Hymenoptera venom immunotherapy: Safety and efficacy of an accelerated induction regimen with depot aluminum adsorbed extracts.

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.

Inflammatory bowel disease and allergic diseases: A Mendelian randomization study.

BACKGROUND: Inflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases. METHOD: We comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary-level data from genome-wide association studies. The analysis results mainly came from the random-effects model of inverse variance weighted (IVW-RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables. RESULTS: The IVW-RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01-1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01-1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00-1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01-1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = 2E-05), AAS (OR = 1.05, 95% CI = 1.02-1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00-1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98-1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis. CONCLUSION: This Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.

Seminal plasma hypersensitivity: A systematic review of clinical presentation, diagnostics, and management options.

INTRODUCTION: Seminal plasma hypersensitivity (SPH) is a rare and often misdiagnosed condition characterized by local and/or systemic reactions to seminal plasma proteins following exposure to semen. We aimed to summarize key symptomatology, diagnostic features, and management options for SPH. METHODS: The databases PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Review were searched with key words "seminal plasma hypersensitivity" and "seminal fluid allergy" through September 2023. Exclusion criteria included non-English articles, in vitro studies, publication before 1990, duplicates, and articles with no clinical relevance to SPH in women. RESULTS: The search yielded 53 articles for review. Of these, 60.5% described systemic SPH and 39.5% described localized. CONCLUSION: Diagnosis of SPH relies on a thorough patient history and confirmatory skin prick testing. The use of IgE assays is controversial and less accurate for cases of localized SPH. Knowledge of disease immunopathology, systemic versus localized symptom presentation, patient preference, and desire to conceive should guide management options. Artificial insemination has the potential for severe adverse reactions in systemic SPH so necessitates extra procedural precautions. SPH does not appear to impair fertility. Additional research on specific allergens implicated in SPH can aid in the development of more targeted immunotherapy approaches with improved safety and efficacy.

Identification of plasma protein markers of allergic disease risk: a mendelian randomization approach to proteomic analysis.

BACKGROUND: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. METHODS: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. RESULTS: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. CONCLUSION: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.

[Mast Cell-Neutrophil Communication Regulates Allergic Diseases].

Allergic diseases (e.g., food allergies) are a growing problem, with increasing numbers of individuals experiencing them worldwide. Congruently, the adverse reactions (e.g., anaphylaxis) associated with the administration of vaccines against emerging infectious diseases such as coronavirus disease 2019 (COVID-19) have become a familiar problem. Allergic diseases, which have a wide variety of symptoms, are difficult to prevent or cure; treatment is currently limited to therapeutic drugs or allergen immunotherapy. Therefore, elucidating new allergic regulatory factors that control the allergic (i.e., mast cell) responses is important. While investigating the regulatory mechanisms of the wide range of allergic responses of mast cells, we found that the affinity of allergens to immunoglobin E (IgE) regulates allergic inflammation through the differences in the secretory responses of mast cells and the types and interactions of the cells infiltrating the tissues. Here, we present our recent findings regarding the affinity of allergens to IgE in regulating allergic inflammation, heterogeneous secretory granules inducing diverse secretory responses, and mast cells interacting with neutrophils, thereby regulating the various allergic responses.

[Diagnosis of allergen components in fungi and microbial communities: patient sensitization characteristics and main sensitizing proteins].

The human body, as a highly complex ecosystem, harbors diverse microbial communities, with major factors triggering allergic reactions encompassing the skin microbiome and fungi. The global diversity of fungi is estimated to range from approximately 600 000 to 1 million species, and theoretically, IgE-mediated sensitization may occur to any fungal species. As of now, the World Health Organization/IUIS official database records 113 fungal allergens originating from 30 different fungi species, covering 42 allergen families. Regarding the skin microbiome, 14 distinct Malassezia allergens have been identified, all derived from three different Malassezia fungi species--M. furfur, M. sympodialis, and M. globosa. The conditions of patients with these allergies are exceptionally complex. This article extensively discusses the latest research advancements and clinical applications related to skin microbiome and fungal allergies from the European Academy of Allergy and Clinical Immunology (EAACI) publication, "Molecular Allergology User's Guide 2.0". Additionally, it compiles information on the sources of fungal allergens, characteristics of allergen component protein families, clinical relevance, and management strategies, both domestically and internationally. The aim is to enhance the profound understanding of allergen components among relevant professionals. Through the application of advanced allergen component diagnostic techniques, the goal is to achieve precise diagnosis and treatment of fungal allergy patients and explore the mechanisms underlying fungal sensitization and pathogenesis, laying the foundation for studying the fungal allergen protein sensitization spectrum in the Chinese population.

The risk of open angle glaucoma in young adults with allergic diseases: a Nationwide cohort study.

This study investigated the potential associations between allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) and the development of primary open-angle glaucoma. We utilized authorized data from the Korean National Health Information Database (KNHID), which provides comprehensive medical claims data and information from the National Health Screening Program. We compared the baseline characteristics of subjects with and without allergic diseases and calculated the incidence and risk of glaucoma development. Cox proportional hazard regression analysis was used to determine the risk of glaucoma development in subjects with allergic diseases. A total of 171,129 subjects aged 20-39 with or without allergic diseases who underwent a general health examination between 2009 and 2015 were included. Subjects with allergic diseases exhibited a higher incidence of glaucoma compared to the control group. The hazard ratio (HR) of glaucoma onset was 1.49 and 1.39 in subjects with at least one allergic disease before and after adjusting for potential confounding factors, respectively. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development (aHR 1.73) after adjusting for confounders. Allergic rhinitis showed an increased risk for incident glaucoma after adjustment (aHR 1.38). Asthma showed the lowest but still increased risk for glaucoma (aHR 1.22). The associations were consistent in all subgroup analyses stratified by sex, smoking, drinking, exercise, diabetes, hypertension, dyslipidemia, or history of steroid. In conclusion, allergic diseases are associated with increased risk of glaucoma development. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development followed by allergic rhinitis and asthma.

[STATE-OF-THE-ART OF GLOBAL START-UP INVESTMENT FOR ALLERGY AND IMMUNOLOGY 2022].

BACKGROUND: In 2022, the "New Capitalism Grand Design and Implementation Plan" was adopted in Japan, emphasizing the promotion and environmental development of startups. Given this context, an investigation into the startup and investment landscape in the allergy sector, both domestically and internationally, becomes imperative. METHODS: We analyzed 156 allergy-related startups from Japan, the US, and Europe from 2010 to 2021. Data on corporate information and investment trends were extracted from databases and VC websites. RESULTS: The total investment reached approximately 7.2 billion USD, with a ratio of 20:6:1 for the US, Europe, and Japan, respectively. The US showed a decline post its peak from 2016-2018, while Europe and Japan experienced growth. Notably, the US primarily invested in biopharmaceuticals for atopic dermatitis and food allergies, Europe in asthma-related apps, and Japan in healthcare apps and cross-border startups. DISCUSSION AND CONCLUSION: While Japan's investment environment in the allergy sector remains in its nascent stages and has room for development, the US and Europe are evidently ahead. Considering the rise of startups and funding limitations in Japan, external funding from regions like the US becomes a potential avenue. These findings are anticipated to contribute to the strategic activation of startups in allergy research and development.

Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias / Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends

Antecedentes: El Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea tiene entre sus objetivos la vigilancia epidemiológica de la dermatitis de contacto. Para ello es importante conocer si se producen alteraciones en el tiempo de las prevalencias de las positividades a los distintos alérgenos. Objetivos: Describir las variaciones en las tendencias temporales en positividades a alérgenos en la serie estándar del GEIDAC en el periodo comprendido entre 2018 y el 31 de diciembre de 2022. Métodos: Estudio observacional multicéntrico de pacientes estudiados consecutivamente mediante pruebas epicutáneas dentro del estudio de un posible eczema alérgico de contacto recogidos de forma prospectiva en el seno del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. Se analizaron los datos mediante 2 pruebas estadísticas: una de homogeneidad (para ver si hay cambios en los diferentes años) y otra de tendencia (para ver si los cambios siguen una tendencia lineal). Resultados: Se incluyeron un total de 11.327 pacientes en el periodo de estudio. Los alérgenos en los que de forma global se detectó una sensibilización mayor fueron sulfato de níquel, metilisotiazolinona, cloruro de cobalto, metilcloroisotiazolinona/metilisotiazolinona y mezcla de fragancias i. Se detectó una disminución estadísticamente significativa en el porcentaje de positividades de metilisotiazolinona a lo largo de años de estudio con una tendencia ordenada. Conclusiones: Si bien se pueden apreciar diferentes cambios en las tendencias a sensibilizaciones a varios de los alérgenos de la batería estándar, se observa que persiste una alta sensibilización al níquel, a la metilcloroisotiazolinona/metilisotiazolinona y a la mezcla de fragancias i. Solo se aprecia una tendencia a disminuir de forma significativa en el caso de la metilisotiazolinona.(AU)

Background: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. Objectives: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. Methods: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). Results: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. Conclusions: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.(AU)

[Translated article] Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends / Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias

Antecedentes: El Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea tiene entre sus objetivos la vigilancia epidemiológica de la dermatitis de contacto. Para ello es importante conocer si se producen alteraciones en el tiempo de las prevalencias de las positividades a los distintos alérgenos. Objetivos: Describir las variaciones en las tendencias temporales en positividades a alérgenos en la serie estándar del GEIDAC en el periodo comprendido entre 2018 y el 31 de diciembre de 2022. Métodos: Estudio observacional multicéntrico de pacientes estudiados consecutivamente mediante pruebas epicutáneas dentro del estudio de un posible eczema alérgico de contacto recogidos de forma prospectiva en el seno del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. Se analizaron los datos mediante 2 pruebas estadísticas: una de homogeneidad (para ver si hay cambios en los diferentes años) y otra de tendencia (para ver si los cambios siguen una tendencia lineal). Resultados: Se incluyeron un total de 11.327 pacientes en el periodo de estudio. Los alérgenos en los que de forma global se detectó una sensibilización mayor fueron sulfato de níquel, metilisotiazolinona, cloruro de cobalto, metilcloroisotiazolinona/metilisotiazolinona y mezcla de fragancias i. Se detectó una disminución estadísticamente significativa en el porcentaje de positividades de metilisotiazolinona a lo largo de años de estudio con una tendencia ordenada. Conclusiones: Si bien se pueden apreciar diferentes cambios en las tendencias a sensibilizaciones a varios de los alérgenos de la batería estándar, se observa que persiste una alta sensibilización al níquel, a la metilcloroisotiazolinona/metilisotiazolinona y a la mezcla de fragancias i. Solo se aprecia una tendencia a disminuir de forma significativa en el caso de la metilisotiazolinona.(AU)

Background: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. Objectives: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. Methods: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). Results: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. Conclusions: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.(AU)

[Understanding hypersensitivity reactions to monoclonal antibodies]. / Comprendre les réactions d'hypersensibilité aux anticorps monoclonaux.

Biologic drugs are complex molecules synthesized by a living organism. Their use is increasingly prevalent across all medical specialties, exposing a growing number of patients to potential adverse reactions. In this review, we discuss the new classification of hypersensitivity reactions, along with the specific characteristics of monoclonal antibodies. We also address the available diagnostic tools and discuss the management of those reactions, including for patients requiring the continuation of these biologic drugs.

Les médicaments biologiques sont des molécules complexes synthétisées par un organisme vivant. Ils sont de plus en plus utilisés dans toutes les spécialités médicales, exposant ainsi les patients à des réactions indésirables. Dans cet article, nous abordons la nouvelle classification des réactions d'hypersensibilité ainsi que les caractéristiques spécifiques des anticorps monoclonaux. Nous évoquons également les outils diagnostiques disponibles et discutons de la prise en charge, y compris pour les patients nécessitant la poursuite de l'administration des médicaments biologiques.

Microscopic Menaces: The Impact of Mites on Human Health.

Mites are highly prevalent arthropods that infest diverse ecological niches globally. Approximately 55,000 species of mites have been identified but many more are yet to be discovered. Of the ones we do know about, most go unnoticed by humans and animals. However, there are several species from the Acariformes superorder that exert a significant impact on global human health. House dust mites are a major source of inhaled allergens, affecting 10-20% of the world's population; storage mites also cause a significant allergy in susceptible individuals; chiggers are the sole vectors for the bacterium that causes scrub typhus; Demodex mites are part of the normal microfauna of humans and their pets, but under certain conditions populations grow out of control and affect the integrity of the integumentary system; and scabies mites cause one of the most common dermatological diseases worldwide. On the other hand, recent genome sequences of mites provide novel tools for mite control and the development of new biomaterial with applications in biomedicine. Despite the palpable disease burden, mites remain understudied in parasitological research. By better understanding mite biology and disease processes, researchers can identify new ways to diagnose, manage, and prevent common mite-induced afflictions. This knowledge can lead to improved clinical outcomes and reduced disease burden from these remarkably widespread yet understudied creatures.