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Allergic contact dermatitis is characterized by its appearance of red, raised and infiltrated, scaling or scabbed skin and intense pruritus, and distinguished from irritant contact dermatitis by its specific immune process and histopathology. Many contact allergens are low-molecular- weight chemicals including metals such as nickel, cobalt, and chromium, preservatives, and adhesives. When such materials are used internally in biomedical devices, they are similarly capable of causing sensitization and an inflammatory response. Sometimes, the reaction remains internal, and presents as swelling, pain, stiffness, decreased range of motion, and internal itching around the implant. Such reactions may, in some cases, also extend to include a localized or, rarely, systemic contact dermatitis indicative of the same process. This review will present an overview of reported skin and local internal reactions to orthopedic implants, which are the largest category of implanted internal metal devices. Immune reactions to smaller categories of medical appliances include cardiac devices and vascular stents, neuromodulation devices, diabetic appliances, Nuss bar surgery for pectus excavatum, and dental and spinal implants. We will review the available diagnostic tools, the consensus on interpretation, and reported strategies for treatment., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Nickel is the leading cause of contact allergy in Europe, with 14.5% of the adult population being sensitized. Despite regulations limiting nickel release from consumer items, the incidence and prevalence of nickel allergy remain high., Objective: To investigate the clinical and subclinical immune response to low-dose nickel exposure on nickel pre-exposed skin to assess the adequacy of current regulatory limits., Method: Nickel-allergic and healthy controls were patch tested with nickel twice with a 3-4 weeks interval. The first exposure used the diagnostic concentration of 2000 μg/cm 2 nickel sulphate, and the same skin areas were then re-exposed to 0.2, 0.5, 12.8 and 370 μg/cm 2 nickel sulphate. After 48 h, the patch reactions were examined for clinical signs of eczema, and skin biopsies were collected. The transcriptomic immune profile was analysed with Nanostring nCounter and quantitative polymerase chain reaction., Results: Two nickel-allergic participants (15%) had clinical reactions to the regulatory limiting doses for nickel (0.2/0.5 μg/cm 2 ) following re-exposure. There was immune activation in all skin areas following re-exposure to nickel, predominantly mediated by up-regulation of cytokines and chemokines. In all nickel re-exposed skin areas, 81 genes were up-regulated independent from the clinical response. In skin areas exposed to 0.2 μg/cm 2 , 101 immune-related genes were differentially expressed, even when no clinical response was observed. Healthy controls showed up-regulation of three genes in response to nickel re-exposures without any clinical reactions., Conclusion: Immune activation can be induced in skin with local memory to nickel upon challenge with nickel doses within the regulatory limits. Our findings suggest that the regulatory limits in the European nickel regulation may not provide sufficient protection for consumers against low-dose exposures., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: According to their parents, some children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing foods by developing dermatitis, granuloma itch and subjective symptoms., Objectives: The objective of this study is to determine whether oral intake of aluminium-containing pancakes can cause adverse events and/or systemic contact dermatitis (SCD) in children with vaccination granulomas and aluminium contact allergy., Patients/methods: A total of 15 children aged 3-9 years (mean age, 5 years) with vaccination granulomas and positive patch-test results to aluminium chloride hexahydrate 2%/10% pet. completed a 3-week blinded randomized controlled crossover oral aluminium/placebo provocation study with pancakes. Granuloma itch and other subjective symptoms were evaluated daily on a visual analogue scale (VAS). Dermatitis was evaluated by the primary investigator, and sleep patterns were tracked with an electronic device. Aluminium bioavailability was assessed by measuring aluminium excretion in the urine. The children served as their own controls with the placebo provocations., Results: All 15 children completed the study. The mean VAS scores were slightly higher during aluminium provocations compared with placebo for granuloma itch (mean VAS, 1.5 vs. 1.4, p = 0.6) but identical for other subjective symptoms (0.6 vs. 0.6, p = 1). There were no differences in sleep patterns and no significant correlation between urinary aluminium excretion and symptom severity. Three children developed a symmetrical rash on the face or buttocks on day 4 of the aluminium provocations, but not during placebo provocations., Conclusions: No difference was found between oral aluminium intake and the occurrence of subjective symptoms and granuloma itch, but on a case-basis oral aluminium may be associated with the development of systemic contact dermatitis., (© 2022 European Academy of Dermatology and Venereology.)

The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Occupational hand eczema is frequent in metalworkers. The contribution of metal allergies is poorly elucidated even though such exposures are common at the workplace. To estimate the prevalence of metal allergy to cobalt (Co), chromium (Cr) and nickel (Ni) in metalworkers and compare these to estimates from the European Surveillance System on Contact Allergies (ESSCA). Two authors independently searched PubMed for studies reporting on the prevalence of metal allergy in metalworkers. Proportion meta-analyses were performed to calculate the pooled proportions of metal allergy in metalworkers. In total, 29 studies (22 from Europe) were included yielding 5691 subjects for quantitative analysis. The pooled proportion (95% confidence interval) of Co, Cr and Ni in European metalworkers with dermatitis referred to patch test clinics was 8.2% (5.3%-11.7%), 8.0% (5.1%-11.4%), and 11.0% (7.3%-15.4%), respectively. The corresponding estimates for unselected metalworkers from workplace studies were 4.9% (2.4%-8.1%), 5.2% (1.0%-12.6%), and 7.6% (3.8%-12.6%), respectively. In comparison, the prevalence of metal allergy in 13 382 consecutive European males with dermatitis was 3.9% (3.6%-4.2%), 4.4% (4.1%-4.8%) and 6.7% (6.3%-7.0%) for Co, Cr and Ni, respectively. Data on sex, age, body piercings and atopic dermatitis in metalworkers with metal allergy was mostly lacking. Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA data, indicating a relationship to occupational exposures, however, confounders could not be accounted for., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Compliance with glove use and safe work practices are important factors in primary prevention of occupational hand eczema (OHE) in hairdressers., Objective: To assess the risk OHE and compliance with skin protective measures in hairdressers trained before and after implementation of a nationwide skin protection program in Danish hairdressing vocational schools in 2011., Methods: A repeated cross-sectional study was performed. A questionnaire was sent in 2009 and 2020. The Danish Labour Market Supplementary Pension Scheme provided information on yearly payments from the hairdressing profession., Results: A response rate of 66.6% (305/460) was obtained in the 2009 survey and of 29.9% (363/1215) in the 2020 survey. The career time prevalence of OHE decreased from 42.8% to 29.0% (adjusted odds ratio 0.55 95% confidence interval [CI] 0.40-0.77) and the incidence rate of OHE decreased from 57.5 (95%CI 48.4-68.4) to 42.0 (95%CI 34.6-50.9) per 1000 person years (incidence rate ratio 0.73 [95%CI 0.56-0.95] between the two surveys). A statistically significant (P < .05) increase in glove use when doing wet-work and when handling hair dyes, permanent wave solutions and bleaching products was observed in the 2020 compared to the 2009 survey., Conclusion: Our data suggest that skin protection training during apprenticeship reduces the risk of OHE in hairdressers. The lack of primary prevention of OHE in hairdressing vocational schools may be a missed opportunity in the prevention of the disease., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients., Objectives: To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema., Method: The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month., Results: Consensus was achieved for several statements and management strategies., Conclusion: The updated guideline should improve management of hand eczema., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Parents report that children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing sunscreen following application., Objectives: To evaluate whether contact dermatitis develops following repeated application of aluminium-containing sunscreens in children with aluminium sensitization and vaccination granulomas., Methods: Sixteen children aged 2-9 years (mean age 5 years) with vaccination granulomas and a positive patch test reaction to aluminium chloride hexahydrate 2%/10% petrolatum completed a blinded repeated open application test (ROAT) with two daily applications of two sunscreens for 14 days. One cream contained aluminium and the other did not. The children served as their own controls., Results: Sixteen children completed the study. Only one child (6%) had a positive skin reaction during ROAT on day 2 to the