Pollen grains induce a rapid and biphasic eczematous immune response in atopic eczema patients

Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6 - 96 h after allergen application and investigated immunohistochemically. Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-gamma in the late phase. The NPT was continuously dominated by IFN-gamma. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase. Copyright (c) 2007 S. Karger AG, Basel

Quality control in clinical raster-scan optoacoustic mesoscopy

Optoacoustic (photoacoustic) mesoscopy bridges the gap between optoacoustic microscopy and macroscopy and enables high-resolution visualization deeper than optical microscopy. Nevertheless, as images may be affected by motion and noise, it is critical to develop methodologies that offer standardization and quality control to ensure that high-quality datasets are reproducibly obtained from patient scans. Such development is particularly important for ensuring reliability in applying machine learning methods or for reliably measuring disease biomarkers. We propose herein a quality control scheme to assess the quality of data collected. A reference scan of a suture phantom is performed to characterize the system noise level before each raster-scan optoacoustic mesoscopy (RSOM) measurement. Using the recorded RSOM data, we develop a method that estimates the amount of motion in the raw data. These motion metrics are employed to classify the quality of raw data collected and derive a quality assessment index (QASIN) for each raw measurement. Using simulations, we propose a selection criterion of images with sufficient QASIN, leading to the compilation of RSOM datasets with consistent quality. Using 160 RSOM measurements from healthy volunteers, we show that RSOM images that were selected using QASIN were of higher quality and fidelity compared to non-selected images. We discuss how this quality control scheme can enable the standardization of RSOM images for clinical and biomedical applicationsThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 871763 (WINTHER) and under grant agreement No 687866 (INNODERM). Dr. He would like to thank the Helmholtz Imaging Platform (HIP: Deep4OM). Dr. Aguirre would like to thank support from the Madrid Autonomous Region Talento Project 2020-T1/TIC-2066

Recurrent eczema herpeticum – a retrospective European multicenter study evaluating the clinical characteristics of eczema herpeticum cases in atopic dermatitis patients

Background Eczema herpeticum (EH ) is a disseminated viral infection of eczematous skin disease with the herpes simplex virus. Knowledge on clinical characteristics, risk factors and recurrent disease is limited. Our aim was to better define clinical characteristics and risk factors for EH and especially for recurrent EH . Methods A retrospective analysis of EH cases assessed the history, clinical signs, prior treatment and laboratory results using a predefined questionnaire. Results A total of 224 EH cases from eight European centres were included. Extrinsic AD was identified as risk factor for EH , and only one patient suffered from intrinsic AD . Early onset of AD was identified as risk factor for recurrent EH . Pretreatment with topical steroids, systemic steroids, topical calcineurin inhibitors or plain emollients reflected standard therapy. Many patients showed AD lesions without EH , but skin without AD lesions was never affected by herpetic lesions. Conclusion Patients with clinically active, extrinsic AD are at risk of EH . Recurrent EH is associated with confounders of severe atopic distortion and requires active AD lesions for clinical manifestation. Recurrent eczema herpeticum mainly affects patients with early onset of AD

Clinical effectiveness of hymenoptera venom immunotherapy

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy

S2k guideline: Diagnosis and treatment of chronic pruritus

Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org

A concept for integrated care pathways for atopic dermatitis-A GA2^{2} LEN ADCARE initiative

Introduction: The integrated care pathways for atopic dermatitis (AD‐ICPs) aim to bridge the gap between existing AD treatment evidence‐based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co‐ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods: The GA$^{2}$LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD‐ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL$^{2}$EN ADCARE centres. Results: The AD‐ICPs outline the diagnostic procedures, possible co‐morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion: The AD‐ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.Peer reviewe

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food—A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe