Atopic dermatitis and hand eczema in Danish adults: A nationwide population-based study.

BACKGROUND: Atopic dermatitis (AD) and hand eczema often co-occur, particularly among adults. OBJECTIVES: To examine the interplay between AD and hand eczema in the general population, by characterising prevalence, disease severity, contact sensitization, and comorbidities in individuals with one or both conditions. MATERIALS AND METHODS: In this cross-sectional study, 100 000 randomly selected adults in the Danish general population received a questionnaire via a secure, digital mailbox linked to their civil registration number. Participants answered questions regarding eczema, disease severity, patch testing, and comorbidities. RESULTS: A total of 40 007 individuals responded to the question on a lifetime prevalence of AD, and the prevalence among adult Danes was 9.0%. Nearly one third of individuals with AD reported moderate to severe disease. AD was associated with contact sensitization and increased hand eczema prevalence. Individuals with both AD and hand eczema reported worse disease severity. Furthermore, having both conditions was associated with an increased risk of psychiatric comorbidities. CONCLUSIONS: This study provided updated information about unselected adults with AD in Denmark. Individuals with both AD and hand eczema represent a vulnerable subgroup that physicians should be attentive to.

Hidden formaldehyde in cosmetic products.

BACKGROUND: Formaldehyde is a common cause of contact allergy. Hidden formaldehyde, that is, formaldehyde in products without formaldehyde releasers, has previously been detected in cosmetic products. OBJECTIVES: The objective of this study was to investigate the content and causes of hidden formaldehyde in leave-on cosmetic products. METHODS: The formaldehyde release from 142 cosmetic products, primarily creams, was analysed using the chromotropic acid (CA) method. The study included 130 products with no formaldehyde releasers on the ingredient list and 12 products with formaldehyde releasers. Products without formaldehyde releasers positive to CA, that is, with formaldehyde ≥2.5 ppm, were additionally analysed using high-performance liquid chromatography (HPLC). Formaldehyde release from selected raw materials and packaging were also investigated. RESULTS: Hidden formaldehyde was found in 23 of the 130 products (18%) without formaldehyde releasers on the ingredient list. The average formaldehyde content was 105 ppm (range: 0.5-507 ppm) in products with hidden formaldehyde and 355 ppm (range: 75-637 ppm) in eight products with formaldehyde releasers, selected for HPLC analysis. Impurities of formaldehyde in dihydroxyacetone may be a cause of hidden formaldehyde in self-tanners. No clear pattern was found for the other products with hidden formaldehyde. CONCLUSIONS: Changes in regulation are needed to prevent allergic contact dermatitis from hidden formaldehyde in cosmetic products.

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.

Chromium and cobalt in leather: A Danish market survey.

INTRODUCTION: Leather has been a significant source of chromium (Cr) allergy in Denmark since the 1990s. More recently, cobalt (Co) allergy has been identified in leather as a source of allergic contact dermatitis. OBJECTIVES: To measure Cr and Co levels in Danish leather goods. METHODS: A total of 87 leather samples were collected, all tanned in Europe. Handheld X-ray fluorescence (XRF) device was used to screen for the presence of Cr and Co. The 20 leather samples with the highest concentrations of Co and Co were tested using International Organization for Standardization (ISO)-standards. RESULTS: XRF analysis showed Cr in 78/87 (83.9%) samples and Co in 52/87 (59.7%), with average concentrations of 41 mg/kg (range: 0.0-77 mg/kg) and 0.22 mg/kg (range: 0.0-2.9 mg/kg), respectively. ISO 10195 and 17 075-1 testing identified Cr (VI) in 7 out of 20 samples (1.4; 0.3-4.2 mg/kg), while ISO 17072-1 detected Co in 6 of 20 samples, averaging 3.95 mg/kg (range: 0.22-7.9 mg/kg). CONCLUSION: Most leather samples contained Cr, which was expected, while Cr (VI) was detectable in seven out of twenty tested samples but only detected in one product above the regulatory limit of 3 mg/kg. A potentially significant concentration was found for Co.

Referral Pathways for Children with Atopic Diseases in Denmark.

Atopic diseases such as atopic dermatitis, food allergy, allergic rhinoconjunctivitis, and/or asthma are common. In Denmark, however, there are multiple referral pathways for these diseases in the healthcare system and they are poorly understood. To describe how children with atopic diseases navigate their way through the Danish healthcare system, a questionnaire was distributed to children aged ≤ 17 years, who were being treated for atopic diseases between August 2020 and June 2021, either by a practising specialist or a hospital department, in the Capital Region of Denmark. A total of 279 children completed the questionnaire and most were referred to a specialist or to a hospital by their general practitioner. No "common track" to hospital existed for patients with ≥ 3 atopic diseases. These patients were more often referred to a hospital compared with children with 2 atopic diseases or fewer (odds ratio [OR] 3.79; 95% CI 2.07-7.24). The primary determinants for hospital treatment were food allergy (OR 4.69; 95% CI 2.07-10.61) and asthma (OR 2.58; 95% CI 1.18-5.63). In conclusion, children with multiple atopic diseases were more likely to be referred to hospital departments than to practising specialists, mainly due to food allergies.

Contact sensitization to fragrance mix I and fragrance mix II among European dermatitis patients: A systematic review.

BACKGROUND: Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability, environmental conditions and cultural practices. OBJECTIVES: To systematically review and gather prevalence of sensitization to fragrance mix I (FM I) and fragrance mix II (FM II) in consecutively patch tested European dermatitis patients. METHOD: A total of 4134 publications on patch test results of European dermatitis patients, published from 1981 to 2022, were systematically reviewed according to a previously registered and published PROSPERO protocol. RESULTS: Eighty-four eligible original articles were analysed. Overall prevalence of sensitization to fragrance mix I (FM I) was 6.81% (95% CI: 6.37-7.28), and FM II was 3.64% (95% CI: 3.3-4.01). Sensitization to FM I was most prevalent in Central and Eastern Europe and to FM II in Western Europe. No clear time trends were observed. Among paediatric dermatitis patients, sensitization prevalence for FM I and FM II was 4.09% (95% CI: 3.37-4.96) and 2.17% (95% CI: 1.53-3.07). CONCLUSION: The frequency of positive patch test results for both FMI and FMII remains high. Sensitization is also prevalent among children. Enhanced regulation and labelling of cosmetic products play a vital role in averting exposure and sensitization to fragrance allergens.

Recognizing and Managing Allergic Contact Dermatitis: Focus on Major Allergens.

Patch testing is the reference standard for the diagnosis of allergic contact dermatitis. Identification and avoidance of culprit allergens are essential in the treatment of this disease. Each year, new allergens are identified as emerging or important. The authors discuss allergens that are common, enduring, emergent, incompletely recognized, and controversial for the practicing allergist and dermatologist. This Clinical Management Review will encompass a review of fragrances, preservatives, rubber, acrylates, metals, and medications; their common sources of exposure; controversies in diagnosis and patch testing; management and how to avoid those allergens. This review will also include practical aspects of diagnosis and management and will provide resources that can be used as guidance for physicians and patients on nickel, methylchloroisothiazolinone/methylisothiazolinone, and fragrance, the most common allergens positive on patch testing.

Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

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.

Stratum Corneum Lipids in Non-Lesional Atopic and Healthy Skin following Moisturizer Application: A Randomized Clinical Experiment.

INTRODUCTION: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). METHODS: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. RESULTS: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. CONCLUSION: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin.

Notification of hand eczema as an occupational disease among Danish hairdressers: a national survey on patients' perception.

OBJECTIVES: Self-reported hand eczema was previously found under-reported as an occupational disease to the authorities among Danish hairdressers graduating from 1985 to 2007. This study investigates whether self-reported hand eczema among Danish hairdressers graduating from 2008 to 2018 is under-reported as an occupational disease to the authorities. METHODS: A cross-sectional study on all Danish hairdressers graduating from 2008 to 2018 was conducted. The participants were identified using information from the Danish Hairdressers' and Beauticians' Union. In May 2020, a self-administered survey on hand eczema was sent to all hairdressers. RESULTS: A response rate of 30.7% (1485/4830) was obtained. The lifetime prevalence of self-reported hand eczema was 40.1%, and 84.1% of hairdressers with hand eczema believed it to be occupational of whom 27.0% answered it was reported as an occupational disease to the authorities. Of hairdressers believing their hand eczema was occupational, consulting a doctor and answering it was reported as an occupational disease, 94.4% had consulted a dermatologist. The main reason for not reporting was 'I would probably not gain anything from it anyway' (40.0%). CONCLUSIONS: Based on hairdressers' perception, occupational hand eczema still seems to be an under-reported disease which may lead to underestimation of the problem and impair prevention, diagnosis and treatment.

BIOSKIN: A Protocol for the Copenhagen Translational Skin Immunology Biobank and Research Programme.

INTRODUCTION: Psoriasis, atopic dermatitis and contact dermatitis are common chronic inflammatory skin diseases that have a significant impact on individuals and society. METHODS AND ANALYSIS: The Copenhagen Translational Skin Immunology Biobank and Research Programme (BIOSKIN) is a translational biobank and research study that aims to prospectively collect high-quality biological samples and clinical data from 3000 patients with psoriasis, atopic dermatitis and contact dermatitis over a minimum period of 5 years. The longitudinal open design allows participants to enter and leave the study at different time points depending on their disease and treatment course. At every visit, the investigator collects biological samples, conducts interviews and assembles self-reported questionnaires on disease-specific and general health-related information. Clinical examination and biological sampling will be conducted at enrolment, during and after disease flare, before and after initiation of new treatment and at least once per year. The clinical examination includes dermatological verification of diagnosis, evaluation of disease severity and detailed information on phenotype. The biological samples include blood and when accessible and relevant, skin biopsies, tape strips and skin swabs. The data collected will undergo rigorous statistical analysis using appropriate analytical methods. As of December 2023, 825 patients have been enrolled in the study. ETHICS AND DISSEMINATION: The study is approved by the Scientific Ethical Committee of the Capital Region (H-21032986) and the Danish Data Protection Agency. Results will be published in peer-reviewed scientific journals and presented at national and international conferences.

Contact allergy to topical corticosteroids.

Topical corticosteroids are commonly used to treat inflammatory skin conditions due to their anti-inflammatory properties. However, patients with long-lasting, non-responsive eczema have to be evaluated for a complicating contact allergy to the topical product. Clinical management of allergic contact dermatitis to corticosteroids can be challenging. The preventive measures should be tailored according to the sensitization patterns and supported by currently available classification systems to avoid cross-reactivity, as argued in this review.

Association between atopic disease and vaccination granulomas: A nested case-control study.

BACKGROUND: Vaccination granulomas are observed in 1% of all children vaccinated with an aluminium-adsorbed vaccine. Most children with granulomas also have aluminium contact allergy (CA). CA and atopic diseases are both highly prevalent among children and may be associated. OBJECTIVE: To investigate the association between vaccination granulomas and atopic dermatitis (AD), asthma and rhinitis in children. METHODS: We sourced a cohort of all Danish children born from 2009 to 2017 and conducted a nested case-control study, with cases defined as children with vaccination granulomas, matched to controls 1:10 on sex, socioeconomic class, gestational age and season of birth. All cases and controls were vaccinated with aluminium-adsorbed vaccines and followed until their second birthday. We used conditional logistic regression to estimate the odds ratios (ORs). RESULTS: The study included 2171 cases with vaccination granulomas, and 21 710 controls. Children with a diagnosis of AD had a significantly higher risk of a vaccination granuloma (OR 1.50, 95% confidence intervals [CI] 1.25-1.80). No significant association was found between granulomas and asthma or rhinitis. The association between granulomas and AD was even higher in an additional sensitivity-analysis, following the children until their fourth birthday (OR 2.71, 95% CI 2.36-3.11). CONCLUSION: AD was significantly associated with vaccination granulomas, but not with other atopic diseases, within both the first 2 and 4 years of life.

Inflammatory plasma signature of chronic hand eczema: Associations with aetiological and clinical subtypes.

BACKGROUND: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures. OBJECTIVES: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes. METHODS: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed. RESULTS: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes. CONCLUSION: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema.

Hand eczema in Danish adolescents-Beyond atopic dermatitis.

BACKGROUND: Hand eczema (HE) is a common inflammatory skin disease that may have serious consequences. The age of HE onset varies, but is estimated to be early- to mid-20s. However, very little is known about HE in childhood and adolescence. OBJECTIVE: We aimed to explore the epidemiology, aetiology and severity of HE among a random sample of Danish adolescents drawn from the general population. METHODS: The study was designed as a self-administered questionnaire study. An electronic questionnaire was sent to a random sample of 13 000 individuals aged 15-19 years. RESULTS: The point-prevalence, 1-year prevalence and life-time prevalence of HE among Danish adolescents was 4.9%, 12.1% and 18.3%, respectively. Among patients with a history of HE, 64.6% of cases were not associated with atopic dermatitis. Of all respondents, 60.2% were either part-time or full-time employed. Among respondents with current HE, 38.2% believed that the occupational exposures either caused or exacerbated the HE. CONCLUSION: We found a high prevalence of HE among Danish adolescents which raises concern. Knowing the potential consequences that HE may have, attention should be paid to the prevention of HE in adolescence, especially on occupational aspects and prevention of skin disease in young workers.

Chronic hand eczema: A prevalent disease in the general population associated with reduced quality of life and poor overall health measures.

BACKGROUND: The impact of hand eczema (HE) on Health-Related Quality of Life (HRQoL) has only been sparsely studied in a general population setting, and never by use of the disease specific Quality Of Life in Hand eczema Questionnaire (QOLHEQ). OBJECTIVES: To examine the HRQoL of unselected individuals with HE using the QOLHEQ. Further, to provide prevalence estimates of severe and chronic HE (CHE), and to contrast overall health related outcomes between individuals with and without HE. METHODS: In this nationwide, cross-sectional study a questionnaire covering questions on HE related outcomes, and overall health was sent to a random sample of 100 000 Danish adults via a secure digital mailbox, linked to their unique civil registration numbers. Data on demographic characteristics were retrieved from the civil registration system. Individuals reporting HE, further answered the QOLHEQ and other disease specific questions. RESULTS: The response rate was 42.7% (n = 42 691). Total estimates of lifetime, 1-year and point prevalences of HE were 24.4%, 13.3% and 5.8%. Of individuals reporting a 1-year prevalence, 35.1% reported moderate-severe disease and 82.6% CHE. Individuals with HE were more likely to report less good or poor overall health, and sick leave (any reason), compared to those without. In the 2176 (92.5%) with current HE who completed the QOLHEQ, median QOLHEQ scores corresponded to a moderate impairment of the symptoms and treatment and prevention domains and a slight impairment overall and for the emotions and functioning domains. Factors that were strongly associated with moderate to severe HRQoL impairment included severe, chronic and occupational HE as well as female sex. CONCLUSIONS: HE is highly prevalent, bears a considerable burden on society and significantly affects the lives of impacted individuals. Our findings indicate a necessity for targeted prevention aimed at high-risk groups, and support and treatment for those most affected.

Fragrance allergens in cosmetic products marketed for children in Denmark.

BACKGROUND: Fragrances are among the most common contact allergens in children. Cosmetic products are the most frequent source of skin exposure. OBJECTIVE: To investigate exposure to fragrance allergens among Danish children, based on a sample of 1179 cosmetic products marketed for children. METHODS: Information regarding cosmetic products marketed to children was obtained using a non-profit smartphone application registry, with data from December 2015 to November 2022. RESULTS: The number of validated products was 26 537, of which 1349 marketed for children. After elimination of duplicates, 1179 (4.4%) individual products remained. The majority 53.8% (634/1179) of the products were fragranced. The highest frequency of declared fragrances was found in 'Facial care'-products: 93.0% (80/86), of which 97.7% were lip balms. The highest number of labelled fragrances in one single product (n = 16) was found in a baby perfume. Fragrance mix I (FMI) or II (FMII) allergens were found in 25.3% (298/1179) of the products. Limonene and linalool were the two most frequently labelled fragrance allergens. CONCLUSION: Children can be exposed to a vast number of fragrance allergens from scented cosmetic products. Allergens from FM I and FMII are widely used in cosmetic products marketed to children. Patch testing with FMI and FMII remains relevant in children.