Diagnosis Of Immediate Hypersensitivity Reactions Research Articles

Basophil Activation Test Shows Poor Sensitivity in Immediate Amoxicillin Allergy

In light of the pandemic of spurious penicillin allergy, correct diagnosis of amoxicillin (AX) allergy is of great importance. The diagnosis of immediate hypersensitivity reactions relies on skin tests and specific IgE, and although reliable, these are not absolutely predictive. Therefore, drug challenges are needed in some cases, which contain the risk of severe reactions. Safe invitro diagnostics as an alternative for the drug challenge in the diagnostic workup of AX allergy would be more than welcome to fill this gap. In this respect, the basophil activation test (BAT) has shown potential, but its clinical reliability is doubtful. To investigate the reliability of the BAT to AX and determining its exact place in the diagnostic algorithm of AX allergy. BAT for AX was performed in 70 exposed control individuals and 66 patients diagnosed according to the European Academy of Allergy and Clinical Immunology guidelines for AX allergy. Upregulation of both CD63 and CD203c was flow-cytometrically assessed. Analyses revealed that 1370 μmol/L and 685 μmol/L were the most discriminative stimulation concentrations for CD63 and CD203c upregulation, respectively, and a diagnostic threshold of 9% for positivity for both markers was identified. At these concentrations, sensitivity and specificity for CD63 upregulation were 13% and 100%, respectively, and for CD203c upregulation, 23% and 98%. BAT with dual analysis of CD63 and CD203c is of poor performance to document AX allergy. The sensitivity is too low to let it occupy a prominent role in the diagnostic algorithm.

Algorithm to guide re-exposure to penicillin in allergic pregnant women with syphilis: Efficacy and safety

BackgroundGestational syphilis is underdiagnosed and undertreated, leading to stillbirth, prematurity, low birthweight, neonatal death, and congenital syphilis. Most patients who label as allergic to penicillin are misdiagnosed. ObjectiveTo assess the efficacy and safety of an algorithm to guide re-exposure to penicillin in pregnant women with syphilis and reporting allergy to the antibiotic. MethodsWe performed a prospective study assessing pregnant women with syphilis and labeled as allergic to penicillin. Based on clinical history, patients were divided in two groups: high-risk and low-risk to penicillin allergy. Low-risk patients with negative skin testing and negative serum specific IgE to penicillin underwent drug provocation test. The remaining patients underwent desensitization. ResultsNinety-one patients were enrolled. Allergy to penicillin was confirmed in 7.69% of pregnant women with syphilis and clinical history of allergy to penicillin; in all cases the diagnosis was made through intradermal testing, which predicted 100% of the breakthrough reactions observed during rapid drug desensitization (p < 0.001). Risk stratification based on the initial clinical reaction and skin testing to guide penicillin re-introduction through drug challenge or desensitization was safe (97.8%) and effective (97.8%). ConclusionWe developed and showed the efficacy and safety of an algorithm to guide re-exposure to penicillin in pregnant women with syphilis and labeled as allergic to this drug. Intradermal test is an excellent biomarker in the diagnosis of immediate hypersensitivity reaction to penicillin and to predict breakthrough reaction during rapid drug desensitization. Further studies may confirm the greater safety of the intravenous protocol compared to the oral protocol.

Role of Skin Tests in the Diagnosis of Immediate Hypersensitivity Reactions to Taxanes: Results of a Multicenter Study