sunscreen with aluminium. None reacted to the sunscreen without aluminium., Conclusions: Use of aluminium-containing sunscreens may on a case basis lead to allergic contact dermatitis in aluminium allergic children., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chromium and cobalt are important skin sensitizers. It has, however, been difficult to identify causative exposures. Studies on nickel allergy have demonstrated piercing as critical for both sensitization and elicitation. It may be speculated that the same applies for chromium and cobalt., Objective: To examine the content and release of chromium and cobalt from earrings randomly purchased in Denmark., Methods: Three hundred four earrings were examined with x-ray fluorescence (XRF) spectrometry. Earrings with measured content of chromium or cobalt were spot tested with diphenylcarbazide spot test (n = 166) or Nitroso-R spot-test (n = 99), respectively. Chromium and cobalt release were quantified in a selected subsample (n = 100) with the artificial sweat test (EN 1811)., Results: Chromium was present in 54.6% (166/304) of earrings and cobalt was present in 72.0% (219/304),- measured by XRF. All chromium spot tests for chromium VI were negative. The cobalt spot test was positive for one component. Chromium release was found from 59/100 (median concentration = -0.06 μg/cm 2 /week) and cobalt release from 29/100 (median concentration = -0.06 μg/cm 2 /week) of earrings in tested subsample., Conclusion: Earrings for piercing release chromium and cobalt and may on a case basis be a source of chromium and cobalt allergy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In March 2014, the European Commission issued a new regulation restricting the content of hexavalent chromium (Cr) in leather to no more than 3 mg/kg. We previously performed a questionnaire study in January 2014 to characterize our patients with Cr contact allergy prior to regulatory intervention., Objectives: To assess whether clinical characteristics, self-reported sources of Cr exposure, and burden of disease changed in patients with Cr allergy over time., Methods: A questionnaire study was performed among 172 adult dermatitis patients with Cr allergy and 587 age- and sex-matched dermatitis patients without Cr allergy. A questionnaire was sent to all dermatitis patients patch tested from 2003 to 2018 in August 2019., Results: The overall response rate was 61.2% (759/1241). Patients with Cr allergy were still more commonly affected by current foot dermatitis (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.07-7.08) and hand dermatitis (OR 1.98, 95% CI 1.13-3.49) compared with controls diagnosed during 2013 to 2018. The proportion of patients with Cr allergy reporting dermatitis caused by leather exposure did not change during 2003 to 2012 vs 2013 to 2018 (71.0% vs 66.2%, P = .5). Furthermore, estimates on occupational performance and disease severity (eg, current dermatitis), number of anatomical locations with dermatitis, worst-case dermatitis, and effect on work were similar in patients with Cr allergy for 2003 to 2012 vs 2013 to 2018., Conclusion: No immediate sign of improvement was found in patients with Cr allergy concerning severity of disease and dermatitis from leather exposures 5 years after adoption of the regulation against hexavalent Cr in leather. The regulation may have to be revised for better protection of those already sensitized., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patch testing is the gold standard for identifying culprit allergens in allergic contact dermatitis; however, it is laborious and positive reactions are difficult to quantitate. Development of complementary in vitro tests is, therefore, of great importance., Objectives: This study aimed to improve the in vitro lymphocyte proliferation test (LPT) to detect allergic responses to nickel (Ni), cobalt (Co), and chromium (Cr)., Methods: Twenty-one metal allergic patients with a positive patch test to Ni (n=16), Co (n=8), and Cr (n=3) and 13 controls were included. All were tested by a flow cytometric LPT., Results: Metal-reactive cells were identified as T helper (Th) cells with high expression of the memory marker CD45RO. Skin-homing (cutaneous lymphocyte-associated antigen positive [CLA+]) Ni-reactive memory Th (Th mem hi ) cells identified individuals with a positive patch test for Ni with 100% sensitivity (95% confidence interval [CI] 81%-100%) and 92% specificity (95% CI 67%-100%). Moreover, Co-specific Th mem hi cells expressing CCR6 identified patients with a positive patch test for Co with 63% sensitivity (95% CI 31%-86%) and 100% specificity (95% CI 77%-100%). In Cr allergic individuals, Cr-reactive Th mem hi cells tended to increased CLA and CCR6 expression., Conclusion: Metal-reactive Th cells with high expression of CD45RO and coexpression of CLA and CCR6 improved the LPT, making it an attractive supplement to the patch test., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Contact dermatitis (CD) is among the most common inflammatory dermatological conditions and includes allergic CD, photoallergic CD, irritant CD, photoirritant CD (also called phototoxic CD) and protein CD. Occupational CD can be of any type and is the most prevalent occupational skin disease. Each CD type is characterized by different immunological mechanisms and/or requisite exposures. Clinical manifestations of CD vary widely and multiple subtypes may occur simultaneously. The diagnosis relies on clinical presentation, thorough exposure assessment and evaluation with techniques such as patch testing and skin-prick testing. Management is based on patient education, avoidance strategies of specific substances, and topical treatments; in severe or recalcitrant cases, which can negatively affect the quality of life of patients, systemic medications may be needed.

Background: In 2005, methylisothiazolinone (MI) was allowed as a stand-alone preservative in cosmetics. This resulted in an epidemic of allergic contact dermatitis to MI, mainly affecting women exposed to leave-on cosmetics. Consequently, a regulation of Annex V in the European Union in 2017 banned the use of MI in leave-on cosmetics and reduced the allowed concentration in rinse-off products., Objective: To analyze the temporal trends in contact allergy to MI in Danish patients in relation to key events including European regulations over time., Methods: A retrospective study of consecutive patients patch tested with methylisothiazolinone from 2005 to 2019. Demographics and clinical characteristics in terms of MOAHLFA (male, occupational, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis and age >40 years), sources of exposure, and clinical relevance were analyzed in relation to key historical events., Results: Three hundred eighty of 12 494 patients (3.0%, 95CI: 2.7-3.4%) tested from 2005 to 2019 were sensitized to MI. An increasing trend in the prevalence of MI contact allergy from 2005 to 2019 (P < .01) was observed, although a decline in the absolute number of patch-test positive patients was seen from 2013 and onward. A reduction in leave-on cosmetics as a source of exposure was observed following the legislative ban in 2017, from 24.8% from in 2010 to 2013 to 6.2% in 2017 to 2019 (P < .01)., Conclusion: The epidemic of MI contact allergy is declining in absolute terms, although the prevalence in the patch-tested population has not returned to its pre-epidemic levels. The legislative regulation of MI in 2017 has been effective in terms of leave-on cosmetics as a source of exposure in MI allergic patients. The process of post-marketing risk assessment of contact allergens in the European Union needs improvement., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: The number of patients with contact dermatitis from glucose sensors and insulin infusion sets is increasing. Patch testing is challenging because of a lack of information concerning the constituent materials of medical devices., Objectives: To report on products and causes of allergic reactions to glucose sensors or insulin infusion sets over a 5-year period and suggest a short screening series., Methods: Analysis of patch test data from consecutive patients suspected of allergic contact dermatitis (ACD) to glucose sensors and/or insulin infusion sets from 2015-2019., Results: Patient numbers increased from 4 to 15 per year; 30/38 (78.9%) were children. In 29 (76.3%), a diagnosis of allergic/probable ACD was established, mostly due to the tapes of the device or allergens in these tapes (n = 23) followed by allergens in the device housing (n = 10). Isobornyl acrylate, abitol, and colophonium were the most common allergens. Information from manufacturers was often difficult to obtain and, if accessible, inadequate. For this reason, the diagnosis was delayed for more than 1.5 years in 12 (31%) patients., Conclusions: The increasing number of patients, mostly children, with ACD from devices used in treatment of type 1 diabetes demonstrates the importance of this problem. Allergies can easily be overlooked, due to the lack of mandatory labeling of the constituent materials of the devices., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Aluminum contact allergy is mostly seen in children with vaccination granulomas, following immunization with aluminum-adsorbed childhood vaccines., Objectives: To characterize a cohort of children with vaccination granulomas and aluminum allergy concerning early life conditions, exacerbating factors, avoidance behavior, treatments, and potential impact on quality of life., Methods: A questionnaire study was conducted among 177 children aged 0 to 15 years with vaccination granulomas and