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Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

Background: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies., Methods: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete., Findings: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab., Interpretation: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies., Funding: Novartis Pharma., Competing Interests: Declaration of interests MM is or recently was a speaker, an adviser for, or has received research funding from Amgen, Allakos, Aralez, AstraZeneca, Celldex, FAES, Genentech, GI Innovation, Kyowa Kirin, Leo Pharma, Menarini, Novartis, Moxie, MSD, Roche, Sanofi, Third Harmonic, UCB, and Uriach. LFE is or recently was a speaker or adviser for Novartis, Sanofi, and AbbVie, and has received research support from Novartis and Sanofi. AMG-A reports roles as a medical adviser for Uriach Pharma, Sanofi, Genentech, Novartis, FAES, GSK, AMGEN, Thermo Fisher, and has received research grants supported by Uriach Pharma, Novartis, and Instituto Carlos III- FEDER; she also participates in educational activities for Uriach Pharma, Novartis, Genentech, Menarini, LEO-PHARMA, GSK, MSD, Almirall, AVENE, and Sanofi. GS has received research support from Aimmune, Amgen, AstraZeneca, DBV technologies, Genentech, Kedrion, Leo Pharma, Novartis, Nuvo Pharmaceuticals, Sanofi, Stallergenes, Merck, and Schering-Plough; and is a medical adviser or has received payment for lectures from Merck, Novartis, CSL Behring, Pfizer, Anaphylaxis Canada, the Allergy Asthma and Immunology Society of Ontario, and the Canadian Hereditary Angioedema Network. MH has received lecture or consultation fees from TAIHO Pharmaceutical, Novartis, MSD, Teikoku Seiyaku, Mitsubishi Tanabe Pharma, Kaken Pharmaceutical, Kyorin Pharmaceutical, Uriach, Sanofi, and Kyowa-Kirin and GI Innovation. SS received grant, research, or clinical trial support from the National Institutes of Health, ITN, Novartis, Regeneron, and is a consultant or advisery board member for Genentech, Novartis, Medimmune, AstraZeneca, Pfizer, Allakos, Eli Lily, and Gossamer Bio. CG has recently been an adviser for Celltrion and has participated in an advisery board for Sanofi. DF is, or recently was, a speaker or adviser for Novartis, Sanofi, AbbVie, Takeda, AstraZeneca, CSL Behring, and Roche. DR received fees as lecturer and advisery board member for Novartis, Leo, Lilly, MSD, UCB, Janssen, Sanofi, Menarini, Genesis pharma, and AbbVie. FB has received payment or honoraria as speaker fees from Novartis. GWC reports having received research grants, as well as being a lecturer or having received advisery board fees, from Menarini, Alk-Abello', Allergy Therapeutics, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Genentech, Guidotti-Malesci, GSK, Hal Allergy, Mylan, Merck, Merck Sharp & Dome, Mundipharma, Novartis, Regeneron, Roche, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes-Greer, UCB Pharma, Uriach Pharma, Valeas, and Vibor-Pharma. HR reports receiving speaker's fees, advisery board fees or funds for research to the institution from Novartis Pharma, Pharming, Sanofi-Genzyme, Third Harmonic, and Leo Pharma. CI reports having received research or clinical trial support, or fees for lectures from Novartis, Sanofi, AstraZeneca, Takeda, and Stallergenes Greer. JCS reports receiving fees for being consultant or advisery board member for Leo Pharma, Novartis, Pfizer, Sanofi-Genzyme, Trevi, UCB, and Vifor; for being speaker for AbbVie, Almirall, Alvotech, Janssen-Cilag, Eli-Lilly, Leo Pharma, Novartis, Pfizer, and Sanofi-Genzyme; for being the investigator in clinical trials for AbbVie, Almirall, Amgen, AnaptysBio, BMS, Boehringer Ingelheim, Celtrion, Galderma, Galapagos, Helm, Kliniksa, Incyte, InfraRX, Janssen-Cilag, Leo Pharma, Medimmune, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, Teva, and Trevi. JAB reports grants and personal fees from Novartis, AstraZeneca, Allakos, Amgen, Celldex, Genentech, and Sanofi Regeneron outside the submitted work. JGP has received travel support, speakers' honoraria, and educational grants from Novartis, Sanofi Regeneron, Takeda, Pharming, and CSL Behring. KK is or recently was a speaker or adviser for Novartis, Sanofi, Takeda, and A Menarini, and has received research grants from Novartis. LA is or recently was a speaker, adviser, or has received research funding from AstraZeneca, GSK, Novartis, OM-Pharma, Regeneron, Shire, Takeda, and Sanofi-Genzyme. PS is or recently was a speaker, adviser, or has received research funding from AbbVie, Allergika, Almirall, Amgen, Beiersdorf, Biocryst, Biogen, BMS, Boehringer-Ingelheim, Celgene, CSL-Behring, Eli-Lilly, Galderma, Hexal, Janssen, Klinge, Klosterfrau, LEO-Pharma, LETI-Pharma, L'Oreal, Medice, Novartis, Octapharma, Pfizer, Pflüger, Pharming, Pierre