Moises Labrador-Horrillo

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.

Background: Chemotherapy (CHT) and monoclonal antibodies (mAbs) have been described as frequent causes of drug allergy. Currently, rapid drug desensitization (RDD) is a widely recognized and safe procedure extensively used to manage patients with drug hypersensitivity reactions (DHR). Nevertheless, despite its effectiveness, RDD can occasionally be hampered by severe breakthrough reactions (BTR) during the procedure, potentially leading to its failure. Objective: Evaluate the usefulness and safety of adrenaline infusion (AI) as a coadjuvant during RDD in patients with severe DHR during standard desensitization protocols. Methods: Retrospective observational study, analyzing data from patients who underwent RDD to CHT or mAbs in a tertiary hospital from January-2015 to January-2024. We included patients who required the use of AI to safely achieve RDD after a severe initial DHR or failure of standard RDD protocol due to repeated DHR. Comorbidities, adrenaline doses and adverse events (AE) were assessed. Results: Forty-two patients met the inclusion criteria. Seventy-seven percent ( n =32) were women with a mean age of 57 years(range 32-83). Most frequent drugs involved in DHR were platinum-salts 58%, mAbs 26% and taxanes 14%. A total of 151 RDD were performed with coadjuvant AI. Skin tests were positive in 69% of patients. The most frequent initial BTR (65%, n=28 ) was moderate or severe anaphylaxis. The most common adverse events (AE) associated with AI were trembling and tachycardia (14% and 7% respectively). These symptoms subsided after reducing the AI infusion rate. The median cumulative dose of adrenaline administrated during the entire RDD procedure was 0.76µg(IQR 0.4-1.2µg SD 3.05), with a median infusion rate of 8ml/h(IQR 4-15ml/h), and median AI maximum rate of 3.33µg/min(IQR 2-5.3µg/min). Conclusions: AI is a useful and safe therapeutic tool for selected high-risk desensitization procedures, contributing to mitigate severe DHR with mostly minor AE.

Systemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity.

Background: There is an urgent need to assess the levels of protection generated by natural infection or SARS-CoV-2 vaccines, especially in individuals professionally exposed. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection. Our aim was to assess the feasibility of a validated assay of T-cell responses applicable to large number of samples. Methods: Twenty health-care-workers (HCW) were included. Antibody test to SARS-CoV-2 N and S-proteins in parallel with a commercially available whole-blood-interferon-gamma-release-assay (IGRA) to S-peptides and two detection methods, CLIA and ELISA were determined. Results: IGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. The correlation by the two detection methods was very high (R>0.9) and sensitivity and specificity ranged between 100 and 86% and 100-73% respectively. Even though there was a very high concordance between antibody and the IGRA assay in the ability to detect immune response to SARS-CoV-2, there was a relatively low quantitative correlation. In the small group primed by natural infection, one vaccine dose was sufficient to reach immune response plateau. IGRA was positive in one, with Ig(S) antibody negative vaccinated immunosuppressed HCW illustrating another advantage of the IGRA-test. Conclusion: Whole-blood-IGRA-tests amenable to automation and constitutes a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become a valuable correlate of protection to COVID-19, particularly for

Background: Recognition of specific allergens triggering immune response is key for the appropriate prescription of allergen‐specific immunotherapy (SIT). This study aimed at evaluating the impact of using the commercially available microarray ImmunoCAP^TM ISAC 112 (Thermo Fisher Scientific) on the etiological diagnosis and SIT prescription compared to the conventional diagnostic methods in patients with allergic rhinitis/rhinoconjunctivitis and/or asthma.Methods: 300 patients with respiratory allergic disease, sensitized to three or more pollen aeroallergens from different species, as assessed by a skin prick test (SPT) and specific IgE assays (sIgE), were included in this multicentric, prospective observational study. SPT and a blood test were performed to all patients. Total serum IgE and sIgE (ImmunoCAPTM) for allergens found positive in the SPT and sIgE allergen components (ImmunoCAPTM ISAC 112) were measured.Results: According to SPT results, the most prevalent pollen sensitizers in our population were Olea europaea followed by grass, Platanus acerifolia and Parietaria judaica. The molecular diagnosis (MD) revealed Ole e 1 as the most prevalent pollen sensitizer, followed by Cup a 1, Phl p 1, Cyn d 1, Par j 2, Pla a 1, 2, and 3 and Phl p 5. Immunotherapy prescription changed, due to MD testing, in 51% of the cases, with an increase of prescription of SIT from 39% to 65%.Conclusion: The identification of the allergen eliciting the respiratory disease is essential for a correct immunotherapy prescription. The advances in allergen characterization using methods, such as the commercial microarray ImmunoCAP^TM ISAC 112, can help clinicians to improve SIT prescription.

The terms control and remission and other key terms used in chronic urticaria (CU) such as flare-up, relapse, exacerbation, and recurrence have not been fully defined in the literature. Disease monitoring and treatment goals in clinical practice are not well established. After a qualitative appraisal of available evidence, we aimed to find a consensus definition of control and remission, clarify key terminology, provide guidance on how to monitor the disease, and establish treatment goals in clinical practice. A modified Delphi consensus approach was used. Based on a literature review, a scientific committee provided 137 statements addressing controversial definitions and terms, available patient-reported outcomes (PROs), and recommendations on how to measure therapeutic objectives in CU. The questionnaire was evaluated by 138 expert allergists and dermatologists. A consensus was reached on 105 out of the 137 proposed items (76.6%). The experts agreed that complete control and remission of CU could be defined as the absence of signs or symptoms while on treatment and in the absence of treatment, respectively. Consensus was not reached on the definition of other key terms such as flare-up, exacerbation, and recurrence. The panel agreed that the objective of therapy in CU should be to achieve complete control. PROs that define the degree of control (complete, good, partial, or absence) were established. An algorithm for disease assessment is provided. In conclusion, this work offers consensus definitions and tools that may be useful in the management of patients with CU.

Background: Recognition of specific allergens triggering immune response is key for the appropriate prescription of allergen-specific immunotherapy (SIT). This study aimed at evaluating the impact of using the commercially available microarray ImmunoCAP ^TM ISAC 112 (Thermo Fisher Scientific) on the etiological diagnosis and SIT prescription compared to the conventional diagnostic methods in patients with allergic rhinitis/rhinoconjunctivitis and/or asthma. Methods: 300 patients with respiratory allergic disease, sensitized to three or more pollen aeroallergens from different species, as assessed by skin prick-test (SPT) and specific IgE assays (sIgE), were included in this multicentric, prospective observational study. SPT and a blood test were performed to all patients. Total serum IgE, sIgE (ImmunoCAP ^TM ) for allergens found positive in the SPT and sIgE allergen components (ImmunoCAP ^TM ISAC 112) were measured. Results: According to SPT results, the most prevalent pollen sensitizers in our population were Olea europaea followed by grass, Platanus acerifolia and Parietaria judaica. The molecular diagnosis (MD) revealed Ole e 1 as the most prevalent pollen sensitizer, followed by Cup a 1, Phl p 1, Cyn d 1, Par j 2, Pla a 1, 2, and 3 and Phl p 5. Immunotherapy prescription changed, due to MD testing, in 51% of the cases, with an increase of prescription of SIT from 39% to 65%. Conclusion: The identification of the allergen eliciting the respiratory disease is essential for a correct immunotherapy prescription. The advances in allergen characterization using methods such as the commercial microarray ImmunoCAP ^TM ISAC 112 can help clinicians to improve SIT prescription.