Quantification Of Specific IgE Research Articles

Relationship between IgE Levels Specific for Ragweed Pollen Extract, Amb a 1 and Cross-Reactive Allergen Molecules

Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization.

An ultra-sensitive homologous chemiluminescence immunoassay to tackle penicillin allergy

Penicillin is one of the most widely used antibiotics to treat bacterial infections in clinical practice. The antibiotic undergoes degradation under physiological conditions to produce reactive compounds that in vivo bind self-proteins. These conjugates might elicit an immune response and trigger allergic reactions challenging to diagnose due to the complex immunogenicity. Penicillin allergy delabeling initiatives are now part of antibiotic stewardship programs and include the use of invasive and risky in vivo tests. Instead, the in vitro quantification of specific IgE is highly useful to confirm immediate allergy to penicillins. However, discrepant results associated with the low sensitivity and accuracy of penicillin allergy in vitro tests have limited their routine diagnostic use for delabeling purposes. We aimed to develop a homologous chemiluminescence-based immunochemical method for the reliable determination of specific IgE to penicillin G, using unprecedented synthetic human-like standards. The synthetic standard targets the major antigenic determinant of penicillin G and the paratope of Omalizumab, acting as human-like specific IgE. It is a potent calibrator, highly stable, easy, and inexpensive to produce, overcoming the limitations of the pooled human serum preparations. The developed method achieved a good agreement and strong positive relationship, reaching a detection limit below 0.1 IU mL−1 and excellent reproducibility (RSD <9%). The clinical sensitivity of the assay significantly increased (66%), doubling the accuracy of the reference method with an overall specificity of 100%. The new diagnostic strategy compares favorably with results obtained by the standard procedure, paving the way towards the standardization of penicillin allergy testing, and enhancing the detection sensitivity of specific IgE in serum to tackle reliably β-lactam allergy delabeling.

Reliability of Early and Late Testing for Suspected Perioperative Hypersensitivity

The optimal timing of diagnostic testing for perioperative hypersensitivity (POH) remains unknown. It has been recommended that investigation is best carried out at least 4 to 6 weeks after the event. On the other hand, guidelines discourage the use of invitro tests later than 3 years after the index reaction. This retrospective study aimed to assess the reliability of early and late skin tests (STs). It also attempted to verify whether discouraging late exvivo and invitro tests is substantiated. For the first aim, patients were stratified over three epochs: an early timing group, with investigations performed within 6 weeks; a recommended timing group, with tests performed between 6 weeks and 6 months; and a late timing group, tested later than 6 months after the event. For the second study purpose, we studied the reliability of specific IgE quantification and basophil activation test rocuronium within 6 weeks and after 3 years in patients who experienced an ST-proven POH to rocuronium. A total of 677 patients were included. Based on a positive ST result, a causative agent was found in 74.2% of the early timing group, 62.6% of the recommended timing group, and 50% of the late timing group. A positive specific IgE for rocuronium or morphine was found in 80% of patients tested within 6 weeks, 63% of patients tested between 6 weeks and 3 years, and 50% of patients tested more than 3 years after the event. A positive basophil activation test was found in 83.3%, 51%, and 20%, respectively, of patients. Our data confirm that evaluation of drug allergy for suspected POH can be performed before 6 weeks after the event, and there is no maximal upper time limit disclosing exvivo and invitro testing.

Multiplexed analytical approaches to beta-lactam allergy in vitro testing standardization

The suspicion of beta-lactam allergy directly contributes to the prescription of antibiotics that diverge from the guidelines, increasing antimicrobial resistance, one of the biggest threats to global health. In vitro quantification of specific IgE is very useful for monitoring allergy, as it confirms or rules out immediate beta-lactam drug allergy and helps find safe alternative antibiotic stewardship. However, reliable in vitro quantification of specific IgE to beta-lactam antibiotics by immunoassay is challenging because of the difficulty of having selective immunoreagents, mainly beta-lactam antigens, and its low concentration levels in serum. Thus, reliable and sensitive in vitro tests for multiplex detection of allergy to different beta-lactam antibiotics is currently essential for clinical diagnosis. Nevertheless, the lack of standardization of quantitative in vitro methods makes the comparison and interpretation of the results difficult. Here, as proof of concept, we report an improved multiplex microimmunoassay for beta-lactam allergy in vitro testing standardization. The results revealed that homologous calibration allows reliable quantification of specific IgE in human serum at very low concentrations (144 ng L−1). Moreover, the reproducibility of the results increases 2-fold using an internal standard, achieving accurate quantitative information: 93% and 106% recovery for penicillin and amoxicillin, respectively. We simultaneously evaluated the reliability of the improved multiplexed in vitro method in a cohort of 40 human serum samples and achieved excellent agreement (0.99) with a currently used in vitro test.

Multiparametric Highly Sensitive Chemiluminescence Immunoassay for Quantification of β-Lactam-Specific Immunoglobulin E.

β-lactams (BLCs) are the most widely used antibiotics and consequently the most common cause of drug allergy in the world. The diagnosis of drug allergy is complex and represents a serious challenge that includes a wide variety of methods. In vitro tests are based on the immunological determination of allergen-specific IgE, but the tests in the market lack the required sensitivity and specificity. In addition, the large sample volume, long incubation times, and single-plex configuration have brought their use into question to complement the clinical information. Here, we report a chemiluminescence immunoassay (CLIA) for multiparametric quantification of specific IgE to penicillin G, penicillin V, amoxicillin, and piperacillin, using histone H1 as a carrier. The developed CLIA allowed the determination of BLC-specific IgE below 0.1 IU/mL, thus allowing identification of allergic patients with better sensitivity, using only 25 μL of a sample (serum). The immunoassay was successfully applied in a cohort of 140 human serum samples, showing good sensitivity (64.6%) as well as specificity (100%), which significantly improve the predictive character of existing BLC-allergy in vitro tests.

Accuracy of penicillin allergy diagnostic tests: A systematic review and meta-analysis

Having a penicillin allergy label associates with a higher risk for antibiotic resistance and increased health care use. We sought to assess the accuracy of skin tests and specific IgE quantification in the diagnostic evaluation of patients reporting a penicillin/β-lactam allergy. We performed a systematic review and diagnostic accuracy meta-analysis, searching on MEDLINE, Scopus, and Web of Science. We included studies conducted in patients reporting a penicillin allergy and in whom skin tests and/or specific IgE quantification were performed and compared with drug challenge results. We quantitatively assessed the accuracy of diagnostic tests with bivariate random-effects meta-analyses. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. Studies' quality was evaluated using QUADAS-2 criteria. We included 105 primary studies, assessing 31,761 participants. Twenty-seven studies were assessed by bivariate meta-analysis. Skin tests had a summary sensitivity of 30.7% (95% CI, 18.9%-45.9%) and a specificity of 96.8% (95% CI, 94.2%-98.3%), with a partial area under the summary receiver-operating characteristic curve of 0.686 (I2= 38.2%). Similar results were observed for subanalyses restricted to patients reporting nonimmediate maculopapular exanthema or urticaria/angioedema. Specific IgE had a summary sensitivity of 19.3% (95% CI, 12.0%-29.4%) and a specificity of 97.4% (95% CI, 95.2%-98.6%), with a partial area under the summary receiver-operating characteristic curve of 0.420 (I2= 8.5%). Projected predictive values mainly reflect the low frequency of true penicillin allergy. Skin tests and specific IgE quantification appear to have low sensitivity and high specificity. Because current evidence is insufficient for assessing the role of these tests in stratifying patients for delabeling, we identified key requirements needed for future studies.

Rocuronium Hypersensitivity: Does Off-Target Occupation of the MRGPRX2 Receptor Play a Role?

The neuromuscular blocking agent (NMBA) rocuronium is a relevant cause of perioperative hypersensitivity (POH) with a significant risk of diagnostic error. Recently, it has been suggested to reclassify hypersensitivity to NMBA as type A reactions resulting from off-target occupation of the nonimmune MRGPRX2 receptor. To investigate whether basophil activation experiments can benefit diagnosis and add to the insights in the pathomechanisms of rocuronium hypersensitivity. A total of 140 patients with a suspected POH to rocuronium in whom peak tryptase was available had complete diagnostic workup for all potential culprits including triple confirmatory testing with skin tests, basophil activation test (BAT), and quantification of specific IgE (sIgE) antibodies to rocuronium and morphine. To further analyze the clinical relevance of sIgE antibodies, quantitative basophil inhibition experiments were performed by coincubation of the cells with rocuronium and morphine, an opiate known to harbor a substituted ammonium structure. Diagnosis of rocuronium hypersensitivity was established in 72 of 140 patients (51.4%), of whom 65 (90.3%) demonstrated mast cell activation. Of the 72 patients, 64 displayed a positive skin test, 8 (11.1%) had their diagnosis documented only by BAT. Coincubation of morphine and rocuronium induced a dose-dependent inhibition of BAT with rocuronium that was restricted to 4 of 6 patients with IgE reactivity to rocuronium and/or morphine. BAT can benefit diagnosis of rocuronium hypersensitivity. As basophils barely express MRGPRX2 and BAT rocuronium can be inhibited by morphine, we believe that hypersensitivity to rocuronium still mainly results from IgE/high-affinity receptor for sIgE (FcεRI)-dependent effector cell activation. However, it cannot be excluded that in a few patients rocuronium hypersensitivity results from off-target occupation of the MRGPRX2 receptor.

The diagnostic usefulness of the basophil activation test (BAT) with annexin V in an allergy to Alternaria alternata.

The basophil activation test (BAT) is an effective diagnostic tool in mold allergy, which is still not sufficiently known. The aim of our study was to assess the degree of annexin V binding to the surface of the basophil cell membrane after stimulation with anti-immunoglobulin E (anti-IgE) and Alternaria alternata allergenic extract. Alternaria alternata allergic patients (n = 32) and healthy volunteers (n = 33) were evaluated using skin prick tests (SPT), quantification of specific IgE (sIgE) and the BAT. Basophil activation was detected as a percentage degree of annexin V binding to the surface of the basophil cell membrane. Receiver operating characteristic (ROC) curve analysis yielded a threshold value of 4.95% of activated basophils when the tested group and control group were studied, with a sensitivity and specificity of 100% (area under curve [AUC] = 1; p = 0.00000) for 100 SBU/mL Alternaria alternata allergen extract. The threshold value was 10.28% with a sensitivity of 93.8% and specificity of 100% (AUC = 0.98958; p = 0.00000) for 10 SBU/mL mold extract, and 9.37% with a sensitivity of 90.3% and specificity of 100% (AUC = 0.96307; p = 0.00000) for 1 SBU/mL Alternaria alternata allergen extract. The method was least efficacious in antiIgE stimulation, where the threshold value was 5.48% with a sensitivity of 90.6% and specificity of 30.3% (AUC = 0.46780; p = 0.67039). The BAT with annexin V and sIgE measurement against Alternaria alternata increase the capability of a diagnostic laboratory for detecting mold sensitization. Both methods may certainly replace SPT, which are currently routinely used in allergy diagnosis. Annexin V may be considered a new basophil activation marker with an efficacy comparable to that of CD63 or CD203c.

In Vitro Diagnosis of Immediate Drug Hypersensitivity During Anesthesia: A Review of the Literature

Quantification of specific IgE (sIgE) antibodies constitutes an important measure to document anesthesia-related immediate hypersensitivity reactions (IHRs). However, only a few drug-specific assays are available and their predictive value is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from cellular tests such as basophil mediator release tests and basophil activation tests (BATs). To review the potential and limitations of quantification of sIgE, mediator release, and BAT in anesthesia-related IHRs, a literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE antibodies, leukotrienes, histamine, and tryptase; this was complemented by the authors' experience. The drugs and compounds that have predominantly been studied are neuromuscular blocking agents (NMBAs), β-lactams, latex, and chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to 92% and 92% to 100%, respectively. For sIgE β-lactams, sensitivity varies between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex, and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea components constitute reliable diagnostics. For drugs, the sensitivity of BAT varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator release tests seem to be abandoned and supplanted by BATs.

Allergen component analysis as a tool in the diagnosis of occupational allergy.

Rapid developments have been seen in molecular allergy diagnosis, based on the detection and quantification of specific IgE to single allergens. This review summarizes and discusses studies on allergen component analysis as a tool in the diagnosis of occupational allergy. More than 400 agents are identified as sensitizers of occupational asthma, but only very few are characterized on the molecular level and available for routine diagnosis. Baker's asthma is one of the most frequently occurring forms of occupational asthma caused by workplace-related inhalation of cereal flour mainly wheat. Wheat sensitization profiles of bakers show great interindividual variability and no wheat allergen could be classified as the major allergen. Component-resolved diagnosis is a useful tool for diagnosing natural rubber latex (NRL) allergy. In cases with unexpected high-latex IgE but without clinical symptoms application of crossreactive carbohydrate determinants are helpful to clarify the cause of IgE binding. Latex is an excellent model for component-resolved diagnosis and demonstrates well how to improve the diagnosis by using single allergens. For diagnosis of baker's asthma, a whole wheat extract is still the best option for specific IgE determination, but single wheat allergens might help to discriminate between wheat-induced food allergy, grass-pollen allergy, and baker's asthma. New diagnostic tools and platforms are promising, but further knowledge of molecules relevant for occupational asthma (as in wood dust allergens, enzymes, laboratory animal allergens, etc.) and for occupational hypersensitivity pneumonitis is necessary to improve and standardize the diagnostic tools.

Basophil Activation Test in IgE-Mediated Food Allergy: Should We Follow the Flow?

IgE-mediated food allergy constitutes an important and increasing health issue with significant impairment of quality of life and significant morbidity and mortality. It affects children, as well as adolescents, and adults. Correct diagnosis of food allergy relies upon history supplemented by quantification of specific IgE (sIgE) antibodies and/or skin tests. Unfortunately, as these tests do not demonstrate absolute predictive values, controlled oral provocation tests might be needed to confirm/exclude diagnosis. However, it is unlikely oral challenges to enter mainstream application, mainly because of obvious ethical reasons. Therefore, correct diagnosis of food allergy might benefit from novel in vitro diagnostics such as allergen component-based sIgE assays and flow cytometric quantification of in vitro activated basophils. As a matter of fact, these tests might prove to be particularly helpful in discriminating genuine allergy from merely sensitization. Furthermore, they might be useful in establishing individual risk profiles, predicting persistence of allergy, and facilitating therapeutic approach. This review focuses on the applications and limitations of the basophil activation test in IgE-mediated food allergy. Anno 2016 we believe that the utility and usefulness of basophil-activation experiments need to be reevaluated thoroughly, in view of difficulties inherent to the correct preparation and storage of allergen extracts, optimizing and standardizing stimulation conditions, and also the potential of alternative diagnostics such as component resolved diagnosis that are becoming more readily accessible.

Molecular allergens and tear investigation

AbstractTears immunological investigations are limited in routine practice because of the small volume of fluid collected. Only few tests can be performed in tears: Total IgE, screening test or specific IgE to aeroallergen to confirm allergic sensitization. Inflammatory mediators in lachrymal fluid are only measured for a research purpose. During the last decade, an increasing number of specific IgE to molecular allergens became available for routine use. Molecular allergens largely contributed to an improvement of allergy diagnosis by distinguishing between true sensitization and cross‐reactivity and a better indication of allergen immunotherapy in polysensitized patients. However, each of these single tests needs 50‐100 µl of serum. More recently, allergen arrayed biochip technology became routinely available (ImmunoCAP ISAC) enabling the quantification of specific IgE against 112 allergens, using only 30 µl of serum. The allergen biochip technology seems to be a promising tool to assess local synthesis of IgE in tears in case of suspicion of allergy and the negativity of both skin prick tests and serum specific IgE. Large‐scale studies are needed to confirm the usefulness of this tool for tears testing in allergic conjunctivitis.

State of the Art and Perspectives in Food Allergy (Part I): Diagnosis

IgE-mediated food allergy is a major and increasing health issue with significant impairment of quality of life and significant morbidity and mortality. It affects children, as well as adolescents and adults. This review focuses on novelties in the diagnosis of food allergy. Correct diagnosis relies upon history supplemented by quantification of specific IgE (sIgE) antibodies and/or skin tests. Unfortunately, as these tests do not demonstrate absolute predictive values, controlled oral provocation tests are needed to confirm/exclude diagnosis. To a certain extent, novel in vitro diagnostics in the form of allergen component-based sIgE assays and flow-assisted quantification of in vitro activated basophils might help to discriminate between genuine allergy and merely sensitization. Furthermore they make it possible to establish individual risk profiles, to predict persistence of allergy, and facilitate therapeutic approach.

Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens

The majority of fish-allergic patients are sensitized to parvalbumin, known to be the cause of important IgE cross-reactivity among fish species. Little is known about the importance of fish allergens other than parvalbumin. The aim of this study was to characterize hitherto undefined fish allergens in three commonly consumed fish species, cod, salmon and tuna, and to evaluate their importance for in vitro IgE-diagnosis in addition to parvalbumin and fish gelatin. Sixty-two patients were diagnosed by clinical history, skin prick tests and specific IgE to fish extracts. Two new fish allergens from cod, salmon and tuna were identified by microsequencing. These proteins were characterized by immunoblot, ELISA and mediator release assay. Purified parvalbumin, enolase, aldolase and fish gelatin were used for quantification of specific IgE in ELISA. Parvalbumin and two other allergens of 50 and 40kDa were detected in IgE-immunoblots of cod, salmon and tuna extracts by most patient sera. The 50 and 40kDa proteins were identified as beta-enolase and fructose-bisphosphate aldolase A respectively. Both purified enzymes showed allergenic activity in the mediator release assay. Indeed, 72.6% of the patients were sensitized to parvalbumin, 20% of these had specific IgE to salmon parvalbumin only. IgE to enolases were found in 62.9% (0.5-95.0kUA /L), to aldolases in 50.0% (0.4-26.0 kUA /L) and to fish gelatin in 19.3% (0.4-20.0kUA /L) of the patients. Inter-species cross-reactivity, even though limited, was found for enolases and aldolases by IgE-inhibition ELISA. Fish enolase and aldolase have been identified as important new fish allergens. In fish allergy diagnosis, IgE to enolase and aldolase are especially relevant when IgE to parvalbumin are absent.

