Study protocol: efficacy of oral alitretinoin versus oral cyclosporine A in patients with severe recurrent vesicular hand eczema (ALICsA): a randomised prospective open-label trial with blinded outcome assessment.

INTRODUCTION: Systemic treatment with alitretinoin is registered for all clinical types of severe chronic hand eczema. However, it is especially effective in the hyperkeratotic subtype and less effective in non-hyperkeratotic forms. Cyclosporine A (cyclosporine) is prescribed for hand eczema in daily practice as well. It has shown to be particularly effective in patients with vesicular hand eczema. The primary objective of this study is to compare efficacy of alitretinoin and cyclosporine in the treatment of severe recurrent vesicular hand eczema. METHODS AND ANALYSIS: This is an investigator-initiated randomised prospective open-label trial with blinded outcome assessment. Severity assessments and laboratory measurements will be conducted corresponding to daily practice. The study population will consist of 72 adult patients (age 18-75 years) with severe recurrent vesicular hand eczema. Patients are treated with either (group I) alitretinoin 30 mg once daily or (group II) cyclosporine with a starting dose of 5 mg/kg/day and a decrease in dosage after 8 weeks to 3-3.5 mg/kg/day. The treatment period is 24 weeks for both drugs. Primary endpoint for efficacy is response to treatment, defined as an improvement of ≥2 steps on a Physician Global Assessment, using a validated Photoguide, after 24 weeks of treatment. Secondary endpoints are improvement of Hand Eczema Severity Index, Quality of Life in Hand Eczema Questionnaire and a Patient Global Assessment. Adverse events and time to response will be registered. Furthermore, cost-utility, quality-adjusted life years and cost-effectiveness will be assessed with the EQ-5D-5L questionnaire while monitoring costs. ETHICS AND DISSEMINATION: This protocol was reviewed and approved by the Medical Ethical Review Board of the University Medical Centre Groningen (reference METc 2015/375). The study will be conducted according to the principles of the Declaration of Helsinki, in accordance with the Dutch Medical Research Involving Human Subjects Act. TRIAL REGISTRATION NUMBER: NCT03026946; Pre-results.

Health utilities for controlled and uncontrolled chronic hand eczema in healthcare employees.

BACKGROUND: Health utilities provide a universally applicable method for measuring the relative preferences or values of specific health states. Health economic studies use health utilities to estimate disease burden and the cost-effectiveness of interventions. Chronic hand eczema (CHE) affects many individuals and adversely affects work productivity. Health utilities for CHE from the perspective of healthcare professionals are lacking. OBJECTIVES: To assess health utilities for CHE from the perspectives of employees in the healthcare sector and affected patients. METHODS: A cross-sectional study with volunteers from the healthcare sector (n = 126) and patients (n = 32) was conducted to establish health utilities (ranging from 1 = perfect health to 0 = death) for mild and severe CHE. RESULTS: The median health utilities of the healthy volunteers derived with the time trade-off method were 0.97 (mean: 0.92) for mild CHE and 0.77 (mean: 0.75) for severe CHE. The median health utilities for mild and severe CHE from the perspective of affected patients were 0.98 (mean: 0.91) and 0.82 (mean: 0.77), respectively. Differences in health utilities between the two study groups were not significant. CONCLUSION: CHE constitutes a considerable burden from the perspective of healthcare employees. Effective control of CHE constitutes an important public health goal.

Systematic review of cost-of-illness studies in hand eczema.

