Medical and pathologic characteristics of fatal anaphylaxis: a Spanish nationwide 17-year series.

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.

Clinical and demographic characteristics of fatal anaphylaxis in Spain (1998-2011): A comparison between a series from the hospital system and a national forensic series.

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.

Relationship Between Anaphylaxis and Use of Beta-Blockers and Angiotensin-Converting Enzyme Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies.

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.

Eosinophilic Esophagitis: Review and Update.

Background: Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia. Probably, in a few years, EoE may no longer be considered a rare disease. Methods: This article discusses new aspects of the pathogenesis, symptoms, diagnosis, and treatment of EoE according to the last published guidelines. Results: The epidemiological studies indicate a multifactorial origin for EoE, where environmental and genetic factors take part. EoE affects both children and adults and it is frequently associated with atopic disease and IgE-mediated food allergies. In patients undergoing oral immunotherapy for desensitization from IgE-mediated food allergy the risk of developing EoE is 2.72%. Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors. There are different patterns of clinical presentation varying with age and can be masked by adaptation habits. Besides, symptoms do not usually correlate with histologic disease activity. The diagnostic criteria for EoE has evolved but mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field. Endoscopies have to be repeated in order to diagnose, monitor, and treat EoE. Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets. The multistage step-up elimination diet management approach of EoE is promising. Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment. Conclusions: Research in recent years has contributed to a better understanding of EoE's pathogenesis, genetic background, natural history, allergy workup, standardization in assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. However, several unmet needs are to be solved urgently, as finding a non-invasive disease-monitoring methods and biomarkers for routine practice, the development or new therapies, novel food allergy testing to detect triggering foods, drug, and doses required for initial therapy and safety issues with long-term maintenance therapy, amongst others. Besides, multidisciplinary management units of EoE, involving gastroenterologists, pediatricians, allergists, pathologists, dietitians, and ENT specialists are needed.

Predicting of anaphylaxis in big data EMR by exploring machine learning approaches.

Anaphylaxis is a life-threatening allergic reaction that occurs suddenly after contact with an allergen. Epidemiological studies about anaphylaxis are very important in planning and evaluating new strategies that prevent this reaction, but also in providing a guide to the treatment of patients who have just suffered an anaphylactic reaction. Electronic Medical Records (EMR) are one of the most effective and richest sources for the epidemiology of anaphylaxis, because they provide a low-cost way of accessing rich longitudinal data on large populations. However, a negative aspect is that researchers have to manually review a huge amount of information, which is a very costly and highly time consuming task. Therefore, our goal is to explore different machine learning techniques to process Big Data EMR, lessening the needed efforts for performing epidemiological studies about anaphylaxis. In particular, we aim to study the incidence of anaphylaxis by the automatic classification of EMR. To do this, we employ the most widely used and efficient classifiers in text classification and compare different document representations, which range from well-known methods such as Bag Of Words (BoW) to more recent ones based on word embedding models, such as a simple average of word embeddings or a bag of centroids of word embeddings. Because the identification of anaphylaxis cases in EMR is a class-imbalanced problem (less than 1% describe anaphylaxis cases), we employ a novel undersampling technique based on clustering to balance our dataset. In addition to classical machine learning algorithms, we also use a Convolutional Neural Network (CNN) to classify our dataset. In general, experiments show that the most classifiers and representations are effective (F1 above 90%). Logistic Regression, Linear SVM, Multilayer Perceptron and Random Forest achieve an F1 around 95%, however linear methods have considerably lower training times. CNN provides slightly better performance (F1 = 95.6%).

Incidence of anaphylaxis in hospitalized patients.

BACKGROUND: Only two studies have analyzed the incidence of anaphylaxis during admission to hospital. We have analyzed the incidence of anaphylaxis among hospitalized patients and determined the timing of and risk factors for episodes of anaphylaxis. METHODS: Our study was performed between 1999 and 2005. We used the definition of anaphylaxis of the NIAID-FAAN symposium. Cases of anaphylaxis were extracted from an official database of discharge diagnoses coded according to the International Classification of Diseases, Clinical Modification, Ninth Revision (ICD-9-CM), Sixth Edition. Specific and generic codes related to anaphylaxis were chosen. This strategy revealed 83.3% (95% confidence interval, CI, 47-99%) of all episodes of anaphylaxis in a pilot study. The incidence of episodes of anaphylaxis and the hazard ratios were calculated for the different variables. RESULTS: We observed a crude cumulative incidence of 1.5 episodes of anaphylaxis (95% CI, 0.9-1.9) in 5,000 admissions. The cumulative incidence according to the Standardized European Population was 1.6 cases in 5,000 admissions (95% CI, 0.8-2.3). Cox regression analysis showed that anaphylaxis occurs mainly in young people (0.97; 95% CI, 0.95-0.99) and its incidence differs according to the clinical unit. The Vascular Surgery Unit had the highest incidence rate (hazard ratio 7.7; 95% CI, 2.1-28.6). Males had a lower risk of suffering from anaphylaxis than females (0.5; 95% CI, 0.2-0.9). CONCLUSIONS: Anaphylaxis is a very rare event among hospitalized patients. Female gender, young age and admission to the Vascular Surgery Unit favored the occurrence of episodes of anaphylaxis among hospitalized patients.