Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

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.

The prevalence of hand dermatitis among intensive care unit nurses.

BACKGROUND: Healthcare workers are at high risk of developing occupational hand dermatitis (HD) due to their frequent exposure to wet-work and use of gloves. Complaints of HD may interfere with work and cause loss of work productivity, or sick leave, and may have impact on job pleasure and performing daily activities. The prevalence of HD among intensive care unit (ICU) nurses is unknown. OBJECTIVES: To investigate the point prevalence and the 1-year prevalence of HD among ICU nurses, and to determine the impact of HD on work and daily activities. METHOD: A questionnaire-based cross-sectional study was performed among ICU nurses. Participants were recruited in the Amsterdam University Medical Centre. A symptom-based questionnaire was used to determine HD and atopic predisposition, and an additional questionnaire was used concerning the influence of HD. ICU nurses with an atopic predisposition or symptoms suiting HD were invited for the hand dermatitis consultation hour (HDCH). Data were analysed with logistic regression. RESULTS: A total of 184 ICU nurses were included. The point prevalence of HD was 9.8% (95% CI: 5.9-15.0) and the 1-year prevalence was 26.6% (95% CI: 20.4-33.6). Sick leave was reported by 0.5%. HD seemed to have more impact on job pleasure than on work productivity. CONCLUSION: The high prevalence rate of HD resulting from our study highlights the need for the prevention of occupational HD among healthcare workers.

Skin Barrier- and Immune Response-Related Biomarkers of Solar UVR Exposure Comparing Indoor and Outdoor Workers.

Outdoor workers have increased risk of developing keratinocyte cancer due to accumulated skin damage resulting from chronic and excessive exposure to UVR. This study aims to identify potential noninvasive biomarkers to assess chronic UVR exposure. We analyzed stratum corneum biomarkers collected from 2 skin locations and 2 occupational groups with contrasting solar UVR exposure: the forehead and retroauricular skin among outdoor workers and indoor workers. Using a linear mixed model adjusting for age and skin phototype, we compared biomarkers between both skin sites in indoor and outdoor workers. We measured markers of the immune response and skin barrier, including cytokines, GFs, 15-hydroxyeicosatetraenoic acid, cis- and trans-urocanic acid, and corneocyte topography, indicated by circular nano objects. Differences between the 2 skin sites were found for cis-urocanic acid, total urocanic acid, IL-1α, IL-1RA, IL-1RA/IL-1α, IL-18, 15-hydroxyeicosatetraenoic acid, CCL4, and circular nano objects. The levels of cis-urocanic acid and CCL4 also differed between indoor and outdoor workers. These findings underscore changes in both immune response and skin barrier induced by UVR. They indicate the potential utility of stratum corneum biomarkers in detecting both chronic UVR exposure in occupational setting and aiding in the development of preventive measures.

A Comparative Analysis of Local and Systemic Immunological Biomarkers in Females With Breast Implants and Capsular Contracture.

Background: The etiology of capsular contracture (CC), the most common complication following breast augmentation, remains unclear. Chronic, fibrotic inflammation resulting in excessive fibrosis has been proposed as a potential mechanism. Objectives: In this study, we aimed to investigate the relation between biomarkers that are associated with inflammation and fibrosis and the severity of CC. Methods: Fifty healthy females were categorized into 3 groups: females with no-to-mild CC (Baker 1-2; n = 15), females with severe CC (Baker 3-4; n = 20), and a control group awaiting breast augmentation (n = 15). We assessed 5 biomarkers (galectin-1 [Gal-1], interferon-ß [INF-ß], interferon-γ [INF-γ], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in breast implant capsules and serum samples. Results: No significant differences in intracapsular cytokine levels were observed between the Baker 1-2 and the Baker 3-4 groups, as the levels were generally low and, in some cases, almost undetectable. In the blood samples, no significant differences in Gal-1, INF-γ, IL-6, or TNF-α levels were found within the 3 groups. We identified significantly increased levels of INF-ß (P = .009) in the blood samples of females with severe CC, driven mainly by 3 extremely high values. Conclusions: The cytokines assessed in this study did not reflect the degree of CC among females with silicone breast implants. However, 3 females with severe CC, who all had prolonged silicone exposure, showed extremely elevated levels of INF-ß in their serum samples. This possible association between prolonged silicone exposure and systemic inflammation in some females should be further investigated.

Results of patch testing with five fragrance materials hitherto not tested: A dose-finding study in the clinical population.

BACKGROUND: Quantitative risk assessment (QRA) for skin sensitization is used to derive safe use levels of sensitising fragrance ingredients in products. Post-marketing surveillance of the prevalence of contact allergy to these ingredients provides relevant data to help evaluate the performance of these measures. OBJECTIVES: To determine a suitable patch test concentration for five fragrance materials that had hitherto not been tested on a regular basis. These concentrations are then to be used in a surveillance study with patch testing consecutive patients over an extended monitoring period. MATERIALS AND METHODS: Furaneol, CAS.3658-77-3; trans-2-hexenal, CAS.6728-26-3; 4,8-dimethyl-4,9-decadienal, CAS.71077-31-1; longifolene, CAS.475-20-7; benzaldehyde, CAS.10052-7, were patch tested with other fragrance allergens in four clinics. Patch testing was conducted in three rounds, starting with the lowest concentrations of the five ingredients. The doses were increased in the subsequent rounds if no late-appearing positive reactions and virtually no irritant reactions were reported. RESULTS: Overall, 373 patients were tested. No positive allergic reaction was reported to the five ingredients. Patch test results of other fragrance allergens are reported. CONCLUSIONS: The highest test concentrations are each considered safe for patch testing consecutive patients. Further surveillance based on these preparations will evaluate the hypothesis that QRA-driven consumer product levels of these fragrances can prevent sensitization.

Functional brain alterations in symptomatic dermographism patients-An exploratory magnetoencephalography study.

Symptomatic dermographism (SD) is a common form of urticaria, which is triggered by stroking the skin. Brain involvement in its aetiology was investigated by means of magnetoencephalography (MEG) after provocation with histamine and dermography. Wheals were induced by histamine skin prick test and dermography in twelve SD patients and fourteen controls. Itch severity was scored on a Visual Analogue Scale (VAS). Relative power and functional connectivity (FC) were measured using a 306-channel whole-head MEG system at baseline and 10 min after histamine and dermography, and contrasted between groups and conditions. Furthermore, wheal diameter and itch scores after these procedures were correlated with the MEG values. SD patients had higher itch scores after histamine and dermography. No significant group-differences were observed in relative power or FC for any condition. In both groups, power decreases were mostly observed in the beta band, and power increases in the alpha bands, after provocation, with more regions involved in patients compared to controls. Increased FC was seen after histamine in patients, and after dermography in controls. In patients only, dermography and histamine wheal size correlated with the alpha2 power in the regions of interest that showed significant condition effects after these procedures. Our findings may be cautiously interpreted as aberrant itch processing, and suggest involvement of the central nervous system in the aetiology of SD.

Contact allergy to acrylate-containing nail cosmetics: A retrospective 8-year study.

BACKGROUND: Over the last 10 years, allergic contact dermatitis (ACD) from acrylate-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been reported repeatedly. OBJECTIVES: To investigate the frequency and clinical features of ACD in nail cosmetics in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: A retrospective study in patients diagnosed with ACD from acrylate-containing nail cosmetics at the Amsterdam University Medical Centers between January 2015 and August 2023. RESULTS: Sixty-seven patients, all women, were diagnosed with ACD from nail cosmetics, representing 1.6% of all individuals and 2.3% of all women patch tested in this period. Sixty-five of sixty-seven (97%) subjects had a positive patch test to 2-hydroxyethyl methacrylate (HEMA). Forty-nine patients (73%) were consumers and 18 (27%) were professional nail stylists. The sites most frequently affected with dermatitis were the fingers (79%), hands (40%) and the head and/or neck. Avoidance of contact with acrylate-containing products resulted in complete clearing of dermatitis in 80% of patients. CONCLUSIONS: ACD from acrylate-containing nail cosmetics is frequent in women patch tested in Amsterdam. Nearly all were identified by a positive patch test to 2-hydroxyethyl methacrylate in the (meth)acrylate series or the European baseline series.

Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial).

BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.

Results of patch testing 2-hydroxyethyl methacrylate (HEMA) in the European baseline series: A 4-year retrospective study.

BACKGROUND: 2-Hydroxyethyl methacrylate (HEMA) was added to the European baseline series (EBS) in 2019. Few recent data are available on the frequency and relevance of positive reactions to this hapten. OBJECTIVES: To investigate the frequency and relevance of positive patch tests to HEMA in the EBS in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: Retrospective study in patients with positive patch tests to HEMA investigated between June 2019 and August 2023. RESULTS: Of 2927 consecutive patients, 88 (79 women and 9 men; 3.0%) had a positive reaction to HEMA. The prevalence in women was 3.9%, in men 1.0%. Forty-three (49%) reactions were judged to be of current clinical relevance and 21 (24%) of past relevance. In this group of 64 patients with relevant reactions, 18 (28%) had occupational contact with (meth)acrylate-containing products, of who 11 (61%) were nail stylists. In 46 patients with non-occupational allergic contact dermatitis, 31 (67%) had allergic reactions to nail cosmetics. Glues and glue-containing products accounted for 22% of the materials causing allergic contact dermatitis and dental products for 8%. CONCLUSIONS: Allergic reactions to HEMA are very frequent in women investigated in Amsterdam. Nearly two thirds of cases were caused by nail cosmetics.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis. Part 2. Cross- and co-sensitization, other skin reactions to HEMA, position of HEMA among (meth)acrylates, sensitivity as screening agent, presence of HEMA in commercial products and practical information on patch test procedures.

This is the second part of a literature review of the clinical aspects of contact allergy to and allergic contact dermatitis from 2-hydroxyethyl methacrylate (HEMA). Topics include cross- and co-sensitization, atypical manifestations of contact allergy, frequency of positive patch tests to HEMA compared with other (meth)acrylates, sensitivity of HEMA as a screening agent, the presence of HEMA in commercial products, and practical information on patch testing procedures. Primary sensitization to methacrylates including HEMA may result in methacrylate and acrylate cross-sensitization. There is a strong cross-allergy between HEMA, ethylene glycol dimethacrylate (EGDMA), and hydroxypropyl methacrylate; many reactions to EGDMA are cross-reactions to primary HEMA sensitization. Rare atypical manifestations of HEMA-allergy include lichen planus, lymphomatoid papulosis, systemic contact dermatitis, leukoderma after positive patch tests, and systemic side effects such as nausea, diarrhoea, malaise, and palpitations. The occurrence of respiratory disease caused by methacrylates such as asthma is not infrequent. HEMA is the most frequently patch test-positive methacrylate. It is a good screening agent for allergy to other (meth)acrylates. Patch test sensitization to HEMA 2% pet. is extremely rare. There are (some) indications that HEMA is frequently used in dental products and nail cosmetics.

Frequency and clinical relevance of contact allergy in dental patients.

BACKGROUND: While many studies have reported on occupational allergic contact dermatitis amongst dental personnel, studies on the relevance of patch testing in dental patients are scarce. OBJECTIVES: To determine the frequency and clinical relevance of contact allergy in patients with intra- and perioral complaints. METHODS: A total of 360 patients with intra- and perioral complaints suspected of having a contact allergy were patch-tested with the dental allergen series, European Baseline Series, and extended Amsterdam Baseline Series at Amsterdam University Medical Centers between January 2015 and November 2021. RESULTS: A total of 285 patients (79.2%) had a positive patch test reaction for either one (18.6%) or multiple allergens (60.6%). Sodium tetrachloropalladate was the most sensitising allergen with 98 patients (27.2%) testing positive, followed by nickel sulphate (23.3%), methylisothiazolinone (15.6%), and fragrance mix I (14.2%). Clinical relevance was found in 68 of 208 patients (32.7%), with patients having one (15.4%) or multiple (17.3%) patch test reactions clinically relevant to their (peri)oral complaints. CONCLUSIONS: Clinically relevant patch test reactions were frequently seen in dental patients. Although this study provides us with a better understanding on the frequency and clinical relevance of contact allergy in dental patients, further studies are needed to confirm our results.

Presence of 2-hydroxyethyl methacrylate (HEMA) and other (meth)acrylates in nail cosmetics, and compliance with EU legislation: An online market survey.

BACKGROUND: During the last 15-20 years, allergic contact dermatitis from acrylates-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been increasingly reported. 2-Hydroxyethyl methacrylate (HEMA) is considered to be the major allergenic culprit; few data on its presence in nail cosmetics are available. OBJECTIVES: To investigate (1) the frequency in which HEMA and di-HEMA trimethylhexyl dicarbamate are present in nail cosmetics; (2) whether nail cosmetics comply with EU regulations; (3) which other (meth)acrylates are present in nail cosmetics and how often. METHODS: One-line market survey. RESULTS: HEMA was present in nearly 60% of 394 cosmetic nail products and di-HEMA trimethylhexyl dicarbamate in 34%. Mandatory warnings on the packages of products containing HEMA were absent in 35% ('For professional use only') resp. 55% ('Can cause an allergic reaction'). Forty-five other (meth)acrylates were identified, of which the most frequent were hydroxypropyl methacrylate (25%), isobornyl methacrylate (16%) and trimethylolpropane triacrylate (12%). Some ingredient lists mentioned non-INCI names or non-specific names. CONCLUSIONS: HEMA was by far the most common ingredient of nail cosmetics, being present in nearly 60% of the products. Violations of EU legislation occurred in >30% (mandatory warnings missing) resp. 10% (mislabelling) of nail cosmetics.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis-Part 1. Introduction, epidemiology, case series and case reports.

2-Hydroxyethyl methacrylate (HEMA) has been increasingly recognised as a contact allergen and was added to the European baseline series in 2019. In this article (2 parts), the results of an extensive literature review of the clinical aspects of contact allergy/allergic contact dermatitis to HEMA are presented. In part 1, the epidemiology of HEMA contact allergy is discussed and detailed information on published case series and case reports presented. HEMA is an important cause of contact allergy/allergic contact dermatitis in North America and Europe with recent prevalences of >3% in the USA + Canada and 1.5%-3.7% in Europe. Currently, most cases are caused by nail cosmetics, both in consumers and professional nail stylists. In our literature review, we have found 24 studies presenting case series of patients with allergic contact dermatitis attributed to HEMA and 168 case reports. However, the presence of HEMA in the products causing ACD was established in only a minority. Part 2 will discuss cross- and co-sensitisation, and other skin reactions to HEMA, will assess whether HEMA is the most frequent (meth)acrylate allergen and how sensitive HEMA as a screening agent is, investigate the presence of HEMA in commercial products and provide practical information on patch testing procedures.

The prevalence of contact dermatitis among surgical assistants, anaesthesia assistants and anaesthesiologists working at the Amsterdam University Medical Centre.

