Drug Provocation Test Research Articles

Practical Approach to Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Children.

We aimed to assess the real-life prevalence, patient profile, and clinical presentation of drug hypersensitivity to NSAIDs in children after an incidence of an adverse event during treatment, verified by a drug challenge test. We included 56 children, aged 4-18 years, referred to our allergy clinic due to the incidence of adverse reaction during treatment. Skin prick tests and a drug provocation test were performed in all patients. Diagnostics for persistent urticaria were performed. In 56 patients suspected of drug allergy, we proved NSAID hypersensitivity in 17 patients (30.1%). In 84.9% (n = 47) of patients, the clinical manifestations of hypersensitivity revealed angioedema and urticaria. The most common culprit drug among NSAIDs in children was ibuprofen. Thirty-one (55.4%) reactions were immediate, and 25 (44.6%) were delayed or late. Previous history of allergy was a risk factor for NSAID hypersensitivity (p = 0.001). Vitamin D deficiency in the blood serum was a risk factor for NASID hypersensitivity (OR = 5.76 (95% Cl: 1.42-23.41)). Hypersensitivity to NSAIDs is a difficult diagnostic problem in pediatric allergy. The most common manifestation of hypersensitivity to ibuprofen in children is acute urticaria and angioedema. Two important problems in the differential diagnosis are cofactors such as vitamin D levels and viral infections, which require further research.

Retrospective evaluation of children with non-steroidal anti-inflammatory drug allergy

Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs and are among the drug-related hypersensitivity reactions after antibiotics. There are limited studies evaluating nonsteroidal drug reactions in children. In this study, we aimed to evaluate the concomitant atopic diseases, admission clinic, laboratory findings and drug provocation test results of children with a pre-diagnosis of nonsteroidal drug reaction and who underwent allergy tests, retrospectively .
 Methods: In this study, patients who applied to the pediatric allergy outpatient clinic due to nonsteroidal drug reaction were included. In this group of patients, age, gender, fx5 (nutrient mix specific IgE), phadiatop (inhalant allergen mix specific IgE), skin prick tests and drug provocation tests were recorded from their files. Demographic and clinical features of the cases were compared.
 Results: 61 patients with suspected NSAIDs allergy were included in the study. When the admission clinics of the patients were evaluated, 54% (n:33) had urticaria, 22.9% (n:14) had isolated angioedema, 6.5% (n:4) had urticaria angioedema, 14.7% (n:9) had maculopapular eruption . Only 1 patient presented with anaphylaxis. NSAIDs allergy was confirmed in 16.3% (n:10) of the patients.. Single ibuprofen sensitivity was detected in 13.1% of patients (n:8), both paracetamol and ibuprofen sensitivity were detected in 1 patient (1.6%), and single paracetamol sensitivity was detected in 1 patient (1.6%).
 Conclusions: It is usually not easy to detect drug allergies in patients. These patients may usually misdiagnosed as NSAIDs allergy. In our study, it was revealed that drug provocation tests should be performed to confirm the diagnosis in case of suspected NSAIDs allergy.

Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives

Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce. To characterize in detail patients reporting DHRs to APs. We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches. Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P= .005 and P= .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P= .0002 and P= .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required. Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

Removal of incorrect penicillin allergy labels in a UK hospital

ObjectivesPenicillin allergy records are common, often incorrect and are associated with broad spectrum antibiotic use. We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling daily ward round to determine the opportunity for penicillin allergy de-labelling in a UK hospital. MethodsA daily ward round, delivered by antibiotic pharmacists or junior doctors, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined (direct de-label on history alone or after direct drug provocation testing). After successful allergy de-label, the antibiotic was switched to a penicillin antibiotic. ResultsOf 7214 inpatients during the study period, 1133 (15.7%) had a penicillin allergy record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for direct de-label and 73 (25.6%) met criteria eligible for direct drug provocation testing. We were unable to obtain a history for 61 (21.4%) patients. Of 45 low-risk patients eligible for direct de-label, 40 (88.9%) were de-labelled of whom 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for direct drug provocation testing, 16 (21.9%) received direct drug provocation testing, of whom 9 were switched to a penicillin antibiotic. Two direct de-label patients experienced harm (thrush within 5 days and delayed skin reaction after day 5); none of the direct drug provocation testing patients had a reaction by day 5. The switches resulted in reduced alternative antibiotic use by 173 Daily Defined Doses (DDDs). DiscussionPenicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams.

P15 Direct provocation test for penicillin allergy delabelling: a 4-year retrospective review

Abstract Background Penicillin allergy is the most commonly reported drug allergy.1 Over 90% of these are mislabelled1. Labelled penicillin allergy is associated with increased broad-spectrum antibiotic use, increased antibiotic costs, and increased length of admission. A recent meta-analysis of delabelling studies showed that drug provocation test (DPT) is a low-risk procedure in patients with multiple clinical and financial benefits.2 Methods Retrospective analysis of all patients who had DPT in hospital across one health trust 2019–2022. Hospital and GP electronic records of drug allergies were reviewed. GPs of patients who retained an allergy status post-DPT were contacted. Results 46 DPTs were documented during this time. The PENFAST3 score was used to identify those suitable for DPT. One delayed reaction was recorded. No anaphylaxis was recorded. Infectious diseases were the primary specialty for DPT (67%). In total, 78% were carried out on medical patients. ID consult service was responsible for 100% of DPTs in surgical specialties. Seven patients who received DPT had been relabelled penicillin allergic post-DPT. Two were self-reported on presentation to hospital. Five were from physician review of historic documentation in hospital settings. In total, 56% of patients had not had GP documentation regarding allergy status updated. Conclusions This review concludes that DPT is safe in an inpatient population and inpatient review of reported penicillin allergy is an opportunity to identify mislabelled allergy. Infection specialists were the primary teams for DPT however given the safety profile of the DPT non-infection, and allergy specialists should be encouraged to use the protocol. Enhanced communication is needed with GPs to ensure the correct status is known in the community. Relabelling of penicillin allergy is a risk, and further education must be given to patients and healthcare providers post-DPT to ensure continuation of delabelled status.

P09 Non-allergist Removal of Incorrect Penicillin Allergy Labels (RIPAL) in a UK hospital

Abstract Objectives We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling (PADL) daily ward round to determine the opportunity for PADL in a UK hospital. Methods A daily ward round, delivered by either an antibiotic pharmacist or a junior doctor, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy (penA) record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined [de-label on history (DOH) or after direct drug provocation testing (DDPT)]. Following successful de-label, in agreement with the responsible clinician, the antibiotic was switched to a penicillin antibiotic. Results Of 7214 inpatients during the study period, 1133 (15.7%) had a penA record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for DOH, 73 (25.6%) met low-risk criteria eligible for DDPT and we were unable to obtain a history from 62 (21.8%) patients. Of 45 low-risk patients eligible for DOH, 40 (88.9%) were de-labelled of which 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for DOC, 16 (21.9%) received DDPT, of which nine were switched to a penicillin antibiotic to complete their antibiotic course. Two DOH patients experienced harm (thrush within the first 5 days and delayed skin reaction after day 5), none of the DPTs had a reaction by day 5. The switches resulted in 170 DDDs of penicillin use (predominantly amoxicillin) and reduced alternative antibiotic use by 174 DDDs (predominantly meropenem and levofloxacin). Conclusions Penicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams. Further work is required to optimize and streamline these patient pathways to maximize patient and health system benefit.

Gyógyszerallergiák tesztelése az SZTE Bőrgyógyászati és Allergológiai Klinika allergológiai osztályán

The authors present protocols of the options, available panels in drug allergy testing applied at the Department of Dermatology and Allergy, University of Szeged. In suspicion of drug induced hypersensitivity reaction we recommend performing lymphocyte transformation test (LTT), prick testing, intradermal testing and patch testing according to the assumed immune -mechanism. If these examinations are negative, the next step is the drug provocation test, which is the gold standard in the diagnosis of drug allergy. We summarize methods, indications, and the evaluation of each tests. There are increasing patients presenting hypersensitivity reactions who require proper identification of the culprit drug.

Relevance of the diagnosis of hypersensitivity reactions to antineoplastic and biological agents: experience with drug provocation test.

Background. Evidence regarding drug provocation test (DPT) with chemotherapeutic agents is scarce. The aim of our study is to describe the experience of DPT in patients with a history of hypersensitivity reactions (HSRs) to antineoplastic and biological agents. Methods. This was an eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemotherapy who were submitted to DPT. Anamnesis, skin tests (ST) and DPT were analyzed. Patients with a negative DPT were submitted to at least one regular supervised administration (RSA). Patients with positive DPT or HSR during RSA were offered rapid drug desensitization (RDD). Results. A total of 54 patients were submitted to DPT. The most common suspected drugs were platins (n = 36), followed by taxanes (n = 11). Most initial reactions were classified as grade II (n = 39) according to Brown's grading system. ST with platinum (n = 35), taxanes (n = 10) and biological agents (n = 4) were negative, except for one intradermal test with paclitaxel, which was positive. A total of 64 DPTs were performed. Eleven percent of all DPTs were positive (platins (n = 6), doxorubicin (n = 1)). Of the 57 RSA with the culprit drugs, 2 were positive (platins). The diagnosis of hypersensitivity was confirmed by DPT/RSA in 9 patients. All patients with positive DPT/RSA presented HSRs of equal or less severity than the initial one. Conclusions. DPT followed by RSA allowed to exclude HSRs in 45 patients (55 culprit drugs). DPT before desensitization prevents non-hypersensitivity patients from undergoing RDD. In our study DPT was safe, all reactions were managed by an allergist.

Diagnostic utility of basophil CD203c expression in β-lactam allergy

Background: A diagnosis of immunoglobulin E (IgE) mediated reactions to β-lactam (BL) antibiotics is still challenging because of the limited availability of skin-prick test (SPT), and standardization issues, particularly with newer BLs, are still ongoing. Because encouraging data are increasingly emerging in the use of basophil activation tests in the diagnosis of IgE-mediated drug hypersensitivity reactions, in this study, we aimed to determine CD203c expression, a basophil surface marker, in the diagnosis of IgE-mediated hypersensitivity to BL antibiotics. Methods: This study included two groups of subjects. The first group (group 1) (n = 20) included patients with a diagnosis of IgE-mediated allergy to BLs as confirmed through STs or drug provocation tests, and the control group consisted of healthy volunteers (group 2) (n = 24). Expression of CD203c by flow cytometry was studied in samples stimulated by two different concentrations of six different BL antibiotics. A stimulation index ≥ 2 was considered a positive response. Results: The study groups had comparable age and sex distribution. In the entire group, the sensitivity and specificity of CD203c were 29.4% (5 out of 17) and 82.6% (19 out of 23), respectively. When considering the single reactors, two among four patients who were allergic to amoxicillin demonstrated upregulation of CD203c with amoxicillin, which makes 50% sensitivity. The specificity was 100%. Conclusion: Our data demonstrated that assessment of CD203c in the diagnosis of IgE-mediated reactions to BLs provided encouraging results, particularly with amoxicillin allergy. However, this finding needs to be verified in a larger number of cases.

Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs on a pediatric Portuguese cohort.

Background. Non-steroidal anti-inflammatory drugs (NSAID)/analgesics (paracetamol) are among the most common causes of drug hypersensitivity reactions in children, with a reported prevalence of around 0.3% in the pediatric population. Paracetamol and ibuprofen are the most commonly reported culprits in the pediatric population. Our objective was to describe the allergy workup to NSAID/paracetamol of a pediatric population monitored in an allergy outpatient clinic. Methods. Retrospective observational study by consulting the medical records of patients evaluated in a pediatric outpatient clinic with history of NSAID/paracetamol, between January 2016 to August 2022. Results. A total of 43 patients have been evaluated for NSAID/paracetamol suspected allergy: 53.5% females, mean age of 9.8 ± 5.1 years, 47.7% atopic. The drugs reported as culprits were: ibuprofen (75.6%), paracetamol (17.8%), metamizole (4.4%) and naproxen (2.2%) and clinical manifestations were mainly urticaria/angioedema and maculopapular exanthema. Skin tests were performed in 7 patients: paracetamol (n = 5) and metamizole (n = 2), which were all negative. Fourty-six drug provocation tests were performed: 28 with the culprit drug and 18 with an alternative one; only 2 were positive (ibuprofen - culprit NSAID group): one immediate periorbital angioedema and one delayed lip edema with oropharyngeal tightness. Conclusions. The investigation of allergy to NSAID/paracetamol in children remains a challenge. In our population, ibuprofen was the most common NSAID reported. There were only 2 (4.3%) mild reactions on DPT. We could allow the use of the culprit NSAID/analgesic in 11 patients and an alternative one in 9 patients. This study highlights the importance of DPT in children for a correct diagnosis of NSAID hypersensitivity and selection of an alternative drug.

Syncope after COVID-19 Vaccination in a Young Man with Unmasking Brugada Syndrome.

A 23-year-old man with no significant medical history was rushed to a hospital due to transient loss of consciousness with incontinence. The patient had developed a fever after his second dose of COVID-19 vaccine, and the patient was found groaning in bed approximately 40 hours after the vaccination in the early morning. The patient was diagnosed with Brugada syndrome (BrS) based on a drug-provocation test. His father had been diagnosed with BrS and died suddenly at 51 years of age. Young adults with a family history of BrS should be cautioned about fever following COVID-19 vaccination.

Clinical validation of the basophil activation test in immediate hypersensitivity reactions to gadolinium-based contrast agents.

Gadolinium based contrast agents (GBCAs) are safe compounds globally used in magnetic resonance imaging (MRI). However, in last years it has been detected an increase of immediate hypersensitivity reactions (IHRs) to them. Diagnosis of IHRs to GBCAs is based on clinical symptoms, skin tests (STs) and drug provocation test (DPT). But DPTs are not without risks, thus it is important to implement an in vitro alternative method such as the basophil activation test (BAT). We described the clinical validation of the BAT using ROC curves from a control population formed by 40 healthy individuals without previous reactions to any contrast agents and 5 patients suffering from IHRs to GBCAs. Four patients presented IHRs to gadoteric acid (GA) as the culprit agent and another one to gadobutrol (G). Basophil reactivity was measured in percentage of CD63 expression and in stimulation index (SI). The optimal cut-off with the highest sensitivity (S) and specificity (E) for the GA was of 4.6% at 1:100 dilution (S=80% and E=85%; AUC=0.880, p=0.006). For the SI with GA, the cut-off of highest sensitivity and specificity was of 2.79 at 1:100 dilution (S=80% and E=100%; AUC=0.920, p=0.002). Sensitivity did not show differences between STs regarding the BAT (p<0.05). Moreover, the BAT was able to detect one case with IHR to GA which had negative STs. Therefore, the BAT is a useful method in diagnosis of IHRs to GBCAs.

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.

Evaluation of the duration of supervised ambulatory drug provocation tests in children with mild non-immediate reactions to beta-lactams

Evaluation of the duration of supervised ambulatory drug provocation tests in children with mild non-immediate reactions to beta-lactams

Can clarithromycin be used without testing in patients with penicillin allergy?

BackgroundPenicillin hypersensitivity is a common cause of suspected and proven drug allergy and drug-induced anaphylaxis in medical records and causes social and economic burdens. ObjectiveSince the rate of clarithromycin hypersensitivity is low in the general population, we aimed to investigate whether clarithromycin can be prescribed to patients with penicillin allergy without a provocation test. MethodsThe medical records of 186 patients referred to our clinic between 2015 and 2021 with a history of penicillin allergy were evaluated retrospectively. Patients having a history of at least two immediate-type hypersensitivity reactions with penicillin antibiotics or having a history of immediate-type hypersensitivity with penicillin and diagnosed by positive penicillin V/G specific IgE and/or penicillin skin tests were included in the study. Penicillin skin tests were performed according to the manufacturer's instructions. Concentrations of serum specific IgE against phenoxymethylpenicillin (penV) and benzylpenicillin (pen G) were determined using The Phadia CAP System FEIA method. An oral drug provocation test with clarithromycin was performed in all patients. ResultsThe data of 64 patients diagnosed with penicillin allergy and who underwent clarithromycin oral provocation test were analyzed. Oral provocation test with clarithromycin was positive in only two of these patients (3%). These two patients had a history of multidrug hypersensitivity, and one of them also had food and venom allergies. ConclusionWe suggest that clarithromycin can be given without an oral provocation test when an alternative antibiotic is required in patients with penicillin allergy and without multidrug hypersensitivity.