Fabre, Regeneron, Shire, Takeda, Regeneron, Sanofi-Genzyme, und UCB Pharma. RS is Director and Founder of Samson Medical Pty, and serves on the pharmaceutical advisery board of Eli Lilly, Pfizer, Leo Pharmaceutical, and reports being on the speaker bureau of Pfizer, AbbVie, and Novartis. He has also been principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer, Biotherapeutics Boehringer Ingelheim, Bristol Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly, Galderma, GSK, F. Hoffman–La Roche, Janssen, MedImmune, Merck, Merck Sharpe & Dohme, Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche, Reistone Biopharma, Samson Clinical, Sanofi-Genzyme, Sun Pharma UCB, Valeant, and Zai Labs. He is President of the Australasian Hair and Wool Research Society, Vice President of the International Society of Dermatology, and The International Academy of Dermatology. SG has consulted or advised for Novartis and IgGenix. SFT is or recently was a speaker, adviser for, or has received research funding from AbbVie, Almirall, Boehringer Ingelheim, CSL, Eli Lilly, Janssen, Leo Pharma, Novartis, Sanofi, Pfizer, UCB, and Union Therapeutics. TT received clinical trial support from Novartis, AstraZeneca, Celldex Therapeutics, Genentech, and GSK. YMY has received research or clinical trial support from Novartis, Amgen, Yuhan, Takeda, and Daewoong ABa, DM, and ES are employees of Novartis Pharmaceuticals, East Hanover, New Jersey, NJ, USA. EH is an employee of Novartis Institutes for Biomedical Research, China. VV is an employee of Novartis Healthcare Private, Hyderabad, India. ABu, KL, MP, and TS are employees of Novartis Pharma, Basel, Switzerland. KG, JL, and OU report no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE ® , the Chronic Urticaria Self Evaluation app, aims to address this unmet need., Methods: CRUSE ® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE ® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE ® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations., Results: CRUSE ® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days., Conclusions: The initial data from CRUSE ® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management., (© 2024 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background: Non-sedating H 1 -antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on-demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long-term disease-modifying effects., Methods: This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double-blind treatment, and 6 weeks of treatment-free follow-up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow-up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU-related quality of life (QoL), and disease control., Results: At Week 4, disease activity and QoL significantly improved in daily versus OD-treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow-up, the disease activity of patients treated OD versus daily was not significantly different., Conclusions: Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Health apps play an increasing role in everyday healthcare, especially for chronic diseases. The Chronic Urticaria Self Evaluation (CRUSE) is a new mobile health app for chronic spontaneous urticaria (CSU) patients, which replaces disease tracking via paper and pen, thus making disease monitoring more convenient, increasing tracking compliance, and improving data quality and access. Methods: CRUSE enables patients to complete patient-reported outcome measures on their smartphone and send the results, along with current medication and pictures, to their treating physician via email. CRUSE captures the urticaria (UAS) and angioedema activity (AAS) scores and the urticaria and angioedema control tests (UCT and AECT). In this work, a descriptive analysis of CRUSE users and reported days was performed. The global network of Urticaria Centers of Reference and Excellence (UCARE) provides the app and its data. Results: CRUSE is now available in Germany, Switzerland, Austria, the UK, Italy, Spain, France, and Turkey. Of 620 newly registered users (from July 1 st until November 18 th of 2022), 72 % were female, and the mean age was 36.6 years (17 - 78 years). The average daily UAS and AAS value (mean ± standard deviation) were 2.1 ± 1.9 and 7.2 ± 3.3, respectively. Most CRUSE patients had poorly controlled disease, with mean UCT values of 7.0 ± 4.4 and mean AECT values of 8.1 ± 4.5. Conclusion: The first days of patients with CSU using CRUSE confirm the high need for an app that helps to monitor disease activity, impact, and control. The first results indicate low levels of disease control in most CRUSE users, with low UCT and AECT values. Future analyses will assess follow-up documentation data and evaluate the effects of treatment changes on CSU activity, impact, and control., (© 2023 Neisinger et al, HBKU Press.)

Chronic spontaneous urticaria (CSU) is a debilitating inflammatory disorder of the skin, characterized by a fluctuating natural history, a complex mechanism of action, and a significant burden on patients, including effect on quality of life, development of psychosocial disorders, and a range of comorbidities. Recent international guidelines recommend a therapeutic approach of first-line treatment with second generation H1-antihistamines and second-line treatment with the biologic omalizumab. Here, the salient aspects of CSU and current status of data for omalizumab for patients with CSU are reviewed, with a focus on mechanism of action, efficacy and real-world effectiveness (including patient outcomes, response, relapse, and remission), and safety (including consideration of the risk of anaphylaxis). The review also considers recent data on COVID-19, CSU, and omalizumab and presents our perspective on future needs. Overall, the data suggest that omalizumab is an effective and well-tolerated treatment for patients with CSU that provides benefits for a wide range of patients., (© 2023. The Author(s).)

Background: Urticarial vasculitis (UV) should be differentiated from chronic spontaneous urticaria (CSU) in patients initially presenting with recurrent wheals, although criteria for differential diagnosis remain ill-defined., Objectives: To set the goals, define criteria and unmet needs in UV diagnosis and differential diagnosis with CSU, and explore the possibility of coexistence of both diseases., Methods: Thirteen experts experienced in UV research participated in a Delphi survey of European Academy of Allergy and Clinical Immunology taskforce. This Delphi survey involved three rounds of anonymous responses to n = 32 questions with the aim to aggregate the experts' opinions and to achieve consensus. Urticaria specialists (n = 130, most from Urticaria Centers of Reference and Excellence) evaluated the consensus statements and recommendations in the fourth and final round., Results: The panel agreed that essential criteria to guide a skin biopsy in patients with recurrent wheals should include at least one of the following features: wheal duration >24 h, bruising/postinflammatory hyperpigmentation, and systemic symptoms. Leukocytoclasia and fibrin deposits were identified as a minimum set of UV histological criteria. As agreed by the panel members, CSU and normocomplementemic UV (NUV) may coexist in some patients., Conclusions: The use of established criteria for the diagnosis and differential diagnosis of UV in patients with recurrent wheals can help guide the diagnostic approach and prompt earlier treatment. Further studies should investigate whether CSU and NUV are different entities or part of a disease spectrum., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background: In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential., Materials and Method: The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs)., Results: We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine., Conclusions: Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society., Objectives: To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations., Methods: The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n = 46 652) in whom an occupational causation was refuted served as comparison group., Results: The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time., Conclusions: Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease., Objective: To analyse the treatment use by CU patients before, during and after pregnancy as well as outcomes of pregnancy., Methods: PREG-CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence network. Data were collected via a 47-item-questionnaire completed by CU patients who became pregnant during their disease course., Results: Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication including standard-dose second generation H1-antihistamines (35.1%), first generation H1-antihistamines (7.6%), high-dose second-generation H1-antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new-borns were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth., Conclusion: Most CU patients used treatment during pregnancy especially second-generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new-borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized., Objective: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination., Methods: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification., Results: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment., Conclusions: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients., (© 2021 British Association of Dermatologists.)

Background: Methyldibromo glutaronitrile (MDBGN) was one of the most frequent and relevant allergens found in patch testing at the beginning of this century. In 2008, this preservative was banned from cosmetics in Europe and ever since the prevalence of contact allergy to MDBGN has progressively decreased. Despite that gradual decline, MDBGN is still patch-tested in most baseline series. This study assessed the frequency of MDBGN sensitization, epidemiological characteristics of allergic patients, and the relevance of positive patch tests in a nationwide Spanish registry (REIDAC)., Patients and Methods: We evaluated consecutively patch-tested patients in all participating centres. Using these data, we calculated the proportion of patients with positive patch tests to MDBGN from June 2018 to June 2020 and evaluated the relevance of the positive patch tests., Results: One hundred and fourteen out of 5072 (2.24 %) tested patients were sensitized to MDBGN. Clinical current relevance was confirmed in only one case., Conclusion: Although the frequency of contact allergy to MDBGN remains high, no clinical significance was found in most of these patients (5072 tests needed to obtain one relevant positive result). The clinical usefulness of this allergen seems weak and its continued inclusion in the European baseline series is questionable., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown., Aim: To analyze the course and features of CU during and after pregnancy., Patients and Methods: PREG-CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47-item questionnaire completed by CU patients, who became pregnant within the last 3 years., Results: A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively., Conclusions: These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

This article discusses contact urticaria syndrome definition, history, epidemiology, occupational relevance, mechanisms, clinical manifestations, diagnostic tools, agents responsible, and how to prevent and treat the patients affected. Contact urticaria syndrome is often misdiagnosed because it is not well known or recognized by physicians. Commonly the patient recognizes the cause of the clinical symptom, but the cause can be exceptional or new. Triggers include proteins, chemical compounds, agricultural chemicals, metals, plants, foods, and other substances. The objective of this article is to help dermatologists, toxicologists, and immunologists by providing diagnostic tools to avoid the culprit agent and treat the patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There are few epidemiological studies of urticaria, published in the indexed literature (PubMed/Medline)., Objective: The study aimed to evaluate the epidemiological and clinical data among patients with urticaria/angioedema attending a reference clinic in Brazil., Methods: Two hundred sixty-seven patients were evaluated retrospectively considering demographic data, time course of the disease, triggering symptoms, the presence of angioedema, complementary laboratory tests including total blood count, reactive-C protein, erythrocyte sedimentation rate, IgE serum levels, and other, as necessary., Results: The most commonly diagnosed type of urticaria was chronic spontaneous urticaria (56.93%). Angioedema was associated with chronic urticaria in 108 patients (40.08%)., Study Limitations: Unicentered and retrospective., Conclusion: Some relevant findings in this study are the observation of a female prevalence of cases (4-females: 1-man), a result more elevated than demonstrated in previous studies in Europe and Asia, the median age was 43-years old and the delay of time between the diagnosis of urticaria and the admission for treatment in a specialized center was approximately 2-years. Other multicenter studies can better establish these differences in Brazilian patients., (Copyright © 2021 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Insights into the real-world treatment paradigm and long-term burden of atopic dermatitis (AD) are needed to inform clinical and health policy decisions., Methods: The prospective, observational EUROSTAD study enrolled adults with moderate-to-severe AD starting or switching systemic therapy (51 sites in 10 European countries). We report the baseline characteristics, treatment patterns, and outcomes of these patients using descriptive statistics., Results: A 12-month enrollment period of EUROSTAD was completed and 308 patients were enrolled: average age 37 years, AD duration 25 years, 43% were female. Most patients reported use of systemic therapy (93%) and ≥1 atopic comorbidity (82%). Mean [standard deviation] disease severity/burden measures were high: Investigator's Global Assessment (3.1 [0.8]), Eczema Area and Severity Index (16.2 [10.9]), Peak Pruritus Numerical Rating Scale (5.5 [2.5]), sleep impairment Visual Analog Scale (49.8 [31.6]) scores, and time lost from work (4.1 [13.7] days/year) or usual activities (16.8 [38.7] days/year). Most patients showed borderline or clinical levels of anxiety (59%) and/or depression (63%) using the Hospital Anxiety and Depression Scale., Conclusions: Adults with moderate-to-severe AD starting/switching systemic treatment enrolled in EUROSTAD have a high burden of longstanding disease despite continuous use of topical drugs, emollients, and systemic therapies.

Background: The real-life data on the effectiveness and safety of omalizumab in chronic spontaneous urticaria (CSU) with validated methods are scarce. There is also a lack of information on the use of combination treatments. Methods: A retrospective cohort study was done to evaluate the effectiveness and safety of omalizumab in real-life conditions. The patients with CSU treated with omalizumab between 2015 and 2018 were included. The response to therapy was evaluated using urticaria activity score over 7 days (UAS7) and urticaria control test (UCT). Results: A total of 106 patients were included. A complete response (CR) (UAS7:0) and a well-controlled activity (WCA) (UAS7:1 to <6) were observed in 50 (47.2%) and 35 (33%) patients, respectively. The number of patients with an UCT score ≥12 was also significantly increased. Higher rates of CR/WCA were observed with omalizumab monotherapy compared to combination with antihistamines. The combination of dapsone, colchicine, and omalizumab provided additional benefit in a small group. Conclusion: Treatment with omalizumab provided a rapid and sustainable improvement in real-life settings. The use of omalizumab as monotherapy or combined with antihistamines does not show differences in the treatment response. The combination of omalizumab with immunomodulatory agents might be of benefit in selected cases.

Background: The subtypes of chronic urticaria (CU) share a common clinical expression, but phenotypically may show differences., Objectives: To evaluate sociodemographic and clinical differences in CU phenotypes, including: (1) isolated chronic spontaneous urticaria (CSU); (2) isolated chronic inducible urticaria (CIndU); (3) CSU with concomitant CIndU (CSU-CIndU); (4) CSU with single or multiple episodes; (5) early and late-onset CSU (<45/65 years vs ≥45/65 years); and (6) CSU with presence vs absence of serum autoreactivity., Materials and Methods: A retrospective observational study of 997 patients with urticaria was performed, with clinical, laboratory and therapeutic comparisons between CU subtypes., Results: A clear female predominance was detected for CU, mostly in patients with serum autoreactivity. CIndU patients were younger, showed less angioedema, and had a better response to antihistamines. Stress and drugs were the main triggering factors for CSU. Patients with exclusive CIndU or recurrent CSU showed less psychiatric comorbidities. Patients with concomitant CIndU and serum autoreactivity showed greater urticaria activity., Conclusion: Knowledge of the clinical differences between CSU subtypes may help to define an individual therapeutic strategy and improve the control of symptoms and quality of life.

Four patients presenting a peculiar clinical variant of erythema annulare centrifugum are reported. The lesions were clinically and histopathologically indistinguishable from classic superficial erythema annulare centrifugum but constant annual and seasonal recurrences for many years or decades were observed. No clear precipitating factor could be identified. No associated symptoms were present and the eruption regressed spontaneously after a variable period of days to months. Annually recurring erythema annulare centrifugum seems to represent a rare distinct clinical entity that has received little attention in literature. Clinicopathologic features of this peculiar clinical disorder and the differential diagnosis with other recurrent seasonal eruptions are reviewed.

The CDKN2A gene has been implicated in cutaneous malignant melanoma (CMM) in about 40% of families with linkage to chromosome 9p21, while a small proportion of families have mutations in the CDK4 gene. In order to estimate the importance of these genes in the predisposition to CMM in Spanish families and patients we have analysed, by SSCA, a total of 56 subjects belonging to 34 CMM families, and nine patients with multiple CMM and other neoplasia. We have detected germline CDKN2A mutations in six out of the 34 families (17%). A frameshift mutation (358delG) and four missense mutations (G59V, G101W (two cases), D84Y, and R87W) were identified. Five CMM patients from different families (14%) carried the A148T variant, which is known not to affect p16 activity. No mutations were detected in the patients with multiple CMM or other neoplasms. We have not found mutations either in exon 1 beta of the CDKN2A gene or in exon 2A of CDK4. Linkage analysis of the 9p21 region showed exclusion for one of the families for CMM and for four families for CMM/dysplastic naevi. This study indicates a small role for CDKN2A in Spanish CMM families and suggests that other genes are also responsible for CMM predisposition.

Visceral involvement in HIV-negative patients with classical Kaposi's sarcoma (KS) has been described only rarely. An unusual case of a 75-year-old Jewish woman with the classical form of KS who presented with cutaneous and pulmonary involvement is presented. Results of several tests for HIV antibodies were negative.