TITLE PAGEFull Title of Manuscript : A case of anaphylaxis caused by the inhalation of sheep’s milk vapors in a child with severe multi-food allergy.Authors’ Full Names : Foti Randazzese Simone, Toscano Fabio, Crisafulli Giuseppe, Galletta Francesca, Manti Sara, Caminiti Lucia.Authors’ Institutional Affiliations : Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Messina (Italy).Running Title : Adverse reactions after inhalation of food allergens.Corresponding Author : Foti Randazzese Simone, Pediatric Resident, Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, via Consolare Valeria, 1, 98121, Messina, Italy. Tel. 0902213165. E-mail:[email protected] count : 1055 words (Main Text).Number of Tables and Figures : 1 table, no figures.

BACKGROUND: Characterization of disease endotypes will open a new window for the treatment of allergic rhinitis (AR). Herein we provide the first attempt to identify specific AR phenotypes/endotypes and/or any biomarker/predictor for specific treatment response based on local biological parameters. METHODS: This observational study was carried out in 142 patients with seasonal AR and 20 non-allergic controls. Total IgE levels, specific IgE to 112 allergenic molecules and 92 proinflammatory and immunologic proteins were measured in both serum and nasal secretions (NS). RESULTS: We found increased values of MCPs and MMPs in adults both in NS and serum when compared with pediatric patients (p<.05). MCPs and MMPs might represent two effective predictors of chronic inflammation. CXCL9, CXCL10, CXCL11, MCPs and MMP1 showed an upward trend both in serum and NS for patients with ≥ 3 comorbidities vs non-allergic controls(p<.05). These data suggest the involvement of these chemokines in the late phase of chronic allergic inflammation in the nose. Serum levels of IL-6, IL-8 and IL-10 (p<.05) were significantly higher in patients with AR+asthma compared to patients with different comorbidities. Conversely, serum levels of neurotrophin-3 values (p<.05) were significantly higher in those with AR+eczema vs other comorbidities groups. A subgroup of patients with a nasal hypersecretory state,called “hypersecreter endotype” was characterized by paediatric age, male gender, grass pollen sensitization and distributed among persistent, mild or moderate to severe cases of AR. CONCLUSIONS: Our study sets the groundwork for an AR endotypization at molecular level, which is highly desirable to deliver a patient-tailored approach.

Atopic dermatitis (AD) is a chronic remitting-relapsing inflammatory skin disorder. Due to the multifactorial pathogenesis, there are numerous therapeutic management approaches, mainly based on symptomatic treatments. In recent years Allergen Immunotherapy (AIT) has been progressively advanced as targeted disease-modifying treatment of allergic disease. The most recent guideline from the American Academy of Dermatology concludes that data available do not support its use in AD. The Joint Task Force and The European Academy of Dermatology suggest that clinicians can consider AIT treatment in selected patients characterized by aeroallergen sensitization, prevalently HDM, severe AD, clinical exacerbation after exposure to the causative allergen. Nevertheless, its role in AD is still under debate, especially in children.

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