Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

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.

Real-world effectiveness and tolerability of a cream containing postbiotic Aquaphilus dolomiae extract-G3 in subjects with sensitive facial skin.

Previous studies indicate that a postbiotic extract from Aquaphilus dolomiae (ADE-G3) improves skin barrier function and relieves neuroinflammation. Evaluation of an ADE-G3-based soothing cream for managing sensitive facial skin. This real-world, international, pre-post comparative study involved adults with sensitive facial skin who used the study product once or twice daily for two to three months according to usual practice. Subjects reported changes in perceived clinical symptoms using self-administered questionnaires. Physicians assessed changes in xerosis severity, overall product effectiveness and tolerability. User satisfaction and quality of life (QoL) assessments, and subgroup analyses according to the factors triggering sensitive skin were also conducted. In total, 2,382 subjects with sensitive facial skin (female: 79%; median age: 40 years) were included. An immediate skin soothing effect after the first ADE-G3-based cream application was reported by 93% of subjects, and improvements in symptoms were reported in 94% after a mean of nine days of product use. After several months of use (mean: 71±21 days), xerosis severity and dermatological-related QoL significantly improved in the whole study population and in the subgroups (p<0.001). At the end of the study, 92% of users were satisfied with the product and 95% reported improvements in their overall skin condition. Physicians found the cream to be effective and well tolerated in 92% and 98% of subjects, respectively. Regular use of the ADE-G3-based cream was shown to be effective in real-world management of sensitive facial skin, regardless of the factors involved in triggering skin sensitivity.

Polysensitization in the Spanish Contact Dermatitis Registry (REIDAC): A 2019-2022 prospective study with cluster and network analysis.

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase 2b multinational, randomised, double-blind, placebo-controlled ARROYO trial.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. OBJECTIVES: To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. METHODS: The 24-week, randomised, double-blind, placebo-controlled, phase 2b portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomised to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in ISS7 at Week 12. The key secondary endpoint was change from baseline in UAS7 at Week 12. Additional secondary endpoints included other metrics to assess CSU at Week 24; blood eosinophil levels; and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups. RESULTS: Of 155 patients, 59 were randomised to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% confidence interval -4.09 to 0.50) nor in change from baseline in UAS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.4016; benralizumab 60 mg vs. placebo, P = 0.0819). Depletion of blood eosinophil levels was observed at Week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab. CONCLUSIONS: Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?

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.

Sensitization to textile dyes in Spain: Epidemiological situation (2019-2022).

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.

A global perspective on stepping down chronic spontaneous urticaria treatment: Results of the Urticaria Centers of Reference and Excellence SDown-CSU study.

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.

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

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.

Efficacy and safety of on-demand versus daily rupatadine in chronic spontaneous urticaria: A randomized trial.

BACKGROUND: Non-sedating H1 -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.

Differential diagnosis between urticarial vasculitis and chronic spontaneous urticaria: An international Delphi survey.

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.

Omalizumab for Patients with Chronic Spontaneous Urticaria: A Narrative Review of Current Status.

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.

Chronic spontaneous urticaria is a skin condition that causes raised red itchy bumps (known as hives) that appear on the skin on most days for 6 weeks or longer. The hives may be big or small, may be warm to touch, may come and go, and may affect a person's quality of life. Omalizumab is a treatment for people living with chronic spontaneous urticaria that can stop the appearance of hives. This article summarizes all the information that we know about omalizumab for chronic spontaneous urticaria, such as how it works, how successful it is at improving hives, how long it takes to work, how it makes patients feel, and how safe it is. The information in this article shows that omalizumab is helpful for many people with chronic spontaneous urticaria.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Allergic reactivity for different dilutions of eugenol in repeated open application test and patch testing.

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.

Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe.

Importance: The common use of isothiazolinones as preservatives is a global cause of allergic contact dermatitis. Differences in allowable concentrations of methylisothiazolinone (MI) exist in Europe, Canada, and the US. Objective: To compare the prevalence of positive patch test reactions to the methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) combination and MI alone in North America and Europe from 2009 to 2018. Design, Setting, and Participants: This retrospective analysis of North American Contact Dermatitis Group, European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) databases included data from patients presenting for patch testing at referral patch test clinics in North America and Europe. Exposures: Patch tests to MCI/MI and MI. Main Outcomes and Measures: Prevalence of allergic contact dermatitis to MCI/MI and MI. Results: From 2009 to 2018, participating sites in North America and Europe patch tested a total of 226 161 individuals to MCI/MI and 118 779 to MI. In Europe, positivity to MCI/MI peaked during 2013 and 2014 at 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) during 2017 and 2018. Positive reactions to MI were 5.5% (ESSCA) and 3.4% (IVDK) during 2017 and 2018. In North America, the frequency of positivity to MCI/MI increased steadily through the study period, reaching 10.8% for MCI/MI during 2017 and 2018. Positive reactions to MI were 15.0% during 2017 and 2018. Conclusions and Relevance: The study results suggest that in contrast to the continued increase in North America, isothiazolinone allergy is decreasing in Europe. This trend may coincide with earlier and more stringent government regulation of MI in Europe.

Sensitization to isothiazolinones in the Spanish Contact Dermatitis Registry (REIDAC): 2019-2021 epidemiological situation.

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.

Study of Excipients in Delayed Skin Reactions to mRNA Vaccines: Positive Delayed Intradermal Reactions to Polyethylene Glycol Provide New Insights for COVID-19 Arm.

BACKGROUND: Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. METHODS: Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. RESULTS: Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. CONCLUSIONS: Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice.