Drug Allergy In Children Research Articles

Don't we overestimate drug allergies in children?

On average about 10% of parents report hypersensitivity to at least 1 drug in their children. After diagnosis process a few of these reactions are being confirmed as drug hypersensitivity reactions. The aim of the study was to assess the real-life prevalence of drug hypersensitivity in children based on drug provocation tests. The authors included 113 children, aged 4-18 years, referred to Pediatrics and Allergy Clinic in Łódź, Poland, due to incidence of adverse reaction during treatment. Medical history regarding allergies to drugs was taken in accordance to the form developed by the United States Food and Drug Administration Adverse Event Reporting System. Skin prick tests, intradermal test and drug provocation test were performed in all patients. In all 113 patients suspected of drug allergy, after all diagnostic procedures, the authors proved IgE-mediated allergy to β-lactams, nonsteroid anti-inflammatory drugs, local anesthetics in 19 patients (16.8%). Previous history of allergy was a risk factor for drug allergy in studied patients (p = 0.001). The most frequent symptoms of allergy were urticaria and erythematous papular rash. Drug allergy is a difficult problem in the practice of a doctor and is difficult to diagnose, especially in the pediatric population. It seems that too often isolated symptoms reported during infection or disease are taken as a symptom of drug allergy, and not as a symptom resulting from the course of the disease. Int J Occup Med Environ Health. 2023;36(5):632-42.

New perspectives on drug allergy in children

The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/pai.13957.

In vitro diagnostic testing for drug allergy in children

Diagnosing Drug Hypersensitivity Reactions (DHRs) could be a complicated process especially in children, since allergic-like manifestation at this age is more often the expression of concomitant infections rather than a actual DHRs. In vivo tests are usually suggested as a first step; however, prick and intradermal tests could be painful and have shown different sensitivity and specificity among published studies. In some cases, in vivo tests such as Drug Provocation test (DPT) could be even contraindicated. Therefore, the need for in vitro testing is compelling, to add useful information along the diagnostic pathway and to limit the need of DPT. In this review, we analyze the different types of in vitro tests, focusing on those used more widely such as specific IgE and on those that are still for research settings, such as basophil activation test and lymphocyte transformation test, but that have shown some useful diagnostic potential.

Confirmation of drug allergy in a general pediatrics outpatient clinic

BackgroundStudies including diagnostic workups on true drug allergy in children are limited. ObjectiveTo evaluate the frequency of confirmed drug allergy in children with a history of suspected drug allergy who had applied to the general pediatric outpatient clinics of our hospital owing to various health problems. MethodsThe history of drug allergy was asked among children who applied to the general pediatric outpatient clinics of our hospital. Allergy tests were performed to confirm drug allergy in children whose history was compatible with drug allergy. ResultsIn this study, parents of 5553 children aged between 4 months and 17.9 years were asked, “Has your child ever developed an allergy after drug use?” A total of 7% of the parents (n = 389/5553) thought that their child had a drug allergy. When these patients were evaluated by a pediatric allergist, it was suspected that 21.1% (n = 82/389) had a drug allergy. When diagnostic tests were performed for drug allergy, drug allergy was confirmed in only 4.2% (n = 3/72). Consequently, the frequency of drug allergy according to the history was 1.47% (n = 82/5553) in the population we studied, whereas the frequency of confirmed drug allergy was found to be 0.05% (n = 3/5553). ConclusionThe patient or parent statements alone are not sufficient for the diagnosis of drug allergy in children. To confirm or rule out drug allergy, drug allergy tests must be performed so unnecessary drug restrictions can be avoided.

Antibiotic allergy in children with cystic fibrosis: A retrospective case-control study.

To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF. In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression. β-lactam allergy was confirmed in eight patients (ceftazidime n = 5, piperacillin-tazobactam n = 3) and non-β-lactam allergy was confirmed in two patients (ciprofloxacin n = 1, azithromycin n = 1). Additionally, multiple drug hypersensitivity in five patients (distant n = 4, sequential n = 1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n = 2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n = 13) with confirmed β-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, p < 0.001) and allergic evaluation in the first six months after the reaction (p = 0.036) were significant risk factors for the prediction of antibiotic hypersensitivity. Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority.

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.

Drug Allergy in Children: What is the Actual Frequency of Drug Allergies?

Drug hypersensitivity reactions are immunologically mediated reactions resulting in the production of drug-specific antibodies and/or T-cells and constituting only <15% of all drug reactions. Based on the clinical observations, both patients and their parents refer to any undesirable drug reactions as drug allergy, regardless of whether the underlying mechanism is immunological or not. After allergy examinations, only a small percentage of the patients who were reported positive for drug reactions based on their clinical history are actually confirmed to have hypersensitivity. This study aims to determine the actual frequency of drug allergies in children, the drugs that cause the most common allergies in patients with a complaint of drug allergy and evaluate the accompanying demographic and clinical features. The study evaluated data from a total of 266 patients (ages of 0-18) with suspected drug allergy during a 3-year period. Twenty-four patients with doctor-diagnosed drug-related anaphylaxis and 85 patients who did not accept diagnostic tests were excluded from the study and the study continued with a total of 157 patients. The allergy work-up consisted of in vivo and in vitro tests, in accordance with the recommendations of the ENDA/EAACI guidelines. Data from a group of 157 patients (M [54.6%]; F [45.4%]) were retrospectively analyzed. Beta-lactams (BLs) were the most common drugs involved in the reported clinical history followed by non-steroidal antiinflammatory drugs (NSAIDs). Allergic reactions occurred on the median 1st day (min: 1-max: 8) after drug intake and were most frequently observed as urticaria (55.3%). Immediate reactions (IRs) were observed in 53.5% and non-IRs in 46.5% of the patients. Our data demonstrated that only 15.5% of patients confirmed to be positive to allergy during testing which is in line with the data in the literature. An allergy work-up is mandatory for excluding suspected hypersensitivity.

Медикаментозная аллергия у детей: что нужно знать?

Реакции на лекарственные препараты являются причиной около 6,5 % всех госпитализаций. Они развиваются у 15 % пациентов, находящихся на стационарном лечении. Возможность их развития следует учитывать при дифференциальной диагностике, когда любая медицинская проблема возникает у человека, который принимает лекарства. У детей основной сложностью в диагностике лекарственной аллергии является дифференциация макулопапулезных высыпаний как реакции на лекарственное средство от вирусной экзантемы, которая часто наблюдается в этой возрастной группе. При лечении аллергических реакций первым шагом является немедленное прекращение действия причинного препарата. Избегание приема безрецептурных препаратов и употребления лекарств внутрь, если это возможно, важно с точки зрения профилактики лекарственной аллергии. При выборе альтернативного препарата следует учитывать перекрестную реактивность между препаратами с похожей структурой. На амбулаторном этапе для профилактики и лечения реакций на лекарственное средство могут быть использованы антигистаминные средства, в частности диметиндена малеат — Эдермик.

Profile of Determinant Factors on Drug Allergy Severity in Indonesian Children at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia

Background: Drug allergy in children is a rare case that needs special attention. Identifying the factorsthat affect the severity of drug allergy is important for the improvement of drug allergy management inIndonesian children. Objective: to analyze the factors that influence drug allergy severity in Indonesianchildren. Methods: This study used a retrospective design and consecutive sampling in 2014-2018. The datacollected included sex, types of allergy-causing drugs, previous allergy history, parental allergy history, andclinical manifestations. The data were analyzed by using a logistic regression test where the statistical testresults were significant if p &lt;0.05. Results: The average age of the participants was 93.00 ± 50.54 monthswith a median value of 84 (12 - 204) months. Drug allergy severity in children is influenced by severalthings, such as the type of drug (? = 5.76; 95% CI 1.29 - 25.70; p = 0.022), sex (? = 1.27; 95% CI 0.30 - 5.36;p = 0.743), previous allergy history (? = 2.44; 95% CI 0.10 - 58.67; p = 0.583), and a drug allergy history onparents (? = 0.65; 95% CI 0.06 - 6.75; p = 0.719). Conclusion: There is a significant relationship betweendrug allergy severity and the type of drug whereas sex, previous allergy history, and a history of allergy onparents do not find a significant connection.

Single-dose prolonged drug provocation test, without previous skin testing, is safe for diagnosing children with mild non-immediate reactions to beta-lactams.

Mild non-immediate reactions (NIRs) to beta-lactams (BLs) are the most frequent manifestation of drug allergy in children. The diagnostic approach is complex as the utility of skin tests (STs) and lymphocyte transformation tests (LTTs) is controversial. Drug provocation test (DPT) is the gold standard, although no standardized protocols exist. We aimed to investigate the utility of DPT in a unique dose without previous STs, and LTTs in the diagnosis of NIRs to BLs in children. We prospectively evaluated children 0-14years old referred to the Regional University Hospital of Málaga during 2017-2020 reporting NIRs to BLs. We performed a DPT with a unique dose followed by regular treatment at home. If positive, STs and LTTs were done after the reaction had disappeared. We included 194 children, having 24 (12.4%) a positive DPT. The main culprit was AX (70.1%) followed by AX-clavulanic acid (CLV) (26.8%) and the main symptoms maculopapular exanthema (MPE) (49.5%) and delayed-urticaria (48.5%). A decrease (p=0.013) in the interval of days between drug administration and onset of symptoms was observed in positive DPT compared with the original reaction (3.5 vs 6days), with no differences in the overall percentage of MPE and delayed-appearing urticaria (p=0.551). No severe reactions occurred during DPT. Moreover, STs were positive in 13.33% and LTTs in 52.9%. Single-dose DPT without previous STs is a safe and useful way to assess NIRs to BLs in children. LTT has shown to be useful, confirming a T-cell mechanism involved in these reactions.

Knowledge gaps of drug allergy in children: a survey of primary care doctors.

IntroductionThere is still lack of knowledge of drug allergy in children. Proper knowledge and management of drug hypersensitivity reactions is important to physicians.AimTo evaluate the approach of primary care doctors regarding drug allergy in children.Material and methodsA total of 195 primary care doctors were questioned in various parts of Lithuania from 2015 to 2016. An original questionnaire was used. The incidence of a suspected drug allergy, culprit drugs, the clinical pattern and management of the suspected drug hypersensitivity were analysed.ResultsThe majority of primary care doctors (74.4%) reported a suspected drug allergy. The main suspected drugs were antibiotics (95.2%) and nonsteroidal anti-inflammatory drugs (32.4%). Skin symptoms (skin rash (100%) and itching (82.1%)) were the main symptoms of the suspected drug allergy. The vast majority of doctors (93.8%) withdrew the use of a suspected drug and 68.3% of respondents prescribed an alternative drug. The fact that skin tests, blood tests and provocation tests could be used in a drug allergy workup were indicated by 43.6% of doctors. Most doctors (69.2%) knew about the opportunity to test children for drug allergy in Lithuania and 41.4% of doctors referred patients for the further drug allergy workup.ConclusionsThe majority of primary care doctors reported a suspected drug allergy in children. The most common suspected drugs were antibiotics and skin symptoms were the main symptoms. Most doctors knew about the possibility to test for the drug allergy but only less than half of them referred patients for the drug allergy workup.

β-Lactam Allergy in Children.

Objective:β-lactam antibiotic allergy is the most common drug allergy in children. Most of the patients with suspected reactions to β-lactam antibiotics can actually tolerate these drugs. The aim of this study is to evaluate clinical and laboratory characteristics of children with β-lactam allergy and to determine cross-reactivity between penicillin and cephalosporins.Methods:The diagnosis of β-lactam allergy was made based on the results of skin tests and/or drug provocation tests (DPT). Penicillin allergy skin tests were performed with DAP penicillin® (Diater laboratories, Madrid, Spain), penicillin G, and ampicillin/amoxicillin preparations. Skin and provocation tests were performed with the culprit cephalosporin in addition to the penicillin skin and/or provocation tests to evaluate cephalosporin allergy.Results:We found that 87.7% (71/81) of patients with β-lactam allergy were able to tolerate the culprit drug. Among ten patients with confirmed diagnosis, two had cross-reactivity (penicillin and cephalosporin) and 8 had a various β-lactam (aminopenicillin n=6, ceftriaxone n=2) allergies. We identified older age and early-type clinical reactions as risk factors for a confirmed β-lactam allergy.Conclusion:Skin tests and DPT appear to be useful procedures in the diagnosis, and determination of an alternative safe antibiotic in patients with β-lactam allergy. Most of the patients tolerated the drugs. A minority of the patients with confirmed allergy should avoid all β-lactam antibiotics due to the probability of cross-reactivity.

Drug hypersensitivity in children: a retrospective analysis of 101 pharmacovigilance reports.

