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Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near-daily basis, over >6 weeks; many patients experience flare-ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.

Background: Hand eczema (HE) is a common skin disease characterized by itch, pain and visible skin changes such as fissures, erythema and vesicles. It is not yet clear which outcome domains are most important for patients. The Hand Eczema Core Outcome Set (HECOS) initiative is developing a consented set of core domains and suitable measurement instruments for the future application in all HE trials. This includes an online Delphi survey about core domains, which requires a ‘Long List’ of all domains that might be important to measure. Objectives: To compile a ‘Long List’ of candidate outcome domains for therapeutic HE trials with suggestions from patients and experts. Methods: First, 60 patients with chronic HE were interviewed at seven study sites in Croatia, Denmark, Germany, the Netherlands and Spain. Patients were asked about domains that were important from their perspectives. Second, 185 HE experts were invited by email to complete an online survey. With an open question, they were asked to suggest up to six domains. Results: Suggestions were provided by 58 patients and 82 experts. Most patients and experts suggested to measure the domains ‘signs’, ‘symptoms’ and ‘HE-related quality of life’. Specifically, >25% of patients said that less itch, pain or fissures indicated a successful treatment. Among experts, >25% suggested ‘itch’ and ‘ability to work’ as core sub-domains. Further outcomes from the domains ‘HE control over time’, ‘patient-reported treatment experience’ and ‘skin barrier function’ were mentioned. Conclusion: ‘Itch’ was rated high among patients with HE and professional HE experts. While patients emphasized fissures as important, experts underlined the ability to work. This investigation allowed us to define a ‘Long List’ of 7 candidate outcome domains with 58 sub-domains. From this list, a panel of stakeholders will select core domains during an online Delphi survey.

BACKGROUND Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients. OBJECTIVES To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema. METHOD The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month. RESULTS Consensus was achieved for several statements and management strategies. CONCLUSION The updated guideline should improve management of hand eczema.

The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023.

Purpose of review: contact urticaria syndrome includes contact urticaria and protein contact dermatitis. Underreport, underdiagnosis, or misdiagnosis of entities within the contact urticaria syndrome is believed to be common, especially in the occupational setting. This review provides a structured overview of the entities comprised in this syndrome as well as the diagnostic work-up and management strategies. Recent findings: contact urticaria syndrome has been increasingly described due to personal protective equipment and hand sanitizers in the context of the COVID-19 pandemic. The use of legal cannabis products has led to a rise in occupational cases of contact urticaria to cannabis. A declining trend in the evolution of contact urticaria has been described for natural rubber latex allergy due to the use of synthetic gloves. Prick test has been proposed as a screening method, particularly if multiple products are to be tested, instead of the classical sequential scheme. Summary: physicians should be aware of the growing number of culprit agents leading to contact urticaria syndrome. Clinical presentation may be challenging since it includes immediate urticaria and/or eczema and even more generalized reactions. Diagnosis requires a high degree of suspicion, detailed occupational history, and complementary tests, including skin testing. The best treatment is to avoid contact with the culprit agent and to implement preventive measures.

In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well.To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe.Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. As patch test outcome, reactions between day (D) 3 and D5 were considered.Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain.Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members.

Background: Disease burden is particularly high in Chronic Spontaneous Urticaria (CSU) patients with angioedema, and patients whose signs and symptoms are inadequately controlled by H1-antihistamines need new treatment options. Here we report an exploratory analysis, from the ligelizumab Phase 2b study, investigating angioedema occurrence in patients with CSU and describe the changes in angioedema following treatment with ligelizumab, omalizumab, or placebo. Methods: Data from the ligelizumab Phase 2b core (ligelizumab 72 mg, 240 mg, omalizumab 300 mg and placebo) and extension study (ligelizumab 240 mg) were used. Changes in Weekly Angioedema Activity Score (AAS7), the Dermatology Life Quality Index (DLQI), and Weekly Urticaria Activity Score (UAS7) among each time point were analyzed for each treatment arm. Results: From a total of 297 patients analyzed, 165 (55.6%) reported angioedema occurrence at baseline, with mean AAS7 ranging 30.6-42.2 across treatment arms. At Week 12 of the core study 87.5%, 84.6%, 75.0%, and 61.0% of patients were angioedema free for ligelizumab 72 mg, 240 mg, omalizumab 300 mg, and placebo arms, respectively. In CSU patients with angioedema at baseline, the largest change from baseline in AAS7 score was observed with ligelizumab 72 mg (-31.9) at week 16 in the core study. Patients with angioedema had a higher mean DLQI at baseline (14.9-16.1) vs. patients without angioedema (10.6-12.0). In patients with angioedema, low AAS7 was significantly associated with complete response on UAS7 (UAS7 = 0) and complete normalization of DLQI (DLQI 0-1). Conclusion: In the Phase 2b study, ligelizumab effectively reduced angioedema and urticaria symptoms, and improve health related quality of life in patients with moderate-to-severe CSU. Clinicaltrails.gov NCT number: NCT02477332; NCT02649218.

Background and Objective: Chronic spontaneous urticaria (CSU) is a distressing disease. We report real-world data from the global Chronic Urticaria Registry (CURE) about associations between various CSU states and sleep impairment, plus important health-related quality-of-life (HRQoL) outcomes and compared different methods to assess CSU states. Methods: CURE data were collected at baseline and 6-monthly follow-ups (FU). Assessments included CSU states using the Urticaria Control Test (UCT), weekly Urticaria Activity Score (UAS7), and Physician Global Assessment (PhyGA) of treatment response. Complete response to treatment (CR, UAS7 = 0), complete control of disease (CC, UCT = 16), and PhyGA = CR were assessed, plus the Dermatology Life Quality Index and the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL) sleep domain. Results: Overall, 2078 patients were included. At baseline, 9.8%, 17.9%, and 42.3% of patients had UCT = 16, UAS7 = 0, or PhyGA = CR, respectively, which increased at FU1 and FU2. Patients with higher UCT scores had better sleep and HRQoL. The presence of angioedema without wheals, episodic disease, omalizumab treatment, and male sex were associated with CC (P

Skin lesions caused by allergic contact dermatitis are an important occupational and environmental disease. Patch testing is the gold-standard procedure used to diagnose allergic contact dermatitis.The present chapter summarizes aspects of patch testing for the diagnosis of contact allergy: important working definitions, relevance of treating contact dermatitis, materials, technique, test result and interpretation, and special consideration regarding individual factors which influence the patch test outcome or necessitate special attention.Performing and interpreting patch tests requires know-how. Knowing how to perform them and the particularities of specific cases is essential to correctly interpret the results. A correct evaluation and diagnosis will significantly impact the natural history of the disease and significantly improve the quality of life of the patient.

Skin lesions caused by allergic contact dermatitis are an important occupational and environmental disease. Patch testing is the gold-standard procedure used to diagnose allergic contact dermatitis.

Chronic spontaneous urticaria (CSU) is characterized by the presence of wheals, angioedema, or both for at least 6 weeks. It may persist for a long time-up to 50% of the patients have been reported to be symptomatic 5 years after the onset. Some patients can suffer more than one episode of CSU during their lifetime. Considering the recurrences, disabling symptoms, and significant impact on quality of life, proper and effective treatment of CSU is critical. The use of antihistamines (AHs) is still the mainstay of treatment. However, given the low rates of response to AHs (38.6% and 63.2% to standard doses and higher doses, respectively), the complete control of symptoms seems difficult to attain. The use of omalizumab for CSU has been a major breakthrough in the care of patients with CSU. However, the partial response and lack of response to omalizumab in a subgroup of patients, as high as 70% in some studies, make the development of alternative treatments desirable. Ever-increasing knowledge on the pathogenesis is making new target molecules available and enabling drug development for CSU. In addition to drug repurposing as in anti-IL-4/13, IL-5, and IL-17 antibodies, novel targeted therapy options such as ligelizumab and Bruton's tyrosine kinase inhibitors are currently undergoing clinical trials and will be available in the near future. This article reviews the current challenges in the treatment of CSU, the pathogenesis and potential target molecules, and the rationale for novel treatments and their rapidly developing status.

In 2011, a multicentre study was conducted in order to determine how hair dye manufacturers instructed consumers to perform a self-test prior to dyeing their hair, in order to identify individuals who are likely to react upon subsequent hair dyeing. A number of concerns were raised concerning the variability in instructions between products and producers, and the safety and validity of this tool.To perform a 5-year follow-up study in order to determine whether manufacturers still recommend a self-test, and if so, whether the procedures have been changed.During March 2016, a total of 40 oxidative hair dye products from 21 different manufacturers were bought in retail stores in 8 European countries.The consumers were instructed to perform a self-test prior to hair dyeing for 39 of the products; however, the procedures varied greatly regarding the method of application, the amount of hair dye applied, the location and size of the application area, the number of applications, whether or not rinsing was performed after application, the reading times, and how a positive reaction was defined.Self-testing is still recommended by almost all manufacturers of permanent hair dyes. There are major variations in the instructions, even in products from the same manufacturer. The previously raised concerns regarding safety and validity still remain.

Urticaria is a common skin disorder defined by the occurrence of itchy and even painful wheals, angioedema, or both. The lifetime prevalence for its acute and chronic form is 20 and 1%, respectively. The patients' quality of life is impaired because of itch, disfigurement, and high associated comorbidity. To understand the pathophysiology of the wheal in order to ensure a correct therapeutic approach is critical. Mast cells are the primary effector cells in urticaria, which produce and secrete a variety of inflammatory mediators, mainly histamine. Their peripheral effects are responsible for the signs and symptoms of the disease, such as cutaneous swelling and pruritus. Management of itch in urticaria includes both nonpharmacological (avoidance or minimization of aggravating factors) and pharmacological treatments. The main therapeutic objective is to obtain complete relief of signs (hives and angioedema) and symptoms (pruritus) as quickly as possible. Licensed and up-dosed nonsedating H1-antihistamines are currently the first- and second-line therapies according to the European guidelines. When antihistamines are not enough, other treatments include anti-IgE antibodies, mast cell modulators, mast cell mediator blockers, and immunomodulators. As the knowledge of the pathogenesis of urticaria improves, the development of alternative therapies targeting these pathways may improve the patient's quality of life through the control of the pruritus, its main symptom.