The individual burden of disease in hand eczema patients is considerable. However, little is known about the socio-economic impact of this disease. The aims of this review were to evaluate the literature on cost-of-illness in hand eczema, and to compose a checklist for future use. The literature was retrieved from the MEDLINE and EMBASE databases up to October 2015. Quality evaluation was based on seven relevant items in cost-of-illness studies. Cost data (direct and indirect) were extracted and converted into euros (2014 price level) by use of the Dutch Consumer Price Index. Six articles were included. The mean annual total cost per patient ranged from €1311 [corrected] to €9792 (direct cost per patient, €521 to €3722; [corrected] and indirect cost per patient, €100 to €6846). Occupational hand eczema patients showed indirect costs up to 70% of total costs, mainly because of absenteeism. A large diversity in hand eczema severity was found between studies. The socio-economic burden of hand eczema is considerable, especially for more severe and/or occupational hand eczema. Absenteeism from paid work leads to a high total cost-of-illness, although disregard of presenteeism often leads to underestimation of indirect costs. Differences in included cost components, the occupational status of patients and hand eczema severity make international comparison difficult. A checklist was added to standardize the approach to cost-of-illness studies in hand eczema.

Economic Evaluation of a Multifaceted Implementation Strategy for the Prevention of Hand Eczema Among Healthcare Workers in Comparison with a Control Group: The Hands4U Study.

The aim of this study was to evaluate the cost-effectiveness of a multifaceted implementation strategy for the prevention of hand eczema in comparison with a control group among healthcare workers. A total of 48 departments (n=1,649) were randomly allocated to the implementation strategy or the control group. Data on hand eczema and costs were collected at baseline and every 3 months. Cost-effectiveness analyses were performed using linear multilevel analyses. The probability of the implementation strategy being cost-effective gradually increased with an increasing willingness-to-pay, to 0.84 at a ceiling ratio of €590,000 per person with hand eczema prevented (societal perspective). The implementation strategy appeared to be not cost-effective in comparison with the control group (societal perspective), nor was it cost-beneficial to the employer. However, this study had some methodological problems which should be taken into account when interpreting the results.

[Hand eczema : disability and impact]. / Eczéma des mains : handicap et impact.

INTRODUCTION: Hand eczema is a dermatological condition that may lead to physical and psychological disability, with psychological impact on social relationships, daily life activities and work. OBJECTIVES: Review of the literature on the impact of eczema of the hands and resulting disabilities. METHODS: Medline and Embase search from 1990 to 2013. RESULTS: Hand eczema is a disabling disease because of its poor prognosis. It has an impact on quality of life, which has been assessed using generic scales (MOS-SF36 and EQ-5D) and generic dermatological scales (DLQI and the Skindex). There are no quality-of-life scales specific to hand eczema. This dermatosis may also have repercussions on work, resulting in absenteeism and at times requiring occupational retraining. Hand eczema has economic repercussions with several factors to be taken into account such as medical consultations, medical expenses, loss of productivity, work leave, changes in job position, compensation, and the need for occupational retraining. CONCLUSION: Management of hand eczema by a dermatologist requires taking into account the importance of the physical and psychological disability and the consequences on social relations, activities of daily life, and work. In this context, measuring quality of life is important in assessing patients'perception of the disease and their experience.

Cooperation between the occupational health insurance and physicians practicing occupational dermatology: optimization potential in quality assurance.

BACKGROUND: Quality assurance is a task of the medical profession, but it is also a duty of the occupational health insurance (OHI). Data on the interaction quality between physicians practicing occupational dermatology and the OHI are limited. MATERIAL AND METHODS: An online survey was performed in 854 German members of the Working Group on Occupational and Environmental Dermatology in October 2013. Items included demographic data, a judgment on the cooperation between the dermatologists and OHI companies, an economic grading of the current compensation scheme, and prioritization of optimization tasks. RESULTS: 182 members (21.3 % of the invited population) participated in the survey. The cooperation with the OHI companies was judged as "very good" by 10.8 %, as "good" by 56.7  %, as "satisfactory" by 24.2 %, as "sufficient" by 7.0 % and as "inadequate" by 1.3 %. 93.4 % of the interviewed mentioned problems and improvement potentials in the cooperation of their practice or clinic with OHI companies. Main points of criticisms were reimbursement (44.7 %), followed by impairments of the treatment options (36.5 %) and the delay or scope of the treatment in the dermatologist's procedure (29.4 %). CONCLUSIONS: While most physicians practicing occupational dermatology give a positive judgment of their cooperation with OHI companies, quality optimization potentials exist regarding the reimbursement of dermatological services, especially regarding time-intensive counselling in the prevention of occupational skin diseases, in the enablement of diagnostic and therapeutic procedures according to current guidelines and in a timely preventive intervention to use the therapeutic window before chronification of skin diseases may occur.

Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids.

BACKGROUND: Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids. OBJECTIVES: To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score. METHODS: A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores. RESULTS: One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other. CONCLUSIONS: Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.

Cost of illness from occupational hand eczema in Germany.

BACKGROUND: There is little knowledge about the costs of occupational hand eczema. OBJECTIVES: To estimate the societal costs of patients with occupational hand eczema in Germany. METHODS: Resource use during the past year, disease severity and quality of life [Dermatology Life Quality Index (DLQI)] were gathered for patients with occupational hand eczema before they entered a special rehabilitation programme. Costs were calculated from the societal perspective. The analysis focused on all patients and the severity groups no signs/mild (group A) and moderate to severe (group B). RESULTS: One hundred and fifty-one patients were analysed, with a mean age of 44.9~years and a mean DLQI score of 10.9; 64.9% were male. Sickness absence was recorded for 62.9% of all patients (76.4~days on average in the last 12~months). Annual societal costs were €8799 per patient. Indirect costs represented 70% of total costs. Quality of life (DLQI) was statistically different across both severity groups (group A, 7.9; group B, 12.9), but direct treatment costs were not (€2705 versus €2610, respectively). There was a trend towards higher indirect costs in patients in severity group B (group A, €5120; group B, €6796). CONCLUSION: The annual societal costs of patients with occupational hand eczema in this study are high, and similar to those for severe psoriasis and atopic dermatitis.

Cost-of-illness analysis of patients with chronic hand eczema in routine care in Germany: focus on the impact of occupational disease.

Chronic hand eczema places a heavy burden on patients, often affecting their ability to work. This paper compares the cost-of-illness and treatment approaches for patients with refractory chronic hand eczema, in relation to whether the disease was occupational or unrelated to work factors. Data from 2 surveys, comprising 310 patients with chronic hand eczema insured by German statutory health insurance (SHI) (including work-impaired patients, work-unaffected patients and non-working patients) and known work-related chronic hand eczema insured by occupational health insurance (OHI). Annual healthcare costs of managing work-impaired patients (SHI) and patients with work-related chronic hand eczema (OHI) were €3,164 and €3,309, respectively, approximately double the costs of managing non-working and work-unaffected (SHI) patients. This analysis shows that the costs associated with chronic hand eczema are affected by the correlation of chronic hand eczema with work, with costs being higher for occupational patients with chronic hand eczema.

Hands4U: a multifaceted strategy to implement guideline-based recommendations to prevent hand eczema in health care workers: design of a randomised controlled trial and (cost) effectiveness evaluation.

BACKGROUND: Workers in wet work occupations have a risk for developing hand eczema. Prevention strategies exist, but compliance to the proposed recommendations is poor. Therefore, a multifaceted implementation strategy (MIS) is developed to implement these recommendations to reduce hand eczema among health care workers performing wet work. METHODS/DESIGN: This study is a randomised controlled trial in three university hospitals in the Netherlands. Randomisation to the control or intervention group is performed at department level. The control group receives a leaflet containing the recommendations only. The intervention group receives the MIS which consists of five parts: 1) within a department, a participatory working group is formed to identify problems with the implementation of the recommendations, to find solutions for it and implement these solutions; 2) role models will help their colleagues in performing the desired behaviour; 3) education to all workers will enhance knowledge about (the prevention of) hand eczema; 4) reminders will be placed at the department reminding workers to use the recommendations; 5) workers receive the same leaflet as the control group containing the recommendations. Data are collected by questionnaires at baseline and after 3, 6, 9 and 12 months. The primary outcome measure is self-reported hand eczema. The most important secondary outcome measures are symptoms of hand eczema; actual use of the recommendations; sick leave; work productivity; and health care costs.Analyses will be performed according to the intention to treat principle. Cost-effectiveness of the MIS will be evaluated from both the societal and the employer's perspective. DISCUSSION: The prevention of hand eczema is important for the hospital environment. If the MIS has proven to be effective, a major improvement in the health of health care workers can be obtained. Results are expected in 2014. TRIAL REGISTRATION NUMBER: NTR2812.