Our objective was to describe and discuss management of recent cases of drug hypersensitivity in children reported in a pharmacovigilance center. Two pediatric allergy units conducted a collaborative retrospective analysis of 101 adverse drug reactions reported to a regional pharmacovigilance center between January 2016 and July 2019. Time lapse between hypersensitivity reaction onset and allergy consultation varied from 1month to 12years. Sixty-two patients (61.4%) presented with immediate reactions, 11 (10.9%) with non-immediate reactions, and 28 (27.7%) had reactions impossible to classify through medical interview. Overall, 92 children (91%) were explored for simultaneously administered drugs. All 113 prick tests were negative, and 2 were uncertain. Among 108 intradermal tests, 2 were positive to penicillin and to an iodinated contrast medium, 105 were negative, and 1 was uncertain. Overall, 129 drug provocation tests were proposed. Nine provocation tests among 80 were positive (11.25%): 6 to penicillin, 1 to sulfonamide antibiotics, and 2 to non-steroidal anti-inflammatory drugs; the remaining 71 were negative. No severe reaction was observed during these tests. Finally, drug allergy was only retained in 11 reported cases (10.9%).Conclusion: These pharmacovigilance reports show the difficulty in defining drug allergy in children only by anamnesis, and that explorations, particularly provocation tests, should take place at a reasonable time lapse after drug hypersensitivity reaction onset. What is Known: • True drug allergy is rarely observed in children. • Absence of full workup leads to falsely labeling children as "allergic." What is New: • Short time lapse between hypersensitivity onset and consultation improves classification of pediatric allergy. • Timely allergy consultations are essential, and tests are useful to confirm or exclude pediatric allergy.

Drug Allergy in children: focus on beta-lactams and NSAIDs.

Drug hypersensitivity reactions (DHRs) are adverse reactions to a drug. In children, most common drugs inducing such reactions include beta-lactams (BLs) and non-steroidal anti-inflammatory drugs (NSAIDs). The aim of the present work was to provide current knowledge on the management of DHRs in the pediatric population, focusing on BLs and NSAIDs hypersensitivity. The clinical feature of DHRs include immediate and non-immediate (delayed and accelerated) reactions, that may be severe or non-severe. A systematic approach to the patient based on the reported clinical history is essential to organize a safe and adapted allergy work-up. Skin tests are the first step to assess a possible DHRs, especially in immediate reactions to BLs. Drugs concentrations for these tests are standardized and validated. The drug provocation test remains the gold standard to reach a firm diagnosis. In selected cases, a therapeutic desensitization protocol may be proposed in children with a confirmed diagnosis of drug hypersensitivity. Clinicians should be aware of the diagnostic and therapeutic options, to provide the best management in children having experienced a history of DHR. (www.actabiomedica.it)

Drug Allergy in Children: What Should We Know?

The drug allergy “label” may have a lifetime of consequences for a child. Many children with alleged drug allergies are proven to be tolerant to the culprit medication when challenged. The field of drug hypersensitivity is a recently evolving field of research, but studies on its epidemiology and diagnostic tools are lacking in children. Clinical history is significant in the diagnosis and classification of drug hypersensitivity in children. Diagnostic tools have been evaluated in a limited number of children; therefore, the guidelines are mainly in line with those for adults. Here, we review the clinical characteristics, main drugs, risk factors, and diagnosis of drug hypersensitivity to aid in its accurate diagnosis in children.

Drug allergy in children: more often suspected than real

Drug allergy in children: more often suspected than real Abstract. Adverse drug reactions are frequent in the pediatric population. However, only a small proportion of all adverse reactions are drug allergic reactions. About 10 % of the parents report a suspected drug allergy in their children. Even though, no accurate epidemiological data are available, studies suggested that as few as 10 % of those reported an allergy really are. The most common drug allergy among children is a drug hypersensitivity to antibiotics, especially to betalactam antibiotics.In children, one of the major difficulty in the diagnosis of drug allergies, and especially to antibiotics, is the differentiation of maculopapular eruption as an allergic reaction from a viral exanthema, which is very common among children. Therefore, a high number of children are inappropriately labeled as "drug allergic". In case of suspicion of an allergy, it is recommended to perform a complete allergy workup.

Hypersensitivity reactions to beta-lactams in children.

To present the most recent evidence on beta-lactam hypersensitivity reactions in children. Drug provocation tests (DPTs) are the gold standard when investigating beta-lactam allergy in children and evidence is increasingly supporting DPTs without skin tests as a safe approach when evaluating children with nonimmediate mild reactions to beta-lactams. Of note, data are limited in the adolescent population, and this attitude may not apply to this age group. Standardization of DPT protocols is required in nonimmediate reactions, as many protocols ranging from 1 to 10 days have been described. The optimal duration of DPT is still unknown, with extended protocols providing slightly more sensitivity and possible higher long-term compliance, at the expense of potential side effects associated with prolonged antibiotic use. On the other hand, 1-day DPTs will identify the vast majority of patients, and the rest will only develop a mild rash during a subsequent full treatment. The natural history of beta-lactam allergy in children is not well studied with recent evidence pointing to the resolution of most confirmed beta-lactam allergies after 3 years. Further studies are needed for the standardization of DPT protocols and to confirm the favourable natural history of beta-lactam drug allergies in children. In addition, multicentric studies are required to confirm the increasingly accepted position of performing DPTs without skin tests in nonimmediate mild reactions to beta-lactams and to further evaluate the possibility of performing DPTs in benign immediate reactions to beta-lactams in children.

