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Cough from an allergological as well as from the ENT aspect Abstract. Cough is a common problem in the allergological, but less so in the rhinological consultation. The differential diagnostic spectrum for cough is extensive and may range from rhinitis and asthma to eosinophilic esophagitis and rarer diseases. In the case of chronic cough (> 2 months), the four most frequent causes must be sought, or be excluded (upper airway cough syndrome, asthma [cough-variant-asthma], non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease). Aeroallergens such as pollen, house-dust mites or occupational substances play a major role in allergies. Nevertheless, it is not uncommon for cough to be a main symptom of an antibody deficiency or a Sicca symptom complex. The more chronic the cough, the more thoroughly an investigation is indicated - often interdisciplinary. Therapy depends on the cause of the cough. In allergic respiratory diseases, allergy-specific immunotherapy may be indicated.

Purpose Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed drug hypersensitivity reaction with exanthema, eosinophilia, and organ manifestations. After culprit drug withdrawal, systemic corticosteroids (CS) are the most widely used treatment, often requiring high doses for months. Blocking the IL-5/IL‑5 receptor axis with mepolizumab, reslizumab, and benralizumab is a promising targeted treatment with a good safety profile and no immunosuppressive effect. The aim of this study is to summarize current experience with the anti-IL5/IL-5-receptor therapy in DRESS. Methods A retrospective analysis of all patients diagnosed with DRESS and treated with mepolizumab, reslizumab, or benralizumab in DRESS was performed. In addition, a PubMed–Medline search for publications on DRESS with anti-IL-5/IL‑5 receptor treatment was performed. Results Of the 14 cases identified, 6 patients were treated with mepolizumab, 6 with benralizumab, 1 patient with reslizumab, and 1 patient was switched from benralizumab to mepolizumab. The main indication for an IL‑5 blockade was a therapy-refractory course (7/14 [50.0%]), recurrent relapses (3/14 [21.4%]), and severe organ dysfunction (2/14 [14.3%]). In 13/14 (93%) cases, a rapid clinical improvement with suppression of eosinophilia and reduction of CS could be achieved. In all but two cases under mepolizumab (dose 100–600 mg) or reslizumab (dose according to body weight), two or more doses were necessary until resolution of DRESS. In 4/7 cases under benralizumab, a single 30 mg dose was sufficient. Conclusion Blockade of the IL-5/IL‑5 receptor axis appears to be a promising treatment in DRESS with fast clinical improvement, which may allow more rapid reduction of CS, and a good safety profile. In addition, a summary of recommendations on when to use blockade of the IL-5/IL‑5 receptor axis in DRESS treatment is provided.

Background The diagnostic approach for beta-lactam (BL) drug hypersensitivity reactions (DHR) is based on the history, clinical signs, skin tests (ST), in vitro tests, and drug provocation tests (DPT). The aim of this study was to assess the performance of an allergy workup with ST in a real-world use. Methods In this cross-sectional study the rate of positive ST in subjects with suspected DHR to penicillins and cephalosporins was investigated. Of special interest were correlations of ST positivity: 1) to the time intervals between index reaction and the allergic work-up, 2) time interval from drug exposure to the onset of signs, 3) pattern of manifestation in delayed DHR and involvement of test area in the index reaction, and 4) potential advantage of patch testing in delayed DHR. Results 175 patients were included between January 2018 and April 2019 (63.4% female), 45 (25.7%) with immediate DHR manifestation and 130 with delayed DHR manifestation (74.3%). A total of 44 patients (25.1%) had a positive ST (immediate DHR 37.8% versus 20.0% in delayed DHR). ST positivity decreased in both groups after 3 years from 47.8% [95%CI 29.2–67] to 23.5% [95%CI 9.6–47.3] in immediate DHR and 23.0% [95%CI 15-4-32.9] to 12.9% [95%CI 5.1–28.9] in delayed DHR. The proportion of positive ST was higher in patients with more severe forms of delayed DHR, and in subjects with a shorter latency period of onset of symptoms after drug exposure: 0-3d: 29.5% [95%CI 19.6–41.9] vs. >3d: 11.6% [95%CI 6.0–21.2]). No sensitization was shown in delayed urticaria or angioedema. ST done outside the skin area involved during the index reaction were negative in all cases (0/38 vs. 26/84 in cases with involved area). The combination of patch test and intradermal test (IDT) revealed an additional positive result in 2/77 cases. Additional in vitro testing reduced the proportion of negative test results to 72%. Conclusion In most patients with negative test results, we could not clarify the cause of the BL-associated adverse events even with further investigations (including DPT). How to prevent new drug-induced adverse events in such patients has hardly been investigated yet. Corresponding cohort studies could improve the data situation.

BACKGROUND Despite the efficacy of allergen-specific immunotherapy (AIT), the role of trained immunity and tolerance in this process has not been elucidated. OBJECTIVE Here, we have performed a comprehensive longitudinal analysis of the systemic innate immune cell repertoire during the course of AIT. METHODS Patients with allergy received standard preseasonal subcutaneous AIT with allergoids to birch and/or grass. Healthy controls were monitored without any intervention. Flow cytometry of innate lymphoid cell (ILC), natural killer cell, monocyte cell, and dendritic cell (DC) subsets was performed at baseline, 3 months (birch season), 6 months (grass seasons), and 12 months after the therapy in patients or at similar seasonal time points in controls. Additional analyses were performed in the third-year birch and grass season. RESULTS We observed a durable decrease in group 2 ILCs and an increase of group 1 ILCs after AIT, with dynamic changes in their composition. We found that an expansion of CD127+CD25++ clusters caused observed shifts in the heterogeneity of group 1 ILCs. In addition, we observed development of CD127+CD25++c-Kit+ group 3 ILC clusters. Moreover, we found an increase in the number of intermediate monocytes in parallel with a reduction in nonclassical monocytes during the first year after AIT. Classical and intermediate monocytes presented significant heterogeneity in patients with allergy, but AIT reduced the HLA-DR++ clusters. Finally, an increase in plasmacytoid DCs and CD141+ myeloid DCs was observed in individuals with allergy, whereas the number of CD1c+ myeloid DCs was reduced during the first year of AIT. CONCLUSION AIT induces changes in the composition and heterogeneity of circulating innate immune cells and brings them to the level observed in healthy individuals. Monitoring of ILCs, monocytes, and DCs during AIT might serve as a novel biomarker strategy.

Cough from an allergological as well as from the ENT aspect

Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that has been known since the early 1990s. Swallowed topical corticosteroids (STC) belong to the therapeutic cornerstones. We describe a delayed hypersensitivity reaction to Jorveza®, a newly developed orodispersible budesonide tablet licensed for the treatment of eosinophilic esophagitis. Case presentation A 32-year-old Caucasian woman with EoE was newly treated with Jorveza®. Hours after the first intake, she felt a “strange pruritus” in the throat. This sensation worsened with each subsequent intake. On day 4 she developed oral mucosal symptoms (paresthesia of the tongue, sore and an itchy throat). Intraoral, throat and facial swellings, but no systemic reaction were observed. Patch testing using two commercial test series as well as the orodispersible budesonide tablet revealed a strong sensitization, proving a T cell mediated allergy to budesonide. Conclusions Orodispersible budesonide is increasingly prescribed for the treatment of eosinophilic esophagitis. The development of oropharyngeal symptoms after initiating should alert the treating physician to the possibility of a hypersensitivity reaction.

The population prevalence of insect venom allergy ranges between 3–5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March–June 2019 compared to March–June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic.

Die Insektengiftallergie ist mit einem Vorkommen von 3-5 % in der Bevölkerung häufig und kann bei bis zu 1 % der Betroffenen potenziell lebensbedrohliche allergische Reaktionen auslösen [1]. Patienten, die eine systemische allergische Reaktion nach einem Insektenstich erlitten haben, sollten allergologisch vorgestellt und versorgt werden. Aufgrund der vielerorts in den letzten Monaten durch die COVID-19-Pandemie reduzierten ambulanten und stationären Versorgungskapazitäten wurden länderspezifisch unterschiedliche Maßnahmen ergriffen, um auch Patienten mit einer Insektengiftallergie fortwährend optimal allergologisch zu versorgen. Eine aktuelle Datenanalyse zeigt, dass es 2020 zu einer Einschränkung von Neueinleitungen der Insektengiftimmuntherapie gekommen ist (März-Juni 2019 im Vergleich März-Juni 2020: Rückgang 48,5 %; Daten aus verschiedenen Zentren in Deutschland, Österreich und Schweiz). Es werden konkrete organisatorische (z. B. Telefon- und Videosprechstunden, die Umgestaltung von Wartebereichen mit Umsetzung von Hygienemaßnahmen und Abstandsregeln bei stabiler Patientenzahl) und medizinische Maßnahmen (Zusammenarbeit mit niedergelassenen Ärzten bzgl. primärer Diagnostik, kurzfristige COVID-19-Testung, die ambulante Fortführung einer begonnenen Insektengiftimmuntherapie unter Ausnutzung der zulässigen Injektionsintervalllängen, Neueinleitung einer Insektengiftimmuntherapie zeitnah innerhalb der Saison, ggf. Einsatz ambulanter Schemata vor allem außerhalb der Saison) zur Betreuung von Insektengiftallergikern während der COVID-19-Pandemie vorgeschlagen.

Allergic patients display abnormal immune responses to harmless antigens, including abnormal Th2 polarization and induction of allergen-specific T and B cells, resulting in development of allergy instead of tolerance. Allergen-specific immunotherapy (AIT) is currently the only causative treatment of allergic disorders. Yet, understanding of the underlying differences in allergen-specific responses between allergy and tolerance is lacking. We investigated whole-genome transcriptomics of circulating birch and grass specific CD4+ T cells in patients before and during AIT, as well in non-allergic healthy controls. Detailed immunophenotyping with flow cytometry and CD4+ MHC class II tetramer staining with low RNA/single cell next generation sequencing were performed. At baseline, out of the season, there were more allergen-specific CD4+ T cells in allergic patients than in controls. At this time, over 1500 genes were differently expressed in allergen-specific CD4+T cells in patients, but they were less upregulated in signal transduction, inflammatory response and coagulation categories as compared to controls. During AIT we noted further increase of allergen-specific CD4+ cells with subsequent gene expression change. Finally, we found increase in allergen-specific Treg cells in patients upon AIT, but not in tolerant controls. Yet, at early AIT time points, allergen-specific Treg cells displayed gene profiles suggesting their insufficient functions. In summary, in vivo allergen exposure causes profound changes in the transcriptomic profiles of allergen-specific T cells. These gene profiles seem to be deficient at baseline in allergic patients, but AIT is skewing them into the tolerant controls levels.

En Suisse, ce sont chaque annee trois a quatre personnes qui decedent en raison d’une reaction allergique severe suite a une piqure d’insecte. Cet article de revue detaille les principaux insectes, facteurs de risque et manifestations cliniques des reactions allergiques consecutives aux piqures d’insectes, ainsi que leur traitement aigu. Les derniers procedes diagnostiques ainsi que les traitements – et en particulier l’immunotherapie specifique au venin d’insectes – y sont egalement presentes.