Marta Ferrer

Allergic diseases are among the most prevalent chronic conditions in Europe, yet undergraduate medical curricula lack structured Allergy and Clinical Immunology (ACI) teaching. Moreover, desite advances in specialist education, postgraduate university training varies due to differences in specialty recognition, regulatory frameworks, and the implementation of the European Training Requirements. These disparities contribute to inconsistent physician competencies, limited academic visibility of the specialty, and unequal access to high‐quality allergy care. This Position Paper, developed within the framework of the Declaration of Salamanca, analyses the current educational landscape, identifies the main barriers to integrating ACI into medical education, and proposes a strategic roadmap for future development. Evidence from an EAACI‐led European survey, published studies, and expert consensus demonstrates substantial variability in undergraduate curricula, limited academic representation of allergists, fragmented integration of basic immunology and clinical allergy, and challenges in educational innovation, including digital learning and artificial intelligence. The Declaration of Salamanca advocates a coordinated European strategy focused on strengthening undergraduate curricula, increasing ACI's academic presence, promoting closer integration between basic immunology and clinical practice, fostering educational innovation, and enhancing collaboration among universities, scientific societies, accreditation bodies, policymakers, and patient organizations. While responsibility for university curricula and specialty recognition remains with national authorities, the EAACI and National Allergy and Immunology Societies, in partnership with patient organizations, can provide scientific leadership, develop educational standards, and advocate for harmonised approaches. The Declaration of Salamanca offers a practical framework to improve the quality, consistency, and sustainability of ACI education across Europe.

Durable tolerance to food allergens is physiologically established early in life through mucosal immune education, whereas most current allergen immunotherapies primarily induce treatment-dependent desensitization. Here we evaluate a biomimetic oral immunotherapy designed to recapitulate this process in peanut allergy. INP20 is an oral nanoparticle formulation encapsulating complete peanut extract within hypoallergenic zein particles engineered to produce innate immune activation through allergen delivery in the ileocecal region of the distal intestine. In preclinical studies, INP20 preferentially localized to the ileocecal region, induced coordinated Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) activation with IL-10–dominant immune signatures, and protected sensitized mice from fatal anaphylaxis after peanut challenge. In a randomized, double-blind, placebo-controlled Phase 1 dose-escalation trial in peanut-allergic participants (n=52), INP20 was well tolerated up to 20 mg peanut protein and induced a significant increase in peanut-specific IgG4, reaching a mean 8.9-fold rise by day 28 that persisted beyond dosing. *Sara Gómez and Juan Manuel Irache equally contributed.

Chronic spontaneous urticaria (CSU) is a mast cell–driven disease that impairs health-related quality of life. Although omalizumab is a cornerstone treatment for patients uncontrolled with up-dosed second-generation H1-antihistamines, some patients remain partially responsive or refractory. This narrative review summarizes current concepts in defining, predicting, and managing omalizumab-refractory CSU. Response assessment should rely on validated patient-reported outcome measures, particularly the 7-day Urticaria Activity Score (UAS7) and Urticaria Control Test (UCT), to distinguish complete response, partial response, and true non-response, while also helping to identify pseudo-resistance related to poor adherence or misdiagnosis. Emerging biomarker data support an endotype-driven approach: higher total immunoglobulin E (IgE) is generally associated with type I autoallergic CSU and a better response to omalizumab, whereas low total IgE, basopenia, positive basophil histamine release assay (BHRA) or basophil activation test (BAT) results, and other autoimmune markers suggest type IIb autoimmune CSU and a greater likelihood of inadequate anti-IgE response. For patients with persistent disease despite omalizumab, cyclosporine A remains an evidence-based option, while newer targeted therapies, including dupilumab, Bruton’s tyrosine kinase inhibitors, and anti-KIT antibodies, are expanding the treatment landscape. Overall, management of omalizumab-refractory CSU is shifting toward precision medicine that integrates validated outcome measures, biomarker-informed endotyping, comorbidities, access, safety, and patient preferences. However, standardized switching algorithms, comparative effectiveness data, and validated predictive biomarkers are still needed to optimize individualized care.

This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA ² LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell‐driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert‐guided and evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Chronic urticaria, defined as having urticaria for over 6 weeks, is divided into two categories; namely, inducible urticaria and chronic spontaneous urticaria (CSU). Inducible urticarias have an initiating stimulus, often “physical”, and actually occur intermittently, but the total duration of symptoms can encompass many years. CSU is more typically chronic, has urticarial lesions most days of the week, has no exogenous cause, and from the patient’s point of view, does seem spontaneous. An algorithm for the diagnosis of CSU is shown in Fig. 1. Angioedema can accompany many inducible urticarias, but is more typically associated with CSU affecting face, extremities, genitalia, lips, tongue, and rarely pharynx, but not the larynx. Thus risk of asphyxiation is nil. The disorder is strongly associated with autoimmunity. The best studied (often referred to as type IIb autoimmunity) involves IgG antibody to the IgE receptor[1](#ref-0001) which cross-links unoccupied IgE receptors of mast cells and activates the cells to cause secretion of histamine, leucotrienes, cytokines, and chemokines. Complement is activated and release of C5a augments the mast cell secretion[2](#ref-0002). There is a second scenario in which patients have IgE antibody to a large variety of autoantigens[3](#ref-0003) including thyroperoxidase and interleukin 24, although which are pathogenic is not yet clear. This is often designated as type I autoimmunity or autoallergy. Clinically, other autoimmune disorders may be present. The most prominent is Hashimoto’s thyroiditis, but also type I diabetes and vitiligo. Antithyroid antibodies (i.e. IgG anti microsomal antigen and IgG antithyroglobulin) are seen in 25% of patients regardless of thyroid status. Total IgE is elevated within this population although much less so than in asthma or atopic dermatitis. Low or very low IgE levels may be seen and such patients are less responsive to omalizumab[4](#ref-0004).