Immediate hypersensitivity reactions (HSRs) to taxanes have been increasing in recent years, but the importance of skin tests in allergological workup has not been established. In our study we tried to evaluate the role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and docetaxel. In this multicenter prospective study, we enrolled patients with immediate HSRs to the aforesaid agents. Skin tests were performed on these subjects and if results were negative, intradermal tests with the culprit drug were conducted. Patients with grade 1 reactions subsequently underwent graded challenge; in cases of grade 2 or 3 reactions and/or positive test results, the culprit drug was administered with a desensitization schedule. Skin tests were also performed in 30 control subjects exposed to the taxanes without HSRs. A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel) were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients (69%) developed grade 2 or 3 reactions. Prick test results were negative in all the cases, whereas intradermal test results were positive in 14 patients (10 with paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests significantly correlated with grade 3 reactions and cutaneous involvement during HSRs. Graded challenge was performed in 16 patients without problems and 58 subjects underwent desensitization, which was well tolerated in all but 2 cases. In the control group, skin test results were negative in all the patients. Skin tests for taxanes seem useful and can be performed in the allergological workup of subjects with HSRs to these agents, especially in cases of severe reactions with cutaneous involvement.

Diagnostic Value of Skin Tests and Serum Specific IgE in the Diagnosis of Immediate Hypersensitivity Reactions to Platins

Diagnostic Value of Skin Tests and Serum Specific IgE in the Diagnosis of Immediate Hypersensitivity Reactions to Platins

IgE to penicillins with different specificities can be identified by a multiepitope macromolecule: Bihaptenic penicillin structures and IgE specificities

Quantitation of specific IgE by immunoassay is a recommended in vitro test for the diagnosis of immediate hypersensitivity reactions to betalactams (BLs), particularly when skin test results are negative. IgE antibodies that recognize the common nuclear structure of all BLs or the specific side chain structure can be mainly distinguished by immunoassays. The aim of this study was to develop an immunoassay system to detect IgE antibodies with different specificities. Cellulose discs conjugated with benzylpenicillin (BP), amoxicillin (AX) or both drugs, with poly-l-lysine (PLL) as carrier molecule, were used as solid phases in the radioallergosorbent test (RAST). Direct and inhibition radioimmunoassay studies were made to verify the structures recognized by serum IgE antibodies from penicillin-allergic patients. Our results indicated that the addition of both haptens did not decrease the capacity to capture IgE when serum specific to either BP or AX was used, at least in terms of sensitivity. In addition, the inclusion of two haptens improved significantly the levels of IgE detection in patients who recognized both BP and AX. Therefore, the use of a solid phase with a carrier molecule conjugated with two determinants (AX and BP) is helpful to recognize IgE antibodies against either of these determinants and is useful for screening sera with different specificities.

Cryptococcose disséminée mortelle a Cryptococcus neoformans chez un greffe rénal

Quantitation of specific IgE by immunoassay is a recommended in vitro test for the diagnosis of immediate hypersensitivity reactions to betalactams (BLs), particularly when skin test results are negative. IgE antibodies that recognize the common nuclear structure of all BLs or the specific side chain structure can be mainly distinguished by immunoassays. The aim of this study was to develop an immunoassay system to detect IgE antibodies with different specificities. Cellulose discs conjugated with benzylpenicillin (BP), amoxicillin (AX) or both drugs, with poly-l-lysine (PLL) as carrier molecule, were used as solid phases in the radioallergosorbent test (RAST). Direct and inhibition radioimmunoassay studies were made to verify the structures recognized by serum IgE antibodies from penicillin-allergic patients. Our results indicated that the addition of both haptens did not decrease the capacity to capture IgE when serum specific to either BP or AX was used, at least in terms of sensitivity. In addition, the inclusion of two haptens improved significantly the levels of IgE detection in patients who recognized both BP and AX. Therefore, the use of a solid phase with a carrier molecule conjugated with two determinants (AX and BP) is helpful to recognize IgE antibodies against either of these determinants and is useful for screening sera with different specificities.

