Influence of Pore Size in Protein G'-Grafted Mesoporous Silica Nanoparticles as a Serum Pretreatment System for In Vitro Allergy Diagnosis.

Particles with the capacity to bind to immunoglobulin G (IgG) can be used for the purification of IgG or to process clinical samples for diagnostic purposes. For in vitro allergy diagnosis, the high IgG levels in serum can interfere with the detection of allergen-specific IgE, the main diagnostic biomarker. Although commercially available, current materials present a low IgG capture capacity at large IgG concentrations or require complex protocols, preventing their use in the clinic. In this work, mesoporous silica nanoparticles are prepared with different pore sizes, to which IgG-binding protein G' is grafted. It is found that for one particular optimal pore size, the IgG capture capacity of the material is greatly enhanced. The capacity of this material to efficiently capture human IgG in a selective way (compared to IgE) is demonstrated in both solutions of known IgG concentrations as well as in complex samples, like serum, from healthy controls and allergic patients using a simple and fast incubation protocol. Interestingly, IgG removal using the best-performing material enhances in vitro IgE detection in sera from patients allergic to amoxicillin. These results highlight the great translation potential of this strategy to the clinic in the context of in vitro allergy diagnosis.

Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study.

BACKGROUND: Amoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE-mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high-risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta-lactams, although controversy exists regarding the best activation marker. We have performed a real-life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs. METHODS: We prospectively evaluated patients with a clinical suspicion of immediate reactions after AX or AX-CLV administration during a 6-year period. The allergological work-up was done following the EAACI recommendations. BAT was performed in all patients using CD63 and CD203c as activation markers. RESULTS: In AX-allergic patients, both activation markers, CD63 and CD203c, showed similar SE values (48.6% and 46.7%, respectively); however, specificity was of 81.1% and 94.6%, respectively, with CD203c showing good positive predictive value and like-hood ratio. In CLV-allergic patients, CD203c showed higher SE (50%) than CD63 (42.9%), maintaining the same value of SP (80%). Combining the results of both markers can slightly increase the sensitivity (51.4% for AX and 54.8% for CLV), although decreasing the specificity (79.7% and 73%, respectively). Interestingly, all patients with an anaphylactic shock showed a positive BAT to CLV using CD203c. CONCLUSIONS: BAT using CD203c showed a good confirmatory power, especially for AX allergy. Placing BAT as a first step in the diagnostic procedure can help reduce the need of performing a complete allergological work-up in 46.6% of patients, diminishing the risk of reinducing allergic reactions.

Drug-induced Anaphylaxis.

Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Many clinical presentations of drug hypersensitivity are complex and take place in the setting of illness and/or polypharmacotherapy. To review the most recent findings in the diagnosis and management of immediate drug hypersensitivity reactions. Studies were selected based on their relevance, originality and date of publication. The understanding of endotypes, biomarkers and phenotypes has improved the categorization of immediate hypersensitivity reactions. In this review, we discussed the short- and long-term management of anaphylaxis with a special focus on in vivo and in vitro diagnostic methods. Moreover, the clinical management of drug-induced anaphylaxis, the role of hidden allergens and the importance of delabeling are discussed. Endophenotyping is crucial to correctly diagnose and treat patients with immediate drug hypersensitivity reactions, preventing future episodes through drug desensitization.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.

Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions.

BACKGROUND: Immediate drug hypersensitivity reactions (IDHRs) to clavulanic acid (CLV) have increased in the last decades due to a higher consumption alongside amoxicillin (AX). Due to its chemical instability, diagnostic procedures to evaluate IDHRs to CLV are difficult, and current in vitro assays do not have an optimal sensitivity. The inclusion of the specific metabolites after CLV degradation, which are efficiently recognised by the immune system, could help to improve sensitivity of in vitro tests. METHODS: Recognition by dendritic cells (DCs) of CLV and the synthetic analogues of two of its hypothesised antigenic determinants (ADs) was evaluated by flow cytometry in 27 allergic patients (AP) and healthy controls (HC). Their ability to trigger the proliferation of T cells was also analysed by flow cytometry. RESULTS: The inclusion of synthetic analogues of CLV ADs, significantly increased the expression of maturation markers on DCs from AP compared to HC. A different recognition pattern could be observed with each AD, and, therefore, the inclusion of both ADs achieves an improved sensitivity. The addition of synthetic ADs analogues increased the proliferative response of CD4+ Th2 compared to the addition of native CLV. The combination of results from both ADs increased the sensitivity of proliferative assays from 19% to 65% with a specificity higher than 90%. CONCLUSIONS: Synthetic ADs from CLV are efficiently recognised by DCs with ability to activate CD4+ Th2 cells from AP. The combination of analogues from both ADs, significantly increased the sensitivity of DC maturation and T-cell proliferation compared to native CLV.

Advances and highlights in T and B cell responses to drug antigens.

The immunological mechanisms involved in drug hypersensitivity reactions (DHRs) are complex, and despite important advances, multiple aspects remain poorly understood. These not fully known aspects are mainly related to the factors that drive towards either a tolerant or a hypersensitivity response and specifically regarding the role of B and T cells. In this review, we focus on recent findings on this knowledge area within the last 2 years. We highlight new evidences of covalent and non-covalent interactions of drug antigen with proteins, as well as the very first characterization of naturally processed flucloxacillin-haptenated human leukocyte antigen (HLA) ligands. Moreover, we have analysed new insights into the identification of risk factors associated with the development of DHRs, such as the role of oxidative metabolism of drugs in the activation of the immune system and the discovery of new associations between DHRs and HLA variants. Finally, evidence of IgG-mediated anaphylaxis in humans and the involvement of specific subpopulations of effector cells associated with different clinical entities are also topics explored in this review. All these recent findings are relevant for the underlying pathology mechanisms and advance the field towards a more precise diagnosis, management and treatment approach for DHRs.

Diagnostic Approach of Hypersensitivity Reactions to Cefazolin in a Large Prospective Cohort.

BACKGROUND: Cefazolin is a common trigger of perioperative anaphylaxis. The diagnostic approach is controversial because the optimal concentration for skin testing is uncertain, drug provocation tests (DPTs) are contraindicated in severe reactions, and in vitro tests are not thoroughly validated. OBJECTIVE: We aimed to characterize a large number of patients reporting cefazolin allergic reactions and to analyze the diagnostic role of in vivo and in vitro tests. METHODS: We prospectively evaluated patients with suspicion for allergic reactions to cefazolin by clinical history, skin tests (STs), and, if negative, DPT. In a subgroup of patients, basophil activation test (BAT) and radioallergosorbent test were done before allergologic workup was performed and the final diagnosis was achieved. RESULTS: We evaluated 184 patients, 76 of whom were confirmed as allergic (41.3%), 90 were nonallergic (48.9%), and 18 were nonconfirmed (9.8%). All patients reporting anaphylactic shock and most reporting anaphylaxis were confirmed to be allergic (P < .001). Forty allergic patients (52.6%) were confirmed by STs, 22 by DPT (28.9%), and 14 by clinical history (18.4%). All subjects manifesting exanthemas and pruritus were nonallergic. The BAT sensitivity was 66.7% when CD63 and CD203c were combined as activation markers. Six of 8 patients with negative STs and positive DPT had a positive BAT. CONCLUSIONS: Patients allergic to cefazolin often reported severe immediate-type reactions. Skin tests enabled a diagnosis in half of patients when using cefazolin at 20 mg/mL. Unfortunately, DPT could not be performed in all patients owing to reaction severity, which makes BAT a promising diagnostic tool. Further research is needed to clarify the underlying mechanisms, especially in severe reactions.

Basophil Activation Test for Allergy Diagnosis.

The basophil activation test (BAT) is a complementary in vitro diagnostic test that can be used in addition to clinical history, skin test (ST), and specific IgE (sIgE) determination in the evaluation of IgE-mediated allergic reactions to food, insect venom, drugs, as well as some forms of chronic urticaria. However, the role of this technique in the diagnostic algorithms is highly variable and not well determined. BAT is based on the determination of basophil response to allergen/drug cross-linking IgE activation through the measurement of activation markers (such as CD63, CD203c) by flow cytometry. This test can be a useful and complementary tool to avoid controlled challenge tests to confirm allergy diagnosis, especially in subjects experiencing severe life-threatening reactions. In general, the performance of BAT should be considered if i) the allergen/drug produces false positive results in ST; ii) there is no allergen/drug source to use for ST or sIgE determination; iii) there is discordance between patient history and ST or sIgE determination; iv) symptoms suggest that ST may result in systemic response; v) before considering a CCT to confirm the culprit allergen/drug. The main limitations of the test are related to non-optimal sensitivity, especially in drug allergy, the need to perform the test no longer than 24 h after sample extraction, and the lack of standardization between laboratories in terms of procedures, concentrations, and cell markers.

Nanoarchitectures for efficient IgE cross-linking on effector cells to study amoxicillin allergy.

BACKGROUND: Amoxicillin (AX) is nowadays the ß-lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non-optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well-precised nanoarchitectures of different lengths. METHOD: We constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600-12,000 Da), end-coupled with polyamidoamine dendrons that were terminally multi-functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody-nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow-derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL-2H3 cells sensitized with polyclonal antibodies from sera of AX-allergic patients. RESULTS: All BiAns were recognized by AX-sIgE. Dose-dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000-12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM. CONCLUSIONS: BiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.

The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition.

The high prevalence of allergy to ß-lactam antibiotics is a worldwide issue. Accuracy of diagnostic methods is important to prove tolerance or allergy, with skin test considered the best validated in vivo method for diagnosing immediate reactions to ß-lactams. Although drug provocation test is the reference standard, it cannot be performed in highly risk reactions or in those with positive skin tests. For skin tests, the inclusion of major and minor determinants of benzylpenicillin (BP) is recommended. Commercial skin test reagents have changed along time, including as minor determinants benzylpenicillin, benzylpenicilloate (BPO), and benzylpenilloate (PO). Major determinants consists of multivalent conjugates of benzylpenicilloyl coupled through amide bond to a carrier polymer, such as penicilloyl-polylysine (PPL) or benzylpenicilloyl-octalysine (BP-OL). The chemical stability of such reagents has influenced the evolution of the composition of the commercial kits, as this requirement is necessary for improving the quality and standardization of the product. In this work, we provide a detailed study of the chemical stability of BP determinants. We observed that those structures suffer from an epimerization process in C-5 at different rates. Butylamine-Benzylpenicilloyl conjugates (5R,6R)-Bu-BPO and (5S,6R)-Bu-BPO were selected as a simple model for mayor determinant to evaluate the role of the different epimers in the immunoreactivity with sera from penicillin-allergic patients. In vitro immunoassays indicate that any change in the chemical structure of the antigenic determinant of BP significantly affects IgE recognition. The inclusion of stereochemically pure compounds or mixtures may have important implications for both the reproducibility and sensitivity of in vivo and in vitro diagnostic tests.

Dendritic cells inclusion and cell-subset assessment improve flow-cytometry-based proliferation test in non-immediate drug hypersensitivity reactions.

BACKGROUND: Lymphocyte transformation test (LTT) has been widely used to evaluate non-immediate drug hypersensitivity reactions (NIDHRs). However, the lack of standardization and the low sensitivity have limited its routine diagnostic use. The drug presentation by dendritic cells (DCs) and the assessment of proliferation on effector cells have shown promising results. Flow-cytometry-based methods can help apply these improvements. We aimed to assess the added value of using drug-primed-DCs and the determination of the proliferative response of different lymphocyte subpopulations in NIDHRs. METHODS: Patients with confirmed NIDHR were evaluated by both conventional (C-LTT) and with drug-primed-DCs LTT (dDC-LTT)analysing the proliferative response in T cells and other effector cell subpopulations by using the fluorescent molecule, carboxyfluorescein diacetate succinimidyl ester (CFSE). RESULTS: The C-LTT showed a significantly lower sensitivity (29.4%) compared with dDC-LTT (61.8%), which was confirmed analysing each particular clinical entity: SJS-TEN (62.5% vs 87.5%), MPE (15% vs 47.4%) and AGEP (33% vs 80%). When including the effector cell subpopulations involved in each clinical entity, CD3+ +CD4+ Th 1 or CD3+ +NK cells in SJS-TEN, CD3+ +CD4+ Th 1+NK cells in MPE and CD3+ +NK cells in AGEP, we could significantly increase the sensitivity of the in vitro test to 100%, 68.4% and 100%, respectively, with an overall sensitivity of 87% and 85% of specificity in NIDHR. CONCLUSIONS: The use of a flow-cytometry-based test, DCs as drug presenting cells, and focusing on effector cell subpopulations for each clinical entity significantly improved the drug-specific proliferative response in NIDHRs with a unique cellular in vitro test.

Advances and novel developments in drug hypersensitivity diagnosis.

A correct diagnosis of drug hypersensitivity reactions (DHRs) is very important for both the patient and health system. However, DHRs diagnosis is complex, time consuming, requires trained personnel, is not standardized for many drugs, involves procedures not exempt of risk, and in most cases lacks standardized in vivo and in vitro tests. Thus, there is an urgent need for improving the different approaches to diagnose patients with suspected DHRs. In this review, we have analyzed the advances performed in immediate and nonimmediate DHRs diagnosis during the last two years and obtained several conclusions: the significant heterogeneity in current practice among centers illustrates the need to re-evaluate, update, and standardize in vivo tests and protocols for the diagnosis and management of patients with suspected drug allergy. Regarding in vitro tests, the latest studies have focused on increasing their sensitivity or on establishing the sensitivity and specificity for the tests performed with new drugs. There seems to be a consensus about combining in vivo and in vitro tests as the best way to increase the diagnostic accuracy.

Early Biomarkers for Severe Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) are typically classified into immediate and delayed reactions based on the time interval between drug exposure and onset of symptoms. Clinical manifestations range from mild to severe and life-threatening reactions. The most severe clinical entities are anaphylaxis and anaphylactic shock for immediate reactions, and severe cutaneous adverse reactions such as Steven Johnson Syndrome and Toxic Epidermal Necrolysis for delayed reactions. The diagnosis is complex and challenging, as drug provocation tests and even skin tests can be very risky procedures, which makes them not recommended. Therefore, it is necessary to search for useful early biomarkers to manage the diagnosis of these reactions. These biomarkers could be useful to determine the clinical entity, but not to identify the culprit drug. Some of the currently available biomarkers are few genetic associations of drug allergy with polymorphisms of human leukocyte antigen (HLA), the detection of inflammatory and lipid mediators in serum, or the detection of cytokines, chemokines, and cytotoxic markers in skin biopsies. In this literature review, it has been summarize the immunological mechanisms involved in severe reactions, both immediate and delayed, and different early biomarkers: those currently used for the diagnosis of these reactions as well as possible early biomarkers that could be useful with further studies to standardize their clinical use.

Recent developments and highlights in drug hypersensitivity.

Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management. Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication. Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs.

Expression of the Tim3-galectin-9 axis is altered in drug-induced maculopapular exanthema.

BACKGROUND: Drug-induced maculopapular exanthemas (MPEs) are mediated by Th1 CD4+ T cells. One of the mechanisms of control of Th1 cells in homeostasis is the interaction between the checkpoint inhibitor Tim3 and its physiological ligand galectin-9 (Gal9). Disorders affecting this axis may be responsible for various autoimmune and immunological diseases. The aim of this study was to determinate the influence of the Tim3-Gal9 axis on the development of MPE induced by drugs. METHODS: Frequencies of different cell subsets and the expression of Tim3 and Gal9 were measured in peripheral blood by flow cytometry and in skin biopsies by immunohistochemistry. Gal9 expression was assessed by RT-qPCR; its release was measured by multiplex assay. The effects of blocking or enhancing the Tim3-Gal9 axis on monocyte-derived dendritic cell (moDC) maturation and T-cell proliferation were determined by flow cytometry. RESULTS: The expression of Tim3 was significantly reduced in peripheral blood Th1 cells and in the skin of MPE patients vs controls. Gal9 expression and release were significantly reduced in patient peripheral blood and moDCs, respectively. The addition of exogenous Gal9 significantly reduced Tim3+ Th1 proliferation, although Treg proliferation increased. CONCLUSION: This study showed the involvement of the Tim3-Gal9 axis in MPE. The reduced expression of Tim3 in Th1 cells together with the impaired expression of Gal9 in PBMCs and DCs appears to have a role in the development of the disease. The potential of Gal9 to suppress Th1 and enhance Treg proliferation makes it a promising tool for treating these reactions.

Identification of an antigenic determinant of clavulanic acid responsible for IgE-mediated reactions.

BACKGROUND: Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin-CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis. METHODS: Based on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD-I (N-protein, 3-oxopropanamide) and AD-II (N-protein, 3-aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches. RESULTS: Two synthetic analogs of AD-I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLV-treated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls. CONCLUSION: We have identified AD-I as one CLV antigenic determinant, which is the drug fragment that remains protein-bound.

Accuracy of the Diagnosis of Allergic Reactions in the Emergency Department.

BACKGROUND AND OBJECTIVE: Suspicion of an acute allergic reaction is a common reason for attending the emergency department (ED). However, there are few comparisons between the initial diagnosis of suspected allergic reaction made in the ED with the definitive diagnosis made subsequently in the allergy department (AD). Objective: To compare details of the initial diagnosis made in the ED relating to allergy with the final diagnosis made in the AD. METHODS: Patients attending the ED of 2 hospitals with suspected allergic reactions were prospectively enrolled based on key words. A certified allergy specialist reviewed the ED records of these patients and, if these were suggestive of an allergic reaction, the patients were scheduled for further evaluation at the allergy clinic. RESULTS: In total, 2000 patients were enrolled between April 2013 and October 2015. Of these, 1333 passed the initial assessment and underwent further evaluation. Of the 1333 patients, 528 underwent an allergological study, and 206 were confirmed as being allergic. With respect to drug allergy, nonsteroidal anti-inflammatory drugs were the most common triggers, followed by ß-lactams; in food allergy, plant-based foods were the most common. Only 16.4% of patients confirmed as having anaphylaxis in the AD were initially diagnosed with the condition in the ED. CONCLUSION: Of the 528 patients who finally underwent the full allergological study, fewer than half were confirmed as allergic. Moreover, anaphylaxis appears to be underdiagnosed in the ED. Better communication between the ED and the AD is necessary to improve the diagnosis and management of these patients.

Accuracy of the diagnosis of allergic reactions in the emergency department

Background: Suspicion of an acute allergic reaction is a common reason for attending the emergency department (ED). However, there are few comparisons between the initial diagnosis of suspected allergic reaction made in the ED with the definitive diagnosis made subsequently in the allergy department (AD).Objective: To compare details of the initial diagnosis made in the ED relating to allergy with the final diagnosis made in the AD. Methods: Patients attending the ED of 2 hospitals with suspected allergic reactions were prospectively enrolled based on key words. A certified allergy specialist reviewed the ED records of these patients and, if these were suggestive of an allergic reaction, the patients were scheduled for further evaluation at the allergy clinic. Results: In total, 2000 patients were enrolled between April 2013 and October 2015. Of these, 1333 passed the initial assessment and underwent further evaluation. Of the 1333 patients, 528 underwent an allergological study, and 206 were confirmed as being allergic. With respect to drug allergy, nonsteroidal anti-inflammatory drugs were the most common triggers, followed by ß-lactams; in food allergy, plant-based foods were the most common. Only 16.4% of patients confirmed as having anaphylaxis in the AD were initially diagnosed with the condition in the ED. Conclusion: Of the 528 patients who finally underwent the full allergological study, fewer than half were confirmed as allergic. Moreover, anaphylaxis appears to be underdiagnosed in the ED. Better communication between the ED and the AD is necessary to improve the diagnosis and management of these patients

Antecedentes: La sospecha de una reacción alérgica aguda es un motivo frecuente de consulta en urgencias. Sin embargo, hay pocos trabajos que comparen el diagnóstico inicial realizado en las unidades de urgencias con el diagnóstico definitivo realizado en las unidades de alergia. Objetivo: Analizar en detalle la sospecha diagnóstica inicial dada en urgencias con el diagnóstico definitivo en las consultas de alergia. Métodos: Estudio prospectivo, que consistió en la selección, en base a palabras claves, de pacientes con sospecha de reacción alérgica. En la fase de screening, se seleccionaron los pacientes en base a las palabras claves, finalmente aquellos pacientes que presentan reacción sugestiva de alergia se seleccionaron para evaluación final. Resultados: Se revisaron 2.000 pacientes entre abril de 2013 y octubre de 2015, de los cuales 1.333 se seleccionaron para la evaluación. Finalmente, 528 se sometieron a un estudio alergológico y 206 se confirmaron como alérgicos. Con respecto a las reacciones por fármacos, los AINE y ß-lactámicos fueron los mayormente implicados; en relación con los alimentos, los de origen vegetal fueron los más frecuentes. Sólo el 16,4% de los pacientes con anafilaxia confirmada tras el estudio de alergia, fueron diagnosticados inicialmente en urgencias. Conclusión: Sólo la mitad de los pacientes que finalizaron en estudio fueron confirmados como alérgicos. Un dato importante es el infradiagnóstico de la anafilaxia en las urgencias. Por ello pensamos que es necesaria una mejor comunicación entre las unidades de urgencias y alergia para mejorar el manejo clínico y terapéutico de estos pacientes