aluminum allergy, and a reference group of 61 children aged 3 to 14 years with various types of dermatitis undergoing patch testing., Results: All children in the granuloma group were reportedly affected by itch. Infection exacerbated the itch in 59%. Other worsening factors were eating tin-foiled/canned food (31%) and use of aluminum-containing sunscreen (46%). Many parents took precautions to avoid aluminum exposure. Children with granulomas were more likely to be nonadherent to the National Vaccination Program than the reference group (27% vs 2%, P < .001). Parents in the granuloma group reported a decreased life quality for both parents and children compared with the reference group., Conclusions: Itching vaccination granulomas and aluminum allergy have a considerable negative impact on affected children and their families, causing avoidance behavior, reduced adherence to vaccination programs, and a negative effect on the overall life quality., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Insulin pump therapy and the use of flash or continuous glucose monitoring in children is increasing. The diabetes devices are attached to the skin for several days to weeks with a strong adhesive, and recently, several cases of allergic contact dermatitis in children caused by components of the adhesive have been reported. In this review, we discuss such problems. The most frequent cause of allergic contact dermatitis is acrylates in the adhesive material, and the problem is serious and calls for rapid development of devices used in the treatment and monitoring of Type 1 diabetes without allergenic agents.

Background: There is currently no agreed cosmetic series for use across Europe., Objectives: To establish allergens currently tested in local and national cosmetic series., Method: Members of the European Surveillance System on Contact Allergy and the European Cooperation in Science and Technology project TD1206 ("StanDerm") were surveyed to establish their current practice., Results: A wide range of allergens was tested but there was significant variation between centres on the allergens considered to be important in screening for allergy to cosmetics. The number of allergens tested in addition to the baseline series varied between 2 and 50., Conclusions: There is a need for further investigation to establish the frequency and relevance of reactions to cosmetic allergens to enable an agreed evidence-based cosmetic series to be produced. Criteria for inclusion need to be established., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cobalt contact allergy is common, but clinical relevance is often difficult to determine., Objectives: To examine the aetiology, prevalence and clinical characteristics of cobalt-allergic patients who were patch tested between 2002 and 2017 at the Department of Dermatology and Allergy, Herlev-Gentofte Hospital., Methods: Patch test data, along with patient characteristics and causative exposures, from all adult dermatitis patients seen and tested between 2002 and 2017 were analysed. Associations were tested with the χ 2 test and logistic regression., Results: A total of 13 475 adults aged 18 to 99 years were patch tested. The overall prevalence of cobalt allergy and the prevalence of isolated cobalt allergy were 3.3% and 1.5%, respectively. The prevalence of isolated cobalt allergy decreased from 2.4% in 2006 to 2009 to 1.1% in 2014 to 2017 (P trend = 0.00003). Leather exposure as a relevant cause of allergic cobalt dermatitis increased from 3.7% in 2002 to 2009 to 8.3% in 2010 to 2017 (P = 0.04). The current clinical relevance of positive patch test reactions, that is, a positive reaction to cobalt combined with a history of current skin exposure to a source of cobalt, was 20.1%., Conclusions: We conclude that cobalt allergy is relatively common, but causative exposures are largely unknown, and the proportion of positive patch test reactions with clinical relevance is low. It is therefore currently unclear how we can better protect consumers and workers from cobalt exposure., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nickel is the most frequent cause of contact allergy worldwide and has been studied extensively. This clinical review provides an updated overview of the epidemiology, exposure sources, methods for exposure quantification, skin deposition and penetration, immunology, diagnosis, thresholds for sensitization and elicitation, clinical pictures, prevention, and treatment. The implementation of a nickel regulation in Europe led to a decrease in the prevalence of nickel allergy, and changes in the clinical picture and disease severity. Nevertheless, the prevalences of nickel allergy in the European general population are approximately 8% to 19% in adults and 8% to 10% in children and adolescents, with a strong female predominance. Well-known