How to Manage Drug-Induced Exanthema in Children

Exanthemas are frequently encountered in the pediatric population and often occur while patients concomitantly receive a drug, leading to a high prevalence of suspicion of drug allergy in children. Although the vast majority of these exanthemas are due to the underlying infection, most of those patients are falsely labeled as “drug allergic” without appropriate testing, mostly due to fear of life-threatening reactions. Overdiagnosis of drug allergy constitutes a major public health problem by increasing health costs and by contributing to overall antibiotic resistance. Thus, an accurate diagnosis is considered as a major contribution to cost-effective health care and will be based on a complete allergic workup (i.e., clinical history, skin tests, in vitro tests, and/or drug provocation test). Specific aspects of the management of drug allergy have been highlighted recently, particularly regarding the importance and safety of the drug provocation test as well as the low diagnostic value of skin tests in the diagnosis of betalactam allergy.

Lack of uniformity in the investigation and management of suspected β-lactam allergy in children.

Beta-lactam allergy is commonly suspected in childhood with health implications for the individual and wider public. Diagnostic modalities include skin prick tests (SPT), specific immunoglobulin-E (sp-IgE) tests, intradermal tests (IDT) and drug provocation challenges (DPC). The aim of this research was to establish whether variation exists around the world in the investigation and management of beta-lactam allergy. Anonymized electronic questionnaire surveys were distributed over 3months through International Allergy Societies for completion by clinicians who investigate drug allergy in children. Eighty-one clinicians, practising in 16 countries, completed the questionnaire. There is variability in the selection of diagnostic tests used by clinicians around the world and poor agreement on positive cut-off values (sp-IgE, SPT and IDT) and practical techniques used to measure SPT or IDT wheal diameters. DPC were considered the gold standard investigation with 94% of respondents undertaking DPC over the last 12months; 64% of respondents considered DPC extremely useful for both exclusion and confirmation of beta-lactam allergy. However, there is a lack of consensus on when and how DPC should be performed. Overall, DPC are safe - only 3% of our respondents had patients who required intramuscular adrenaline and none had patients requiring admission to intensive care. There is lack of consistency amongst clinicians in different countries in the diagnosis and management of suspected beta-lactam allergy. The development of a standardized approach is a priority.

Actual drug allergy during childhood: Five years’ experience at a tertiary referral centre

BackgroundDrug hypersensitivity reactions (DHR) are common in the paediatric population, representing a public health problem. Recent studies have confirmed that the frequency of drug allergy is overestimated by both parents and physicians. The aim of this study is to determine the prevalence and risk factors of actual drug allergies in children admitted to a tertiary referral allergy centre. MethodsMedical records covering the period of 2005–2010 of children with a history of DHR were reviewed. Demographic features of the patients and results of skin and drug provocation tests were noted. The European Network for Drug Allergy (ENDA) questionnaire was filled by using medical records and making phone calls with parents. ResultsNinety-six patients with 140 DHRs were evaluated. Seventeen children had confirmed drug allergy by positive skin tests (n=11) and drug provocation tests (n=5). One patient underwent severe anaphylaxis and subsequent cardiac arrest during infusion of the drug, and therefore diagnostic tests were not performed. Actual drug allergy was more frequent in children with chronic diseases (58.8% vs. 26.5%, p=0.018) and histories of anaphylaxis during DHR (58.8% vs. 24%, p=0.001). The patients’ history of anaphylaxis [OR: 5.789, 95%CI: 1.880–17.554, p=0.002], sweating [OR: 7.8, 95%CI: 1.041–58.443, p=0.046] and dyspnoea [OR: 5.230, 95%CI: 1.836–14.894, p=0.002] during suspicious DHRs increased the risk for actual drug allergy. ConclusionActual drug allergy was determined in 17.7% of the patients with a suspicious DHR. Having a history of anaphylaxis during suspected drug reactions as well as symptoms of sweating and dyspnoea increased the risk for actual drug allergy.