An interdisciplinary approach to characterize peanut-allergic patients-First data from the FOOD@ consortium.

Background: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. Methods: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. Results: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. Conclusion: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies.

Elicitors and phenotypes of adult patients with proven IgE-mediated food allergy and non-immune-mediated food hypersensitivity to food additives.

BACKGROUND: Food allergy is a growing health concern with a prevalence of 2%-3% in the adult population in Europe. Non-immune-mediated food hypersensitivities, which include reactions after ingestion of food additives, affect 1% of adults and may resemble IgE-induced allergic reactions without identifiable immunologic sensitization. A double-blind placebo-controlled food challenge (DBPCFC) is the gold standard for the diagnosis of any food hypersensitivity. OBJECTIVE: We analysed a large group of adult patients with suspected food hypersensitivity, who had undergone DBPCFC, to better understand IgE-mediated food allergy and non-immune-dependent food hypersensitivity to food additives in adults regarding elicitors, symptoms and positivity rates of oral challenges. METHODS: Data from 541 patients with suspected food hypersensitivity were analysed, who underwent an oral food challenge between 2010 and 2019. RESULTS: IgE-dependent food allergy was confirmed in 114 of 329 adult patients (34.6%). The confirmation rate was lower in the group of patients with suspected non-immune-mediated reactions to food additives (65 of 286, 22.7%). Urticaria and angioedema appeared more frequently in patients with IgE-mediated food allergies. By contrast, flush and diarrhoea were the most frequent symptoms after a challenge in the group with the non-immune-mediated reactions to food additives. Wheat and celery were the most frequently identified food allergens in adults, whereas colourings and preservatives were the most frequent elicitors of non-immune-mediated food hypersensitivity. CONCLUSION: The importance of oral food challenges for the diagnosis of food hypersensitivity is confirmed. IgE-dependent food allergy is more frequently proven, reaching a positivity rate of one-third and only about 20% for non-immune-mediated hypersensitivity. Future studies should elaborate on the mechanisms of non-immune-mediated food hypersensitivity and the clinical impact of cofactors in this setting.

Management of suspected and confirmed COVID-19 (SARS-CoV-2) vaccine hypersensitivity.

BACKGROUND: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS-CoV-2 vaccine hypersensitivity. METHODS: Totally, 334 individuals underwent an allergy work up regarding SARS-CoV-2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine-related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS-CoV-2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination. RESULTS: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)-vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B). CONCLUSION: Proven IgE-mediated hypersensitivity to SARS-CoV-2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered.

Tolerance induction through non-avoidance to prevent persistent food allergy (TINA) in children and adults with peanut or tree nut allergy: rationale, study design and methods of a randomized controlled trial and observational cohort study.

BACKGROUND: Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy. METHODS: The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1-67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose. DISCUSSION: This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid. TRIAL REGISTRATION: German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de .

[Management of severe nut allergy in adults]. / Management einer schweren Nussallergie im Erwachsenenalter.

We present a case of walnut allergy in a 24-year-old man. The allergy work up revealed sensitization to walnut including a positive skin prick test and a high value of walnut-specific IgEs. The patient showed an anaphylactic reaction during the double blind placebo-controlled food challenge, to a cumulative dose of 3.723 g of walnut protein. The oral food challenge resulted in counseling regarding strict walnut avoidance and optimization of the emergency management. At follow-up the patient reported that having adhered to the recommended dietary measures resulted in no further allergic reactions.

Safety of dupilumab in patients with atopic dermatitis: expert opinion.

Introduction: Dupilumab, the first biologic drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown efficacy and safety in clinical trials. Data on long-term safety is limited but crucial for pharmacovigilance. Therefore, we performed this review to evaluate available real-world data on the long-term safety of dupilumab in atopic dermatitis.Areas covered: PubMed and Google Scholar databases were searched for randomized controlled clinical trials (RCTs), observational studies, case series, and case reports regarding the use of dupilumab for the treatment of atopic dermatitis. Adverse events were summarized and critically evaluated.Expert opinion: Atopic dermatitis patients receiving dupilumab reported ocular surface disease more often than patients receiving placebo. Real-world data show previously unreported adverse events (blood eosinophilia, rosacea-like skin lesions, weight gain), but their mechanistic association to dupilumab treatment still requires clarification. Cutaneous T-cell lymphomas occurring under the therapy with dupilumab might be unrelated to the drug use itself but long-term follow-up data of large patient cohorts is necessary to rule out such possibility. Real-world data show that dupilumab is well tolerated in atopic dermatitis; however, ocular adverse events are not rare. Registries are needed to monitor future adverse events.

Use of biologics in food allergy management.

Food allergies are a common medical problem, with children being the most affected patient group. The standard of care of food allergy consists of the acute treatment in case of a reaction and food avoidance in the long term, which influences the quality of life of patients. In this article, current developments for the causal treatment of food allergy including specific immunotherapy and biologics will be discussed. Epicutaneous and oral immunotherapy are currently in clinical development for the treatment of food allergy, and the results demonstrate good tolerability and efficacy with an increase in the oral threshold level. Biologics and, in particular, anti-IgE are currently investigated for their therapeutic use in food allergies. The results are promising, suggesting efficacy and tolerability.

Modern therapies in atopic dermatitis: biologics and small molecule drugs.

Atopic dermatitis (AD) is a frequent, chronic remittent skin disease. The pathophysiology of AD has been increasingly understood within the last years, which may help to identify different endotypes suitable for defined therapies in the future. A patient-oriented therapy considers phenotypical features in addition to genetic and biological markers. The most recent developments in biologics and small-molecule drugs for AD treatment are presented in this article. These molecules, if approved, could change the perspectives for future therapies. Dupilumab is the first approved biologic for the treatment of moderate to severe atopic dermatitis in adolescence and adulthood and has led to a significant improvement in the treatment of this chronic disease. In the present article we present real-life data on the efficacy of dupilumab in adult dermatitis patients. We also discuss other data relevant to the use of dupilumab, and address open questions important for the standard care of atopic dermatitis patients.