Limonene and linalool are common fragrance terpenes widely used in cosmetic, household and hygiene products. Their primary oxidation products formed after air exposure, the hydroperoxides, have been recognized as important contact haptens.To investigate the prevalence of contact allergy to hydroperoxides of limonene (Lim-OOHs) and hydroperoxides of linalool (Lin-OOHs) in Spain, and to define the optimal concentration for screening in consecutive patients.Three different concentrations of Lim-OOHs (0.1%, 0.2% and 0.3% pet.) and Lin-OOHs (0.25%, 0.5% and 1.0% pet.) were simultaneously tested in 3639 consecutive patients at 22 departments of dermatology in Spain.Lim-OOHs at 0.1%, 0.2% and 0.3% yielded positive patch test reactions in 1.4%, 3.4% and 5.1% of the tested patients, respectively; and Lin-OOHs at 0.25%, 0.5% and 1.0% yielded positive reactions in 1.3%, 2.9% and 4.9% of the tested patients, respectively. Few irritant (1.5-1.9%) and doubtful reactions (0.4-0.5%) to both terpene hydroperoxides were registered at the highest concentrations tested.Lim-OOHs and Lin-OOHs can be considered as common causes of contact allergy, and their inclusion in an extended baseline patch test series therefore seems to be appropriate. The patch test preparations of Lim-OOHs 0.3% pet. and Lin-OOHs 1.0% pet. are useful tools for screening of contact sensitization.

Contact dermatitis of the hands is by far the most frequent condition suffered by health-care workers. Among health-care workers, nurses suffer the highest prevalence of hand eczema. Atopy, wet work, and a previous history of hand eczema are well-known risk factors.

p-Phenylenediamine (PPD) is the primary patch test screening agent for hair dye contact allergy, and approximately 100 different hair dye chemicals are allowed.To examine whether PPD is an optimal screening agent for diagnosing hair dye allergy or whether other clinically important sensitizers exist.Two thousand nine hundred and thirty-nine consecutive patients in 12 dermatology clinics were patch tested with five hair dyes available from patch test suppliers. Furthermore, 22 frequently used hair dye ingredients not available from patch test suppliers were tested in subgroups of ~500 patients each.A positive reaction to PPD was found in 4.5% of patients, and 2.8% reacted to toluene-2,5-diamine (PTD), 1.8% to p-aminophenol, 1% to m-aminophenol, and 0.1% to resorcinol; all together, 5.3% (n = 156). Dying hair was the most frequently reported cause of the allergy (55.4%); so-called 'temporary henna' tattoos were the cause in 8.5% of the cases. p-Methylaminophenol gave a reaction in 20 patients (2.2%), 3 of them with clinical relevance, and no co-reaction with the above five well-known hair dyes.Hair dyes are the prime cause of PPD allergy. PPD identifies the majority of positive reactions to PTD, p-aminophenol and m-aminophenol, but not all, which justifies additional testing with hair dye ingredients from the used product.

Health care personnel shows high occupational risk mainly from irritant and/or allergic contact dermatitis and less frequently contact urticaria. The spectrum of occupations involved is broad. The specialized nature of the tasks developed by some of these workers makes it somewhat difficult to relocate or substitute them. Although atopic condition and wet work increases the risk of hand eczema in health care workers, the hazard of sensitization is also very high. The agents capable of inducing contact allergy show different chemical structures including proteins and low molecular weight molecules. This chapter reviews the causes of occupational contact dermatitis and urticaria in nurses, clinical assistants and cleaners, surgeons, laboratory personnel, other therapist, veterinarians and laboratory animal handlers. Skin complaints should be assessed habitually with both Prick and Patch testing. The identification of the responsible agents is always necessary, being fundamental for developing effective preventive measures, some of which has already been demonstrated.

Circulating CLA+ T cells represent a subset of lymphocytes functionally associated to several cutaneous diseases. This population of peripheral lymphocytes is poorly characterized in acute stage psoriasis. We studied, by flow cytometry, the relationship between disease severity and extension and different subsets of circulating T cells in 31 psoriatic patients (7 guttate, 8 acute and 16 chronic psoriasis). An inverse correlation between circulating CLA+ CD3+/CD4+ subsets and disease severity and extension was found in the acute form of psoriasis. Interestingly, we also observed that circulating CLA+CD4+CD25+ cells inversely correlated with PASI and BSA in guttate patients, which had not been shown previously. These results may contribute to clarify the role of circulating T cells in psoriasis, especially in early stages of psoriasis.