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Background: Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells. Methods: Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years. Results: We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was p-phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases. Interpretation: Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments. [ABSTRACT FROM AUTHOR]

A systematic review and narrative synthesis of publications was undertaken to analyze the role of component-resolved diagnosis technology in identifying polysensitization for the provision of allergen-specific immunotherapy to patients with seasonal allergic rhinitis. A search of publications was carried out in electronic databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search helped to identify 568 publications, 12 of which were included in this review. Overall, 3302 patients were enrolled. The major finding was that component-resolved diagnostics change the choice of relevant allergens for allergen-specific immunotherapy in at least 50% of cases. Sensitization to allergen components differs with age, type of disease, and overall disease duration. Patients who had both bronchial asthma and allergic rhinitis were sensitized to a larger number of allergens than patients who had bronchial asthma alone. [ABSTRACT FROM AUTHOR]

Allergen Immunotherapy (AIT) is a well-established, efficient, and safe way to treat respiratory and insect-venom allergies. After determining the diagnosis of the clinically relevant culprit allergen, AIT can be prescribed. However, not all patients are eligible for AIT, since some diseases/conditions represent contraindications to AIT use, as described in several guidelines. Allergists are often preoccupied on whether an extensive workup should be ordered in apparently healthy AIT candidates in order to detect contra-indicated diseases and conditions. These preoccupations often arise from clinical, ethical and legal issues. The aim of this article is to suggest an approach to the workup and assessment of the presence of any underlying diseases/conditions in patients with no case history before the start of AIT. Notably, there is a lack of published studies on the appropriate evaluation of AIT candidates, with no globally accepted guidelines. It appears that Allergists are mostly deciding based on their AIT training, as well as their clinical experience. Guidance is based mainly on experts' opinions; the suggested preliminary workup can be divided into mandatory and optional testing. The evaluation for possible underlying neoplastic, autoimmune, and cardiovascular diseases, primary and acquired immunodeficiencies and pregnancy, might be helpful but only in subjects for whom the history and clinical examination raise suspicion of these conditions. A workup without any reasonable correlation with potential contraindications is useless. In conclusion, the evaluation of each individual candidate for possible medical conditions should be determined on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Background: We evaluated the value of positive intradermal dilution testing (IDT) after negative skin prick tests (SPT) by retrospectively determining allergy immunotherapy (AIT) outcomes. Methods: This private practice, cohort study compared the relative value of SPT vs. IDT in 371 adults and children with suspected manifestations of allergy: chronic allergic rhinitis (AR), asthma and/or chronic otitis media with effusion (OME). The primary outcome measure was symptom resolution following immunotherapy, as determined by symptom severity questionnaires completed by patients before and after AIT. Results: Positive IDT identified 193 (52%) patients who would not otherwise have been diagnosed. IDT detected 3.7-fold more allergens per patient than SPT (8.56 vs. 2.3; p < 0.01). Patients positive only on IDT responded to AIT equally well as those identifiable by SPT, independent of allergen sensitivity (67% by SPT vs. 62% by IDT; p = 0.69, not significantly different). Conclusion: Intradermal titration can identify patients who will benefit from allergy immunotherapy more accurately than SPT. Outcomes analysis in 371 patients shows that IDT doubled their chance of successful treatment with no greater risk of therapeutic failure. Positive IDT, following negative SPT, is clinically relevant and offers superior sensitivity over SPT for detecting allergens clinically relevant to diagnosis of AIT-responsive atopic disease. [ABSTRACT FROM AUTHOR]