Negative Drug Provocation Tests Research Articles

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 Value of Oral Provocation Tests in Drug Hypersensitivity Reactions Induced by Nonsteroidal Anti-Inflammatory Drugs and Paracetamol.

Oral drug provocation tests (DPT) are the basic diagnostic tool for the detection of hypersensitivity to non-opioid analgesics and for selecting a safe alternative for a patient. They are of great practical importance due to their common use, but the data on the follow-up of patients after negative DPT are still very scarce. We examined the further fate of 164 such adult patients after negative NSAID or paracetamol tests and analyzed which excipients in the studied drugs they could be exposed to after the diagnostic workup. A structured medical interview was performed 32.9 months (mean) after the provocation tests. Of the 164 patients, 131 (79.9%) retook the tested drug and 12 developed another hypersensitivity reaction, giving the estimated negative predictive value of 90.8%. These reactions were induced by acetylsalicylic acid, paracetamol, meloxicam, and diclofenac, and were clinically similar to the initial ones (most commonly urticaria and angioedema). There are 93 generics of these drugs on the local market, containing a total of 33 excipients for which hypersensitivity reactions have been reported. All available generics contain such excipients. Thirty-one patients (20.1%) did not take the previously tested drug again, most often because it was not needed or because they were afraid of another reaction. DPT with analgesics has a high diagnostic performance. A minority of patients had relapsed after reexposure. One of the underestimated reasons for this may be drug excipients provoking a reaction, so it is advisable to use exactly the same medical product that has been negatively tested. Many patients avoid reexposure to a given drug, despite negative tests, therefore very reliable patient education in connection with DPT is highly needed.

Drug allergy evaluation in children with suspected mild antibiotic allergy.

Adverse antibiotic reactions caused by an immunological mechanism are known as allergic reactions. The percentage of reported antibiotic allergies is likely to differ from the one validated after a drug provocation test (DPT) with the culprit antibiotic. This study aimed to compare the percentage of children who were thought to be allergic to a certain antibiotic with those who have a true allergy, as confirmed by DPTs. We also validated Skin Prick Tests (SPTs) and Intradermal Tests (IDTs) by assessing their sensitivity and specificity, in diagnosing antibiotic allergies using DPT as the gold standard. Furthermore, we investigated epidemiological risk factors such as personal and family history of atopic disease and eosinophilia. Children with a history of possible allergic reaction to an antibiotic underwent a diagnostic procedure that included: (1) Eosinophil blood count, (2) SPTs, (3) IDTs and (4) DPTs. The parameters were compared with Pearson's Chi-Square and Fisher's Exact Test. Several risk factors that were found significant in univariate analysis, such as personal and family history of atopic disease, and positive SPTs and IDTs were examined with multiple logistic regression analysis to see if they were related to a higher risk for a positive DPT. Semi-synthetic penicillin was the most common group of antibiotics thought to cause allergic reactions in this study. Overall, 123 children with a personal history of an adverse reaction to a certain antibiotic, were evaluated. In 87.8% of the cases, the symptoms had occurred several hours after administration of the culprit antibiotic. Both SPTs and IDTs had low sensitivity but high specificity. Moreover, they had a high positive predictive value (PPV). In contrast, eosinophilia was not recognized as a risk factor. Seventeen patients (13.8%) had a true antibiotic allergy, as confirmed by a positive DPT. A positive IDT was a strong predictor of a positive DPT, along with a positive personal and family history of atopy. SPTs and IDTs are very reliable in confirming antibiotic allergy when found positive. A negative result of a SPT highly predicts a negative DPT. A positive IDT and a positive personal and family history of atopy were recognized as significant risk factors for antibiotic allergy.

Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) consensus statements for penicillin allergy testing by nonallergists.

IntroductionPenicillin allergy testing has been traditionally performed by allergists, but there remains a huge deficit of specialists. A multidisciplinary effort with nonallergists would be invaluable to overcome the magnitude of penicillin allergy labels via the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). These consensus statements (CSs) offer recommendations and guidance to enable nonallergists to screen for low-risk (LR) patients and perform penicillin allergy testing.MethodsCSs were formulated by the HK-DADI Group using the Delphi method. An agreement was defined as greater than or equal to 80% consensus.ResultsA total of 26 CSs reached consensus after multiple rounds of Delphi. CSs were categorized into risk assessment, skin testing, drug provocation testing (DPT), and post-testing management. For risk assessment, the essentials of allergy history and exclusion criteria were detailed. Patients with only LR features can proceed with testing by nonallergists. Skin tests should be performed prior to DPT. Details regarding the timing, preparation, and interpretation of skin tests were elaborated. DPT remains the gold standard to diagnose genuine allergy or tolerance and should be performed when there is a low pretest probability following negative skin testing. Details of DPT preparations, dosing protocols, and interpretation were elaborated. For post-testing management, inaccurate allergy labels should be delabeled following negative DPT with proper patient counseling.ConclusionCSs support penicillin allergy testing by nonallergists in Hong Kong. LR cases can be managed by nonallergists at Spoke Clinics, with training and support of an allergist-led Hub.

M056 SUSPECTED OCRELIZUMAB-INDUCED IMMEDIATE HYPERSENSITIVITY: NEGATIVE SKIN TESTING AND DRUG PROVOCATION TEST

Ocrelizumab is a monoclonal antibody commonly used in the treatment of multiple sclerosis (MS). Hypersensitivity reactions to ocrelizumab have been reported in up to 5.6 % in non-African American patients. To date, non-irritating skin testing concentrations for ocrelizumab have not yet been established. We present a patient with negative skin testing (ST) and a negative drug provocation test (DPT) to ocrelizumab.

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

Intradermal Testing Identifies 1 in 4 Patients with Nonimmediate Penicillin Allergy

Background: Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr. Methods: Fifty-seven patients with a positive DPT occurring >2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin. Results: In total 25% (n = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (p < 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr. Conclusion: Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.

Prevalence and Impact of Reported Drug Allergies among Rheumatology Patients.

Background: Drug allergies (DA) are immunologically mediated adverse drug reactions and their manifestations depend on a variety of drug- and patient-specific factors. The dysregulated immune system underpinning rheumatological diseases may also lead to an increase in hypersensitivity reactions, including DA. The higher prevalence of reported DA, especially anti-microbials, also restricts the medication repertoire for these already immunocompromised patients. However, few studies have examined the prevalence and impact of reported DA in this group of patients. Methods: Patients with a diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA), or systemic lupus erythematosus (SLE) were recruited from the rheumatology clinics in a tertiary referral hospital between 2018 and 2019. Prevalence and clinical outcomes of reported DA among different rheumatological diseases were calculated and compared to a cohort of hospitalized non-rheumatology patients within the same period. Results: A total of 6081 patients (2541 rheumatology patients: 1286 RA, 759 SpA, and 496 SLE; and 3540 controls) were included. DA was more frequently reported among rheumatology patients compared to controls (23.8% vs. 13.8%, p < 0.01). Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) were the two most commonly reported categories of DA with a prevalence of 12.0% and 5.1%, respectively. Reported antibiotics allergies were more frequent in patients with RA (OR = 1.20, 95% CI = 1.02–1.62, p = 0.03) and SLE (OR = 4.69, 95% CI = 3.69–5.95, p < 0.01); and associated with increased infection-related admissions among rheumatology patients (OR = 1.79, 95% CI = 1.09–2.95, p = 0.02). Among the subgroup of patients referred for allergy testing, 85.7% of beta-lactam antibiotic allergy labels were found to be inaccurate and de-labelled after negative drug provocation testing. Conclusion: The prevalence of reported DA was significantly higher in rheumatology patients. Reported antibiotic allergy was associated with increased rate of infection-related admissions. However, the rate of genuine antibiotic allergy was low. Further studies are needed to guide proper assessment of reported DA and impact of comprehensive allergy testing in this group of patients.

Diagnostic approach to hypersensitivity reactions to iodinated contrast media: a single-center experience on 98 patients

Adverse reactions to iodinated contrast media (ICM) are reported in 1%-3% of diagnostic procedures. They represent a relevant problem involving patients' safety as well as relevant costs for healthcare systems. Premedication with antihistamines and corticosteroids is still widely used, but evidence of its efficacy is lacking and there is a risk for under-estimation of possible severe adverse reactions to ICM in those who undergo premedication. Data from 98 patients with a previous reaction to ICM that consecutively referred to our unit between 2015 and 2018 were retrospectively analyzed. They underwent an allergologic workup comprehending skin tests and drug provocation tests (DPT) with ICM. The skin test showed a very high negative predictive value (NPV) compared to DPT in patients with a previous immediate adverse reaction, while the NPV in patients with a previous delayed adverse reaction was lower. After completion of the allergologic workup, 94 patients (95.9%) could tolerate a DPT with the culprit or alternative ICM. Subsequently, 90 patients were reached by phone to assess if they had been re-exposed to ICM for radiologic procedure. Thirty-nine patients had been re-exposed, without any premedication in 13 cases: 12 of them had tolerated the ICM, while one reacted again despite a negative DPT with the same ICM. Overall, the NPV of this protocol was elevated (92.3%) for patients undergoing DPT and subsequent exposure to the same ICM in a real-life setting. Collaboration between the prescribing physician, the radiologist and the allergist, and an accurate allergologic workup are essential to ensure maximum safety for the patient.

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.

The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children

BackgroundExtending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation. ObjectiveWe aimed to determine the negative predictive value (NPV) of the 5-day extended DPT. MethodsParents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT. ResultsA total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%. ConclusionThe 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.

Opioid Hypersensitivity: Predictors of Allergy and Role of Drug Provocation Testing

True IgE-mediated hypersensitivity to opioids is rare and many reactions are due to direct mast cell degranulation. Opioid drug provocation testing (DPT) is the gold standard for diagnosis but is underutilized. The objective of this study was to evaluate the clinical characteristics and predictors of opioid hypersensitivity, as well as outcomes of opioid DPT. Patients referred for opioid DPT over the past 9 years were studied. Patient characteristics, indications for opioid use, symptoms of index reaction, and outcomes of DPT were analyzed. Association analysis was performed to study variables associated with a diagnosis of opioid hypersensitivity. Of the total of 98 patients referred with suspected opioid hypersensitivity, 15 (15%) were diagnosed with opioid allergy. Angioedema (odds ratio [OR]: 5.66; 95% confidence interval [CI]: 1.49-21.47; P= .011) and hypotension (OR: 5.00; 95% CI: 1.15-21.70; P= .032) were significantly more frequent in opioid allergic patients than those with a negative DPT. Patients who received opioids during anesthesia were significantly more likely to be opioid allergic (OR: 6.74; 95% CI: 2.05-22.13; P= .001). In contrast, a negative association was identified with patients who received opioids for analgesia (OR:0.27; 95% CI: 0.08-0.86; P= .008). Only 15% of our cohort were diagnosed with opioid allergy, emphasizing the importance of DPT in preventing erroneous overdiagnosis. Patients with a history of angioedema or hypotension as their index reaction were significantly more likely to be opioid allergic. DPT are safe when performed by experienced clinicians after risk stratification and using individualized protocols.

Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid

Background: Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help evaluate patients with selective hypersensitivity to CLV. Methods: Eighteen patients with immediate selective hypersensitivity reactions to CLV (positive skin tests to CLV but negative to the major and minor determinants of benzylpenicillin and amoxicillin; negative DPT to benzylpenicillin and amoxicillin) and 21 controls with tolerance to CLV were included. Direct and passive HRT, using patient whole blood or ‘IgE-stripped' donor blood sensitized by patient serum, respectively, were performed by stimulating the blood with CLV, and basophil histamine release was detected by fluorometric determination. Results: The clinical symptoms were anaphylaxis (n = 6), urticaria (n = 9) and urticaria-angioedema (n = 3). The median time interval between the reaction and the study was 225 days (interquartile range, IQR: 120-387.5) and between drug intake and the development of symptoms 30 min (IQR: 6.25-30). We obtained similar data for both the direct and passive HRT, with a sensitivity and specificity of 55 and 85%, respectively, a positive predictive value of 76% and a negative predictive value of 69%. Conclusions: The sensitivity of both the direct and passive HRT for diagnosing patients with immediate allergy to CLV is less than 60%. However, the passive HRT has the advantage that it is based on the testing of serum samples that can be handled more easily than fresh blood samples.

Hypersensitivity reactions to racemic calcium folinate (leucovorin) during FOLFOX and FOLFIRI chemotherapy administrations

Hypersensitivity reactions to racemic calcium folinate (leucovorin) during FOLFOX and FOLFIRI chemotherapy administrations

Negative predictive value of drug provocation tests in children.

The negative predictive value of the drug provocation test is important for both the patient and the physician. However, in children, this predictive value is unresolved. The study included patients who had drug provocation test with a suspected drug and was diagnosed as 'not allergic to the drug'. Three months after allergy workup, the patients were contacted and asked for reexposure to the tested drug. Patients who have reported reactions during reexposure were reevaluated with skin tests and drug provocation. During the study period, 217 provocations were performed to 203 patients. Of these, 163 patients (80.3%) with 175 negative drug provocation tests could be contacted. Ninety-one (52%) of the 175 cases reported to use the tested drug again, and 11 (12%) of these cases declared that they had a new reaction. Two of the eleven cases refused reevaluation. Nine cases were evaluated by drug allergy workup. Two of the nine cases were classified as allergic after retests. Collectively, the negative predictive value was 95.6% (87 of 91 cases) for all drug challenges. The negative predictive value of the drug provocation test is abundant in children; however, negative drug provocation tests do not necessarily predict tolerance for the drug.

Avoidance of nonsteroidal anti-inflammatory drugs after negative provocation tests in urticaria/angioedema reactions: Real-world experience.

Drug provocation tests (DPTs) are the gold standard in diagnosing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity; however, only few data about follow-up of patients with negative DPTs are actually available. The aim of this study was to assess patients' behavior in taking NSAIDs again and to evaluate NSAID tolerability after negative allergological workup. This is a follow-up study involving patients evaluated for history of cutaneous reactions (urticaria and or angioedema) after NSAID intake and with negative DPTs with the suspected NSAID. Patients were asked during a phone interview about the intake of NSAIDs, tolerance, or reasons of avoidance. The negative predictive value (NPV) of NSAIDs DPTs was calculated. One hundred eleven of 142 patients were successfully contacted; 46/111 (41.44%) took the same NSAID previously tested with two adverse reactions reported (4.34%). Fifty-three of 111 (47.74%) patients did not take the same NSAID, but 34 of them took at least another strong cyclooxygenase (COX) 1 inhibitor, with 1 adverse reaction (2.94%) and 19 of them took only weak COX-1 inhibitors. Twelve of 111 patients (10.8%) did not take any NSAID. Reasons for drug avoidance were mainly fear of reactions (70.8%) and no need (29.2%). NPV, overall, was 96.97% (95% confidence interval, 91-99%). Although NSAID hypersensitivity diagnosis was ruled out by oral provocation test, the majority of patients with a history of urticaria/angioedema avoided the intake of the tested NSAIDs for fear of new reactions, particularly when strong COX-1 inhibitor NSAIDs were involved. The high NPV value of DPT resulting from this study should reassure NSAID intake.

Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity?

BackgroundCOX-2 inhibitors are safe alternatives in patients with cross-reactive non-steroidal anti-inflammatory drug (NSAID) hypersensitivity. These drugs are recommended to these patients after negative drug provocation tests (DPTs). However, cumulative data on encouraging results about the safety of COX-2 inhibitors in the majority of these patients bring the idea as to whether a DPT is always mandatory for introducing these drugs in all patients with cross-reactive NSAID hypersensitivity. ObjectiveTo document the safety of COX-2 inhibitors currently available and to check whether or not any factor predicts a positive response. MethodsThis study included the retrospective analysis of cases with cross-reactive NSAID hypersensitivity who underwent DPTs with COX-2 inhibitors in order to find safe alternatives. DPTs were single-blinded and placebo controlled. ResultsThe study group consisted of 309 patients. COX-2 inhibitors were well tolerated in the majority of the patients [nimesulide: 91.9%; meloxicam: 90.2%; rofecoxib: 94.9%; and celecoxib: 94.9%)]. Twenty-five patients (30 provocations) reacted to COX-2 inhibitors. None of the factors were found be associated with positive response. ConclusionOur results suggest to follow the traditional DPT method to introduce COX-2 inhibitors for finding safe alternatives in all patients with cross-reactive NSAID hypersensitivity before prescription as uncertainty of any predictive factor for a positive response continues. However, these tests should be performed in hospital settings in which emergency equipment and experienced personnel are available.

Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy

To confirm allergy to beta-lactam (BL), a basophil activation test in flow cytometry based on CD63 up-regulation was described. CD203c is a more recent basophil activation marker and up to day there is no consensus about which marker is the more sensitive one. CD203c has not yet been evaluated in the diagnosis of BL allergy. The aim of the study was to compare the reliability of CD203c to CD63 for the diagnosis of amoxicillin (AX) allergy, which is nowadays the most frequent BL allergy. Twenty-seven patients with an immediate positive skin test (ST) to AX, 20 had had anaphylaxis with AX and 7 had urticaria and/or angioedema, were compared with 14 controls with no allergy to BL and to six patients with delayed positive ST to AX. In the anaphylaxis group, AX induced up-regulation of CD203c in the basophils of 12 patients out of 20 (60%) and of CD63 in four patients (20%) (P<0.02). Two patients out of seven with urticaria or angioedema had a positive result with CD203c and CD63. In patients who had anaphylaxis, ampicillin (AMP) induced CD203c up-regulation in eight out of 12 (67%) patients tested, and CD63 up-regulation in 4 out of 12 (33%) (all patients who had anaphylaxis could not be tested with AMP). False-positive results were observed with CD203c as well as CD63, and for 10 patients indeed this was confirmed by a negative drug provocation test. The origin of conflicting results between CD63 and CD203c might be at least the targeting of basophils based on anti-IgE labelling. Among IgE(+) gated cells, by means of CD33, a marker of monocytes, a contamination up to 50% by monocytes was detected. In contrast to CD63, CD203c is an activation marker specific of basophils with a basal low-level expression in resting basophils. Thus, IgE and CD203c double targeting of basophils avoids the contamination by monocytes. CD203c seems to be a more sensitive activation marker of basophils than CD63 for the diagnosis of amoxicillin allergy.

β-lactam allergy in clinical practice, relevance of clinical history and/or laboratory test

Rationale Hypersensitivity reactions to β-lactam are common and may be severe, these include immediate (IgE-mediated) and non-immediate reactions. The value of biological test like; basophil degranulation test, in a non-selected population of patients suspected of drug allergy has never been fully established. Methods We randomly studied 35 patients who consulted for a suspected immediate hypersensitivity reaction to β-lactams. Clinical history, skin tests or drug provocation test (DPT) and/or serum specific IgE antibodies were performed to establish the diagnosis of allergy to β-lactam. The Basotest, based upon the expression of CD63 in the presence of specific allergens was evaluated as biological test to confirmed the clinical analysis in this unselected population. 35 β-lactam suspected allergic patients (13 urticaria, 9 macula papular eruption, 7 choc, 3 angioedema), 40 atopic subjects non-allergic to β-lactam were studied. History, provocation test and Basotest, to detect a specific sensitization to β-lactam were studied in all subjects. Results No statistical difference in the basal CD63 expression was observed between basophils of β-lactam allergic patients and those from control subject. In the 35 β-lactam allergic patients, Basotest, was positive in 3 subjects, two with a confirmed allergy (amoxicillin or ceftriaxon) and another one with a negative DPT (ceftriaxon), all control were negative. Conclusion This study does not confirm the data of Sanz et al (Clin Exp Allergy 2002) who used a different method of activation of basophils and analysis method. Thus, the Basotest® cannot be used in patients with immediate hypersensitivity reactions to β-lactams.

Dimensional stability and properties of steels for precision tools: O.Sandberg, O.Hillskog. (Uddeholm Tooling AB, Sweden.)

True IgE-mediated hypersensitivity to opioids is rare and many reactions are due to direct mast cell degranulation. Opioid drug provocation testing (DPT) is the gold standard for diagnosis but is underutilized.The objective of this study was to evaluate the clinical characteristics and predictors of opioid hypersensitivity, as well as outcomes of opioid DPT.Patients referred for opioid DPT over the past 9 years were studied. Patient characteristics, indications for opioid use, symptoms of index reaction, and outcomes of DPT were analyzed. Association analysis was performed to study variables associated with a diagnosis of opioid hypersensitivity.Of the total of 98 patients referred with suspected opioid hypersensitivity, 15 (15%) were diagnosed with opioid allergy. Angioedema (odds ratio [OR]: 5.66; 95% confidence interval [CI]: 1.49-21.47; P = .011) and hypotension (OR: 5.00; 95% CI: 1.15-21.70; P = .032) were significantly more frequent in opioid allergic patients than those with a negative DPT. Patients who received opioids during anesthesia were significantly more likely to be opioid allergic (OR: 6.74; 95% CI: 2.05-22.13; P = .001). In contrast, a negative association was identified with patients who received opioids for analgesia (OR: 0.27; 95% CI: 0.08-0.86; P = .008).Only 15% of our cohort were diagnosed with opioid allergy, emphasizing the importance of DPT in preventing erroneous overdiagnosis. Patients with a history of angioedema or hypotension as their index reaction were significantly more likely to be opioid allergic. DPT are safe when performed by experienced clinicians after risk stratification and using individualized protocols.