Cost-of-illness of patients with chronic hand eczema in routine care: results from a multicentre study in Germany.

BACKGROUND: It is broadly assumed that costs caused by chronic hand eczema (CHE) are significant. However, there is a lack of cost-of-illness studies on CHE. OBJECTIVES: To determine the direct and indirect costs of CHE under routine conditions in Germany from the societal perspective. METHODS: A cross-sectional survey was conducted in 24 outpatient practices and clinics across Germany. Patients with CHE refractory to potent topical steroids and insured by statutory health insurance were eligible. Clinical and cost data were collected using standardized questionnaires. Severity classes were defined according to a photographic guide and physician global assessment (PGA). Four treatment stages were defined based on the German CHE guidelines: topical treatments only (stage I), additionally ultraviolet (UV) radiation therapy (II), systemic therapy (III) and inpatient treatment (IV). Bivariate associations between costs and severity as well as treatment stage were assessed. RESULTS: Two hundred and twenty-three patients with CHE (mean age 45·7years, 56% women) enrolled in the study, of whom 63·2% were treated only with topical treatments, 15·7% additionally with UV radiation and 11·7% with systemic treatments. Of all patients, 9·4% had been admitted to hospital. Total costs per year and patient were €2128, including €1742 direct costs and €386 indirect costs. The total costs increased with treatment stages I-IV (P<0·001): €1044, €2307, €2697 and €8407, respectively. Accordingly, costs also correlated with clinical severity. CONCLUSIONS: Patients with CHE refractory to topical steroids incur marked costs to society. The costs increase disproportionately with escalating treatment stages, especially in patients admitted to hospital. Hence, new treatments may help to reduce the societal costs of CHE.

[Health services research: the example of hand eczema]. / Versorgungsforschung am Beispiel des Handekzems.

Hand eczema is one of the most frequent skin diseases with a lifetime prevalence of up to 15% and a median incidence rate of 6 cases per 1000 person-years. Female gender, contact allergy, atopic eczema and wet work have been identified as the most important associated risk factors. Hand eczema has a high public health and socio-economic significance, since the vast majority of occupational skin disease is hand eczema. Hand eczema is often chronic, chronically relapsing or persisting. It entails substantial impairment of health-related quality of life for the affected individual. The cost-of-illness of hand eczema is estimated to be in the range of moderate to severe psoriasis and even higher than that of atopic eczema. Although various therapeutic options to treat hand eczema exist, an assessment of these options in randomized, controlled clinical trials to build up an evidence base is mostly lacking. The investigation of the treatment of chronic hand eczema under everyday conditions in dermatological clinics and private practices has only just begun. The first register of patients with chronic hand eczema (acronym: carpe) is expected to yield substantial insights in the effectiveness and safety of different therapeutic measures. A related task is the assessment of the quality of care in the light of the guidelines for the management of chronic hand eczema.

