Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

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Nonsteroidal anti‐inflammatory drugs (NSAIDs), the medications most commonly used for treating pain and inflammation, are the main triggers of drug hypersensitivity reactions. The latest classification of NSAIDs hypersensitivity by the European Academy of Allergy and Clinical Immunology (EAACI) differentiates between cross‐hypersensitivity reactions (CRs), associated with COX‐1 inhibition, and selective reactions, associated with immunological mechanisms. Three phenotypes fill into the first group: NSAIDs‐exacerbated respiratory disease, NSAIDs‐exacerbated cutaneous disease and NSAIDs‐induced urticaria/angioedema. Two phenotypes fill into the second one: single‐NSAID‐induced urticaria/angioedema/anaphylaxis and single‐NSAID‐induced delayed reactions. Diagnosis of NSAIDs hypersensitivity is hampered by different factors, including the lack of validated in vitro biomarkers and the uselessness of skin tests. The advances achieved over recent years recommend a re‐evaluation of the EAACI classification, as it does not consider other phenotypes such as blended reactions (coexistence of cutaneous and respiratory symptoms) or food‐dependent NSAID‐induced anaphylaxis. In addition, it does not regard the natural evolution of phenotypes and their potential interconversion, the development of tolerance over time or the role of atopy. Here, we address these topics. A state of the art on the underlying mechanisms and on the approaches for biomarkers discovery is also provided, including genetic studies and available information on transcriptomics and metabolomics.

Section: The Search For Biomarkersmentioning

confidence: 99%

Progress in understanding hypersensitivity reactions to nonsteroidal anti‐inflammatory drugs

Doña

Pérez‐Sánchez

Eguiluz‐Gracia

et al. 2019

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“…162 Thus, more data are needed to better understand the risks and develop tools to predict residual reactivity. 167 Dupilumab, which is approved for atopic dermatitis, is currently being extensively studied for treatment of peanut allergy (NCT03793608) and for OIT in combination with AR101 (NCT03682770). 156 By suppressing IL-4 and IL-13, which are key for IgE class-switching, expansion, maintenance, and activation of effector cells, food-allergic responses may be abolished as suggested by recent case reports.…”

Section: Antig En -Uns Pecific and Additive A Pproache Smentioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Self Cite

The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

“…A better understanding of the underlying immunological mechanisms is still needed. 195,196 All these are the main causes of the great rate of misdiagnosis that may be influenced by self-reported reactions without a subsequent accurate evaluation, the deficient training of nonspecialized healthcare professionals and patients. Recently published guidelines and consensus position papers have outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, as well as the need to generalize the use of allergy cards to avoid the induction of DHRs due to the prescription of wrong medication.…”

Section: Con Clus Ionsmentioning

confidence: 99%

Recent developments and highlights in drug hypersensitivity

Mayorga

Fernandez

Montañez

et al. 2019

Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management.Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs. K E Y W O R D Sallergy diagnosis, allergy treatment, basic mechanisms, drug allergy, epidemiology | 2369