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Luis A Pérez de Llano,1,&ast; Borja G Cosío,2,&ast; Ignacio Lobato Astiárraga,3 Gregorio Soto Campos,4 Miguel Ángel Tejedor Alonso,5 Nuria Marina Malanda,6 Alicia Padilla Galo,7 Isabel Urrutia Landa,8 Francisco J Michel de la Rosa,9 Ismael García-Moguel10 On behalf of the Reslizumab Real-Life Spanish Group1Pneumology Service, Hospital Lucus Augusti, Lugo, Spain; 2Pneumology Service, Hospital Universitario Son Espases-IdISBa-Ciberes, Palma de Mallorca, Spain; 3Pneumology Service, Complejo Asistencial de Ávila, Ávila, Spain; 4Pneumology and Allergy Unit, University Hospital of Jerez, Jerez de la Frontera, Cádiz, Spain; 5Allergy Unit, Hospital Universitario Fundación Alcorcón, Madrid, Spain; 6Pneumology Service, Hospital Universitario de Cruces, Barakaldo, Bizkaia, Spain; 7Pneumology Service, Hospital Costa del Sol, Marbella, Málaga, Spain; 8Respiratory Department, Galdakao Hospital, Galdakao, Bizkaia, Spain; 9Pneumology Service, Hospital Universitario Donostia, San Sebastian, Spain; 10Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spain&ast;These authors contributed equally to this workCorrespondence: Borja G CosíoDepartment of Respiratory Medicine, Hospital Universitario Son ESPASES-IDISBA, Palma de Mallorca, SpainEmail borja.cosio@ssib.esBackground: Reslizumab is an anti-interleukin 5 monoclonal antibody that has demonstrated to reduce the risk of severe exacerbations and to improve symptoms, lung function, and quality of life in randomized controlled trials that included patients with severe eosinophilic uncontrolled asthma (SEUA) and a history of severe exacerbations.Objective: The aim of the present study was to evaluate the effectiveness of add-on reslizumab in a cohort of patients with SEUA under real-life conditions.Methods: This was a multi-centre, retrospective, real-life study that included subjects with SEUA treated with reslizumab in 44 asthma units throughout Spain. Eligible patients were those who had received at least one dose of reslizumab as part of normal clinical practice. The primary endpoint was complete asthma control at 52 weeks, defined as absence of severe exacerbations, ACT ≥ 20 and no maintenance oral corticosteroids (OCS). Demographic, clinical, and functional data were collected at baseline (T0), after four to six months (T1); after 12 months (T2) and beyond 12 months of therapy (T3).Results: Treatment with reslizumab achieved complete asthma control in 40% of the 208 included SEUA patients and led to a significant reduction in exacerbations (from 3.0; IQR: 2.0– 4.0 at V0 to 0.0; IQR: 0.0– 0.0 at V2), maintenance OCS use (from 54.8% (95% CI: 48.0– 61.6 at T0 to 18.5% (95% CI: 12.5– 24.5 at T2) and a meaningful improvement in symptoms in the entire treated population: ACT increased from 12.8 ± 4.5 at V0 to 20.0 ± 5.1 at V2 (p < 0.001). Most of the improvement achieved at 12 months was obtained at 4– 6 months. The retention (continuation) rate of reslizumab was 75% through 2 years (95CI%: 1.9– 2.1). Overall, reslizumab showed an adequate safety profile.Conclusion: Reslizumab is an effective therapy for SEUA with adequate safety profile in real-life conditions.Keywords: eosinophilic asthma, reslizumab, asthma control, monoclonal antibodies

Cow's milk allergy can result in anaphylactic reactions. The estimated prevalence of cow's milk allergy in developed countries ranges from 0.5% to 3% at age 1 year. Our objective was to perform a systematic review and, if possible, a meta-analysis to assess the frequency of fatal and recurrent anaphylaxis induced by cow's milk. We searched PubMed/MEDLINE, EMBASE, and the Web of Science for studies that had assessed fatal and recurrent anaphylaxis induced by cow's milk for the population of a country or at least an administrative region. Our review included cohort, cross-sectional, and registry studies that had assessed the incidence or prevalence of recurrent anaphylaxis or the incidence of fatal anaphylaxis due to cow's milk. The pooled prevalence of