Alitretinoin for the treatment of severe chronic hand eczema.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer's model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

Alitretinoin for severe chronic hand eczema: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved 'clear' or 'almost clear' hands by week 24 with alitretinoin than those using placebo: 48% with alitretinoin 30 mg (p < 0.001); 28% with alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the alitretinoin 30 mg group and 11% in the alitretinoin 10 mg group, respectively. Serious adverse events were rare, although alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of alitretinoin with any of the relevant treatment comparators (psoralen + UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were pound8614 per QALY versus ciclosporin, - pound469 per QALY versus PUVA (with alitretinoin dominant) and pound10 612 per QALY versus azathioprine (year 2007-8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared alitretinoin only with placebo, for which the ICER was reported to be pound12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around pound30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of alitretinoin's efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of alitretinoin versus the relevant treatment comparators. The Appraisal Committee recommended that alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

Integrated, multidisciplinary care for hand eczema: design of a randomized controlled trial and cost-effectiveness study.

BACKGROUND: The individual and societal burden of hand eczema is high. Literature indicates that moderate to severe hand eczema is a disease with a poor prognosis. Many patients are hampered in their daily activities, including work. High costs are related to high medical consumption, productivity loss and sick leave. Usual care is suboptimal, due to a lack of optimal instruction and coordination of care, and communication with the general practitioner/occupational physician and people involved at the workplace. Therefore, an integrated, multidisciplinary intervention involving a dermatologist, a care manager, a specialized nurse and a clinical occupational physician was developed. This paper describes the design of a study to investigate the effectiveness and cost-effectiveness of integrated care for hand eczema by a multidisciplinary team, coordinated by a care manager, consisting of instruction on avoiding relevant contact factors, both in the occupational and in the private environment, optimal skin care and treatment, compared to usual, dermatologist-led care. METHODS: The study is a multicentre, randomized, controlled trial with an economic evaluation alongside. The study population consists of patients with chronic, moderate to severe hand eczema, who visit an outpatient clinic of one of the participating 5 (three university and two general) hospitals. Integrated, multidisciplinary care, coordinated by a care manager, including allergo-dermatological evaluation by a dermatologist, occupational intervention by a clinical occupational physician, and counselling by a specialized nurse on optimizing topical treatment and skin care will be compared with usual care by a dermatologist. The primary outcome measure is the cumulative difference in reduction of the clinical severity score HECSI between the groups. Secondary outcome measures are the patient's global assessment, specific quality of life with regard to the hands, generic quality of life, sick leave and patient satisfaction. An economic evaluation will be conducted alongside the RCT. Direct and indirect costs will be measured. Outcome measures will be assessed at baseline and after 4, 12, 26 and 52 weeks. All statistical analyses will be performed on the intention-to-treat principle. In addition, per protocol analyses will be carried out. DISCUSSION: To improve societal participation of patients with moderate to severe hand eczema, an integrated care intervention was developed involving both person-related and environmental factors. Such integrated care is expected to improve the patients' clinical signs, quality of life and to reduce sick leave and medical costs. Results will become available in 2011.

The association between hand eczema and nickel allergy has weakened among young women in the general population following the Danish nickel regulation: results from two cross-sectional studies.

BACKGROUND: An association between nickel contact allergy and hand eczema has previously been demonstrated. In 1990, Denmark regulated the extent of nickel release in the ear-piercing process as well as nickel release from consumer products. OBJECTIVES: This study aimed to evaluate the effect of the Danish nickel regulation by comparing the prevalence of concomitant nickel allergy and hand eczema observed in two repeated cross-sectional studies performed in the same general population in Copenhagen. MATERIALS: In 1990 and 2006, 3881 18-69 year olds completed a postal questionnaire and were patch tested with nickel. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The prevalence of concomitant nickel contact allergy and a history of hand eczema decreased among 18-35-year-old women from 9.0% in 1990 to 2.1% in 2006 (P < 0.01). The association between nickel contact allergy and a history of hand eczema decreased in this age group between 1990 (OR = 3.63; CI = 1.33-9.96) and 2006 (OR = 0.65; CI = 0.29-1.46). Among older women, no significant changes were observed in the association between nickel contact allergy and hand eczema. CONCLUSIONS: Regulatory control of nickel exposure may have reduced the effect of nickel on hand eczema in the young female population.