SENSITIZATION TO THE MAMMALIAN OLIGOSACCHARIDE GALACTOSE-ALPHA-1,3- GALACTOSE (ALPHA-GAL): EXPERIENCE IN A FLEMISH CASE SERIES

Background. Recent observations have disclosed that the galactose-α(1,3)-galactose (α-gal) moiety of non-primate glycoproteins can constitute a target for meat allergy.Objective. To describe adults with allergic reactions to mammalian meat, dairy products and gelatin. To investigate whether patients could demonstrate sensitization to activated recombinant human coagulation factor VII ectapog alpha that is produced in baby hamster kidney cells.Methods. Ten adults with mammalian meat, dairy products and gelatin allergies were examined using quantification of specific IgE and/or skin prick test for red meat, milk, milk components, gelatin, cetuximab and eptacog alpha.Results. Most patients demonstrate quite typical clinical histories and serological profiles, with anti-α-gal titers varying from less than 1% to over 25% of total serum IgE. All patients demonstrate negative sIgE for gelatin, except the patient with a genuine gelatin allergy. All patients also demonstrated a negative sIgE to recombinant milk components casein, lactalbumin and lactoglobulin. Specific IgE to eptacog was positive in 5 out of the 9 patients sensitized to α-gal and none of the 10 control individuals.Conclusion. This series confirms the importance of the α-gal carbohydrate moiety as a potential target for allergy to mammalian meat, dairy products and gelatin (oral, topical or parenteral) in a Flemish population of meat allergic adults. It also confirms in vitro tests to mammalian meat generally to be more reliable than mammalian meat skin tests, but that diagnosis can benefit from skin testing with cetuximab. Specific IgE to gelatin is far too insensitive to diagnose α-gal related gelatin allergy. IgE binding studies indicate a potential risk of α-gal-containing human recombinant proteins produced in mammalians.

IgE‐mediated allergy to pholcodine and cross‐reactivity to neuromuscular blocking agents: Lessons from flow cytometry

Immunoglubulin E antibody-mediated allergic reactions to opioids are rare and difficult to document correctly. Assessment of the basophil activation test in the diagnosis of IgE-mediated allergy to the antitussive pholcodine and associated sensitizations to neuromuscular blocking agents (NMBA). Three patients with a suspected IgE-mediated allergy to pholcodine were investigated using skin tests, quantification of specific IgE, and flow cytometric activation of basophils. Flow cytometric activation of basophils, with simultaneous analysis of CD63 appearance and median histamine content per cell, is the only technique capable to correctly document pholcodine allergy. The negative predictive value of basophil activation tests might help to elucidate on the controversial putative cross-reactivity between pholcodine and NMBA.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

The in vitro diagnosis of drug allergy: status and perspectives

Adverse drug reactions (ADR) can result from immune-mediated (drug allergy) and nonimmune-mediated mechanisms. In both types of reaction, conclusive diagnosis and appropriate management remain major problems in daily clinical practice. This review summarizes the potentials and shortcomings of the currently available in vitro tests in the diagnosis of immediate (mostly IgE mediated) and nonimmediate (mostly T-cell mediated) drug allergy, particularly quantification of specific IgE, flow-assisted analysis of in vitro activated lymphocytes and basophils and the enzyme-linked immunosorbent spot.

Allergy to rocuronium: from clinical suspicion to correct diagnosis

Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error. To assess skin testing, quantification of specific IgE (sIgE) and flow-assisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy. This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests. The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 92-99%), 97% (CI 95%: 88-100%) and 83% (CI 95%: 74-89%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 86-99%), 75% (CI 95%: 67-75%) and 72% (CI 95%: 58-83%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients. Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result. Optimal assessment of cross-reactivity between rocuronium and vecuronium implies both skin testing and BAT.

Allergy To Rocuronium: From Clinical Suspicion To Correct Diagnosis

Background: Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error. Objective: To assess skin testing, quantification of specific IgE (sIgE) and flowassisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy. Methods: This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests. Results: The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 92–99%), 97% (CI 95%: 88–100%) and 83% (CI 95%: 74–89%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 86–99%), 75% (CI 95%: 67–75%) and 72% (CI 95%: 58–83%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients. Conclusion: Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result. Optimal assessment of cross-reactivity between rocuronium and vecuronium implies both skin testing and BAT.