Assessing the efficacy of a German‐inspired intervention on occupational contact dermatitis in Denmark: A randomised controlled trial with 3‐month follow‐up

Occupational contact dermatitis (OCD) is a prevalent, often chronic disease that poses a risk for job loss and decreased quality of life. In Germany, a multi‐step prevention programme emphasising early detection and highly specialised multidisciplinary treatment has been implemented with great success.


| INTRODUCTION
Occupational contact dermatitis (OCD) is a debilitating disease that often evolves into a chronic condition, characterised by severe symptoms, 1 decline in quality of life, 2,3 job loss, 1,4 and diminished income. 58][9][10][11] In 2005, the German Statutory Accident Insurance (DGUV) implemented a comprehensive multi-step prevention programme. 12Upon receiving a notification about a worker with OCD, the DGUV considers the severity and chronicity risk of the worker's symptoms and the associated risk of job loss when determining the most appropriate step for each patient. 13This prevention concept has since been adopted and implemented in Austria. 14e multi-step prevention programme involves three steps of individual prevention, with Tertiary Individual Prevention (TIP) being offered to workers with severe OCD and/or if the workers face an elevated risk of abandoning their profession due to their condition's severity.TIP is specifically designed to reduce disease severity, improve quality of life, and, crucially, enable affected workers to remain in their profession.This programme involves a three-week interdisciplinary inpatient rehabilitation, a subsequent 3-week offwork period, and continuous dermatological follow-up.
There are several structural differences between the Danish and German healthcare and occupational accident insurance systems, 15 necessitating an adapted approach in the Danish setting.Our research group has therefore developed a prevention intervention suitable for a Danish hospital setting focusing on fast medical diagnostics and treatment, education on skin-protective behaviour and highly specialised diagnostics and treatment performed by a multidisciplinary team inspired by the German TIP effort.
The present study aims to examine the effectiveness of this Danish-adapted intervention on OCD severity, quality of life and occupational consequences.

| Study design
The study was unblinded, controlled and randomised, with an allocation ratio of 1:1.The study was conducted and reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines to ensure a methodological approach and transparent reporting of findings. 16,17For the primary analysis, only participants who adhered to the study protocol in either the intervention group (IG) or control group (CG) were included, as per a per-protocol analysis.This allowed for an evaluation of participants based on their group assignment and compliance with the protocol.The study was registered at ClinicalTrials.gov(identifier: NCT04790799).

| Recruitment and study population
The participants were recruited from the Danish National Referral Database, which holds information on all active referrals from one doctor to another in Denmark.Inclusion criteria were as follows: age between 15 and 65 years, referral to a dermatologist with hand eczema, hand eczema presence within the past 3 months, suspected occupational cause (by participant or doctor), and ability to provide informed consent.Exclusion criteria were as follows: current pregnancy, breastfeeding or severe psychiatric condition that might overshadow hand eczema issue.Participants were recruited following their first referral from a general practitioner to a dermatologist with suspected occupational hand eczema (OHE).The participants were contacted via secure email (eBooks) and via phone with written and oral information about the study.The enrolment period was from June 2020 to December 2022, with a break in recruitment from January 2021 until December 2021 due to technical difficulties in the National Referral Database system, making the active recruitment period approximately 18 months.Participants gave informed consent complying with the Helsinki Declaration before entering the study.

| Power calculation and sample size
The power calculation for this study was conducted based on the estimation that 75% of the IG participants and 50% of the CG participants would experience an improvement in their hand eczema during the follow-up period.The power calculation was conducted with a desired power of 80% and a 95% confidence interval. 17The result of this calculation suggested a total sample size of 116 participants for the study.However, due to constraints in recruitment, the study was unable to reach this suggested sample size.

| Randomisation
The randomisation of study participants was performed using a block randomisation approach with a block size of six, stratified by sex and age.The randomisation list was computer-generated using a tool developed by Sealed Envelope Ltd. 18 The randomisation process was carried out using the RedCAP randomisation module to ensure secure and unbiased allocation.Participants were enrolled and assigned to either the IG or CG by a project nurse affiliated with the study.

| Participant flow and follow-up
A total of 284 individuals were assessed for eligibility.Of these, 228 were excluded due to not meeting the inclusion criteria, declining to participate, or because their general practitioner did not allow contact (see Figure S1 for details).
Fifty-six participants were randomised into the study, with 30 allocated to the IG and 26 to the CG.Out of the IG, four participants did not receive the intervention due to non-attendance, resulting in 26 participants receiving the intervention.
There was a minor attrition during the follow-up phase, with three participants lost to follow-up in the IG and four in the CG.Therefore, at 3-month follow-up, 23 participants from the IG and 22 participants from the CG were analysed for the primary outcomes.

| Attrition analysis
Given the attrition observed during the follow-up phase, an attrition analysis was performed to identify any potential bias resulting from participant drop-out.This analysis involved a comparison of baseline characteristics between participants who completed the study and those who did not, with the aim of identifying any systematic differences between them.

| Blinding
Given the nature of the interventions, the study was conducted in an unblinded manner.Both the participants and the healthcare providers were aware of the group assignments.Similarly, the data collectors and analysts were not blinded to the group assignments.

| Intervention
The intervention consisted of several components.Participants in the IG were invited to a consultation with a dermatologist at the Department of Dermatology at Gentofte Hospital within 2-3 weeks of study inclusion.Before this consultation, a chemical engineer examined the ingredient information of all the products the participant had been in contact with, both at work and at home.In collaboration with the treating dermatologist, the chemical engineer then compiled a list of potential allergens for subsequent testing.The initial treatment plan was established during the first doctor consultation based on a pre-defined standardised treatment strategy.Subsequently, IG participants underwent extended allergen testing using patch and prick tests.In relation to the doctor consultation, the IG participants received education on skin protective behaviour and glove counselling.IG participants were also shown a video, specifically produced for this research project, covering essential aspects of hand eczema, its prevention, treatment strategies, and the importance of skin-protective behaviour.In relevant cases, referrals were made to the Department of Social Medicine and/or the Department of Occupational and Environmental Medicine.
The CG navigated the Danish healthcare system independently, without any intervention from the research team, receiving treatment for OHE at the local dermatologist they were referred to.

| Questionnaire
The study participants were asked to fill out a questionnaire at inclusion and at 3-month follow-up.The questionnaire was evaluated and revised before the study based on interviews with peers and hand eczema outpatients.The questionnaire included questions about the severity of eczema, occupational status, occupational consequences, overall health, use of medicine and the medical system and quality of life.The questions were mainly drawn from the Nordic Occupational Skin Questionnaire (NOSQ-2002) and the Health 2006 survey. 19,20Questions pertinent to the findings presented in this manuscript are translated into English and provided in Table S5.
Severity of current hand eczema was assessed by a question about degree of eczema within the last 3 months, self-administered photographic guide 21 and a visual analogue scale (VAS).History of atopic dermatitis was based on confirmatory answer to a question about doctor-diagnosed atopic dermatitis. 22Wet work was defined as having wet hands >2 h per shift, wearing occlusive gloves >2 h per shift and/or washing their hands >20 times per shift.4][25] Baseline information about sex, age, occupation and disease duration at the time of referral were established during the enrolment phone call.

| Assessment of treatment
The treatment of both the IG and CG participants was assessed by accessing their online Shared Medication Record.The Shared Medication Record is a system used in Denmark where all information about a patient's current and past prescribed medications are centrally stored and can be assessed by authorised healthcare professionals.
The treatment within the last year was assessed at baseline, and within the last 3 months at 3-month follow-up.

| Outcome measures
The primary outcomes, assessed at both baseline and 3-month follow-up, included several parameters.Hand eczema severity was self-assessed using three different measures: the degree of eczema experienced within the last 3 months on an ordinal scale, the severity of current eczema using a VAS from 0 to 10, and a photographic guide assessing hand eczema severity.Occupational consequences were self-assessed based on whether the participant experienced job loss or sick leave within the last 3 months.Quality of life was also self-assessed using: DLQI, Skindex-29 and EQ-5D-5L.
Medication use was assessed based on self-reported use of topical corticosteroids within the last 3 months, and review of the online Shared Medication Record by a research physician.

| Statistical analysis
Study data were collected and managed using REDCap Electronic Data Capture tools hosted at the Capital Region of Denmark. 26,27Statistical analyses were conducted using R version 4.2.2.

Differences in the distribution of baseline characteristics between
the IG and CG were tested using Fisher's exact test and Wilcoxon rank-sum test.
For ordinal outcome variables, ordinal logistic regression using the proportional odds model was performed.The models were adjusted for age, sex, atopic dermatitis and baseline values of the variable comparing the IG and CG groups.The proportional odds assumption was tested using the Brant test.
The Brant test, employed to the model examining the degree of eczema during the last 3 months at 3-month follow-up, suggested a potential violation for the variable doctor-diagnosed atopic dermatitis yes/no (p < 0.05).Atopic dermatitis is an important variable for eczema degree and severity, and we do not expect the effect to vary across different levels of the outcome.Additionally, the absence of certain combinations of variable levels is likely due to random variation in our sample of 45 participants.Given these considerations, we continued with our predetermined analysis.
Analysis of covariance models were used to examine the difference between the IG and CG in the continuous outcome variables, adjusting for sex, age, atopic dermatitis and baseline values of the respective outcomes.Diagnostics for linearity, homoscedasticity, homogeneity of regression slopes and normality of residuals were visually assessed.
All p values were two-sided, and a 5% level of statistical significance was used.

| Missing data
In the present study, not all participants completed every question in the questionnaire.Therefore, the analysis of primary and secondary outcomes was based on available case analysis, meaning that each analysis included only participants who had provided responses to the specific variables being analysed.The exact sample size for each outcome variable is provided in the result tables.

| Ethics statement
The study was approved by the Danish Patient Safety Authority

| Baseline characteristics
The baseline characteristics of the study population can be found in  Characteristics relating to disease duration at baseline and severity of all-time worst eczema can be seen in Table 2.The distribution of disease duration was similar in the IG and CG, with the majority of participants in both groups having a disease duration of less than 1 year.Similarly, the groups were comparable in terms of the severity of all-time worst eczema both assessed by VAS score and photographic guide.The IG had a higher share of participants with atopic dermatitis (26.1% compared to 9.1% in the CG), but this difference was not statistically significant ( p = 0.2).

| Attrition analysis
In the analysis of attrition, there were 45 participants who were retained in the study and 11 who dropped out.The groups were balanced in terms of intervention assignment, sex, age, country of birth, VAS score of worst eczema, and self-reported doctor-diagnosed atopic dermatitis.A notable difference was observed in disease duration since onset, where 90.9% of drop-outs had a disease duration of less than 1 year, compared to 48.9% of the retained participants ( p < 0.05).Further details of the attrition analysis are presented in Table S1.A project nurse scored IG participants' Hand Eczema Severity Index (HECSI) at their initial consultation and again at the 3-month follow-up.
During this period, there was an observed decrease in average HECSI score, from 32.4 at baseline to 19.1 at the 3-month follow-up.
Irritant contact dermatitis was the most common final diagnosis (78.3%), followed by allergic contact dermatitis (17.4%), with atopic dermatitis being the most common supplementary diagnosis (27.8%).
All the IG participants were diagnosed with OCD (Table 3).
An overview of the patch-testing and the patch-test results for the IG participants can be found in Tables S2 and S3.

| Wet work and skin protective behaviour
The IG's and CG's exposure to wet work at baseline is illustrated in Table 4 and is found to be similar in the IG and CG.Table 5 T A B L E 2 Characteristics related to disease duration and severity of all-time worst eczema in the intervention and control groups.demonstrates the daily use of hand moisturisers in both the IG and CG.From baseline to the 3-month follow-up, the IG showed a remarkable shift towards more frequent use.Specifically, the proportion of workers using moisturisers several times daily increased by approximately 30%.While the proportion of workers in the CG never using moisturisers increased by 7%, and the proportion using it several times daily only saw a small increase of 14%.However, this difference was not statistically significant.

| Doctor visits
Table 6 presents the proportion of workers in the IG and CG who have had a consultation with a dermatologist at the 3-month follow-up.All participants in the IG (n = 23) had seen a dermatologist within the first 3 months of the study, compared with 68.2% (n = 15) in the CG.This difference was found to be statistically significant.

| Topical treatment
In both groups, potent topical corticosteroids were the most commonly prescribed treatments.Within the IG, 87% were prescribed potent corticosteroids, in contrast to the CG, where 50% of the participants were prescribed potent corticosteroids (Table 7).Topical treatment with mild, moderate or very potent corticosteroids, as well as tacrolimus, was less prescribed in both groups, with more participants in the IG being prescribed tacrolimus and more participants in the CG being prescribed very potent corticosteroids.
Participants were also asked about their use of topical corticosteroids in the last 3 months (Table 8).We found a tendency for the IG  T A B L E 5 Daily use of hand moisturizers in the intervention and control groups at baseline and 3-month follow-up.participants to have used topical corticosteroid treatment for a longer period of time within the last 3 months compared to the CG, but this difference was not statistically significant (Table 8).

| Systemic treatment
The use of systemic treatment within the last 3 months, showed a different pattern (Table 7).No participants from the IG were prescribed systemic treatment including antibiotics for their OHE.In the CG, acitretin was prescribed to 4.5% (n = 1) and antibiotics were prescribed to 9.1% (n = 2).

| Severity of hand eczema
The self-assessed severity of hand eczema in both the IG and CG was evaluated at baseline and 3-month follow-up (Table 9).Measurements of severity considered the degree of eczema within the last 3 months, severity as per the VAS scale and self-assessment using the photographic guide.
In the context of the degree of eczema within the past 3 months, the IG demonstrated an improvement in their condition at the 3-month follow-up compared to baseline.Specifically, the proportion of participants who reported having eczema 'all the time' decreased from 56.5% at baseline to 30.4% at 3-month follow-up.In contrast, the CG saw an increase in the same parameter, with 50% reporting constant eczema at baseline, rising slightly to 59.1% at the 3-month follow-up.The difference in changes between the two groups was statistically significant, with an adjusted odds ratio (OR) of 4.5 (95% confidence interval [CI]: 1.3-16.9,p < 0.05) for the CG to have a higher degree of eczema compared to the IG (adjusted for sex, age, atopic dermatitis and degree of eczema at baseline).
Self-reported severity of eczema over the last 3 months on the VAS scale displayed a decrease in both groups.However, the mean severity score was lower in the IG (4.1 ± 2.3) than the CG (4.8 ± 2.7) at the 3-month follow-up, but this difference did not reach statistical significance.
In the analysis of self-assessed severity of hand eczema within the last 3 months using the photographic guide, it was observed that the IG experienced notable improvement at the 3-month follow-up.
The proportion of IG participants reporting 'No eczema' or 'Almost clear' eczema increased, whereas those reporting 'Moderate', 'Severe' or 'Very severe' eczema decreased from baseline to 3-month follow-up.In comparison, changes in the CG were less pronounced.
Notably, the adjusted OR for having a higher severity of hand eczema for the CG was found to be 8.0 (95% CI: 2.0-37.6,p < 0.01).

| Occupational consequences
Occupational consequences of OCD were examined at the 3-month follow-up, focusing on events within the last 3 months directly caused by their OCD (Table 10).In the IG, 4.5% reported sick leave compared to none in the CG.A similar proportion of participants reported changes to their work assignments in the IG (4.3%) and CG (9.1%).
Notably, no one in the IG reported changing their workplace within the same field, contrasting with 9.1% in the CG.
Job loss due to OCD was similar across groups (4.3% in the IG and 4.5% in the CG), with a majority reporting no consequences (60.9% in IG and 59.1% in CG).

| Quality of life
The IG and CG displayed comparable scores across the examined quality of life instruments at baseline and at follow-up (Table S4).For both groups, the mean DLQI score indicated a small impact on life at baseline and follow-up, and similarly, Skindex-29 scores remained moderate for emotions and functioning, while symptoms moved from 'extremely severe' to 'severe'.Overall, no statistically significant differences were observed between the IG and CG, demonstrating similar quality of life in both groups at baseline and 3-month follow-up.decreasing trend in the VAS score in the IG compared to the CG, but this did not reach statistical significance.[30] Studies conducted in Germany have examined the effect of TIP on the severity of OCD after intervention, although these studies lacked a CG.OCD severity was found to decrease statistically significantly 1 month, 1 year and 3 years after intervention compared to baseline. 11,12,31e findings suggest potential benefits of the intervention, possibly due to the immediate initiation of highly specialised diagnostics and treatment provided in the intervention setting.This interpretation is consistent with previous research by Hald et al., 32 which demonstrated that delays in medical attention for hand eczema correlated with poorer prognosis.

| Treatment and skin protective behaviour
We found that all the IG participants and 68.2% of the CG had seen a dermatologist at 3-month follow-up.The waiting list for the first consultation at a local dermatologist is on average 5 months in Denmark. 33Furthermore, there will often be a subsequent waiting period for patch testing of unknown duration.Concurrently, we noted a tendency for the IG T A B L E 9 Severity of hand eczema at baseline and at 3-month follow-up for the intervention and control groups assessed by degree of eczema within the last 3 months, self-assessed severity by VAS and self-assessed severity using the photographic guide (n = 45).T A B L E 1 0 Consequences experienced by the intervention and control groups within the last 3 months at 3-month followup (n = 45).

( 31 -
1521-161) and the Knowledge Centre on Data Protection Compliance in the Capital Region of Denmark on behalf of the Danish Data Protection Board (P-2019-650).The study was conducted according to the Declaration of Helsinki, and participation required signed consent forms.
the CG.The mean age of the participants was slightly higher in the IG (40.5 ± 14.5 years) compared to the CG (35.1 ± 14.6 years), but the difference was not statistically significant ( p = 0.3).Almost all of the participants were born in Denmark (95.2% in the IG and 100% in the CG).In terms of occupations, both groups demonstrated a diverse distribution, with healthcare workers and mechanics, fitters and technicians being the most common groups in the IG, and healthcare workers and kitchen personnel being the most common groups in the CG.

3. 1 . 3 |
Description of the IG and Hand Eczema Severity Index score IG participants had their first consultation with a dermatologist at the Department of Dermatology, on average, 34.7 days after referral (interquartile range 16.5-48 days).This delay was solely due to patients choosing to postpone their consultation due to conflicts with work schedules, exams or travel plans.IG participants had, on average, 2.2 doctor consultations within the first 3 months of inclusion in the study.

T A B L E 3
Characteristics of the intervention group and their diagnosis and treatment course at Department of Dermatology at Gentofte Hospital, Denmark, (n = 23).

4 | DISCUSSION 4 . 1 |
Severity of OCDOur findings demonstrated a statistically significant reduction in the severity of OCD in the IG compared to the CG based on the degree of eczema within the last 3 months and self-assessed severity of hand eczema using the photographic guide.Additionally, we found a T A B L E 7 Medical treatment during the last 3 months of the intervention and control groups at 3-month follow-up (n = 45).

Table 1 .
The sex distribution was approximately equal across the groups, with males accounting for 39.1% of the IG and 50% of T A B L E 1 Baseline characteristics of the intervention and control groups.
a Fisher's exact test.b Wilcoxon rank-sum test.
Proportion of workers in the intervention and control groups meeting the different criteria for the definition of wet work at baseline.
T A B L E 4 Proportion of workers in the intervention and control groups who have had a doctor-consultation with a dermatologist at 3-month follow-up (n = 45).
a Fisher's exact test.
Use of topical corticosteroid treatment within the last 3 months at 3-month follow-up (n = 44).
Intervention group, n (%)Control group, n (%)Severity of hand eczema within the last 3 months self-assessed by the photographic guide Abbreviations: CI, confidence interval; OR, odds ratio; VAS, visual analogue scale.a Adjusted for age, sex and atopic dermatitis.