Allergologie Select最新文献

Introduction: Treatment effects in allergen immunotherapy (AIT) studies are based on symptomatic improvement, and evaluations of naturally exposed patients do often show weak efficacy. Allergen challenge tests, such as conjunctival (CAC), nasal (NAC), or bronchial (BAC) challenge tests, or challenges in allergen exposure chambers (AEC) are accepted by regulators for AIT phase II studies only.

Materials and methods: This review aims to describe different allergen challenge test methods, summarizes safety and limitations for each, and discusses their potential for use in AIT trials.

Results: Organ-specific allergen challenges provide information about individual reactivity, reaction threshold, and organ-specific efficacy of AIT. AECs, targeting all affected organs simultaneously, were developed to investigate disease mechanisms and treatment effects under controlled and reproducible conditions.

Conclusion: A high level of standardization is existing for NAC only; in CAC and BAC, the toolbox is limited to subjective symptom scoring with no validated objective parameters identified yet. AECs are complex and heterogenous; correlation of systems and comparability of study data is claimed. All challenge methods are safe when conducted by experienced staff.

Not available.

Chronic urticarial rash, mostly due to chronic spontaneous urticaria (CSU), is seen in up to 1 - 4% of the general population. Urticarial vasculitis (UV) and autoinflammatory syndromes, i.e., cryopyrin-associated periodic syndromes (CAPS) and Schnitzler syndrome (SchS), can mimic CSU-like rash but represent rare disorders with systemic symptoms including fever, headache, conjunctivitis, and arthralgia. Clinical and laboratory features can point to the presence of any of these diseases in patients initially presenting with chronic urticarial rash. These include long-lasting wheals (> 24 hours), lesional burning, systemic symptoms, and/or increase in inflammatory markers (e.g., C-reactive protein, serum amyloid A, and/or S100A8/9). Lesional skin biopsy usually demonstrates leukocytoclastic vasculitis (UV) or neutrophil-rich infiltrate (CAPS and SchS). In contrast to CSU, where second-generation H1 antihistamines and omalizumab allow to control symptoms in most patients, systemic immunosuppression and anti-interleukin (IL)-1 therapies are needed in case of UV and autoinflammatory diseases, respectively. The rarity and low awareness of CSU differential diagnoses may be related to the longer delays in diagnosis and therapy in those affected with UV, CAPS, and SchS. Knowledge of the differential diagnoses of CSU is important because only correct diagnosis allows adequate therapy. Complications such as the development of lymphoproliferative disease in SchS and amyloidosis in CAPS, and the presence of comorbid diseases, such as systemic lupus erythematosus in UV, must be considered and monitored.

In regard to cow's milk allergy, the current option of avoiding can be expanded by (re-)introducing milk using a milk ladder. So-called "food ladders" are internationally well known and utilized for both non-IgE-mediated and IgE-mediated cow's milk allergy. Stepping up the stairs from highly processed baked goods with milk via cooked milk products to pasteurized fresh milk reflects the status of acquired tolerance of each level. The allergenicity of milk depends on processing and amount. By implementing the milk ladder, it can enhance the clinical process of tolerance development, lead to meeting nutrient requirements quickly, and involve parents actively in the therapeutical process. The milk ladder, for the first time being published and adapted for Germany, describes a structured framework that might be adapted individually regarding the time period on a certain level or other variations such as preparation/amount of milk products. From a safety perspective, healthcare professionals should pay great attention to patient selection and education prior to implementing the milk ladder. Detailed advice as well as recipes and a graphical presentation can be found in the supplemental material.

Aim: The efficacy and safety of allergen immunotherapy (AIT) in allergic rhinitis has been classically assessed using randomized controlled trials (RCTs). However, RCTs may have limitations in their external validity, and their evidence may be complemented with that from real-world studies. We aimed to review the mHealth apps that can be used for retrieving real-world data on AIT in allergic rhinitis.

Materials and methods: We applied an automatic tool to identify the mHealth apps (available in the Google Play and Apple App stores) that can be used to assess patients under AIT for allergic rhinitis. Apps meeting the inclusion criteria were reviewed, and the corresponding scientific evidence was assessed.

Results: We identified five apps with scientific publications in the context of allergic rhinitis: AirRater, AllergyMonitor, MASK-air, Husteblume, and Pollen App. Of those, only MASK-air and AllergyMonitor assessed AIT in patients with allergic rhinitis. MASK-air has enabled the comparison of reported symptoms among patients treated vs. not-treated with AIT. MASK-air has also allowed for the development of combined symptom-medication scores that can be used as endpoints for AIT trials. AllergyMonitor has identified that mobile technology can improve adherence to AIT and is set to support the prescription of AIT for patients with allergic rhinitis by a more precise identification of the pollen season.

Conclusion: Mobile health tools allow for the collection of large volumes of real-world data and can be useful for generating hypotheses on AIT. However, such hypotheses require confirmation by epidemiological studies and RCTs.

Omalizumab, a monoclonal antibody targeting IgE, has been approved in 2014 for the treatment of H1 antihistamine-refractory chronic urticaria. Data on long-term effectiveness and predictive factors for treatment response are currently limited. In this monocentric, prospective, observational study, 112 patients with chronic spontaneous urticaria (CSU) and 32 patients with chronic inducible urticaria (CIndU) were included. In addition to a rapid response, omalizumab also showed good effectiveness on both forms of chronic urticaria over 2 years. Low total IgE and elevated Yersinia IgA were identified as potential predictive markers for slower treatment responses in CSU. In conclusion, the present study highlights the efficacy of omalizumab for the treatment of chronic urticaria. With emerging new therapeutic options for chronic urticaria, further genetic as well as molecular markers are needed to establish patient-specific therapy selection.

Allergen immunotherapy (AIT) and vaccination against infectious agents (VIA) are treatments actively interfering with the immune system. This raises the question of whether these therapies influence each other positively and/or negatively if applied simultaneously. For AIT, it should be taken into account that the mechanisms of subcutaneous and sublingual allergen application are in principle similar, but must be assessed in respect to vaccination differently due to their different routes of allergen administration. Here, the immunological mechanisms of both AIT application forms in respect to VIA are discussed in more detail followed by a critical discussion based on the literature and considering current practice.

Allergen immunotherapy (AIT) is the only disease-modifying treatment in allergy. However clinical trials as well as real-life studies revealed poor treatment adherence. This article is intended to provide an overview of the current literature of the last 10 years, to outline reasons for poor treatment adherence in AIT and to provide possible solutions for improving adherence.

Background: Allergen-specific immunotherapy (AIT) is currently the only treatment with potential long-term disease-modifying effects for patients suffering from allergic diseases such as allergic rhinitis, allergic asthma, venom allergy, or IgE-mediated food allergy. A better understanding of the molecular mechanisms underlying immune responses during successful AIT is of utmost importance and it may help to develop more effective and safer treatments.

Materials and methods: PubMed literature review was performed using keywords such as allergen-specific immunotherapy; regulatory T cells; regulatory B cells; regulatory innate lymphoid cells; and allergen-specific antibody from years 2018 to 2021.

Results: The proposed mechanism of long-term tolerance induction in AIT, even upon treatment discontinuation, involves basophils, mast cells, innate lymphoid cells, dendritic cells, allergen-specific regulatory T and B cells, downregulation of effector type 2 responses, decrease in the production of IgE and increase in production of allergen-specific blocking antibodies, such as IgG2 and IgG4.

Conclusion: We summarize the most recent advances related to mechanisms involved in the restoration of healthy immune responses to allergens during AIT. Our knowledge in this regard has significantly improved over the last years, which might well contribute to design novel and improved therapeutic approaches.

Allergic rhinitis is an IgE-mediated inflammation that remains a clinical challenge, affecting 40% of the UK population with a wide range of severity from nasal discomfort to life-threatening anaphylaxis. It can be managed by pharmacotherapeutics and in selected patients by allergen immunotherapy (AIT), which provides long-term clinical efficacy, especially during peak allergy season. However, there are no definitive biomarkers for AIT efficacy. Here, we aim to summarize the key adaptive, innate, humoral, and metabolic advances in biomarker identification in response to AIT. Mechanisms of efficacy consist of an immune deviation towards T_H1-secreting IFN-γ, as well as an induction of IL10⁺ cT_FR and T_REG have been observed. T_H2 cells undergo exhaustion after AIT due to chronic allergen exposure and correlates with the exhaustion markers PD-1, CTLA-4, TIGIT, and LAG3. IL10⁺ DC_REG expressing C1Q and STAB are induced. KLRG1⁺ IL10⁺ ILC2 were shown to be induced in AIT in correlation with efficacy. B_REG cells secreting IL-10, IL-35, and TGF-β are induced. Blocking antibodies IgG, IgA, and IgG4 are increased during AIT; whereas inflammatory metabolites, such as eicosanoids, are reduced. There are multiple promising biomarkers for AIT currently being evaluated. A panomic approach is essential to better understand cellular, molecular mechanisms and their correlation with clinical outcomes. Identification of predictive biomarkers of AIT efficacy will hugely impact current practice allowing physicians to select eligible patients that are likely to respond to treatment as well as improve patients' compliance to complete the course of treatment.