BACKGROUND: Professions requiring frequent and/or long lasting wet-work are at high risk for contact dermatitis (CD). CD may lead to loss of work productivity, sick leave and reduced quality of work. The 1-year prevalence of healthcare workers varies between 12% and 65%. However, the prevalence of CD among surgical assistants, anaesthesia assistants and anaesthesiologists is unknown. OBJECTIVES: (1) To establish the point-prevalence and 1-year prevalence among surgical assistants, anaesthesia assistants and anaesthesiologists and (2) to determine the impact of CD on work and daily activities. METHOD: A single-centre cross-sectional prevalence study was conducted among surgical assistants, anaesthesia assistants and anaesthesiologists. Data were obtained from the Amsterdam University Medical Centre between the 1 June 2022 and 20 July 2022. For data collection, a questionnaire was used, derived from the Dutch Association for Occupational Medicine (NVAB). Participants with an atopic predisposition or symptoms of CD were invited to the contact dermatitis consultation hour (CDCH). RESULTS: A total of 269 employees were included. The total point prevalence of CD was 7.8%; 95% CI: 4.9-11.7, the total 1-year prevalence was 28.3%; 95% CI: 23.0-34.0. The point-prevalence among surgical assistants, anaesthesia assistants and anaesthesiologists was 14%, 4% and 2%, respectively. The 1-year prevalence was 49%, 19% and 3%, respectively. Two employees reported changed work-tasks because of symptoms, no sick days were reported. The majority of the visitors of the CDCH indicated an impact on work productivity and daily activities because of CD; however, the extent to which varied widely. CONCLUSION: This study established that CD is a relevant occupational health disease among surgical assistants, anaesthesia assistants and anaesthesiologists.

Skin cancer incidence in transgender individuals receiving gender-affirming hormone treatment: a nationwide cohort study in the Netherlands.

BACKGROUND: Development of skin cancer, in particular melanoma, has been linked to sex hormones. We aimed to determine the incidence of skin cancer in transgender individuals receiving gender-affirming hormone treatment (GAHT). METHODS: In this nationwide retrospective cohort study, clinical information of participants who visited our clinic between (the years) 1972 and 2018 and received GAHT was integrated with national pathology and cancer statistics data in order to assess skin cancer incidence. Standardized incidence ratios (SIRs) were calculated. RESULTS: The cohort consisted of 2,436 trans women and 1,444 trans men. The median age at the start of GAHT was 31 years (IQR 24-42) in trans women and 24 years (IQR 20-32) in trans men. The median follow-up time for trans women was 8 years (IQR 3-18) with a total follow-up time of 29,152 years and 4 years (IQR 2-12) with a total follow-up time of 12,469 years for trans men. Eight trans women were diagnosed with melanoma (SIR 1.80 [95% CI 0.83-3.41] vs. all men; SIR 1.40 [0.65-2.65] vs. all women), and seven developed squamous cell carcinoma (SIR 0.78 [0.34-1.55] vs. all men; SIR 1.15 [0.50-2.27] vs. all women). Two trans men developed melanoma (SIR 1.05 [0.18-3.47] vs. all men; SIR 0.77 [0.14-2.70] vs. all women). CONCLUSIONS: GAHT did not appear to affect skin cancer incidence in this large cohort of transgender individuals. As skin cancer incidence increases with age and the proportion of elderly subjects is currently limited in this cohort, it will be worthwhile to repeat this analysis in the future.

The Complexity of the Post-Burn Immune Response: An Overview of the Associated Local and Systemic Complications.

Burn injury induces a complex inflammatory response, both locally and systemically, and is not yet completely unravelled and understood. In order to enable the development of accurate treatment options, it is of paramount importance to fully understand post-burn immunology. Research in the last decades describes insights into the prolonged and excessive inflammatory response that could exist after both severe and milder burn trauma and that this response differs from that of none-burn acute trauma. Persistent activity of complement, acute phase proteins and pro- and anti-inflammatory mediators, changes in lymphocyte activity, activation of the stress response and infiltration of immune cells have all been related to post-burn local and systemic pathology. This "narrative" review explores the current state of knowledge, focusing on both the local and systemic immunology post-burn, and further questions how it is linked to the clinical outcome. Moreover, it illustrates the complexity of post-burn immunology and the existing gaps in knowledge on underlying mechanisms of burn pathology.

Occupational contact allergy: The European perspective-Analysis of patch test data from ESSCA between 2011 and 2020.

BACKGROUND: Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. OBJECTIVES: To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. METHODS: The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n = 46 652) in whom an occupational causation was refuted served as comparison group. RESULTS: The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. CONCLUSIONS: Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives.