Results Of Drug Provocation Tests Research Articles

The safety of initial single therapeutic dose challenge with a 5-day prolonged drug provocation test in children with a history of low-risk non-immediate reactions to beta-lactam antibiotics.

Background: Although the gold standard for diagnosing beta-lactam antibiotic (BLA) allergy is the drug provocation test (DPT), there is no standardized protocol for children. Objective: We aimed to evaluate the clinical features and DPT results of children with a history of low-risk non-immediate reactions (NIR) to BLA who underwent initial direct single therapeutic dose challenge with a 5-day prolonged DPT. Methods: We retrospectively evaluated children ages 0-18 years with a history of low-risk NIRs to BLAs. On the first day of provocation, a single-dose DPT protocol without any skin test was administered at the clinic. The therapeutic dose was adjusted to not exceed the maximum single-unit dose (MSUD) for age and weight. The DPT protocol was administered with 100% of MSUD. To identify children with delayed reactions, the parents or caregivers were told to continue giving the medication at home for 5 days. Results: One hundred and nine children were included in this study. The median (interquartile range) age of the children was 62.5 months (26.5-94 months). Of the suspected drugs, the main culprit drug was amoxicillin-clavulanic acid for 89 children (81.7%). The most common clinical manifestation was maculopapular exanthema, which occurred in 85 children (78%), and 8 (7.3%) had a positive DPT result. Three children (2.8%) developed a reaction after the first DPT dose. The remaining children continued to use the suspected BLA at home. Five children (4.7%) developed a reaction while using the drug at home. All the children with positive DPT results developed mild cutaneous signs and presented with a reaction to amoxicillin-clavulanic acid. None had a systemic or severe cutaneous reaction. Conclusion: Initial direct single therapeutic dose challenge with a 5-day prolonged DPT is a useful and safe way to assess low-risk NIRs to BLAs in children.

Polyethylene glycol hypersensitivity, patient outcomes in a 7-year retrospective study

BackgroundImmediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited. ObjectiveTo evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported. MethodsA total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed. ResultsPEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H1-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered. ConclusionPEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.

Safety of partial selective COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity and factors affecting safety

Aims: Partial selective COX-2 inhibitors, such as nimesulide, or meloxicam are tolerated by the majority of the patients with cross-reactive NSAID hypersensitivity. This study aimed to obtain more information about the safety of partial selective COX-2 inhibitors; nimesulide and meloxicam in non-immunologic type, cross-reactive NSAID hypersensitivity and to detect risk factors for intolerance to these drugs.
 Methods: This is a retrospective study of patients with suggestive of cross-reactive NSAID hypersensitivity who admitted to our clinic over a period of 10 years. Patients who had a reliable history of immediate type NSAIDs hypersensitivity with at least 2 chemically unrelated class and/or positive ASA provocation test and who underwent alternative drug provocation test with partial selective COX-2 inhibitors (nimesulide and/or meloxicam) were included to study. Patients’ demographics, comorbidities, atopy status, duration of NSAID hypersensitivity, total number of reactions, reaction grades, clinical phenotypes, pulmonary function test parameters and results of alternative drug provocation test results are recorded. Patients with and without reactions during alternative provocation tests with nimesulide and/or meloxicam were compared in terms of these data. 
 Results: A total of 560 patients were included in the study, 378 (67.5%) of them were female. Allergic comorbidities were detected in 394 (72.6%) patients. Asthma, other drug allergies and nasal polyp were the most common comorbidities. Alternative drug provocation test positivity with nimesulide and/or meloxicam was detected in 50 of 560 (8.9%) patients. Provocation test positivity was 33/541 (6.1%) with nimesulide, 30/517 (5.8%) with meloxicam and 13/498 (2.3%) with both nimesulide and meloxicam. Duration of NSAID hypersensitivity was shorter and allergic comorbidities, asthma, nasal polyp and the coexistence of asthma and nasal polyp were more common in patients with a positive provocation test.
 Conclusion: The partial selective COX-2 inhibitors nimesulide and meloxicam are well tolerated alternatives in patients with cross-reactive NSAID hypersensitivity. Hypersensitivity to these drugs is significantly higher in patients with asthma and/or nasal polyp than other group of cross-reactive NSAID hypersensitive patients and also in patients with a shorter duration of NSAID hypersensitivity.

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.

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.

Review of Patients with Immediate-Type Drug Reactions and Test Results: Retrospective Study from the Malatya Province

Aim: Drug hypersensitivity is an important issue encountered by clinicians during clinical practice in Turkey and in the world. Any drug used for diagnosis or treatment has the potential to cause hypersensitivity reactions. The aim of the present study was to review the distribution of drugs reported to cause hypersensitivity reactions and to determine the distribution of tests and test results among patients that presented to the adult allergy and immunology outpatient clinic with immediate-type drug hypersensitivity in the Malatya province. Materials and Methods: The study included adult patients who were admitted with immediate-type drug hypersensitivity (allergic and/or non-allergic) between October 2017 and October 2020 and underwent testing for drugs. Age, sex, atopic diseases (asthma, allergic rhinitis, urticaria, eczema), culprit drug(s), drug reaction types, time of reaction onset, and skin and drug provocation test results were evaluated. Results: Of the 107 patients included, 83 (77.6%) were female and 24 (22.4%) were male. The mean age was 40.74 ± 11.28 years. There was a history of drug hypersensitivity to antibiotics in 44 patients (41.1%) and analgesics in 56 patients (52.3%). Urticaria and/or angioedema were the most common reactions to culprit drugs. Overall, 148 tests for drug hypersensitivity were performed, and the positivity rate was 6.1%. Conclusion: Analgesics and antibiotics were the most common causative agents in patients presenting to allergy outpatient clinics with drug allergy, and reactions occurred even with alternative agents. Thus, patients reporting drug reactions should undergo drug tests before physicians recommend drugs.

Macrolide Allergy in Children and the Negative Predictive Value of Drug Provocation Tests in Mild Index Reactions

ABSTRACT Objective: Macrolide allergy is rarely reported, and there is limited knowledge of hypersensitivity reactions (HRs) in children. The negative predictive value (NPV) of drug provocation tests (DPTs) for macrolides is unresolved. We aim to evaluate the clinical features of macrolide allergy in children, and determine the NPV of macrolide DPTs. Materials and Methods: Pediatric patients who were referred to our allergy department with a suspicion of macrolide allergy were evaluated by DPTs with or without prior skin tests between 2011 and 2020. Characteristics of the HRs and patients, the results of skin and DPTs were recorded. At least three months after evaluation of the patients with allergy work up, telephone interviews were performed. Patients were asked whether they had reused the suspected macrolide or not. Patients who reported HR during subsequent drug intake were invited for reevaluation. Results: A total of 160 children (161 reactions) (55.6% male) with a suspicion of macrolide allergy were enrolled for the study, and all children had a mild index reaction. The median age was 48 (18-102) months, and the median time between the suspected allergic reaction and allergy work-up was 3 (2-8) months. The most frequently reported suspected agent was clarithromycin, in 151 patients (94.4%). Macrolide allergy was confirmed in 8 (5%) patients. Only one patient reported skin eruptions upon reuse despite a negative DPT and he was invited to be reevaluated. A second DPT was performed resulting in urticarial lesions. The NPV was found to be 97.4% for negative DPT with macrolides. Conclusion: Confirmed macrolide allergy is rare in children, and DPTs are the gold standard to assess suspected macrolide allergy. The NPV of macrolide provocation tests seems to be high in children. Keywords: Children, drug hypersensitivity, drug provocation test, macrolide, negative predictive value

Piperacillin-Tazobactam Hypersensitivity: A Large, Multicenter Analysis

Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis. Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity. Retrospective analysis of the demographic characteristics, clinical presentation, investigation, and management of 87 patients presenting to 5 European allergy centers. Patients underwent skin prick and intradermal testing with piperacillin/tazobactam, major (penicilloyl-polylysine) and minor (sodium penilloate) determinants, amoxicillin, benzylpenicillin, flucloxacillin, co-amoxiclav, clavulanic acid, and meropenem with immediate and, where appropriate, delayed reading of tests. Skin test-negative patients underwent drug provocation to piperacillin/tazobactam and/or other penicillins. A multistep protocol was used, depending on risk assessment. Forty-eight of 87 (55%) patients were diagnosed with hypersensitivity to piperacillin/tazobactam with either positive skin or drug provocation test results, of whom 10 (21%) had a diagnosis of cystic fibrosis. Twenty-six (54%) patients presented with immediate and 22 (45%) with nonimmediate hypersensitivity. Patients with cystic fibrosis predominantly presented with nonimmediate hypersensitivity (70%). Reactions were severe in 52% of immediate reactors (Brown's anaphylaxis grade 3) and moderately severe (systemic involvement) in 75% of nonimmediate reactors. The number of patients with negative skin test results tolerating reintroduction was comparable in immediate (80%) and nonimmediate (88%) hypersensitivity. One-third of patients were cross-sensitized to other penicillins. The cross-sensitization pattern raised the possibility of tazobactam allergy in 3 patients. In 21 patients selectively sensitized to piperacillin/tazobactam (12 immediate, 9 nonimmediate), tolerance to other beta-lactams was demonstrated by drug provocation testing. Piperacillin-tazobactam caused immediate and nonimmediate hypersensitivity with similar frequency. Most patients were selectively sensitized and tolerated other penicillins. Some patients may be allergic to the beta-lactamase inhibitor only.

Negative predictive value of provocation tests for nonsteroidal anti-inflammatory drugs in children.

Background: After antibiotics, nonsteroidal anti-inflammatory drugs (NSAID) are one of the leading drug classes responsible for hypersensitivity reactions in children. The drug provocation test (DPT) is the criterion standard for diagnosis. Objective: The aim of the present study was to determine the negative predictive values (NPV) of DPTs with NSAIDs in pediatric patients and to evaluate their attitudes toward NSAID use after a negative DPT result. Methods: The study included all patients who had undergone DPTs between January 1, 2014, and December 31, 2018, in our pediatric allergy clinic for suspected NSAID hypersensitivity reaction and who had a negative result for the suspected agent. Those patients who could be contacted were asked whether the patient had used the same drug again since the DPT and, if so, whether he or she had a reaction. Patients who were reported to have had a reaction were invited to the clinic for reevaluation. Based on the findings from this retesting, the NPVs of the DPTs with NSAIDs were calculated. Results: During the 5-year study period, DPT results were negative for 230 suspected agents in 215 patients. Of these, 143 patients (66.5%) were able to be contacted. A total of 108 patients (75.5%) had used the tested NSAIDs at least once after the provocation test, and five patients (4.6%) reported a reaction on reexposure. Four of these patients declined reevaluation, one patient exhibited no reaction in a second DPT. Therefore, the NPV was calculated as 96.3% (94.3% for ibuprofen, and 100% for paracetamol). Conclusion: The NPVs of DPTs with NSAIDs, especially of paracetamol DPT, is high in children. This finding should reassure the parents of patients who may require NSAID therapy again.

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

BackgroundNonsteroidal 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. ObjectiveTo evaluate the results of drug provocation tests (DPTs) with NSAIDs and to evaluate the difficulties encountered in the classification of NSAID-H in children. MethodsThe 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. ResultsA 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. ConclusionPerforming 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.

Effects of Drug Provocation Test on the Quality of life in Caregivers of Children with Drug Hypersensitivity

An assessment of the quality of life in caregivers of drug hypersensitive children has rarely been considered. Generally, only one-quarter of the children with suspected drug hypersensitivity are confirmed drug allergy by a drug provocation test (DPT). It would be of great benefit to consider implementing a DPT that may help improve the quality of life of the caregivers. This was a prospective study. The subjects were caregivers of children with drug hypersensitivity who underwent a DPT at the Pediatric Allergy Clinic at Songklanagarind Hospital between November 2017 and April 2019. The PSU-Parent-reported Drug Hypersensitivity Quality of Life Questionnaire (PSU-PDrHy-Q) was used to evaluate the quality of life of the caregivers before and at 2 weeks after the children underwent a DPT. Sixty-eight caregivers were recruited into the study. The median age (IQR) was 38.0 (35.0, 44.0) years. The median age (IQR) of the children with drug hypersensitivity was 6.7 (3.3, 10.5) years. Positive DPT results occurred in 17 (25%) children. According to the PSU-PDrHy-Q, the median total scores (IQR) after the DPTs were lower than before the DPTs (32.6 [20.6, 46.5] vs. 48.3 [26.8, 65.5], p < 0.001). The median score for mental health before and after the DPT were 35.7 (18.3, 49.8) and 24.4 (14.5, 36.2) and for social activity were 10.9 (4.6, 17.7) and 9.1 (5.8, 12.6), respectively (p < 0.001). Taking care of children with drug hypersensitivity affected the quality of life of the caregivers. The quality of life improved after the DPT.

Tolerability to paracetamol and preferential COX-2 inhibitors in patients with cross-reactive nonsteroidal anti-inflammatory drugs hypersensitivity.

BackgroundAcetylsalicylic acid/aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used drugs that may cause hypersensitivity reactions in a substantial proportion of patients. Physicians ought to be aware of these situations.ObjectiveWe aimed to present the clinical characteristics and rates of tolerability to cyclooxygenase (COX)-2 inhibitor analgesics in patients who had admitted due to multiple cross-reactive type of NSAID hypersensitivity.MethodsThe files of the patients who had admitted with multiple NSAIDs-induced symptoms were investigated retrospectively. Age, sex, underlying diseases, clinical manifestation, skin test results, and drug provocation test results were analyzed.ResultsIn 105 patients with multiple cross-reactive type of NSAID hypersensitivity, we found the rate of cross-reactivity to any of the relatively safe alternatives including paracetamol, meloxicam, and nimesulide to be 16.1%. The rate of cross-reactivity to these relatively safe drugs was significantly higher in patients with a history of anaphylaxis induced by NSAID intake (p = 0.006).ConclusionThe diagnosis of COX-1-mediated multiple NSAID hypersensitivity can be often established with a detailed history. Although rare, severe hypersensitivity reactions may be observed in these patients. Undesired situations for both patients and physicians may be avoided by testing relatively safe paracetamol and COX-2 inhibitors in experienced centers.

Prospective Assessment of Diagnostic Tests for Pediatric Penicillin Allergy: From Clinical History to Challenge Tests

To determine the efficacy of available diagnostic tools in penicillin allergy relative to the results of drug provocation tests (DPTs).The population included 732 children ≤14 years of age presenting to participating allergy departments who reported an adverse drug reaction with benzylpenicillin (penicillin G), phenoxymethyl penicillin (penicillin V), amoxicillin-clavulanic acid, or cloxacillin. Patients with a history of severe skin conditions during the index reaction (IR), presence of skin disease not allowing skin testing, and/or any condition for which epinephrine use was contraindicated were excluded.This was a multicenter study (38 allergists from 23 centers) across Spanish allergy departments (from the Spanish Society of Allergy and Clinical Immunology). After a detailed history, IRs were classified as immediate (symptoms within 1 hour of the first dose) or nonimmediate. Researchers then classified reactions as a “clear-positive” case, “doubtful” case, or a “clear-negative” case to assess accuracy of clinical history alone. Then, every patient underwent a uniform protocol of skin tests (skin prick test and intradermal test), serum-specific immunoglobulin E (IgE) tests, and then, regardless of the results of these tests, DPTs.Of the 732 participants who completed the study, 35 (4.8%) were diagnosed with a penicillin allergy at the end of the tests: 6 (17% of the patients with a penicillin allergy) with immediate reactions and 29 (83%) with nonimmediate reactions. A family history of drug allergy was associated with a higher risk of penicillin allergy (odds ratio: 2.56). Amoxicillin alone or with clavulanic acid was the most frequent trigger. The most frequently reported symptom was an exanthema and was more commonly associated with nonimmediate IR (58.4% vs 30% in immediate IR). Urticaria was next most common, associated more with an immediate IR (55.5% vs 37.6% of nonimmediate IRs). Thirty-one cases (4.2%) were classified as clear positive on the basis of history alone, 518 were classified (70.8%) as clear negative, and 183 (25%) were classified as doubtful. One of the clear-positive cases turned out to be a true penicillin allergy on the basis of DPTs. Twenty-three of the cases initially classified as clear negative and 12 of the doubtful cases turned out to be a true allergy. Only 1 positive skin prick test result was recorded for benzylpenicilloyl polylysine, and none were recorded for the other tests. Few had positive intradermal test results. Overall skin testing had low sensitivity (0% to 20%) and high specificity (97% to 100%) for skin testing. For serum-specific IgE, sensitivity was low (2.9% to 17%), but specificity was high (94.4% to 99.9%).Currently available diagnostic methods (clinical history, skin testing, and serum-specific IgE) performed poorly compared with DPT. DPTs performed in specialized centers should be used as the first diagnostic tool to evaluate children with mild to moderate penicillin IRs when anaphylaxis and severe skin syndromes have been excluded.With the knowledge that most adults labeled as penicillin allergic are not and a push to confirm the diagnosis, the allergist is performing more penicillin allergy evaluations. With regards to a pediatric population, this study shows the need for DPTs to best evaluate children labeled as penicillin allergic, despite the logistic difficulties in performing this diagnostic test.

Efficacy and Safety of 5-Day Challenge for the Evaluation of Nonsevere Amoxicillin Allergy in Children

To determine if the use of a 5-day challenge with amoxicillin would not only be safe but also lead to an increase in future amoxicillin use in nonallergic patients compared with a single-dose graded drug provocation.The population included 130 consecutive children <18 years of age referred to the allergy unit with a history of amoxicillin or amoxicillin and clavulanate. Children with life-threatening reactions or severe non–immunoglobulin E–mediated reactions were excluded. A total of 57.7% presented with a maculopapular rash, 35.4% presented with hives.Initial evaluation included skin testing done in a blinded fashion and a graded drug provocation test (DPT) with 45 mg/kg amoxicillin in 3 steps (1/100, 1/10, and full dose) at 30-minute intervals, independent of skin test results. Patients with negative single-dose DPT results were sent home with a 4-day course of amoxicillin. Phone follow-up was done 2 years later.A total of 2.3% had an immediate reaction during the single-dose DPT, and all were mild. Three of the remaining 127 patients had a confirmed nonimmediate reaction during the 4-day challenge (1 on the second day, 1 on the third day, and 1 3 days after completion). All 3 reactions were a mild, isolated maculopapular rash. Three patients had equivocal reactions that were determined to be negative with reassessment. At 2 years, 65.8% had used antibiotics again, and 89.3% had used amoxicillin. Three patients (4.5%) had a mild delayed cutaneous reaction with later use of amoxicillin. In a previous study using a single-dose provocation, 18.3% of patients had refusal to use amoxicillin again compared with 1.3% of the current study.Five-day oral challenge with amoxicillin is safe and effective and greatly increases the compliance with future use of penicillin antibiotics.It is important to note that the majority of patients in the study presented with a maculopapular rash, which is usually not an immunoglobulin E–mediated reaction. In this largely low-risk population, DPT with a single-dose regimen would be safe without skin testing, and a subsequent 5-day challenge in those that passed the single-dose challenge is safe (with a small number of minor reactions) and does increase the chance that patients would be willing to use this class of antibiotics in the future.

Prospective Assessment of Diagnostic Tests for Pediatric Penicillin Allergy, From Clinical History to Challenge Tests

MD Ibanez, PR del Rio, EM Lasa. Ann Allergy Asthma Immunol. 2018;121(2):235–244.e3 To determine the efficacy of available diagnostic tools in penicillin allergy relative to the results of drug provocation tests (DPTs). The tools used for comparison were clinical history, skin testing (skin prick and ID), and specific immunoglobulin E (sIgE) to penicillin and its determinants. Included were 732 consecutive children ≤14 years of age who presented to 1 of multiple allergy departments and reported an adverse drug reaction to penicillin G, penicillin V, Amoxicillin Clavulanate, or Cloxacillin. Twenty-three allergy centers participated. A uniform protocol was used at all centers and included a clinical history (after which the clinical researcher was asked, in their expert opinion if this as a clear-positive, doubtful, or clear-negative case of allergy), skin prick …

Retrospective Analysis of Skin and Drug Provocation Test Results of Children with Suspected Betalactam Allergy

Retrospective Analysis of Skin and Drug Provocation Test Results of Children with Suspected Betalactam Allergy

Frequency of selective immediate responders to aminopenicillins and cephalosporins in Turkish children.

Beta-lactam antibiotics (BLA) are the most commonly prescribed antibiotics and are responsible for the majority of immediate hypersensitivity reactions to drugs in children. Cross-reactivity is important in hypersensitivity to BLAs because these drugs all share a common beta-lactam structure and some share similar side chains. The aim of this study was to evaluate the clinical characteristics of patients who are diagnosed with immediate-type BLA hypersensitivity and frequency of patients with side chain hypersensitivity, "selective responders." The study included patients who were diagnosed with immediate-type BLA hypersensitivity between January 2011 and May 2016 in a pediatric allergy outpatient clinic. The patients who had negative penicillin test (minor determinant mixture, benzylpenicilloylpoly-L-lysine, penicillin G) results and could tolerate penicillin V and/or BLAs with dissimilar side chains but had positive skin and/or provocation test results with the suspected drug were diagnosed as selective responders. During the study period, 357 patients (55.2% girls) were admitted to our clinic with suspected immediate-type BLA hypersensitivity. Parents of 11 patients did not give consent for an allergy workup with the suspected drug. Forty-five of the patients were diagnosed (45/346 [13%]) based on skin test or drug provocation test results. The most common susceptible agent was amoxicillin-clavulanate. Of the patients, 71.4% with a reaction to sulbactam-ampicillin /or amoxicillin-clavulanate and 93.7% with a reaction to cephalosporin were classified as selective responders. Among children with immediate BLA hypersensitivity, selective responders constituted an important group. Most of the patients with reactions to aminopenicillin and cephalosporins safely tolerated penicillin V and BLAs with dissimilar side chains after negative allergy workup results.

Evaluation of drug provocation tests in Korean children: a single center experience.

Drug provocation tests (DPTs) are difficult to perform in clinical practice, even though they are the gold standard for the diagnosis of adverse drug reactions (ADRs). The aims of this study were to evaluate the common causative drugs of type B ADRs and to analyze the relationships between host factors and the results of DPTs in Korean children. We retrospectively reviewed the medical records of all children younger than 19 years of age who underwent a DPT between November 1994 and November 2014. Open provocation tests were performed with non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, aminopenicillins, cephalosporins, non-β-lactam antibiotics, antiepileptic drugs, or other drugs. Overall, 84 DPTs were performed in 56 patients whose median age was 7.5 years (range, 6 months to 18 years). DPTs were positive in 25 (29.8%) of 84 cases, which translated to 18 (32.1%) positive findings in 56 patients. Drugs that provided positive results included NSAIDs (7 cases, 28.0%), aminopenicillins (5 cases, 20.0%), acetaminophen (4 cases, 16.0%), cephalosporins (3 cases, 12.0%), and non-β-lactams (2 cases, 8.0%). Anaphylaxis was noted in 5 (20.0%) of 25 cases. There were no serious complications of DPTs in any of the subjects. The median age was 10.5 years for children who had a positive result following the DPT and 5.0 years for those with negative results (P value = 0.019). DPTs can be performed safely in children with suspected ADRs in order to achieve a correct diagnosis.

Provocation proven drug allergy in Thai children with adverse drug reactions.

Adverse drug reactions (ADRs) are a common healthcare problem. The drug provocation test (DPT) is a gold standard for ADR diagnosis. To evaluate a correlation between history of ADRs, skin prick test (SPT), intradermal test (ID) and DPT in Thai children. This was a retrospective review of 211 children under 16 years of age who had a history of ADRs and underwent DPT from January 2006 to December 2012. Two hundred and thirty six (236) DPTs were performed in 211 children with a history of ADRs. The median age at which DPTs were performed was 4 years. Thirty-four children (14.4%) had positive DPT. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, likelihood ratio (LR) + and LR- of SPT were 50, 85.7, 6.9, 98.8%, 5.8 and 0.9, respectively. The PPV, NPV, sensitivity, specificity, LR+ and LR- of ID were 33.3, 84.6, 20, 91.7%, 2.4 and 0.9, respectively. Different presentation of symptoms (maculopapular rashes, urticaria, angioedema and anaphylaxis) did not predict SPT, ID and DPT results. Positive human immunodeficiency virus (HIV), but not atopy, was a risk in the present scope of evaluation for drug allergy (odds ratio 11.44, 95% confidence interval 2.60-50.41). Drug allergy, denoted by positive DPT, was present in 14.4% of Thai children with a history of ADRs. Antibiotics were the most common cause of ADRs. Both SPT and ID had high NPV and specificity but did not predict DPT results. HIV positivity is a risk factor of drug allergy in Thai children.

Hypersensitivity to betalactam antibiotics: a three years characterization of an Immunoallergy Outpatients' Hospital

Methods Retrospective analysis of clinical files and results of skin testing and DPT (drug provocation tests) from January 2011 to December 2013. All patients were studied according to standardized diagnostic procedures of ENDA/EAACI: serum sIgE (specific IgE) (ImmunoCAP, ThermoFisher) to penicillin G/V, amoxicillin and ampicillin; skin prick and IDT (intradermal tests) to PPL/MD (DAP, Diater), penicillin G, amoxicillin and cefuroxime with immediate and delayed reading. Other penicillin derivatives/cephalosporins were tested if they were the culprit drug. DPT with culprit drug was performed if previous investigation was negative. In confirmed cases an alternative BL was tested.