consumer items such as jewellery and metal in clothing are still the main causes of nickel allergy and dermatitis, although a wide range of items for both private and occupational use may cause dermatitis. Allergic nickel dermatitis may be localized to the nickel exposure site, be more widespread, or present as hand eczema. Today, efficient methods for exposure quantification exist, and new insights regarding associated risk factors and immunological mechanisms underlying the disease have been obtained. Nevertheless, questions remain in relation to the pathogenesis, the persistent high prevalence, and the treatment of severe cases., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In 2012, Danish authorities submitted a proposal to the European Chemical Agency restricting the content of hexavalent chromium to a maximum of 3 ppm in leather goods. Following its adoption, this proposal was implemented in 2015 as a directive in the EU., Objectives: To examine the temporal trend of chromium contact allergy in adult dermatitis patients patch tested between 2002 and 2017, and to determine clinical characteristics and causative exposures in these patients., Methods: All adult dermatitis patients patch tested between 2002 and 2017 were included. Patch test data were reviewed retrospectively. Comparisons were performed with the χ 2 test and logistic regression analysis., Results: A total of 13 379 adults aged 18 to 99 years were patch tested between 2002 and 2017. The overall prevalence of chromium allergy was 2.2%. An overall decreasing trend was found for the prevalence of chromium allergy (P trend = 0.00002). Specifically, a significant difference was found for the study periods 2010 to 2013 (P trend  = 0.002) and 2014 to 2017 (P trend  < 0.0001) as compared with 2002 to 2005. Leather remained the most important single cause of allergic contact dermatitis caused by chromium. The proportion of clinically relevant leather exposures increased from 42.3% during 2002 to 2009 to 54.8% during 2010 to 2017 (P = 0.04)., Conclusions: The prevalence of chromium allergy is decreasing. The EU Directive restricting the use of hexavalent chromium in leather goods is thought to be playing a central role in this change., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Knowledge about the skin deposition and penetration of nickel into the stratum corneum (SC) after short contact with metallic items is limited., Objective: To quantify nickel skin deposition and penetration into the SC after short contact with metallic nickel., Methods: Sixteen nickel-allergic participants and 10 controls were exposed to 3 pure nickel discs and 1 aluminium disc on each volar forearm for 3 × 10 minutes. Before exposure, 1 forearm was irritated with 0.5% sodium lauryl sulfate under 24-hour occlusion. Immediately, as well as 24 and 72 hours after metallic disc exposure, outer SC layers were removed with adhesive tapes and the nickel content was measured., Results: Nickel deposition and SC penetration capable of eliciting allergic nickel dermatitis were found immediately and after 24 hours. Significantly higher nickel amounts were found on normal skin and in the SC of nickel-allergic participants than in controls both immediately and after 24 hours, and on irritated skin immediately after exposure., Conclusions: Nickel deposition and SC penetration is considerable after nickel skin exposure of 3 × 10 minutes. Combined with the allergic responses resulting from the same exposures reported previously, this study highlights that short skin exposure to nickel-releasing items may cause allergic nickel dermatitis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Contact allergy and allergic contact dermatitis are frequent conditions in the general population., Objectives: To provide an updated estimate of the prevalence of contact allergy in the general population based on data from our previous review combined with new data from an updated search for relevant studies published between 2007 and 2017., Methods: Two authors independently searched PubMed for studies reporting on the prevalence of contact allergy in samples of the general population. Proportion meta-analyses were performed to calculate the pooled prevalence estimates of contact allergy., Results: A total of 28 studies were included in the analysis, covering 20 107 patch tested individuals from the general population. Overall, the pooled prevalence of contact allergy was 20.1% (95% confidence interval [CI]: 16.8%-23.7%). In children and adolescents (<18 years), the prevalence was 16.5% (95%CI: 13.6%-19.7%). The prevalence was significantly higher in women (27.9% [95%CI: 21.7%-34.5%]) than in men (13.2% [95%CI: 9.3%-17.6%]). The most common allergen was nickel (11.4% [95%CI: 9.4%-13.5%]), followed by fragrance mix I (3.5% [95%CI: 2.1%-5.4%]), cobalt (2.7% [95%CI: 2.1%-3.4%]), Myroxylon pereirae (1.8% [95%CI: 1.0%-2.7%]), chromium (1.8% [95%CI: 1.3%-2.6%]), p-phenylenediamine (1.5% [95%CI: 1.0%-2.1%]), methylchloroisothiazolinone/methylisothiazolinone (1.5% [95%CI: 0.8%-2.5%]), and colophonium (1.3% [95%CI: 1.0%-1.6%])., Conclusions: This meta-analysis confirmed that at least 20% of the general population are contact-allergic to common environmental allergens. It highlights the need for more effective preventive strategies for common allergens in consumer goods, cosmetics, and the workplace., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Contact allergy is common in children, but may be underdiagnosed. Importantly, the clinical relevance of specific allergies is subject to constant change, and it is therefore important to continuously monitor the trends and changes of contact allergies in the paediatric population., Objectives: To identify possible changes in contact allergy and allergic contact dermatitis among Danish children referred for patch testing., Methods: A retrospective study was performed based on patch test data from the Danish National Database of Contact allergy. The current data were compared with previously published data on Danish children referred for patch testing., Results: Between 2012 and 2016, 1573 children and adolescents were patch tested. Overall, 385 (24.5%) had at least 1 positive patch test reaction. The overall prevalence was similar in boys and girls, across age groups, and in patients with and without atopic dermatitis. Statistically significant increases in contact allergy to fragrances and isothiazoliones were seen, whereas a decrease in nickel allergy was found., Conclusion: Allergic contact dermatitis continues to be a common disease in children, and is even significantly increasing for some allergens., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lanolin has been tested as lanolin alcohols (30% pet.) in baseline patch test series since 1969, and this has shown clinically relevant allergic contact dermatitis cases., Objectives: To investigate the temporal development of lanolin allergy (i.e. positive reaction to lanolin alcohols and/or Amerchol™ L-101), and the association between contact allergy to lanolin and patient characteristics from the MOAHLFA index., Methods: A retrospective observational study of consecutively patch tested dermatitis patients (n = 9577) between 1 January 2004 and 31 December 2015 with lanolin alcohols 30% pet. and Amerchol™ L-101 50% pet. was performed., Results: The prevalence of lanolin allergy increased from 0.45% in 2004 to 1.81% in 2015. In age-adjusted and sex-adjusted analyses, weak, significant associations were found between atopic dermatitis and lanolin and lanolin alcohols allergy, respectively, but no association with Amerchol™ L-101 allergy was found. Among 9286 dermatitis patients who were tested with both allergens, 108 had a positive test reaction to either lanolin alcohols or Amerchol™ L-101, whereas only 29 patients had positive test reactions to both markers., Conclusions: The prevalence of lanolin contact allergy has increased over a 12-year period, and inclusion of Amerchol™ L-101 will increase the chance of detecting lanolin contact allergy. Patch testing with lanolin is helpful in atopics with dermatitis and suspected cosmetic allergy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nickel contact allergy remains a problem in EU countries, despite the EU Nickel Directive. To study the prevalence of nickel allergy in EU countries following the implementation of the EU Nickel Directive, we performed a systematic search in PubMed for studies that examined the prevalence of nickel allergy in EU countries published during 2005-2016. We identified 46 studies: 10 in the general population and 36 in patch tested dermatitis patients. A significantly lower prevalence of nickel allergy after than before the implementation of the EU Nickel Directive was found in women aged 18-35 years (11.4% versus 19.8%) (p = 0.02), in female dermatitis patients aged ≤17 years (14.3% versus 29.2%) (p < 0.0001), and in dermatitis patients aged 18-30 years (women: 20.2% versus 36.6%) (p < 0.0001) (men: 4.9% versus 6.6%) (p < 0.0001). Overall, the prevalence was higher in southern than in northern EU countries, and generally remained high, affecting 8-18% of the general population. A consistent pattern of decreasing prevalence of nickel allergy in some EU countries was observed, although the prevalence among young women remains high. Steps should be taken for better prevention of nickel allergy in EU countries., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Contact sensitization is common and affects up to 20% of the general population. The clinical manifestation of contact sensitization is allergic contact dermatitis. This is a clinical expression