Introduction
Drug allergy is an immune system-mediated response to a specific substance in a sensitised individual [1]. Clinical manifestations of drug allergy are limited to specific syndromes that are thought to be allergic and may manifest as reactions ranging from mild to life-threatening severity [2]. The estimated incidence of drug allergy varies between 0.018 and 4.2 per 1000 hospitalisations [3, 4], while deaths related to drug allergy are estimated to be 0.09 per 1000 hospitalisations [4]. The diagnosis of drug allergy is usually made on the basis of clinical symptoms and/or patient history. However, only a small proportion of adverse drug reactions are true drug allergy [5, 6]. Including allergic reactions to vaccine components, drug allergies constitute an important safety concern in the paediatric population [7].
Correct management of drug allergy is mandatory and very important for patients. Patients are often labelled as drug allergic as a result of vague symptoms that do not correspond to true allergic reactions [8]. Therefore, the diagnosis and appropriate management of drug allergy is a major challenge for physicians and an important need for patients. Ensuring drug safety for individuals of all ages in the community should be one of the main goals of the healthcare system. Despite the great benefits of medicines, drug hypersensitivity reactions are recognised as one of the main causes of harm to individuals. These reactions not only adversely affect the patient care process, but also have serious consequences on the healthcare system, leading to high morbidity and mortality rates and growing economic burdens. Drug hypersensitivity reactions should be addressed as an important risk factor that threatens the effectiveness of healthcare services.
Aim
Our study aimed to evaluate the knowledge and attitudes of paediatric resident and attending physicians about drug hypersensitivity reactions in paediatric patients.
Material and methods
Paediatric residents and paediatric specialists of our hospital were included in the study between 1 July 2024 and 1 August 2024. The physicians who agreed to participate in the study were asked to fill out questionnaires consisting of 34 questions about demographic information, general information about drug allergies, frequency of encountering drug allergies, recognition and treatment approaches of severe drug reactions, and alternative drug choices in patients with drug allergies, which were formed by using the current literature [9, 10]. The questionnaires were completed face to face.
Statistical analysis
Data analysis of the study was performed with IBM SPSS version 29 software. The data relating to the individual characteristics of the participants were presented as number (n), ratio (%), mean, and standard deviation values. The conformity of numerical variables to normal distribution was evaluated by Kolmogorov-Smirnov and Shapiro-Wilk tests. Correct response rates to knowledge level questions were calculated. The relationships between individual characteristics and total correct response rates and correct response rates in the questions belonging to subcategories were evaluated by Mann-Whitney U and Kruskal-Wallis tests. Corrected p-values were taken into consideration in post-hoc pairwise comparisons. P < 0.05 was accepted as the level of statistical significance.
Results
Eighty-six physicians participated in the study. Of the participants, 70.9% were female and 29.1% were male. The mean age was 30.7 ±4.3 years. 74.4% of the participants were assistant physicians and 25.6% were specialists. In terms of professional experience, 68.6% had 1–5 years of experience, 22.1% had 6–10 years of experience, and 9.3% had more than 11 years of experience. Among the participants, 15.1% (n = 13) stated that they never encountered drug allergy, 43% (n = 37) rarely encountered drug allergy, 34.9% (n = 30) frequently encountered drug allergy, and 6.9% (n = 6) very frequently encountered drug allergy. Table 1 shows the demographic and occupational characteristics of the individuals participating in the study.
Table 1
Individual characteristics
The correct response rate for all questions except demographic characteristics (28 questions) was 71.3 ±14.1%. The correct response rate was 77.6 ±15.5% for drug allergy (12 questions), 61.0 ±29.4% for 4 questions measuring the level of knowledge about severe drug reactions, and 64.5 ±21.7% for findings suggestive of severe drug reactions (9 questions). The correct response rate for alternative drugs (3 questions) was 80.6 ±24.2%. These findings show that the participants had a higher rate of correct answers about drug allergy and alternative drugs in general, but their level of knowledge about severe drug reactions was lower (Table 2).
Table 2
Correct response rates
Table 3 shows the correct response rates to the questions in the study. It can be seen that the correct response rates were higher in the questions evaluating the basic knowledge of the participants about drug allergy compared to the other questions. The most common cause of drug allergy in children was beta-lactam group antibiotics, with a correct response rate of 86.0%. The correct response rate to the question stating that the most common skin finding in drug allergy is maculopapular rash was 91.9%, and the correct response rate to the question that adrenaline should be preferred as the first treatment option in post-drug anaphylaxis was 97.7%. These data show that the participants have a good command of the basic knowledge of drug allergy.
Table 3
Questions and correct answer rates
In the questions examining their knowledge about severe drug reactions, it was found that 89.5% of the participants correctly answered the question that severe reactions such as Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS) may occur after drug intake, 57% correctly answered the question that DRESS syndrome is a type IV hypersensitivity reaction, and 25.6% correctly answered the question that acute generalised exanthematous pustulosis (AGEP) is a type IV hypersensitivity reaction. These rates indicate that the participants may have limited knowledge about the subtypes of severe drug reactions.
In the questions related to clinical findings suggestive of severe drug reactions, 94.2% correctly answered the question about the presence of mucosal lesion as a sign of severe drug reaction. The correct response rate to the question about the sign of skin peeling was 80.2%, and the correct response rate to the finding of eosinophilia was 84.9%. Mucosal involvement, skin peeling, and eosinophilia were associated with a higher rate of severe drug reaction, while other findings (painful skin lesions, purpuric rash, conjunctival involvement, lymphadenopathy, deterioration in liver and kidney function tests) were associated with a lower rate of severe drug reaction.
In the questions related to alternative drug preferences, when asked which antibiotic should be preferred when prescribing to a patient with penicillin allergy, 88.4% gave the correct answer with macrolide group antibiotic, 8.1% preferred cephalosporin, and 3.5% preferred meropenem. In the question about the alternative antibiotic to be preferred in a patient with cephalosporin allergy, the correct response rate was high at 94.2% with the answer macrolide, while a lower correct response was given with answering 55.8% yes to the question that the frequency of reaction with cephalosporin is ten times less frequent than penicillin. The question of which analgesic/antipyretic should not be given to a patient with paracetamol allergy was answered correctly with aspirin by 59.3%. The participants answered nimesulide at 5.8% and ibuprofen at 4.7%. It has been reported that cross-reactive cephalosporin allergy is observed in 10% of patients with penicillin allergy [11]. Therefore, patients with a history of penicillin allergy should be tested before cephalosporin use. However, the correct response rate was 62.8%. In general, it was revealed that the participants had adequate knowledge about drug allergies and alternative drugs, but they lacked knowledge about some subtypes of severe drug reactions (Table 3).
When the responses of specialists and residents were compared, the overall correct response rate of specialists (78.6%) was significantly higher than that of residents (67.9%) (p < 0.001). Similarly, when the knowledge of drug allergy (87.5% and 75.0%, respectively; p = 0.001) and severe drug reaction (75.0% and 50.0%, respectively; p = 0.010) of specialist and resident physicians were compared, the correct response rate of specialist physicians was significantly higher. It was also observed that specialised physicians (77.8%) had a higher correct response rate than resident physicians (55.6%) regarding findings suggestive of severe drug reaction (p = 0.050). Regarding alternative drug preferences, the correct response rate of specialists (100%) was significantly higher than that of residents (66.7%) (p = 0.012) (Table 4).
Table 4
Comparison of correct response rates with individual characteristics
The overall total correct response rate of participants with more than 11 years of experience (82.1%) was significantly higher than that of participants with 1–5 years of experience (67.9%) (p = 0.028). Regarding knowledge of drug allergy, participants with more than 11 years of experience (91.7%) had a significantly higher correct response rate than those with 1–5 years of experience (75.0%) (p = 0.009). However, no significant difference was observed in other question groups according to professional experience (Table 4).
Discussion
Drug hypersensitivity reactions constitute approximately 15% of all drug adverse reactions and are a source of concern for clinicians and patients [5]. In this study, the level of knowledge of paediatric resident and specialist physicians about drug allergy was evaluated. The findings revealed that, in general, physicians had basic knowledge about drug allergy, but they lacked knowledge about the subtypes of severe drug reactions and some clinical findings suggestive of such reactions.
The question about the first treatment option for anaphylaxis developing after drug administration was answered correctly with a rate of 97.7%. In the questionnaire conducted by Gökmirza et al. on drug allergy in intern and resident physicians, 84.7% answered the same question correctly [9]. Drugs are the most common cause of anaphylaxis in hospitalised patients, so it is important to have knowledge about the treatment of life-threatening reactions triggered by drugs [12].
Participants stated that they would refer their patients who reported drug allergy to an allergist with a rate of 88.4%. A history of drug allergy may lead to an increase in healthcare costs. Less than 5% of patients with a history of penicillin allergy have been confirmed to be allergic to penicillin, but physicians usually prefer to prescribe a different class of antibiotics [8, 13–16]. Patients may attribute symptoms not related to viral disease rash or sensitisation to drug allergy.
The question of whether maculopapular rash was the most common skin finding in drug allergy was answered correctly by 91.9%. In the drug allergy questionnaire conducted by Güvenir et al. among family physicians and paediatric residents, this question was answered correctly with a rate of 64.6% [10]. The reason for the higher rate of correct answers in our study may be that paediatric specialist physicians also participated in the questionnaire.
The rate of those who thought that the presence of drug allergy in the parent would increase the possibility of development of drug allergy in the child was 67.4%. Similar to our study, a rate of 73.2% was found in the study by Güvenir et al. [10]. The correct response to the statement ‘drug allergy may persist for life’ was yes, with a rate of 59.3%. Approximately 80% of patients with IgE-mediated penicillin allergy lose their sensitisation after 10 years [1], but drug allergy may persist for life.
In our study, physicians were found to be inadequate in identifying severe drug reactions. Low correct response rates were observed especially in defining hypersensitivity mechanisms of severe reactions including SJS, DRESS syndrome, and AGEP. In the study conducted by Güvenir et al. it was found that participants had a greater lack of the general knowledge and knowledge about the findings of severe drug reactions [10]. These deficiencies indicate that physicians need more training in the recognition and management of such reactions. Although such reactions are rare, they may be life-threatening, and early diagnosis and appropriate management are critical for patient health.
Regarding alternative drug preferences, it was observed that 88.4% of physicians made the correct choice in patients with penicillin allergy. In the study by Güvenir et al. it was found that family physicians and paediatric assistants prescribed macrolides in 95% of patients with penicillin allergy [10]. Beta-lactams are the most commonly used first-line antibiotics worldwide and cephalosporin use has approached penicillin use in recent years [17–19]. It has been previously reported that cross-reactive cephalosporin allergy was observed in 10% of patients allergic to penicillin. The rate of those who responded yes to the statement that the frequency of reaction with cephalosporin is ten times less frequent than penicillin was low, at 55.8%.
Conclusions
This study reveals that residents and specialists working in the field of paediatrics have an adequate level of knowledge about drug allergies in general, but they lack knowledge on specific issues such as severe drug reactions. Our study shows that more training is needed to increase the knowledge of physicians in drug allergy management.