IgE To Penicillins With Different Specificities Can Be Identified By a Multiepitope Macromolecule. Bihaptenic Penicillin Structures and IgE Specificities

Quantitation of specific IgE by immunoassay is a recommended in vitro test for the diagnosis of immediate hypersensitivity reactions to betalactams (BLs), particularly when skin test results are negative.IgEantibodiesthatrecognizethe commonnuclear structure ofall BLsor the specificside chain structure can be mainly distinguished by immunoassays. The aim of this study was to develop an immunoassay system to detect IgE antibodies with different specificities. Cellulose discs conjugated with benzylpenicillin (BP), amoxicillin (AX) or both drugs, with poly-L-lysine (PLL) as carrier molecule, were used as solid phases in the radioallergosorbent test (RAST). Direct and inhibition radioimmunoassay studies were made to verify the structures recognized by serum IgE antibodies from penicillin-allergic patients. Our results indicated that the addition of both haptens did not decrease the capacity to capture IgE when serum specific to either BP or AX was used, at least in terms of sensitivity. In addition, the inclusion of two haptens improved significantly the levels of IgE detection in patients who recognized both BP and AX. Therefore, the use of a solid phase with a carrier molecule conjugated with two determinants (AX and BP) is helpful torecognize IgE antibodiesagainst eitherofthese determinantsandisuseful for screening sera with different specificities.

Basophil activation test (BAT) in the diagnosis of immediate hypersensitivity reactions to radiocontrast media

Basophil activation test (BAT) in the diagnosis of immediate hypersensitivity reactions to radiocontrast media

Diagnosis of immediate hypersensitivity reactions to radiocontrast media

No consensus exists on the diagnostic approach for immediate hypersensitivity reactions (IHR) to radiocontrast media (RCM). We analyzed the diagnostic value of a skin test (ST), drug provocation test (DPT) and basophil activation test (BAT) in patients with symptoms compatible with IHR to RCM. Ninety patients with symptoms suggestive of IHR to RCM were evaluated. ST with a panel of RCM was performed, and if negative, DPT was carried out with the culprit RCM. If ST or DPT were positive, tolerance was assessed with an alternative RCM and BAT was carried out with the same panel used for ST. Eight (8.9%) cases were confirmed as having IHR, 5 (62.5%) by ST and 3 (37.5%) by DPT. Five from those confirmed as IHR (62.5%) had a positive BAT. Hypersensitivity to RCM was confirmed in 9%, by ST or DPT. BAT proved a valuable method for diagnosis.

Immunoglobulin E‐mediated hypersensitivity to amoxicillin: in vivo and in vitro comparative studies between an injectable therapeutic compound and a new commercial compound

Skin testing with amoxicillin (AX) is necessary to diagnose immediate hypersensitivity reactions to this β-lactam. A commercial AX (DIA-AX) has recently become available for skin testing. The aim of this study was to compare DIA-AX with the injectable form (INJ-AX) in patients who have well-demonstrated IgE-mediated hypersensitivity to AX. Chemical characterization using high-performance liquid chromatography of both DIA-AX and INJ-AX reagents was performed. Patients diagnosed with an immediate allergic reaction to AX and a positive skin test to INJ-AX (N=55) were re-evaluated within 6 months by performing skin testing with INJ-AX and DIA-AX. Basophil activation test (BAT) and Radioallergosorbent test (RAST) inhibition assay using both reagents were performed in a selected group of patients. The chemical analysis indicated that both DIA-AX and INJ-AX contained an AX compound with a purity above 95%. In the re-evaluation, 53 (96.4%) cases maintained skin test positivity to INJ-AX and were also positive to DIA-AX. Comparison of the papule area between the two reagents showed no significant differences between both reagents. BAT was performed in 30 samples and was positive to both compounds in 15 cases; no patient had a positive result to just one reagent. RAST inhibition studies using three individual cases and a pool of positive sera showed that the percentage inhibition detected with DIA-AX and INJ-AX was parallel and almost exactly the same. This study shows that DIA-AX is equivalent to INJ-AX in terms of skin test response, as well as with in vitro immunochemical and biological tests. DIA-AX can therefore be used in the diagnosis of immediate hypersensitivity reactions.

Hypersensitivity reactions to quinolones

The purpose of this review is to examine in detail the new advances in the pathomechanisms and diagnosis of immediate and nonimmediate hypersensitivity reactions to quinolones, as well as analyze cross-reactivity among different quinolones. Hypersensitivity reactions to quinolones, especially anaphylactic reactions, have become more common in the past decade. This phenomenon could be related to their increased consumption. Although attempts have been made to standardize skin testing, the diagnosis of immediate hypersensitivity reactions to quinolones is mainly based on drug provocation. Some in-vitro, radioimmunoassay and basophil activation tests have also been used for diagnostic purposes, with results indicating that they could be complementary to in-vivo tests. Cross-reactivity seems to exist between first and second-generation quinolones, with lower levels with the third and fourth generations. However, no general rules exist for predicting cross-reactivity and it needs to be analyzed patient by patient. Nonimmediate hypersensitivity reactions also exist, especially maculopapular exanthema and fixed drug eruptions, and a T-cell mechanism has been demonstrated. Over the past decade the number of hypersensitivity reactions to quinolones has increased. These reactions can be severe and diagnosis difficult to confirm. Although new in-vitro tests hold promise, drug provocation testing remains the most frequently used and reliable diagnostic method.

Skin Testing for the Diagnosis of Immediate Hypersensitivity Reaction to Iodinated Contrast Media

Skin Testing for the Diagnosis of Immediate Hypersensitivity Reaction to Iodinated Contrast Media

Diagnostic and predictive value of skin testing in platinum salt hypersensitivity

Hypersensitivity reactions to platinum salts are potentially lethal adverse events in chemotherapy, and often require its discontinuation. Several preventive procedures have been proposed: premedication, desensitization regimens, or replacement with a different platinum salt. We therefore assessed the value of skin tests with platinum salts. A positive result would confirm their responsibility in hypersensitivity reaction, whereas a negative result would identify candidates for continuation of therapy using a different platinum salt. Patch tests, prick tests, and intradermal tests with cisplatin, carboplatin, and oxaliplatin were performed in 21 patients. Skin tests were positive in 14 of 21 cases. Prick tests were positive in 5 cases with the suspected platinum salt. Intradermal tests were positive in 12 of 19 cases, always when the hypersensitivity occurred less than 2 hours after infusion. Cross-reactions were observed in 4 cases. Delayed readings of skin tests at 24 hours and 48 hours were positive in 3 patients. Patch tests were negative in all the 21 patients tested. Replacement with another platinum salt was performed in 13 patients using one that gave a negative skin test. A relapse of symptoms occurred in 1 patient. Intradermal tests are particularly indicated for the diagnosis of immediate hypersensitivity reaction. Their good negative predictive value allows safe retreatment by detecting a potential cross-reaction. The frequency of cross-reactions among cisplatin, carboplatin, and oxaliplatin has not been clearly established. Skin tests allow different platinum salts to be given and avoid discontinuation of chemotherapy.

Immediate hypersensitivity reactions to food antigens detection of human IgE antibodies in vitro and exploration of immunologic mechanisms using the rat mast cell system

Sera from 25 subjects with clear-cut clinical histories of immediate-type hypersensitivity reactions to foods (fish, peanut, chocolate, milk, egg, walnut, and shellfish) were studied with the use of the in vitro rat mast cell system in a series of controlled experiments. Significant rat mast cell alteration was produced by the sera in presence of either the suspected antigen or a preparation of monospecific anti-IgE. No degranulation occurred with unrelated food antigens or with anti-IgG, IgA, or IgM preparations in equivalent concentrations. The rat mast cell results correlated well with the clinical histories and the skin tests, except in 3 patients in whom significant degranulation occurred despite negative skin tests. In one patient no degranulation occurred despite a positive skin test. Specific degranulation was shown to occur as a result of either passive sensitization with reaginic serum or of the possible formation of antigen-antibody complexes. Complement seems to play no role in either mechanism. Heating the reaginic sera at 56° C. for 2 hours to abolish the cell-fixing properties of IgE resulted in the loss of the degranulatiog property of the sera in passive sensitization experiments. This test is proposed as a useful adjunct in the diagnosis of immediate hypersensitivity reactions to foods.