that is sometimes difficult to distinguish from other types of dermatitis, for example irritant and atopic dermatitis. Several studies have examined the pathogenesis and severity of allergic contact dermatitis by measuring the absence or presence of various biomarkers. In this review, we provide a non-systematic overview of biomarkers that have been studied in allergic contact dermatitis. These include genetic variations and mutations, inflammatory mediators, alarmins, proteases, immunoproteomics, lipids, natural moisturizing factors, tight junctions, and antimicrobial peptides. We conclude that, despite the enormous amount of data, convincing specific biomarkers for allergic contact dermatitis are yet to be described., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nickel in metallic items has been regulated in Denmark since 1990; however, 10% of young Danish women are still sensitized to nickel. There is a need for continuous surveillance of the effect of regulation., Objectives: To identify current self-reported metallic exposures leading to dermatitis in nickel-allergic patients, and the minimum contact time needed for dermatitis to occur., Methods: A questionnaire was sent to all patients who reacted positively to nickel sulfate 5% pet. within the last 5 years at the Department of Dermatology and Allergy, Gentofte Hospital., Results: The response rate was 63.2%. Earrings were the foremost cause of dermatitis after the EU Nickel Directive had been implemented, followed by other jewellery, buttons on clothing, belt buckles, and wrist watches. Dermatitis reactions within 10 min of contact were reported by 21.4% of patients, and dermatitis reactions within 30 min of contact were reported by 30.7% of patients., Conclusions: Nickel exposures that led to the implementation of a nickel regulation seem to persist. The durations of contact with metallic items to fall under the current REACH regulation of nickel correspond well with the results of this study., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin., Objectives: To examine patch test reactivity to chromium-coated discs., Methods: We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate., Results: Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients., Conclusions: Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cobalt release from dental prostheses has been shown to elicit allergic reactions in cobalt-allergic patients. It is therefore important to investigate whether these prostheses are possible sources of sensitization., Objectives: To assess (i) cobalt release from dental prostheses and (ii) allergic reactions to components of dental prostheses, and (iii) to investigate the oral mucosa for inflammation 1-5 years after insertion of the prostheses., Method: Clinical oral examination was conducted in 66 patients with 84 dental prostheses. Cobalt release from 84 functional (used) and 32 non-functional (new) prostheses was investigated with the cobalt spot test. Contact allergy was assessed by patch testing. Smear tests for Candida spp. were performed in patients showing signs of inflammation of the oral mucosa. The prostheses were assessed for biological and technical complications., Results: None of the functional prostheses released cobalt, whereas this was observed in 24 of 32 non-functional prostheses. None of the patients had contact allergy to cobalt. Of the 66 patients, 11 showed signs of inflammation of the oral mucosa, 2 had oral candidiasis, 16 had ill-fitting prostheses, and all had insufficient oral hygiene., Conclusions: Dental prostheses released cobalt during the fabrication stages, but not 1-5 years after insertion. No allergic reactions were observed. Signs of inflammation were related to candidiasis, insufficient oral hygiene, and ill-fitting prostheses., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Allergic contact dermatitis (ACD) may complicate the clinical course of atopic dermatitis (AD), and patch testing remains the criterion standard for diagnosing ACD. To date, there have been no guidelines or consensus recommendations on when and how to patch test individuals with AD. Failure to patch test when appropriate may result in overlooking an important and potentially curable complicating comorbidity. In this article, we present consensus recommendations regarding when to perform patch testing in the AD patient, best practices, and common pitfalls. Patch testing should be considered in AD patients with dermatitis that fails to improve with topical therapy; with atypical/changing distribution of dermatitis, or pattern suggestive of ACD; with therapy-resistant hand eczema in the working population; with adult- or adolescent-onset AD; and/or before initiating systemic immunosuppressants for the treatment of dermatitis. A suggested patch testing algorithm for AD patients is provided.