Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

BACKGROUND: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). OBJECTIVE: To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. METHODS: A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. RESULTS: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. CONCLUSION: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials.

BACKGROUND: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema. METHODS: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101. FINDINGS: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis. INTERPRETATION: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids. FUNDING: LEO Pharma.

Topical Corticosteroid Phobia among Danish Pharmacy Staff.

INTRODUCTION: Topical corticosteroid (TCS) phobia may negatively impact treatment adherence. Currently, there are few studies exploring trust and knowledge of TCS use among pharmacy staff. The objective of this work was to examine TCS knowledge and possible phobia among Danish pharmacy staff. METHODS: A questionnaire, based on Topical Corticosteroid Phobia (TOPICOP©) questionnaire, was developed and rephrased to fit pharmacy staff. The questions were Likert scales and numerical rating scales (NRS) (0-10). In October/November 2021, 64 pharmacies were invited. If the pharmacies agreed to participate, a researcher visited the pharmacies and distributed the questionnaires. RESULTS: A total of 244 pharmacy workers from 59 pharmacies participated. The majority (95.4%) responded that they were aware of side effects of TCS; however, misconceptions regarding side effects were found in up to 34% of participants. Regarding TCS use, 40% sometimes advised the patients to wait as long as possible before initiating treatment with TCS. Confidence in dispensing TCS to patients was high, with a mean of 8.45 (NRS). CONCLUSION: Danish pharmacy staff generally reported high confidence in TCS use. Misconceptions regarding side effects were common, and there was a tendency to giving advices on TCS treatment that may indicate low confidence in TCS. Thorough education of pharmacy staff is needed to improve the knowledge of TCS.

Validation of the Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE): a new clinician reported outcome measure of CHE severity.

The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) is a novel Clinician-Reported Outcome measure that allows investigators to assess cross-sectional CHE global disease severity using clinical characteristics of erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, and fissures as guidelines for overall severity assessment. This study aimed to evaluate the psychometric properties of the IGA-CHE for use as an outcome measure in CHE clinical trials and clinical practice. Psychometric analyses were performed using data from a sample of 280 patients with moderate to severe CHE from a phase 3 trial of delgocitinib cream, pooled across treatment groups. Test-retest reliability results were moderate to strong with kappa coefficients ranging from 0.63 to 0.76. Correlations with measures assessing related concepts were moderate or strong (range 0.65-0.72) and exceeded a priori hypotheses, providing evidence of convergent validity. Known-groups validity was supported by statistically significant differences between severity groups (< 0.001). Within-group effect sizes were consistently larger for improved groups compared to stable groups, providing evidence of ability to detect change. Anchor-based analyses generated within-subject meaningful change estimates ranging from - 0.8 to - 2.3. A correlation weighted average suggested a single value of - 1.7 in change from baseline. These findings provide evidence the IGA-CHE scale has strong reliability, construct validity, and ability to detect change, supporting its use as an endpoint in CHE clinical trials and clinical practice. Based on the evidence, 2-level changes in IGA-CHE score are considered a conservative meaningful change threshold; however, findings also indicate 1-level change in IGA-CHE scores reflects a clinically meaningful improvement for patients.Clinical trial registration: NCT04871711.

Prevalence and incidence of hand eczema in healthcare workers: A systematic review and meta-analysis.

Healthcare workers (HCWs) are considered a high-risk group for developing hand eczema (HE), mainly owing to wet work and contact with allergens at work. To meta-analyse the prevalence and incidence of HE in HCWs, as well as mapping the prevalence of atopic dermatitis (AD) and HE severity in HCWs. A systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. Published literature from 2000 to 2022 was eligible based on predefined inclusion and exclusion criteria. A total of 18 studies were included. Pooled life-time, 1-year and point prevalence of self-reported HE in HCWs was 33.4% (95% confidence interval [CI]: 28.3-38.6), 27.4% (95% CI: 19.3-36.5) and 13.5% (95% CI: 9.3-18.4), respectively. AD prevalence was 15.4% (95% CI: 11.3-19.9). Overall, the majority of HCWs reported mild HE. One included study assessed HE incidence reporting 34 cases/1000 person years. Most studies scored low-moderate using the New Ottawa Scale and the pooled point prevalence data showed broad CIs. In conclusion, the high prevalence of HE in HCWs underlines the increased risk and need for preventive measures for this professional group. There is, however, a need of further standardized high-quality studies.

Demographics, characteristics and medical treatment among adults with hand eczema in Denmark. A cross-sectional validation and registry-based study.

BACKGROUND: The international classification of diseases, 10th revision (ICD-10) includes several unvalidated diagnostic codes for hand eczema (HE). Knowledge is sparse on HE patient characteristics. OBJECTIVES: To validate selected HE ICD-10 codes in the Danish National Patient Registry (DNPR) and describe disease characteristics, lifestyle factors and medication use in adult HE patients. METHODS: Nineteen HE ICD-10 codes were selected and validated based on patient charts. Five cohorts were constructed based on the diagnostic code, DL30.8H (HE unspecified), in the DNPR: (i) patients with DL30.8H code (n = 8386), (ii) patients with DL30.8H code, but without atopic dermatitis (AD) (n = 7406), (iii) sex- and age-matched general population (n = 8386) without HE. Two additional cohorts nested in the DNPR included participants from the Danish Skin Cohort, (iv) patients with DL30.8H code but without AD (n = 1340) and (v) general population cohort (n = 9876). RESULTS: ICD-10 codes revealed positive predictive values ≥90% except irritant contact dermatitis (unspecified) (79.7%) and hyperkeratotic hand and foot eczema (84.1%). HE patients were most often women, middle-aged or older, of Danish ethnicity, had an atopic medical history and were smokers. Topical corticosteroid prescriptions were almost doubled in HE cohorts compared to general populations. CONCLUSION: We validated several HE ICD-10 codes and identified important HE patient characteristics.

A simplified bacterial community found within the epidermis than at the epidermal surface of atopic dermatitis patients and healthy controls.

There has been considerable research into the understanding of the healthy skin microbiome. Similarly, there is also a considerable body of research into whether specific microbes contribute to skin disorders, with atopic dermatitis (AD) routinely linked to increased Staphylococcus aureus (S. aureus) colonisation. In this study, the epidermal surface of participants was sampled using swabs, while serial tape-stripping (35 tapes) was performed to sample through the stratum corneum. Samples were taken from AD patients and healthy controls, and the bacterial communities were profiled by metabarcoding the universal V3-V4 16S rRNA region. Results show that the majority of bacterial richness is located within the outermost layers of the stratum corneum, however there were many taxa that were found almost exclusively at the very outermost layer of the epidermis. We therefore hypothesise that tape-stripping can be performed to investigate the 'core microbiome' of participants by removing environmental contaminants. Interestingly, significant community variation between AD patients and healthy controls was only observable at the epidermal surface, yet a number of individual taxa were found to consistently differ with AD status across the entire epidermis (i.e. both the epidermal surface and within the epidermis). Sampling strategy could therefore be tailored dependent on the hypothesis, with sampling for forensic applications best performed using surface swabs and outer tapes, while profiling sub-surface communities may better reflect host genome and immunological status.

Assessment of hand eczema severity by patients using the hand eczema severity index (HECSI).

BACKGROUND: Hand eczema severity index (HECSI) is a widely used tool for assessment of hand eczema (HE) severity. Generally, HECSI has been used by health care providers, and a validation of the HECSI tool when used by patients is lacking. OBJECTIVES: To evaluate the construct validity and reliability of HECSI as a tool for patients based on comparison to HECSI assessments by physicians. METHODS: Patients with HE, enrolled from the dermatological outpatient clinic, Bispebjerg Hospital, assessed HE severity with a patient version of HECSI (patient-HECSI). Afterwards, HECSI was assessed by a trained physician (physician-HECSI). RESULTS: This study found a strong correlation and very good absolute agreement between patient-HECSI and physician-HECSI assessments with a correlation coefficient of 0.756 and intraclass correlation coefficient (ICC) of 0.844. Cronbach's alpha was 0.861 indicating very good internal consistency. CONCLUSION: With a strong construct validity and reliability, the patient-HECSI may be used by patients as a patient-reported outcome assessing their personal HE severity.

Treatment with delgocitinib cream improves itch, pain and other signs and symptoms of chronic hand eczema: Results from the Hand Eczema Symptom Diary in a phase IIb randomized clinical trial.

BACKGROUND: Measuring patient-reported outcomes is crucial to fully capture the burden of chronic hand eczema (CHE). OBJECTIVES: To assess the effect of delgocitinib cream on itch, pain and nine additional key signs and symptoms reported by patients with CHE using the Hand Eczema Symptom Diary (HESD). METHODS: In a double-blind, phase IIb dose-ranging trial (NCT03683719), 258 adults with mild to severe CHE were randomized to delgocitinib cream 1, 3, 8 or 20 mg/g or cream vehicle twice daily for 16 weeks. Patients assessed 11 signs and symptoms of CHE daily through the HESD using an 11-point numeric rating scale; this was an exploratory endpoint. RESULTS: Delgocitinib cream 20 mg/g was associated with an early and sustained reduction in itch and pain, along with clinically relevant reductions of ≥4 points from baseline to Week 16 in 48.4% and 63.6% of patients, respectively (17.9% and 5.9% with cream vehicle). There were improvements versus cream vehicle in all assessed CHE signs and symptoms (20 mg/g, p < 0.05). CONCLUSIONS: Delgocitinib cream reduced itch, pain and other signs and symptoms in patients with CHE. This data correlated with clinician-reported outcomes, indicating that the HESD may be a useful assessment tool for CHE management.

A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis.

BACKGROUND: Evaluation of effectiveness and safety of new systemic treatments for atopic dermatitis (AD) after approval is important. There are few published data exceeding 52-week therapy with dupilumab. OBJECTIVES: To examine the safety, effectiveness and drug survival of dupilumab in a Danish nationwide cohort with moderate-to-severe AD up to 104 weeks exposure. METHODS: We included 347 adult patients with AD who were treated with dupilumab and registered in the SCRATCH registry during 2017-2022. RESULTS: At all visits, we observed improvement in AD severity measured by Eczema Area and Severity Index (EASI) [median (IQR)]. EASI score at baseline was 18.0 (10.6-25.2), at week 4: 6.5 (3.5-11.6), at week 16: 3.7 (1.2-6.2), at week 52: 2.0 (0.8-3.6), at week 104: 1.7 (0.8-3.8). While drug survival was high (week 52: 90%; week 104: 86%), AD in the head-and-neck area remained present in most patients at high levels; proportion with head-and-neck AD at baseline was 76% and 68% at week 104. 35% of patients reported any AE. Conjunctivitis was the most frequent (25% of all patients) and median time to first registration of conjunctivitis was 201 days. CONCLUSIONS: While 2-year drug survival was 86%, dupilumab was unable to effectively treat AD in the head-and-neck area, and conjunctivitis was found in 25% of patients.

The association between atopic dermatitis, cognitive function and school performance in children and young adults.

BACKGROUND: Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school. OBJECTIVES: To examine the association between hospital-managed paediatric AD, school performance and cognitive function. METHODS: In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription. RESULTS: In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference -0.29 [95% confidence interval (CI) -0.45 to -0.13, P < 0.001], difference -0.26 (95% CI -0.42 to -0.10, P = 0.0016) and difference -0.30 (95% CI -0.49 to -0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference -0.60 (95% CI -0.87 to -0.32, P < 0.001). CONCLUSIONS: AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.

Which outcomes should be measured in hand eczema trials? Results from patient interviews and an expert survey.

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.

Atopic dermatitis influences educational performance.

This review investigates the correlation between atopic dermatis and educational performance. Atopic dermatitis (AD) leads to intense itching, affecting sleep and health-related quality of life. AD negatively influences working life and poses a financial burden on society. Information about the impact of AD in childhood/adolescence on school life and the completion of education is sparse and previous studies have not found an association between AD and educational attainment. Recent studies have found AD to be associated with learning disability and decreased educational attainment. Future studies should investigate causality and the effects of optimised treatment.

Prevalence and incidence of hand eczema in healthcare workers: protocol for a systematic review and meta-analysis.

INTRODUCTION: Healthcare workers (HCWs) constitute a high-risk group for developing occupational hand eczema (HE). The present systematic review and meta-analysis will compile and appraise evidence regarding prevalence and incidence of HE in HCWs. METHODS AND ANALYSIS: Systematic searches will be performed in three electronic literature databases (PubMed/Medline, Web of Science-Core Collection and Embase). Further references will be retrieved by a manual search of included studies' reference lists using snowballing techniques. We will include experimental studies, observational studies, survey-based studies and clinical studies (publications in English, French and German from 2000 onwards) reporting on certified and apprentice HCWs, who actively work in the job. We will look at the following outcomes: Prevalence and incidence of clinically assessed as well as self-reported HE in the style of the Nordic Occupational Skin Questionnaire-2002; HE severity (measured by eg, Hand Eczema Severity Index, Osnabrück Hand Eczema Severity Index, Physician Global Assessment or other validated instruments as well as self-reported or by using undefined categories such as 'mild', 'moderate' or 'severe'); clinically assessed (eg, clinical diagnosis, UK Working Party's diagnostic criteria, Hanifin and Rajka diagnostic criteria for atopic dermatitis (AD)) and self-reported AD. We will assess the risk of bias within studies using detailed criteria according to the Newcastle-Ottawa Scale. As we expect heterogeneity in methods and outcomes, we will conduct sensitivity analyses. A narrative synthesis of results instead of a meta-analysis will be done in case that quantitative pooling is not feasible. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required as this work is based on published studies. The results will be published in an international, peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022303044.

Altered Maturation of the Skin Microbiome in Infants with Atopic Dermatitis.

The aim of this study was to investigate the early-life development of the skin microbiome in atopic dermatitis. Nineteen infants with atopic dermatitis and 19 healthy infants were evaluated 3 times, at 3 months intervals, within the first 30 months of life. Tape-strips were collected from volar forearms, cheeks, and eczema lesions, and the skin microbiome was assessed by 16S rRNA sequencing. Both the community structure and richness of the skin microbiome of infants with atopic dermatitis differed significantly from that of healthy infants, with greater richness in healthy infants. For infants with atopic dermatitis, the community composition was not dominated by Staphylococci. For healthy infants, community composition and richness correlated significantly with age, while such a pattern was not revealed in infants with atopic dermatitis. This suggests a slower maturation of the skin microbiome in atopic dermatitis, which precedes the staphylococcal predominance observed in older children and adults.

A comparison between self-reported hand eczema and self-reported signs and symptoms of skin lesions indicating hand eczema.

BACKGROUND: The accuracy of self-reported hand eczema (HE) is currently unclear, and it is unknown how well self-reported signs and symptoms of skin lesions that indicate HE correlate with self-reported HE. OBJECTIVES: To correlate self-reported signs and symptoms of skin lesions on the hands with self-reported HE, to assess the sensitivity and specificity, and to suggest a definition for HE. METHOD: Seven hundred ninety-five (47.8%) of 1663 invited healthcare workers completed a digital questionnaire, and were asked to report if they experienced HE or any of the following skin signs/symptoms in past 11 months: scaling, erythema, fissures, vesicles, dryness, itch, stinging. RESULTS: HE during the past 11 months was reported by 11.9%. Of these, 91.4% reported at least one skin sign versus 32.3% of those without self-reported HE. The highest sensitivity and specificity were found for erythema (77.4% and 78.2%, respectively) and itch (78.5% and 78.6%, respectively), both separately and combined. The combination of ≥2 signs (erythema, scaling, fissures and vesicles) and itch, reached a sensitivity of 52.7% and specificity of 93.9%. CONCLUSION: The marked difference between self-reported HE and signs/symptoms highlights the importance of differentiating between data based on self-reported HE and signs/symptoms. As a first step towards diagnostic HE criteria, ≥2 signs combined with itch could be considered, but clinical studies are needed to verify the precision.

Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH): A Danish Real-world Evidence Atopic Dermatitis Treatment Registry.

Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to describe the baseline characteristics of adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29-54 years), and median age at onset of AD was 1 year (IQR 0-6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9-25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0-25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0-19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0-9.0) and 6.0 (IQR 4.0-8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies.