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Background: Reports of allergic contact dermatitis (ACD) to phytonadione epoxide (PE) in cosmetics suggest that PE is as powerful a sensitiser as its parent compound phytonadione. Objective: To evaluate a case series of ACD to PE in Spain. Methods: We reviewed the records of 20 patients with ACD to cosmetics containing PE diagnosed across Spain between January 2019 and June 2023. Results: All 20 patients developed patch test (PT) or repeated open application test (ROAT) reactions to cosmetics containing PE. All involved women with eyelid eczema. PT or ROAT with PE preparations were positive in 17/20 (85%). PE at 1%, 5%, 10% and 20% in pet. was patch‐tested in 8/17, 14/17, 11/17 and 8/17 patients; being positive in 6/8 (75%), 13/14 (92.85%), 11/11 (100%) and 8/8 (100%), respectively. Conclusion: Regulators should, not only ban the specific dangerous cosmetic ingredients, but also consider to ban or keep under close surveillance those closely related products or derivatives that might potentially cause similar harmful effects. PTs with PE are suggested to be performed at a 5% concentration in pet. Higher concentrations (10% pet.) should be tested whenever PTs with 5% pet. PE are negative. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. Objectives: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. Methods: We analysed two groups (AD and non‐AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. Results: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non‐AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age‐adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61–0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non‐AD individuals. Conclusions: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non‐AD population, except for a negative relationship between AD and sensitisation to nickel sulphate. [ABSTRACT FROM AUTHOR]

The article in Clinical & Experimental Allergy explores the connection between lymphopenia, basopenia, and eosinopenia in chronic spontaneous urticaria (CSU) patients, particularly those with autoimmune CSU. The study involved 300 CSU patients and found that lymphopenia was associated with lower counts of basophils, eosinophils, monocytes, and platelets. The research suggests that lymphopenia may reflect the migration of lymphocytes from the bloodstream into skin lesions, similar to basophils and eosinophils. The study also identified associations between basopenia and high anti-C1q levels, supporting the hypothesis that these antibodies may be a marker of autoimmune CSU. [Extracted from the article]

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co‐exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. Objectives: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. Methods: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. Results: A total of 4338 patients were tested. Twenty‐four patients were allergic to budesonide (0.55%, 95% CI: 0.37–0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11–0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35–0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. Conclusions: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids. [ABSTRACT FROM AUTHOR]

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients. Against this background, the European Society of Contact Dermatitis (ESCD) has created a task force (TF) (i) to explore the current availability of PT substances in different member states, (ii) to highlight some of the unique characteristics of Type IV vs. other allergens and (iii) to suggest ways forward to promote and ensure availability of high‐quality patch testing substances for the diagnosis of Type IV allergies throughout Europe. The suggestions of the TF on how to improve the availability of PT allergens are supported by the ESCD, the European Academy of Allergy and Clinical Immunology, and the European Academy of Dermatology and Venereology and intend to provide potential means to resolve the present medical crisis. [ABSTRACT FROM AUTHOR]

Background: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. Objectives: To evaluate the frequency of sensitization to 2‐hydroxyethyl methacrylate (2‐HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. Methods: From January 2019 to December 2022, 2‐HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. Results: Six thousand one hundred thirty‐four patients were consecutively patch tested with 2‐HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2‐HEMA (OR: 10.9; 95% CI: 8.1–14.9). Conclusion: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2‐HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means. [ABSTRACT FROM AUTHOR]

Background: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. Objectives: To study the frequency, clinical features and simultaneous positivity between TDM, para‐phenylenediamine (PPD) and specific disperse dyes. Materials and Methods: We analysed all consecutive patients patch‐tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch‐tested with a textile dye series. Results: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM‐positive patients, 57% were positive to PPD. One hundred and sixty‐four patients were patch‐tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch‐tested with the TDM alone. Conclusions: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series. [ABSTRACT FROM AUTHOR]

This article discusses the prevalence of contact allergy to sodium metabisulfite (SMB) in Spain. The study found that out of 6,471 patients who were patch-tested with SMB, 2.1% had a positive reaction. The most commonly affected locations were the hands, and the most frequently involved products were topical medications and cosmetics. However, only 25.34% of positive reactions were considered currently relevant. The study concludes that the low current relevance of sensitization to SMB in Spanish patients suggests that it should only be included as a candidate allergen in the Extended Standard series in Spain with caution. [Extracted from the article]

Background: Although there have been significant advances in the treatment of chronic spontaneous urticaria (CSU) in recent years, there remains a lack of clear guidance on when and how to step down treatment in responders. This study aims to investigate stepping down approaches of different steps of CSU treatment from a global perspective. Methods: "Stepping down chronic spontaneous urticaria treatment" (SDown‐CSU) is an international, multicenter, observational, cross‐sectional, survey‐based study of the Urticaria Centers of Reference and Excellence (UCARE) network. The questionnaire included 48 questions completed by physicians in the UCARE network. Results: Surveys completed by 103 physicians from 81 UCAREs and 34 countries were analyzed. Seventy‐eight percent of the participants responded that they had a national urticaria management guideline written by their professional societies and 28% responded that they had to operate under a regulatory guideline proposed by central health funding organizations. Seventy‐two and 58.7% of these national recommendations do not contain any detailed information on when and/or how CSU treatment should be discontinued. There was a lack of detailed information on antihistamines and cyclosporine in particular. A predefined maximum duration was generally not applicable to omalizumab and cyclosporine (81% and 82%, respectively). Nearly all UCAREs step down omalizumab within 6 months from the first controlled status and 42% discontinue cyclosporine after 6 months regardless of the control status. Conclusions: The findings from the SDown‐CSU study clearly highlight a global need for guidance on the process of stepping down treatment in CSU. Additionally, the study offers a step‐down algorithm applicable to all stages of CSU treatment. [ABSTRACT FROM AUTHOR]

Background: Eugenol is a known contact sensitiser included in fragrance mix I. Objective: To assess the allergic reactivity to eugenol in different concentrations using patch test as well as repeated open application test (ROAT). Methods: Overall 67 subjects from 6 European dermatology clinics participated in the study. The ROAT was performed for 21 days twice a day, applying 3 dilutions of eugenol (2.7%–0.5%) and a control. Before and after the ROAT, patch testing with 17 dilutions of eugenol (2.0%–0.00006%) and controls was performed. Results: Out of the 34 subjects with contact allergy to eugenol, 21 (61.8%) showed a positive patch test before ROAT was performed, the lowest positive concentration was 0.031%. The ROAT was positive in 19 (55.9%) of the 34 subjects, the time until a positive reaction occurred was negatively associated with the concentration of the ROAT solution, as well as with the allergic reactivity of the subjects as defined by patch testing. In the patch test after ROAT, 20 of the 34 test subjects (58.8%) showed a positive reaction. In 13 (38.2%) of the 34 test subjects, the patch test result was not reproduceable, still 4 (31.0%) of these 13 subjects developed a positive ROAT. Conclusion: Eugenol can provoke a positive patch test reaction in a very low dose; besides, this hypersensitivity may persist even if a former positive patch test is not reproduceable. [ABSTRACT FROM AUTHOR]

Background: Chronic hand eczema (CHE) is a very common skin disease among the European population. It causes itch and pain and, in more severe cases, seriously impairs hand functioning at work and in private life. Objectives: To explore perspectives of people with lived experience on CHE‐related problems, wishes and goals. Methods: Following a qualitative approach, we conducted topic‐guided interviews in five European countries and applied template analysis to identify recurrent themes among patients with CHE. Results: We interviewed 60 patients in seven outpatient dermatological and occupational medicine clinics in Croatia, Denmark, Germany, the Netherlands and Spain. Five main themes were identified: (1) knowledge about the disease and its course, (2) preventive behaviour, (3) hand eczema therapy, (4) impact on everyday life and (5) attitudes towards CHE and healthcare. Participants did not feel well informed about CHE, especially about causes, triggers and treatment options. Preventive measures were experienced as more or less effective but also cumbersome. Experiences with therapy were diverse. Treatment satisfaction depended on the results and on the perceived support from the treatment teams. Participants found it important to be taken seriously, to receive practical advice, to try out additional treatments or examinations, find new hope and have occupational perspectives. They wished that others could better understand the physical and emotional burden of CHE. Patient support groups were not mentioned. Participants found it important to learn to take care of themselves and accept life with CHE. Conclusions: Due to its annoying symptoms, high visibility and impaired functioning at work and in private life, CHE has a high emotional and social impact. Some people may require support to learn coping with CHE and its prevention. Patients wish for information about causes and triggers. They value physicians who listen to them and keep looking for solutions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Limonene and linalool are among the most common fragrance terpenes used in everyday products. They are pre‐haptens, forming hydroperoxides (Lim‐OOHs, Lin‐OOHs) upon oxidation and inducing frequent positive patch test reactions in patients with dermatitis, and yet they are not routinely tested in Europe. This review evaluates current patch testing with Lim‐OOHs and Lin‐OOHs by asking whether hydroperoxide patch testing is warranted, examining the difficulties or challenges related to reading and interpreting hydroperoxide patch test results with currently available material, and assessing their relevance. Studies are increasingly pointing to high percentages of positive reactions in patients consecutively patch tested with these oxidized products. An association between a positive clinical history and a strong patch test reaction has been described, but problems with doubtful/irritant reactions have also been reported. Considering the high frequency of relevant positive reactions, the incorporation of Lim‐OOHs 0.3% and Lin‐OOHs 1% in the baseline series may be justified. Since exposure, sensitization, and elicitation limits of Lim‐OOHs and Lin‐OOHs in the products still need to be better determined, an assessment of previous exposure, possible sensitizations, and reactions may help to improve the clinical assessment. [ABSTRACT FROM AUTHOR]

Dear Editor, The Spanish Registry of Contact Dermatitis (REIDAC) is an active project of the Spanish Research Group on Contact Dermatitis and Skin Allergy (GEIDAC) to describe the epidemiology of allergic contact dermatitis (ACD) in Spain.[1] Since January 2019, in parallel with the European Society of Contact Dermatitis (ESCD), a series of allergens have been consecutively patched by the GEIDAC group. In this observational, multicentre study, 3629 patients were patch-tested to alkyl glucosides (DG and LG), from January 2019 to December 2021, with positive results in 30 of these (0.8%) (Table 1). Among these allergens are alkyl glucosides (AG).[[1]] AG are a family of nonionic surfactants synthesized through the condensation of glucose with long-chain fatty alcohols.[[3]] This makes the AG completely biodegradable, having recently increased their fame due to their ecological nature. [Extracted from the article]

Background: Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation. Objective: We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34+‐derived mast cells activation induced by serum obtained from chronic urticaria patients. Methods: Twenty‐two patients with chronic spontaneous urticaria (mean age 52 years, 27% women) and 22 patients with chronic inducible urticaria (46 years, 27% women) were included in the study together with a sex‐matched control group. Patients were classified as responders or non‐responders to anti‐IgE therapy on the basis of their clinical data, FcεR1a expression on blood basophils and total IgE levels. Changes on CD63 expression—as an activation marker‐, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib. Results: Remibrutinib inhibits degranulation induced by IgE cross‐linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness. Conclusion: Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab. [ABSTRACT FROM AUTHOR]

Background: Current frequency and risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in Spain are not well known. Objectives: To study the frequency of sensitization, risk factors and simultaneous sensitization between the four isothiazolinones. Materials and Methods: We analysed all 2019–2021 consecutive patients patch‐tested with MI (0.2% aq.), MCI/MI (0.02% aq.), BIT (0.1% pet.) and OIT (0.1% pet) within the Spanish Contact Dermatitis Registry (REIDAC). Results: A total of 2511 patients were analysed. Frequencies of sensitization were: any isothiazolinone 15.7%, MI 6.8%, MCI/MI 4.8%, BIT 3.5% and OIT 0.5%. MI and MCI/MI sensitization was associated with being occupationally active, hand dermatitis, detergents and age over 40. BIT sensitization was associated with leg dermatitis and age over 40. About one in nine MI‐positive patients were positive to BIT, whereas one in five BIT‐positive patients were positive to MI. Conclusions: Sensitization to MI, MCI/MI and BIT is still common in Spain, while sensitization to OIT is rare. Currently, sensitization to MI and MCI/MI seems to be occupationally related. Although its origin is unknown, sensitization to BIT is more frequent in patients aged over 40 years. Simultaneous sensitization between MI and BIT is uncommon. [ABSTRACT FROM AUTHOR]

This article discusses the use of cyclosporine (CsA) as a third-line treatment for chronic spontaneous urticaria (CSU) that is unresponsive to antihistamines and omalizumab. The study analyzed the outcomes of CsA treatment in 28 patients with refractory CSU across multiple hospitals. The results showed that low doses of CsA (2-3 mg/kg/day) were effective and safe in these patients, with a complete response achieved in 30.8% of patients. The study did not identify any predictors for a positive response to CsA treatment. However, the study has limitations, including its retrospective design and small sample size. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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

Background: Different textile constituents may act as allergens and/or irritants and provoke textile contact dermatitis (TCD). Objectives: To report a case of TCD caused by ethylene glycol monododecyl ether and 2,4‐dichlorophenol, present in a bikini. Methods: A woman presented with an eczematous, pruritic rash in the area of the bikini straps and back. Patch testing was performed with the European baseline, textile, sunscreen, and photo‐patch series, the bikini "as is", and ethanol and acetone extracts of the bikini. Thin‐layer chromatography (TLC) of the extracts and gas chromatography–mass spectrometry (GC–MS) analysis were used to elucidate the culprit agents. Results: Positive reactions were found to the bikini "as is" and to the ethanol and acetone extracts. Patch testing with TLC strips showed a strong reaction to spots‐fractions 3 and 4. GC–MS was performed to identify substances in each fraction and those suspected to be skin sensitisers were patch tested. On day (D) 4 positive reactions to ethylene glycol monododecyl ether (irritant reaction) and 2,4‐dichlorophenol (++) were observed. Conclusion: A myriad of chemical compounds can be found in clothing. Ethylene glycol monododecyl ether and 2,4‐dichlorophenol were identified as the potential culprits of this bikini TCD. Highlights: We have combined chemical analyses (thin‐layer chromatography and gas chromatography–mass spectrometry) to study a case of textile contact dermatitis.As such, the presence of a myriad of chemical compounds was found in a bikini, suggesting that clothing in general may become impregnated or contaminated by a wide range of external substances that may be harmful to the skin.Textile contact dermatitis could in this case be attributed to ethylene glycol monododecyl ether (CAS No. 4536‐30‐5) and 2,4‐dichlorophenol (CAS No. 120‐83‐2), the latter not yet previously described as a textile contact allergen. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the pathogenic and treatment relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU). The expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF‐AH) in patients with moderate/severe CSU (n = 45) and healthy controls (HCs, n = 17) were studied. Skin samples from the active wheal (LS‐CSU, 13 samples for qPCR and 33 for immunohistochemistry) and non‐lesional skin (NLS‐CSU, 13 samples) of CSU patients and HCs (13 samples and 5 for immunohistochemistry) were analyzed. Serum PAF and PAF‐AH levels were measured by ELISA and compared between HC (10 samples) and CSU patients (25 samples) and, among them, between those refractory and non‐refractory to second‐generation H1‐antihistamines (sgAH). PAFR mRNA expression was significantly higher in LS‐CSU versus HCs (p = 0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, whereas it was broadly present along the epidermis in LS‐CSU samples. Endothelial cells showed PAFR expression exclusively in LS‐CSU and NLS‐CSU samples. PAFR expression was observed in the nerves of HC, LS‐CSU, and NLS‐CSU samples. Double PAFR/CD43 expression showed that T‐lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF‐AH/PAF ratio was observed in sgAH non‐responders versus responders (6.1 vs. 12.6; p = 0.049). Our study confirms that PAF is a mediator of wheal pathogenesis in CSU. The significantly lower PAF‐AH/PAF ratio in sgAH non‐responders vs responders suggests that PAF could be a potential biomarker of sgAH refractoriness. [ABSTRACT FROM AUTHOR]

Background: Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. Objectives: To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. Methods: Anonymised or pseudonymised individual data and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. Results: In 2019 and 2020, 22 581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 [19.2–20.4]% positivity [95% confidence interval]). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43–7.19)% and 6.62 (6.25–7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 [2.16–2.85]% vs. 1.59 [1.33–1.88]); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 [3.16–3.82]%), followed by 2‐hydroxyethyl methacrylate (2.32 [2.0–2.68]%). Conclusion: Ongoing surveillance on the prevalence of contact sensitization contributes to an up‐to‐date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe. [ABSTRACT FROM AUTHOR]

Background: Ligelizumab, a next‐generation, humanized anti‐immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard‐of‐care therapy. Objective: To evaluate the long‐term safety and re‐treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods: This open‐label, single‐arm, long‐term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose‐finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post‐treatment for 48 weeks. Results: Overall, ligelizumab was well‐tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment‐emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion: The long‐term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re‐treatment efficacy was shown. Trial Registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218. [ABSTRACT FROM AUTHOR]

Keywords: adrenaline autoinjector; cold urticaria; COLD-CE; cold-induced anaphylaxis EN adrenaline autoinjector cold urticaria COLD-CE cold-induced anaphylaxis 2224 2229 6 07/04/22 20220701 NES 220701 ACKNOWLEDGMENT This manuscript benefited from the support of the GA SP 2 sp LEN UCARE network (www.ga2len-ucare.com). 5 a Any cold trigger (i.e., complete cold water immersion, cold ambient air exposure, transition from cold outdoors to warm indoors, localized contact with cold liquids without immersion or ice, and contact with cold surfaces). [Extracted from the article]

Background: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. Methods: An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. Results: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p =.003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. Conclusion: ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector. [ABSTRACT FROM AUTHOR]

Background: 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. Objectives: To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. Methods: 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. Results: 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. Conclusions: 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. Highlights: Twelve preservatives, fragrances, and emulsifiers were evaluated as potential additions to the European Baseline Series (EBS)The highest prevalences of positive reactions were to linalool hydroperoxides 1% pet. or 0.5% pet. and limonene hydroperoxides 0.3% pet. Benzisothiazolinone 0.1% pet. was positive in 4.7%, followed by sodium metabisulfite 1% pet. (3.8%) and Compositae mix 5% pet. (2.3%).The results are a basis for further discussion and ultimately a decision on their implementation into routine testing among the European Society of Contact Dermatitis (ESCD) members. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A major research topic consists of revealing the contribution of radical‐mediated reactions in dermatological diseases related to xenobiotic‐induced stress to succeed risk‐assessment procedures protecting producers and consumers. Allergic contact dermatitis is the clinically relevant consequence of skin sensitization, one of the most critical occupational and environmental health issues related to xenobiotics exposure. The first key event identified for the skin sensitization process to a chemical is its aptitude to react with epidermal proteins and form antigenic structures that will further trigger the immune response. Many chemical sensitizers are suspected to react through mechanisms involving radical intermediates. This review focuses on the recent progress we have accomplished over the last few years studying radical intermediates derived from skin‐sensitizing chemicals by electron paramagnetic resonance in combination with the spin‐trapping technique. Our work is carried out "from the molecule", performing studies in solution, "to the tissue", by the development of a methodology on a reconstructed human epidermis model, very close in terms of histology and metabolic/enzymatic activity to real human epidermis, that can be used as suitable biological tissue model. The benefits are to test chemicals under conditions close to human use and real‐life sensitization exposures and benefit from the three‐dimensional (3D) microenvironment. [ABSTRACT FROM AUTHOR]

Case report, contact dermatitis, hydroxychloroquine, patch test, photoallergy, drug-induced photosensitivity, phototoxicity (D) Phototest positivity (+) for hydroxychloroquine (HC) 48 h following irradiation (first test session, Dolquine being the commercial name for the drug in Spain). gl With the suspicion of a drug-induced reaction, and HC being the only imputable drug, patch testing (extended European baseline series and in-house prepared HC 5% pet.[5]) and photopatch testing (including HC 5% pet.) Keywords: case report; contact dermatitis; drug-induced photosensitivity; hydroxychloroquine; patch test; photoallergy; phototoxicity EN case report contact dermatitis drug-induced photosensitivity hydroxychloroquine patch test photoallergy phototoxicity 168 170 3 01/13/23 20230201 NES 230201 Despite hydroxychloroquine (HC) having well-known photoprotective properties, photo-induced dermatoses may occasionally be triggered by this drug.[[1], [3]] CASE REPORT A 73-year-old woman, with a past history of oral lichen planus and frontal fibrosing alopecia, consulted our department due to a skin rash located in photo-distributed areas (neck, arms, dorsum of the hands, and face) which developed in the previous 4 weeks (Figure 1A,B). [Extracted from the article]

Background: Chronic spontaneous urticaria (CSU) negatively impacts patients' sleep, thereby reducing health‐related quality of life (HRQoL). Half of patients with inadequately controlled CSU report sleep interference often or every night, which can lead to depression, anxiety, social, and work‐related problems. Methods: This randomized, double‐blind, placebo‐controlled Phase 2b core study (NCT02477332) included adult patients ≥18 years with moderate to severe CSU inadequately controlled with H1‐antihistamines. The current analysis includes patients randomized to receive ligelizumab 72 or 240 mg, omalizumab 300 mg or placebo every 4 weeks (q4w) for five injections over 20 weeks with treatment‐free follow‐up for 24 weeks. Patients could enter the open‐label extension study (NCT02649218) from Week 32 onwards if their weekly urticaria activity score was ≥12, which included an open‐label treatment (52 weeks of ligelizumab 240 mg q4w) and a 48‐week post‐treatment follow‐up. Weekly Sleep Interference Scores (SIS7, range 0 [no interference]–21 [substantial interference]), Weekly Activity Interference Score (AIS7), Dermatology Life Quality Index (DLQI) scores, and Overall Work Impairment were assessed. Results: Mean baseline SIS7 scores were balanced between the treatment arms for ligelizumab 72 mg (n = 84) and 240 mg (n = 85), omalizumab 300 mg (n = 85), and placebo (n = 43). By Week 12, patients experienced large improvements in sleep interference, with least square mean (standard error) changes from baseline (CFB) in SIS7 of −7.84 (0.58), −7.55 (0.61), −6.98 (0.60), and −5.85 (0.81), respectively. By Week 12, CFB in AIS7 were −8.25 (0.57), −8.25 (0.59), −7.30 (0.60), and −5.62 (0.79), DLQI scores were −9.79 (0.77), −9.93 (0.81), −8.35 (0.79), and −6.99 (1.11), and Overall Work Impairment scores were −28.96 (3.73), −30.76 (3.71), −25.74 (3.91), and −20.13 (5.10) for ligelizumab 72 and 240 mg, omalizumab 300 mg and placebo, respectively. Improvements in each patient‐reported outcome were sustained with ligelizumab 240 mg treatment during the extension study. Conclusions: Ligelizumab showed effective and sustained responses in managing sleep interference in patients with CSU, and numerically higher responses than with omalizumab and placebo. Treating the symptoms of CSU with ligelizumab improved disease burden, HRQoL, and markedly improved sleep quality. [ABSTRACT FROM AUTHOR]

Background: IgE and high‐affinity IgE receptor (FcεRI) expression on basophils have been scarcely explored in patients with chronic inducible urticaria (CIndU). Objectives: To investigate baseline serum IgE and FcεRI expression on blood basophils in a large cohort of CIndU patients and its relationship to treatment response. Methods: Baseline total serum IgE and basophil FcεRI expression measured by flow cytometry in 165 patients with CIndU was studied. The relationship of both parameters with the response to antihistamine and anti‐IgE (omalizumab) treatment was considered in a subsample of CIndU patients. FcεRI expression in basophils was assessed by mean fluorescence intensity (MFI) and basophil FcεRI standardized density (receptors/cell). Results: The median FcεRI expression standardized per density in blood basophils was found significantly higher in patients with CIndU compared to HCs. A positive correlation was found between IgE serum levels and basophil FcεRI expression. Basal FcεRI expression was not related to antihistamine treatment response. However, it was related to omalizumab, and patients responding to omalizumab showed higher basal basophil expression of FcεRI levels. Non‐responders to the antihistamine showed significantly higher IgE serum levels. Conclusions: FcεRI receptor overexpression in patients with CIndU shows almost the same pattern than chronic spontaneous urticaria. It seems to be independent of CIndU subtypes. Although additional studies would be welcome, our work highlights the relevance of FcεRI receptor regulation in CIndU supporting autoimmune basophil and mast cell activation and may be a biomarker for response to anti‐IgE therapy. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H1R‐antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based) and its cost‐effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis from glucose sensors may interfere with their ongoing application. Objective: To evaluate a series of Spanish patients with contact dermatitis to glucose sensors regarding former sources of contact allergens, patch test results, and outcomes from the ongoing use of the device. Methods: A series of patients with contact dermatitis from glucose sensors was investigated in eight dermatology departments across Spain (epidemiological features, brands, latency time to develop dermatitis, the ability to continue using the devices as well as the patch test results). Results: Thirty patients were evaluated (mean age 20.9 years). A total of 66.7% were children and 66.7% female. Ninety per cent used Freestyle Libre (FSL). Eight of 26 (30.8%) reacted to isobornyl acrylate (IBOA) and two of 20 (10.0%) to N,N dimethylacrylamide (DMAA). The mean latency time to develop dermatitis was 9 months. Sixteen of 29 (55.2%) patients continued using the same sensor causing the reaction. Thirteen of 29 (44.8%) patients were unable to continue using the sensor because of severe reactions. Of these, five were positive to IBOA, one to IBOA and DMAA, one to DMAA, one to colophony, and one to isopropyl alcohol wipes. In one patient, the outcome was unknown. Conclusion: The frequency of sensitisation to IBOA and DMAA, was lower than in other European series, but similar to a previously published Spanish article. Legislation requiring manufacturers to provide information regarding the composition of medical devices and cooperate with the investigations into contact dermatitis is urgently needed. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, an international consensus is lacking regarding the development of an adequate informed consent form for a patch test (PT) and the information that should be included in such document. Objectives: The aim of the study was to reach a consensus on the specific points that need to be addressed in a PT consent form. Methods: A Delphi survey, comprising 2 rounds and 1 final discussion, was used to gather and analyse data, which was conducted over the Internet. Each statement that reached a consensus with the respondents (9 expert dermatologists from Europe) was defined as a median consensus score (MED) of ≥7 and agreement among panelists as an interquartile range (IQR) of ≤3. All study participants were members of the EADV task force on contact dermatitis. Results: The expert panel addressed several topics that should be included in an informed consent form for a PT: introduction, preparation for PT, testing procedure, allowed activities, adverse events and additional authorizations. Conclusions: Our results assess recommendations regarding points to be contained in an informed consent form for a PR. Future actions towards standardization and harmonization of this specific consent form are needed. [ABSTRACT FROM AUTHOR]

Existing criteria for inclusion in the European baseline series are summarized. Additional criteria are developed to aid decision making where the current criteria do not yield an unequivocal result. These include a consideration of whether an allergen (hapten) is better placed in a special series and the frequency with which an allergen cross-reacts with existing markers in the baseline series. [ABSTRACT FROM AUTHOR]

Background: In recent years, skin reactions secondary to the use of medical devices (MD), such as allergic contact dermatitis have increasingly been observed (e.g. to continuous blood sugar monitoring systems, insulin pumps, wound dressings, medical gloves, etc.): this is regarded as a developing epidemic. Lack of labelling of the composition of MD, as well as frequent lack of cooperation of manufacturers to disclose this relevant information, even when contacted by the clinician for the individual case of an established adverse reaction, significantly impede patient care. Objectives: To advocate for full ingredient labelling in the implementation of EU regulation for MD. Methods: This position paper reviews the scientific literature, the current regulatory framework adopted for MD to date, and the likely impact, including some costs data in case of the absence of such labelling. Results: Efforts made by several scientific teams, who are trying to identify the culprit of such adverse effects, either via asking for cooperation from companies, or using costly chemical analyses of MD, can only partly, and with considerable delay, compensate for the absence of meaningful information on the composition of MD; hence, patient management is compromised. Indeed, without knowing the chemical substances present, physicians are unable to inform patients about which substances they should avoid, and which alternative MD may be suitable/tolerated. Conclusion: There is an urgent need for full and accurate labelling of the chemical composition of MD in contact with the human body. [ABSTRACT FROM AUTHOR]

Background: Fragrances constitute the second most frequent cause of allergic contact dermatitis in Spain. Objectives: To determine the rate of sensitization to the individual fragrances of fragrance mix (FM) I and FM II for each of the demographic and clinical factors included in the MOAHLFA (male, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, age) index. Methods: We conducted a 5‐year retrospective study in 23 Spanish centres. We identified the patients who had undergone patch testing with a specific fragrance series after reacting positively to fragrance markers in a baseline series. We obtained the MOAHLFA index items in this population, then calculated for each demographic and clinical factor the frequencies of sensitization to the individual fragrances of FM I and FM II. Results: A specific fragrance series was patch tested in 1013 patients. The most frequent allergens in men, women, children, and retired people were Evernia prunastri (16%), geraniol (16.6%), isoeugenol (17.9%), and geraniol (22.4%), respectively. Citral (20.5%) and hydroxyisohexyl 3‐cyclohexene carboxaldehyde (HICC) (14.5%) were the most common allergens in occupational eczemas and were also associated with a large proportion of hand and facial dermatitis. Conclusions: Frequency of sensitization to the individual fragrances of FM I and FM II varies with age, sex, affected body region, and history of occupational or atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co‐morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based), its cost‐effectiveness and long‐term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria (CU) is a common disease, characterized by the recurrent appearance of wheals, angioedema or both for more than 6 weeks. Its underlying biology is not well understood, and many patients do not obtain sufficient relief from recommended treatments. Patient registries are rapidly growing as a form of research, because they can provide powerful, data‐driven insights about the epidemiology of diseases, real‐world effectiveness of treatments, rare patient types, safety monitoring, healthcare costs and opportunities for quality improvement of healthcare delivery. Objectives: The Chronic Urticaria Registry (CURE) has been designed to improve the scientific understanding, clinical treatment and healthcare planning of CU patients. This report describes the rationale, methods and initial implementation of this registry. Methods: Chronic Urticaria Registry is an ongoing, prospective, international, multicentre, observational, voluntary registry of patients with CU. Participation in CURE is open to any physician treating CU patients, regardless of location, medical specialty or type of practice setting. CURE aims to collect data on all CU patients, with no intentional selection or exclusion criteria. It collects baseline and follow‐up data on the patient's demographics, history, symptoms, trigger and risk factors, therapies and healthcare utilization. Results: Chronic Urticaria Registry is a landmark achievement of the global urticaria medical community. As of 26 February 2020, 39 centres around the world have joined the registry and 35 have entered baseline data on a total of 2946 patients. Publications of this data will be forthcoming soon. Conclusions: Chronic Urticaria Registry is eagerly seeking the participation of more physicians and the support of more governmental, charitable and commercial sponsors from around the world. Here, in this paper, we invite other physicians to join this unique project to improve the lives of patients with CU. [ABSTRACT FROM AUTHOR]