recurrence (PR) for at least an episode of anaphylaxis was 26.98% (3.85-189.1). Teymourpour et al (Iran) reported the highest PR (53.10%); the two studies with the lowest PR were from France (5.2 and 0.42, respectively) (p < .01). Nine studies on fatal anaphylaxis were selected (41 deaths) and found to be highly heterogeneous (I 2  = 75.9%). Levy et al and Bassagio et al reported the highest incidence rate (IR 0.15 and 0.6 deaths per million persons-year). The PR of anaphylaxis was approximately one quarter of patients with anaphylaxis due to cow's milk, while deaths from anaphylaxis caused by cow's milk were very rare, although some studies report rates as high as 15 times the lowest IR., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: The drug provocation test (DPT) is the gold standard for the drug allergy workup; however, it is not free from severe adverse reactions. Our aim was to obtain robust data that predict a reaction during or after the DPT at the first contact with the patient in the allergy outpatient clinic., Methods: The population of this cross-sectional study comprised all patients undergoing a drug allergy workup (clinical assessment, specific IgE, or skin tests, or DPT) at University Hospital Fundacion Alcorcon in 2016. DPTs were performed until therapeutic doses were reached, and late reactions were checked. The clinical disorders assessed in our study were classified mainly as absence of allergic reactions, morbilliform rash, urticaria, anaphylaxis, and other cutaneous disorders., Results: Physicians from the Allergy Unit programmed drug allergy workups in 977 patients (median age, 52 years; women, 64.54%). DPTs were not performed for 165 drugs involved in the reactions. Patients who did not undergo DPT were older than patients who did (positive or negative) (p = 0.0001). Positive DPT results were detected in 6.00% of DPTs performed, and most were for amoxicillin and metamizole (15-25% each). Multinomial logistic regression showed that positive reactions were more probable after DPT if the same clinical disorder was diagnosed at the first visit, including the episodes not considered allergic episodes (OR = 0.2, <0.01), except for anaphylaxis, which favored not performing DPTs (OR = 11, p < 0.001)., Conclusion: We conclude that clinical practice in the diagnosis of drug allergy in our Allergy Department is safe, without over-diagnosis., (© 2023 S. Karger AG, Basel.)

Introduction: The drug allergy alert system reduces the frequency of adverse drug events, although it is subjected to collateral effects, since 80-90% of alerts are not real, and a large percentage of alerts are overridden (46.2-96.2%). We reviewed how the alert system is used at University Hospital Fundación Alcorcon (HUFA)., Methods: Data were obtained from the drug allergy alert and the alert overriding notification forms (both in the period 2011-20). We also recorded drug allergy diagnoses at HUFA, drug consumption in primary care in 2016. We calculated the incidence of drug allergy alert activation, temporal trends in use, and correlations between the number of drugs in several datasets., Results: We collected 15,535 alerts. NSAIDs and penicillins were the drugs with the highest number of drug allergy alerts (36.55% and 26.91%, respectively). A correlation was found between the number of drug alerts and the type of drug allergy in HUFA in 2016. Only 6.83% of the alerts were removed, and, of these, 21.77% were reactivated. Approximately 100 overrides were recorded per year from 2016 (6.8% of 8,434 activated alerts during 2014-2020)., Conclusions: The number of drug allergy alerts recorded via the drug allergy alert system of HUFA correlates with the distribution of drug allergy diagnoses in the hospital, although many of the alerts could be false positives (as per current published evidence). We detected a very low frequency of removed alerts (6.83%), a relevant frequency of reactivations (one quarter), and a very low frequency of overrides (6.8%)., (© 2023 S. Karger AG, Basel.)

Background: Penicillin allergy is a common problem in the management of infectious diseases. The aim of this study was to determine the impact of penicillin allergy on length of hospital stay (LOHS) among hospitalized adult patients and on in-hospital mortality at a national level., Methods: A retrospective cohort study of adult patients discharged from the Spanish Hospital System between 2006 and 2015 was conducted using the Minimum Basic Data Set (MBDS). We compared LOHS and in-hospital mortality of adult patients whose records contained penicillin allergy code V14.0 (International Classification of Diseases, Ninth Revision, Clinical Modification) as a secondary diagnosis, with a random sample without such a code., Results: We identified 981,291 admissions with code V14.0, which corresponded to 2.63% of all hospitalizations. Adults patients with a penicillin allergy label were significantly older than patients without such a label, with a median of 70 years (interquartile range [IQR]: 51-80) versus 63 years (IQR: 40-77). The proportion of women and the prevalence of infectious diseases were higher in the group with a penicillin allergy label (61.40% vs. 53.84%; 34.04% vs. 30.01%; respectively). We found a higher median Elixhauser-Van Walraven score in hospitalized patients with an allergy label. The median LOHS for hospitalizations with a penicillin allergy label (5 [IQR: 2-9]) was significantly longer than that in those without such a label (4 [IQR: 2-9]). Multivariate analysis showed an increase in LOHS due to the penicillin allergy label (odds ratio [OR] [95% confidence interval [CI]: 1.061 [1.057-1.065]) and a decrease in mortality in penicillin allergy records (OR [95% CI]: 0.834 [0.825-0.844])., Conclusion: In our study, the prevalence of a penicillin allergy label in hospitalized patients, using the MBDS, is low. Hospitalizations with an allergy label was associated with a longer LOHS. However, penicillin-allergic patients did not show higher mortality rates. Inaccurate reporting of penicillin allergies may have an impact on healthcare resources., (© 2021 S. Karger AG, Basel.)

Forensic series on fatal anaphylaxis are scarce, probably because the diagnosis of anaphylaxis is often complex and the incidence is low. We report on the medicolegal, demographic and histopathological characteristics of a series of sudden deaths which were investigated for anaphylaxis at the Spanish National Institute of Toxicology and Forensic Sciences (INTCF) over a 17-year period (1998-2015). A total of 122 undetermined sudden deaths from a high percentage of Spanish regions (81.5% of the total population) were sent to the INTCF with anaphylaxis as the suspected cause of death for histological, biochemical, and medicolegal investigation. Two certified allergists confirmed that 46 of the 122 cases were fatal anaphylaxis. The results indicated a median age of 51 years (IQR = 29) and a male predominance (76%). The main causes of anaphylaxis were drugs (41%), hymenoptera stings (33%), and food (13%). A previous allergic event had been reported in both food anaphylaxis (67%) and drug anaphylaxis (53%). The deaths occurred in health care settings (37%), at home (22%), and outside the home (26.09%). Histopathology data were available for 40 individuals. The most frequent autopsy findings were angioedema of the upper airways (50%), pulmonary edema (47.5%), atheromatosis of coronary vessels (32.5%), and pulmonary congestion (27.5%). Our findings for fatal anaphylaxis indicated a predominance of men, older age (≥50 years) and death in a health care setting (one-third of cases). Previous episodes had occurred in two-thirds of cases of food-induced anaphylaxis and in half of the cases of drug-induced anaphylaxis.

Background: Beta-blockers (BBs) and angiotensin-converting enzyme inhibitors (ACEIs) have been associated with an increased risk and severity of anaphylaxis. However, the evidence supporting these findings is contradictory., Objective: We carried out a systematic review and meta-analysis of studies that assess the influence of BBs and ACEIs on anaphylaxis., Methods: We searched PubMed/MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Web of Science for relevant observational studies. We searched for studies where the presence and severity of anaphylaxis were compared between patients taking BBs, ACEIs, both types of drug, or neither type of drug. We performed a meta-analysis using a random-effects model., Results: A total of 21 studies met the study criteria. Of these, 15 assessed the severity and 9 the incidence of anaphylaxis. The studies brought together 22,313 anaphylaxis episodes for the severity studies and 18,101 anaphylaxis episodes for the studies of new cases of anaphylaxis. BBs and ACEIs increased the severity of anaphylaxis (BBs, odds ratio [OR] 2.19, 95% confidence interval [CI] 1.25-3.84; ACEIs, OR 1.56, 95% CI 1.12-2.16), but not the presence of new cases of anaphylaxis (BBs, OR 1.40, 95% CI 0.91-2.14; ACEIs, OR 1.38, 95% CI 0.39-4.86). It was not possible to perform an analysis adjusted for cardiovascular diseases, because only 1 study each for BBs and ACEIs, respectively, had adjusted data., Conclusions: The quality of evidence showing that the use of BBs and ACEI increases the severity of anaphylaxis is low owing to differences in the control of confounders arising from the concomitant presence of cardiovascular diseases., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Reports of fatal anaphylaxis remain scarce because of the rarity of the condition and the fact that information is limited to a few countries., Objective: Our objective was to investigate clinical and demographic characteristics and the causes of fatal anaphylaxis in Spain using two databases of cases of fatal anaphylaxis., Methods: We analysed fatal anaphylaxis in a series from the Spanish hospital system and a series from the National Institute of Toxicology and Forensic Sciences (Instituto Nacional de Toxicología y Ciencias Forenses [INTCF]), which predominantly comprise extrahospital deaths. Deaths from the Spanish hospital system were retrieved from among all deaths occurring during 1998-2011 using codes related to anaphylaxis. Deaths due to anaphylaxis in the INTCF database during the same period were retrieved by 2 allergists, who identified cases in which anaphylaxis was a possible cause of death. A logistic regression model was constructed to predict the characteristics of fatal anaphylaxis in each database., Results: The incidence of death by anaphylaxis in Spain using both databases was 0.25 (95% CI, 0.24-0.26) deaths per million person-years. The most frequent causes of death in the hospital system were drugs (46.1%), unknown causes (40.0%), and foods (10.4%); in the INTCF, the most common causes of death were drugs (47.2%), insect stings (30.6%), and foods (11.1%). The logistic regression model showed that fatal anaphylaxis due to unknown causes (OR 15.2, 95% CI 1.8-129.8) was more likely in the hospital database, whereas insect stings (OR 100, 95% CI 10-833.3) and previous atopic comorbidity (OR 15.2, 95% CI 6.3-33.3) were more likely in the INTCF database., Conclusions & Clinical Relevance: The estimated frequency of fatal anaphylaxis in Spain was among the lowest reported. Future studies of fatal anaphylaxis should use databases from different origins in order to show the considerable heterogeneity in this type of death., (© 2018 John Wiley & Sons Ltd.)

Background and Objective: Studies assessing the severity of anaphylaxis lack a comprehensive approach to collecting data on comorbidities that may worsen prognosis. Objective: Using the Elixhauser score (a systematic index associated with longer stay, hospital charges, and mortality), we determined which comorbidities were associated with more severe anaphylaxis., Methods: We based our study on the Spanish Ministry of Health database of hospital discharges in Spain between 1997 and 2011. We constructed logistic regression models in which the dependent variables were outcomes related to greater severity (death, cardiac arrest, need for invasive mechanical ventilation or vasopressor drugs, admission to the intensive care unit, and length of stay) and the independent variables were the 30 comorbidities that comprise the Elixhauser score, age, sex, and main causes of anaphylaxis., Results: We found that a higher risk of severe anaphylaxis was associated (3 or more logistic regressions) with age >50 years or having experienced cardiac arrhythmia, coagulation disorder, associated fluid-electrolyte imbalance, chronic pulmonary disease, or Echinococcus anaphylaxis. Likewise, in the adjusted analysis, a higher Elixhauser score was associated with most of the outcomes analyzed for severity of anaphylaxis., Conclusions: Cardiovascular and respiratory diseases increase the severity of anaphylaxis, and the resulting poor health status (represented as a higher Elixhauser score) is associated with more severe anaphylaxis.

We report on trends in anaphylaxis admissions in the Spanish hospital system during the period 1998-2011. Data on admissions for anaphylaxis were obtained from the Spanish Information System for Hospital Data for the period 1998-2011. Patients were selected using the codes for anaphylaxis in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Poisson regression models were used to estimate incidence rate ratios. We recorded a 1.89-fold increase in admissions for anaphylaxis in Spanish hospitals during the study period, particularly in patients aged 0-14 years (1.65- to 3.22-fold until 2009 and 4.09- to 12.59-fold until 2011) and in food anaphylaxis in all age groups (2.78-fold until 2009 and 8.74-fold until 2011). The incidence of anaphylaxis is perceived as having increased in recent years, especially anaphylaxis caused by food and anaphylaxis affecting the pediatric population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Knowledge about the epidemiology of anaphylaxis is based on data from various sources: clinical practice, large secondary clinical and administrative databases of primary care or hospitalized patients, and recent surveys with representative samples of the general population. As several similar results are often reported in several publications and populations, such findings are highly like to be robust. One such finding is that the incidence and prevalence of anaphylaxis are higher than previously thought. Publications from the last 5 years reveal an incidence of between 50 and 112 episodes per 100 000 person-years; estimated prevalence is 0.3-5.1% depending on the rigour of the definitions used. Figures are higher in children, especially those aged 0-4 years. Publications from various geographical areas based on clinical and administrative data on hospitalized patients suggest that the frequency of admissions due to anaphylaxis has increased (5-7-fold in the last 10-15 years). Other publications point to a geographic gradient in the incidence of anaphylaxis, with higher frequencies recorded in areas with few hours of sunlight. However, these trends could be the result of factors other than a real change in the incidence of anaphylaxis, such as changes in disease coding and in the care provided. Based on data from the records of voluntary declarations of death by physicians and from large national databases, death from anaphylaxis remains very infrequent and stands at 0.35-1.06 deaths per million people per year, with no increases observed in the last 10-15 years. Although anaphylaxis can be fatal, recurrence of anaphylaxis--especially that associated with atopic diseases and hymenoptera stings--affects 26.5-54% of patients., (© 2014 John Wiley & Sons Ltd.)

Background: Our objective was to ascertain the degree of adherence to recommendations made to patients with anaphylaxis, most of whom were attended in our allergy outpatient clinic., Methods: A questionnaire was sent to 1512 patients who had experienced anaphylaxis and completed by 887. The chosen definition of anaphylaxis was that of the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network Symposium. We evaluated the prescription, purchase, and use of epinephrine auto-injectors and oral drugs, as well as the avoidance of allergens involved in previous anaphylaxis episodes., Results: Most patients (94.53%) reported that they had received advice on avoidance of responsible allergens after their allergy workup. Epinephrine auto-injectors and oral drugs were prescribed according to the subtype of anaphylaxis. Only 30.74% of patients used the epinephrine auto-injector; 54.26% took oral medication. Most patients (88.3%) avoided the allergen., Conclusions: Despite general agreement that anaphylaxis occurring in the community should be treated with epinephrine auto-injectors, use of these devices to treat recurrences was low in our patients. Oral medication intake was more common than the epinephrine auto-injector in all subtypes. In order to increase adherence to epinephrine auto-injectors, it is necessary to think beyond the measures recommended during regular visits to allergy outpatient clinics.