Rapid response to dupilumab in an adult patient with eosinophilic esophagitis and allergic asthma.

BACKGROUND: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus that belongs to the spectrum of Th2-mediated diseases. It is often associated with atopic comorbidities such as allergic asthma (AA) and poses a therapeutic challenge. CASE REPORT: We report on a 43-year-old patient with EoE and AA who did not show sufficient therapeutic control despite standard therapy. We started treatment with dupilumab, whereupon both EoE and AA rapidly improved and complete symptom resolution could be documented. The response to dupilumab was assessed by laboratory monitoring and gastroscopy, which showed a reduction of markers of type II inflammation and eosinophilic infiltrates in the esophagus. SUMMARY: Our report emphasizes the effective and safe use of dupilumab as a treatment option for EoE with concomitant beneficial effects on AA.

Emerging and Novel Elicitors of Anaphylaxis: Collegium Internationale Allergologicum Update 2024.

BACKGROUND: Anaphylaxis represents the most severe end of the spectrum of allergic reactions. Frequent elicitors of anaphylaxis are insects, foods, and drugs. This paper summarizes recent development with regard to emerging and novel elicitors of anaphylaxis. SUMMARY: Food allergens on the rise include pulses (like pea, chickpea), seeds (hemp, chia), nuts (cashew), pseudograins (buckwheat, quinoa), fruits, and microalgae. Novel foods are foods that were not consumed to any significant extent in the European Union before May 1997, which includes four edible insects (mealworm, migratory locust, house cricket, and buffalo worm). Recent investigations have pointed out the risk of anaphylaxis associated with the consumption of yellow mealworm for people allergic to shellfish and house dust mites. In Europe, fire ants (mostly Solenopsis invicta) and Vespa velutina nigrithorax represent invasive species, which account for increasing numbers of anaphylactic reactions. Also, several new drugs, especially biologicals, have been associated with anaphylaxis. KEY MESSAGES: Elicitors of anaphylaxis are changing as a result of (i) increase in demand for plant-based food, (ii) introduction of novel foods, (iii) spreading of allergens by climate changes and globalization, or (iv) due to exposure to newly developed drugs.

[Which augmentation and trigger factors are relevant in urticaria?] / Welche Augmentations- und Triggerfaktoren sind bei der Urtikaria relevant?

The aim of this review is to present relevant trigger as well as augmentation factors that can induce or exacerbate urticaria on the basis of a current, PubMed-based literature search. In addition to a brief description of relevant influencing factors in acute and chronic inducible urticaria, the focus will be on chronic spontaneous urticaria. In particular, the aggravating role of medication, stress, food, psychological and metabolic comorbidities, infections and inflammation as well as hormonal processes will be discussed.

Occupational anaphylaxis-Data from the anaphylaxis registry.

BACKGROUND: Epidemiologic data on occupational anaphylaxis is scarce, and there is a need of more knowledge about work-related anaphylactic episodes. METHODS: Based on the data of the Anaphylaxis Registry, we identified cases related to occupational exposure and analyzed the elicitors, demographics, severity of clinical reaction and management. RESULTS: Since 2017, 5851 cases with an information about the occupational relation of the anaphylactic episode were registered whereby 225 (3.8%) were assigned to be caused by an occupational allergen. The vast majority of these occupational anaphylaxis cases were caused by insects (n = 186, 82.7%) followed by food (n = 27, 12.0%) and drugs (n = 8, 3.6%). Latex elicited occupational anaphylaxis in only two cases. Beekeepers, gardeners, farmers, and individuals working in professions associated with food handling, for example, employees in restaurants, bakery, pastry, and cooks were most frequently affected. The comparison of the occupational insect venom-induced anaphylaxis to a group of non-occupational insect anaphylaxis in adults (n = 1842) revealed a significant younger age in occupational anaphylaxis (46 vs. 53 years), a predominance of bee-induced cases (38% vs. 17%), and a higher rate of venom immunotherapy in a primary care setting (3.3% vs. 1.3%, p = .044). In the occupational- versus non-occupational adults with food-induced anaphylaxis atopic dermatitis as concomitant atopic disease was observed more frequently (n = 486; 20% vs. 10%), although this was not significant. CONCLUSION: Our data demonstrate the impact of venom allergy in work-related anaphylaxis. Foods and drugs are less frequently elicitors, and latex-induced occupational anaphylaxis was rare. More data are needed to determine risk factors associated with occupational anaphylaxis.

Fatal and Near-Fatal Anaphylaxis: Data From the European Anaphylaxis Registry and National Health Statistics.

BACKGROUND: Anaphylaxis is a serious systemic reaction-data on fatal and near-fatal reactions are limited. OBJECTIVE: To better understand clinical patterns and risks factors of severe anaphylaxis by a deep analysis of data from fatal and near-fatal anaphylaxis. METHODS: Data from the European Anaphylaxis Registry on fatal/near-fatal anaphylactic reactions and national data on anaphylaxis fatalities were investigated. RESULTS: A total of 305 fatal/near-fatal reactions among children and adults including 35 fatalities from the European Anaphylaxis Registry were identified. The most frequent elicitors were drugs, insects, and food. Male patients (66%/60%) were more frequently affected. Male sex, higher age, concomitant mastocytosis, and cardiovascular disease were associated with a more severe outcome. With increasing reaction severity, skin symptoms were less frequently observed (45% of fatal reactions). In parallel, anaphylaxis mortality rates were studied. The data show that anaphylaxis mortality rates increased in Germany from 0.48 (2009) to 0.59 per 1,000,000 population per year (2020). This increase was apparent only in the female population. In this data set, drugs were the most frequent elicitor of anaphylaxis fatalities, and the rate for this increased over time. CONCLUSIONS: We identified not only elicitors but also individual factors to be associated with an increased risk of fatal anaphylaxis. Such patients should be recognized and managed with great caution. The increase in drug-induced fatalities points to the need for a better allergological care of patients suffering from drug hypersensitivity.

Contact allergies to dental materials in patients.

BACKGROUND: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy. OBJECTIVES: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy. METHODS: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series. RESULTS: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%). CONCLUSIONS: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'.

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Allergy and Environmental Medicine (GPA), German Respiratory Society (DGP), and the Austrian Society for Allergy and Immunology (ÖGAI).

Hymenoptera venom (HV) is injected into the skin during a sting by Hymenoptera such as bees or wasps. Some components of HV are potential allergens and can cause large local and/or systemic allergic reactions (SAR) in sensitized individuals. During their lifetime, ~ 3% of the general population will develop SAR following a Hymenoptera sting. This guideline presents the diagnostic and therapeutic approach to SAR following Hymenoptera stings. Symptomatic therapy is usually required after a severe local reaction, but specific diagnosis or allergen immunotherapy (AIT) with HV (VIT) is not necessary. When taking a patient's medical history after SAR, clinicians should discuss possible risk factors for more frequent stings and more severe anaphylactic reactions. The most important risk factors for more severe SAR are mast cell disease and, especially in children, uncontrolled asthma. Therefore, if the SAR extends beyond the skin (according to the Ring and Messmer classification: grade > I), the baseline serum tryptase concentration shall be measured and the skin shall be examined for possible mastocytosis. The medical history should also include questions specific to asthma symptoms. To demonstrate sensitization to HV, allergists shall determine concentrations of specific IgE antibodies (sIgE) to bee and/or vespid venoms, their constituents and other venoms as appropriate. If the results are negative less than 2 weeks after the sting, the tests shall be repeated (at least 4 - 6 weeks after the sting). If only sIgE to the total venom extracts have been determined, if there is double sensitization, or if the results are implausible, allergists shall determine sIgE to the different venom components. Skin testing may be omitted if in-vitro methods have provided a definitive diagnosis. If neither laboratory diagnosis nor skin testing has led to conclusive results, additional cellular testing can be performed. Therapy for HV allergy includes prophylaxis of reexposure, patient self treatment measures (including use of rescue medication) in the event of re-stings, and VIT. Following a grade I SAR and in the absence of other risk factors for repeated sting exposure or more severe anaphylaxis, it is not necessary to prescribe an adrenaline auto-injector (AAI) or to administer VIT. Under certain conditions, VIT can be administered even in the presence of previous grade I anaphylaxis, e.g., if there are additional risk factors or if quality of life would be reduced without VIT. Physicians should be aware of the contraindications to VIT, although they can be overridden in justified individual cases after weighing benefits and risks. The use of ß-blockers and ACE inhibitors is not a contraindication to VIT. Patients should be informed about possible interactions. For VIT, the venom extract shall be used that, according to the patient's history and the results of the allergy diagnostics, was the trigger of the disease. If, in the case of double sensitization and an unclear history regarding the trigger, it is not possible to determine the culprit venom even with additional diagnostic procedures, VIT shall be performed with both venom extracts. The standard maintenance dose of VIT is 100 µg HV. In adult patients with bee venom allergy and an increased risk of sting exposure or particularly severe anaphylaxis, a maintenance dose of 200 µg can be considered from the start of VIT. Administration of a non-sedating H1-blocking antihistamine can be considered to reduce side effects. The maintenance dose should be given at 4-weekly intervals during the first year and, following the manufacturer's instructions, every 5 - 6 weeks from the second year, depending on the preparation used; if a depot preparation is used, the interval can be extended to 8 weeks from the third year onwards. If significant recurrent systemic reactions occur during VIT, clinicians shall identify and as possible eliminate co-factors that promote these reactions. If this is not possible or if there are no such co-factors, if prophylactic administration of an H1-blocking antihistamine is not effective, and if a higher dose of VIT has not led to tolerability of VIT, physicians should should consider additional treatment with an anti IgE antibody such as omalizumab as off lable use. For practical reasons, only a small number of patients are able to undergo sting challenge tests to check the success of the therapy, which requires in-hospital monitoring and emergency standby. To perform such a provocation test, patients must have tolerated VIT at the planned maintenance dose. In the event of treatment failure while on treatment with an ACE inhibitor, physicians should consider discontinuing the ACE inhibitor. In the absence of tolerance induction, physicians shall increase the maintenance dose (200 µg to a maximum of 400 µg in adults, maximum of 200 µg HV in children). If increasing the maintenance dose does not provide adequate protection and there are risk factors for a severe anaphylactic reaction, physicians should consider a co-medication based on an anti-IgE antibody (omalizumab; off-label use) during the insect flight season. In patients without specific risk factors, VIT can be discontinued after 3 - 5 years if maintenance therapy has been tolerated without recurrent anaphylactic events. Prolonged or permanent VIT can be considered in patients with mastocytosis, a history of cardiovascular or respiratory arrest due to Hymenoptera sting (severity grade IV), or other specific constellations associated with an increased individual risk of recurrent and/or severe SAR (e.g., hereditary α-tryptasemia). In cases of strongly increased, unavoidable insect exposure, adults may receive VIT until the end of intense contact. The prescription of an AAI can be omitted in patients with a history of SAR grade I and II when the maintenance dose of VIT has been reached and tolerated, provided that there are no additional risk factors. The same holds true once the VIT has been terminated after the regular treatment period. Patients with a history of SAR grade ≥ III reaction, or grade II reaction combined with additional factors that increase the risk of non response or repeated severe sting reactions, should carry an emergency kit, including an AAI, during VIT and after regular termination of the VIT.

Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for Pediatric Allergology (GPA), the German Contact Dermatitis Research Group (DKG), the German Society for Pneumology (DGP), the German Society of Otorhinolaryngology, Head and Neck Surgery, the Austrian Society of Allergology and Immunology (ÖGAI), the Austrian Society of Dermatology and Venereology (ÖGDV), the German Academy of Allergology and Environmental Medicine (DAAU), and the German Documentation Center for Severe Skin Reactions (dZh).

Not available.

Food allergy - New risks through vegan diet? Overview of new allergen sources and current data on the potential risk of anaphylaxis.

A vegan diet is increasingly en vogue, i.e., a diet based on plants, in which animal products are completely avoided, often for health and environmental reasons. The menu is supplemented with pulses (e.g., soy, lentils, peas), nuts (e.g., cashew, macadamia, almond, pecan, para, walnut) and seeds (e.g., chia, flaxseed) or pseudo-grains (quinoa, buckwheat). Indeed, the product range is expanding to include vegan foods such as milk alternatives (e.g., oat, almond, soy drinks) and cheese or meat substitutes (e.g., soy-based). Food allergies are also on the rise, with an increasing prevalence worldwide. It is worthy of note that the main allergens of anaphylactic reactions to food in adults are predominantly of plant origin, mainly pulses and nuts - the very foods that form the main source of protein in the vegan diet. In this context, allergies to storage proteins (e.g., Gly m 5 and Gly m 6 from soya beans) can lead to severe anaphylactic reactions, while highly processed substitute products containing plant protein isolates (e.g., pea flour) in concentrated form continue to be of particular concern and may therefore be allergologically problematic. In this article, we aim to provide an overview of allergens and emerging allergen sources in vegan foods and highlight the anaphylaxis risk of the vegan diet.

Current situation of allergological health care at German hospitals.

BACKGROUND: Allergic medical care in Germany is organized on an interdisciplinary basis. An overview of the current care situation is necessary to manage and improve interdisciplinary cooperation. METHODS: Between January and February 2022, questionnaires were sent online and by mail to chief physicians of inpatient clinical departments to which most allergological diseases are assigned (dermatology, otorhinolaryngology [ENT], pulmonology, pediatrics, environmental/occupational medicine, gastroenterology; n = 899). RESULTS: The response rate was 52.1%. Allergology departments of dermatology, ENT and pulmonology were predominantly located in metropolitan areas (> 100,000 inhabitants), whereas responses of pediatric departments were mostly from smaller towns. 76.8% of the respondents reported existing interdisciplinary treatment plans with other specialties. Pediatric and pulmonology clinics stated disproportionately few interdisciplinary treatment concepts with dermatology and ENT clinics, especially in smaller cities with < 100,000 inhabitants. Diagnosis and therapy of allergic rhinitis were performed in particular by the departments of ENT, asthma mainly by the pulmonology departments. Care of other allergological diseases was most frequently reported by chief physicians of dermatology and pediatrics. CONCLUSIONS: In metropolitan areas, participating departments provide allergology care in a cooperative manner. A large spectrum of care is covered in cooperation with dermatological clinics. In more rural areas, cooperation is rarer; here, mainly pediatric departments provide allergological care, which may explain the more limited range of services compared to metropolitan areas.

Contact allergy to ingredients of hair cosmetics in female hairdressers and female consumers-An update based on IVDK data 2013-2020.

BACKGROUND: Hair cosmetic products contain several, partly potent contact allergens, including excipients like preservatives. Hand dermatitis in hairdressers is common, scalp and face dermatitis in clients or self-users (summarised here as 'consumers') may be severe. OBJECTIVE: To compare frequencies of sensitization to hair cosmetic ingredients and other selected allergens between female patch tested patients working as hairdressers and consumers without professional background, respectively, who were tested for suspected allergic contact dermatitis to such products. METHODS: Patch test and clinical data collected by the IVDK (https://www.ivdk.org) between 01/2013 and 12/2020 were descriptively analysed, focusing on age-adjusted sensitization prevalences in the two subgroups. RESULTS: Amongst the 920 hairdressers (median age: 28 years, 84% hand dermatitis) and 2321 consumers (median age: 49 years, 71.8% head/face dermatitis), sensitization to p-phenylenediamine (age-standardised prevalence: 19.7% and 31.6%, respectively) and toluene-2,5-diamine (20 and 30.8%) were most common. Contact allergy to other oxidative hair dye ingredients was also more commonly diagnosed in consumers, whereas ammonium persulphate (14.4% vs. 2.3%) and glyceryl thioglycolate (3.9 vs. 1.2%) as well as most notably methylisothiazolinone (10.5% vs. 3.1%) were more frequent allergens in hairdressers. CONCLUSIONS: Hair dyes were the most frequent sensitizers both in hairdressers and in consumers; however, as indication for patch testing may differ, prevalences cannot directly be compared. The importance of hair dye allergy is evident, often with marked coupled reactivity. Workplace and product safety need to be further improved.

Limited Reimbursement and Underuse of Digital Healthcare Concepts Are Major Barriers to Clinical Allergological Care in Germany.

INTRODUCTION: Allergic diseases represent a broad spectrum of high-prevalence, chronic conditions that remain underdiagnosed and undertreated. The aims of this interdisciplinary, questionnaire-based, non-interventional study were to identify and analyze potential barriers to clinical allergological care in Germany. METHODS: All hospitals listed in the German hospital register involved in the treatment of allergological patients (n = 899) were invited to participate. The study yielded a response rate of 52.1% (n = 468). RESULTS: Overall, 88.5% of clinics agreed that allergological care in Germany needs improvement, especially in terms of reimbursement for diagnostics and therapy. More than 80% of participating clinics reported that the decreased availability of test substances and the time-intensity of allergological testing represent relevant barriers. For dermatology and pulmonology, the former is the strongest barrier, while for pediatric and ENT clinics, time-intensity is regarded as the strongest barrier. The availability of good therapy and appropriate guidelines present no barriers to allergological care. Regarding the use of digital healthcare concepts, a very large majority of clinics (n = 352; 91.4%) do not offer video consultations or the use of health applications in patient care. CONCLUSION: In conclusion, we have identified several structural barriers to allergological care in Germany. Reimbursement and the use of digital healthcare concepts in German clinics providing allergological care need improvement. Based on the results of this study, there is an urgent need for researchers and policymakers to further investigate and support allergology departments in their clinical work and in their implementation of digital healthcare concepts.

Vegan diets from an allergy point of view - Position paper of the DGAKI working group on food allergy.

Vegan diets are currently attracting a great deal of attention. However, avoiding animal-based foods restricts the diet and is associated with risks, the extent and medical implications of which are at present not sufficiently understood. Elimination diets represent the usual therapeutic long-term management in the presence of food allergy. In order to understand the risks of vegan diets and to discuss these critically from the perspective of food allergies, the expertise of a nutritionist/dietitian with expertise in this area is indispensable. This position paper deals with the incentives behind and the benefits of a plant-based diet. The knowledge required to cover macro- and micronutrient dietary requirements is presented. Using the avoidance of cow's milk as an example, the challenges of adequately meeting nutritional needs are identified and (so-called) milk alternatives are evaluated from an allergy and nutritional point of view. Finally, other plant-based (substitute) products are evaluated from the same perspective, as significant protein sources in vegan diets (e.g., legumes, nuts, and seeds) are at the same time potential and potent triggers of allergic reactions. However, the allergic potential of many substitute products cannot be fully assessed at present due to gaps in research. Wheat as the most important trigger for anaphylaxis in adults is also evaluated. Finally, the increase in ultra-processed products in the (vegan) food sector and their potential consequences for the immune system are discussed.

Developments and perspectives in allergology.

Allergology is a key part of dermatological care. This paper reviews current pathophysiological, diagnostic and therapeutic developments in immediate-type allergies. Type-2 inflammation is involved in several allergological diseases such as allergic rhinitis and asthma. Allergen immunotherapy as an important therapeutic procedure is regulated in Germany by an official legal directive (Therapieallergene-Verordnung). Therapeutically, several biologics are already available that target interleukin (IL)-4, -5, -13, -33, or TSLP (thymic stromal lymphopoietin). Collateral efficacy may result in simultaneous treatment of allergological comorbidities. In mast cell mediated diseases (urticaria, anaphylaxis), there is increasing understanding of mast cell activation pathways. Several mast cell receptors such as MRGPRX2 (mas-related G protein coupled receptor X2) and Siglec-8 (sialinic acid binding Ig like lectin-8) as well as intracellular signaling pathways have recently been identified. Clinical trials are underway with drugs acting on mast cell receptors and intracellular signaling, i.e., Bruton's tyrosine kinase inhibitors. Further perspectives on biomarkers, novel therapeutics and unmet needs for future research activities are presented.