaphylaxis' and 'epinephrine auto-injector' among the beekeepers were 55.1% and 30.4% and among the restaurant staff were 23.1% and 3.8%, respectively. Of the beekeepers, 74% were able to identify the potential symptoms of anaphylaxis among the given choices; 2.9% and 5.8% reported anaphylaxis related to bee-stings in themselves and in their family members, respectively. None of the restaurant staff had experienced or encountered anaphylaxis before but 3.8% of their family members had anaphylaxis and those reactions were induced by drugs. CONCLUSION: It is essential that implementation of focused training programs about anaphylaxis symptoms and signs as well as practical instructions of when and how to use an epinephrine auto-injector will decrease preventable morbidities and mortalities due to bee-stings in this selected high-risk population of beekeepers and their family members, as well as other fieldworkers under risk.