Cardiovascular Changes during Oral Food Challenge and Drug Provocation Test in Children Detected by Noninvasive Hemodynamic Monitoring

The prompt recognition of allergic reactions during oral food and drug challenge (OFC/DPT) in children is crucial. Non-invasive hemodynamic monitoring may help in early detection of the reactions. We sought to describe cardiovascular changes and test their performance in predicting the reaction during OFC/DPT.

Prevalence of beta-lactam hypersensitivity reaction (BL-HSR) by direct drug provocation test (DPT), and the safety of direct DPT for BL-HSR in children: A systematic review and meta-analysis

Direct drug provocation test (DPT) without prior skin testing (ST) has been investigated in children suspected of being at risk for beta-lactam hypersensitivity reaction (BL-HSR). However, no systematic review and meta-analysis has been reported previously. This study aims to investigate the prevalence of BL-HSR by direct DPT, and the safety of direct DPT in children.

Utility And Safety of Drug Provocation Testing in Pediatric Ibuprofen Allergy

There is limited research on the diagnosis and management of Ibuprofen associated reactions in children. The aim of this study was to determine the likelihood of Ibuprofen allergy following a graded oral challenge (GOC).

Roles of exercise treadmill test in the diagnosis &amp; risk stratification of cardiac channelopathies

Channelopathies are the leading causes of SCD in patients without structural heart disease. Missing the diagnosis of high-risk but concealed channelopathies could have lethal clinical consequences. However, the diagnosis of channelopathies is often challenging due to the dynamic clinical presentations and elusive ECG manifestations of these diseases. An integrated approach including clinical assessment, repeated electrocardiography, drug provocation tests, exercise stress test and genetic studies is often required for establishing the diagnosis. Pharmacological provocation tests may have limited sensitivity and may be associated with false positive results. Wide-spread use of genetic studies are limited by low yield, cost-effectiveness and availability issue. Variances of unknown significance could also complicate the interpretation of the genetic screening results. This article reviews the roles of exercise stress test in the diagnosis and risk stratification of patients with Brugada Syndrome, Long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.

Analysis of the Safety of Drug Allergy Workups in a Spanish University Hospital: Drug Characteristics, Type of Reaction, and Patients’ Age at the Initial Assessment

Introduction: The drug provocation test (DPT) is the gold standard for the drug allergy workup; however, it is not free from severe adverse reactions. Our aim was to obtain robust data that predict a reaction during or after the DPT at the first contact with the patient in the allergy outpatient clinic. Methods: The population of this cross-sectional study comprised all patients undergoing a drug allergy workup (clinical assessment, specific IgE, or skin tests, or DPT) at University Hospital Fundacion Alcorcon in 2016. DPTs were performed until therapeutic doses were reached, and late reactions were checked. The clinical disorders assessed in our study were classified mainly as absence of allergic reactions, morbilliform rash, urticaria, anaphylaxis, and other cutaneous disorders. Results: Physicians from the Allergy Unit programmed drug allergy workups in 977 patients (median age, 52 years; women, 64.54%). DPTs were not performed for 165 drugs involved in the reactions. Patients who did not undergo DPT were older than patients who did (positive or negative) (p = 0.0001). Positive DPT results were detected in 6.00% of DPTs performed, and most were for amoxicillin and metamizole (15–25% each). Multinomial logistic regression showed that positive reactions were more probable after DPT if the same clinical disorder was diagnosed at the first visit, including the episodes not considered allergic episodes (OR = 0.2, <0.01), except for anaphylaxis, which favored not performing DPTs (OR = 11, p < 0.001). Conclusion: We conclude that clinical practice in the diagnosis of drug allergy in our Allergy Department is safe, without over-diagnosis.