Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Comparison of Perceptions of Skin Condition, Product Use and Allergen Reactivity Between People with Psoriasis and Controls in the European Dermato-Epidemiology Network (EDEN) Fragrance Study.

Psoriasis, a chronic inflammatory skin disease, goes beyond visible symptoms and affects the general well-being of patients. The aim of this study is to understand how patients with psoriasis perceive their skin characteristics and reactivity to allergens. The study population includes 11,283 participants within the European Dermato-Epidemiology Network (EDEN) Fragrance study, covering several European regions. The study compared perceptions of skin dryness, sensitivity, product avoidance and reactivity to allergens between patients with psoriasis and controls, evaluating the potential influence of psoriasis severity. The results showed that subjects with psoriasis reported dry skin (71.1%) and sensitive skin (49.4%) more often than did controls (51.6% and 38.5%, respectively). Psoriasis patients were more likely to avoid specific products. Interestingly, there were no significant differences in patch-test results between the 2 groups and the severity of psoriasis did not have a consistent impact on these perceptions. In conclusion, people with psoriasis tend to perceive their skin as drier and more sensitive. Notably, the severity of psoriasis did not consistently influence these perceptions and objective reactivity to allergens did not align with subjective perception. Understanding these aspects is crucial for tailoring treatments to improve the well-being of patients with psoriasis, which warrants further research to explore subjective perceptions of skin well-being in patients with psoriasis.

Transcriptional differences between vesicular hand eczema and atopic dermatitis.

BACKGROUND: Transcriptome analyses of vesicular hand eczema (VHE) indicated a large overlap with atopic dermatitis (AD). However, differentially expressed genes (DEGs) that differentiate VHE from AD are unknown. OBJECTIVE: To identify distinctive transcriptional features of VHE in comparison to AD. METHODS: We re-analysed RNA sequencing data of 10 lesional palmar VHE epidermal biopsies and performed DEG analyses. We adjusted the obtained DEG results of 57 lesional whole AD skin biopsies of the upper extremities or trunk to our criteria. Up- and down-regulated DEGs in both skin diseases, VHE-only, AD-only, and opposite regulated DEGs were identified. Enrichment analyses and Chi-squared tests were conducted to test for differences in gene set enrichment between both skin diseases. RESULTS: Comparing 3028 DEGs in VHE (1645 up; 1383 down) with 5391 DEGs in AD (3842 up; 1549 down), revealed 1516 shared DEGs (1179 up; 337 down) and 1512 DEGs unique to VHE (466 up, 1046 down). Interferon signalling and necroptosis were significantly more prominent in VHE compared to AD. Downregulated genes identified only in VHE (like DNASE1L2, KRT2, KRT9 and KRT25) indicate an aberrant epidermal differentiation. CONCLUSION: Our study indicates a common pathophysiology between VHE and AD, but also reveals transcriptional differences between VHE and AD.

Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

BACKGROUND: Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. OBJECTIVES: To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. METHODS: This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. RESULTS: A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was €3 977 033.98 for 401 patients between January 2019 and June 2022. CONCLUSIONS: This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective.

Analysis of Hexavalent Chromium in Cement Samples From Countries Within and Outside the EU: A Study From the International Contact Dermatitis Research Group.

Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).

Hazard identification and the prevalence of occupational skin disease in Indonesian Batik workers.

Batik, a resist-dyeing technique to decorate a special cotton fabric, has been practiced for centuries in Indonesia. Unfortunately, as an informal enterprise, batik industry activities lack work safety and health regulations. This study aimed to identify potential health hazards, including inventorying the chemicals to which the workers are exposed, the PPE profile, and investigating the prevalence of occupational skin diseases (OSD) in the batik industry. A cross-sectional study and an inventory of exposure to the chemicals were done in traditional batik workplaces in 5 districts in Yogyakarta province, Indonesia. The chemicals were classified as potential sensitizers/irritants, and the workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. Of 222 traditional batik workers, OSD were diagnosed in 61 (27.5%) workers, with occupational contact dermatitis was the most common OSD encountered (n = 23/61; 37.7%) (allergic contact dermatitis n = 7/23; irritant contact dermatitis n = 16/23). A smaller portion of other OSD was also encountered including callus, miliaria, and nail disorder (9%, 6.3%, and 5.9%, respectively). During each step of the traditional batik manufacturing process, the workers are exposed to substances that act as irritants and/or as potential contact allergens. However, only one-fourth of the workers used PPE regularly, particularly during the coloring process and wax removal (wet processes). Traditional batik manufacturing process exposes the worker to various physical and chemical hazards, resulting in a high prevalence of occupational skin diseases, especially contact dermatitis among the employees.

Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe.

Importance: The common use of isothiazolinones as preservatives is a global cause of allergic contact dermatitis. Differences in allowable concentrations of methylisothiazolinone (MI) exist in Europe, Canada, and the US. Objective: To compare the prevalence of positive patch test reactions to the methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) combination and MI alone in North America and Europe from 2009 to 2018. Design, Setting, and Participants: This retrospective analysis of North American Contact Dermatitis Group, European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) databases included data from patients presenting for patch testing at referral patch test clinics in North America and Europe. Exposures: Patch tests to MCI/MI and MI. Main Outcomes and Measures: Prevalence of allergic contact dermatitis to MCI/MI and MI. Results: From 2009 to 2018, participating sites in North America and Europe patch tested a total of 226 161 individuals to MCI/MI and 118 779 to MI. In Europe, positivity to MCI/MI peaked during 2013 and 2014 at 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) during 2017 and 2018. Positive reactions to MI were 5.5% (ESSCA) and 3.4% (IVDK) during 2017 and 2018. In North America, the frequency of positivity to MCI/MI increased steadily through the study period, reaching 10.8% for MCI/MI during 2017 and 2018. Positive reactions to MI were 15.0% during 2017 and 2018. Conclusions and Relevance: The study results suggest that in contrast to the continued increase in North America, isothiazolinone allergy is decreasing in Europe. This trend may coincide with earlier and more stringent government regulation of MI in Europe.

Dupilumab Drug Survival and Associated Predictors in Patients With Moderate to Severe Atopic Dermatitis: Long-term Results From the Daily Practice BioDay Registry.

Importance: Long-term data on dupilumab drug survival in patients with atopic dermatitis (AD) are scarce. Furthermore, little is known about the factors associated with drug survival of dupilumab in AD. Objective: To describe the drug survival of dupilumab in patients with AD and to identify associated predictors. Design, Setting, and Participants: This cohort study was based on data from the multicenter prospective daily practice BioDay registry, in which 4 university and 10 nonuniversity hospitals in the Netherlands participated. Analysis included patients (age ≥18 years) participating in the BioDay registry with a follow-up of at least 4 weeks. The first patient treated with dupilumab was recorded in the BioDay registry in October 2017; data lock took place in December 2020, and data analysis was performed from October 2017 to December 2020. Main Outcomes and Measures: Drug survival was analyzed by Kaplan-Meier survival curves and associated characteristics by using univariate and multivariate Cox regression analysis. Results: A total of 715 adult patients with AD (mean [SD] age, 41.8 [16.0] years; 418 [58.5%] were male) were included with a 1-year, 2-year, and 3-year overall dupilumab drug survival of 90.3%, 85.9%, and 78.6%, respectively. Characteristics associated with shorter drug survival owing to ineffectiveness were the use of immunosuppressant drugs at baseline (hazard ratio [HR], 2.64; 95% CI, 1.10-6.37) and being a nonresponder at 4 weeks (HR, 8.68; 95% CI, 2.97-25.35). Characteristics associated with shorter drug survival owing to adverse effects were the use of immunosuppressant drugs at baseline (HR, 2.69; 95% CI, 1.32-5.48), age 65 years or older (HR, 2.94; 95% CI, 1.10-7.87), and Investigator Global Assessment score of very severe AD (HR, 3.51; 95% CI, 1.20-10.28). Conclusions and Relevance: This cohort study demonstrated a good overall 1-year, 2-year, and 3-year dupilumab drug survival. Patients using immunosuppressive therapy at baseline and those with an absence of treatment effect at week 4 tended to discontinue treatment owing to ineffectiveness more frequently. Using immunosuppressant drugs at baseline, older age, and Investigator Global Assessment score of very severe AD were characteristics associated with an increased risk for discontinuation owing to adverse effects. These data provide more insight and new perspectives regarding dupilumab treatment in AD and can contribute to the optimization of patient outcomes.

Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis.

BACKGROUND: At present, no real-world studies are available on different dupilumab dosing regimens in controlled atopic dermatitis (AD). The aim of this study was to clinically evaluate a patient-centered dupilumab dosing regimen in patients with controlled AD and to relate this to serum drug levels and serum biomarkers. METHODS: Ninety adult AD patients from the prospective BioDay registry were included based on their dupilumab administration interval according to a predefined patient-centered dosing regimen. Group A (n = 30) did not fulfill the criteria for interval prolongation and continued using the standard dupilumab dosage (300 mg/2 weeks), group B (n = 30) prolonged dupilumab interval with 50% (300 mg/4 weeks), and group C (n = 30) prolonged dupilumab interval with 66%-75% (300 mg/6-8 weeks). AD severity score, patient-reported outcomes, serum dupilumab levels, and serum biomarkers were analyzed over time. RESULTS: Disease severity scores did not significantly change over time during the tapering period in any of the groups. In groups B and C, the Numeric Rating Scale (NRS)-pruritus temporarily significantly increased after interval prolongation but remained low (median NRS-pruritus≤4). Median dupilumab levels remained stable in group A (standard dosage), but significantly decreased in groups B and C (24.1 mg/L (IQR = 17.1-45.6); 12.5 mg/L (IQR = 1.7-22.3)) compared with the levels during the standard dosage (88.2 mg/L [IQR = 67.1-123.0, p < .001]). Disease severity biomarker levels (CCL17/CCL18) remained low in all study groups during the whole observation period. CONCLUSIONS: This study showed that dose reduction was successful in a subgroup of patients with controlled AD by using a patient-centered dosing regimen. These patients showed stable low disease activity and low severity biomarkers over time.

European patch test results with audit allergens as candidates for inclusion in the European Baseline Series, 2019/20: Joint results of the ESSCAA and the EBSB working groups of the ESCD, and the GEIDACC.

BACKGROUND: In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well. OBJECTIVES: To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. METHODS: Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. As patch test outcome, reactions between day (D) 3 and D5 were considered. RESULTS: Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain. CONCLUSIONS: Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members.

Prevalence of contact allergies in the population compared to a tertiary referral patch test clinic in Jena/Germany.

BACKGROUND: The contact allergy prevalences in patch-tested patients are usually higher than those in the population, owing to morbidity-driven selection. OBJECTIVES: To examine the differences between two samples, one from the population, one from the patch test clinic, in one area of Germany (Jena, Thuringia). METHODS: Between August 2008 and October 2011, a total of 519 participants of the population-based european dermato-epidemiology network (EDEN) fragrance study were patch tested in Jena using a TRUE Test baseline series extended with some pet.-based (fragrance) allergen preparations. Between 2007 and 2012 (inclusive), 1906 routine patients were patch tested for suspected allergic contact dermatitis (ACD) in the Jena University Hospital Department; of these 1694 (83.2%) with the German baseline series using pet./aq.-based, investigator-loaded allergens. RESULTS: In the population (clinical) sample, 19.6% (41.1%) were sensitized to at least one of the allergens considered. The most common baseline series allergens in the population/clinical sample were nickel (10.5%/13.2%), fragrance mix (FM) II (2.9%/6.7%), FM I (2.3%/8.3%), and cobalt (1.6%/5%). The clinical sample was slightly older (71.5% vs 55.9% age 40+) and included less males (36% vs 49.3%). CONCLUSIONS: Results are quite similar, although prevalences are usually higher in the clinical setting, with the exception of p-tert-butylphenol formaldehyde resin.

A survey of members of the European Surveillance System on Contact Allergy and the EU project "StanDerm" to identify allergens tested in cosmetic series across Europe.

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.

Socioeconomic Status and the Prevalence of Skin and Atopic Diseases in Five European Countries.

The aim of this study was to investigate the association between socioeconomic status and the prevalence of self-reported skin and atopic diseases in the general population of 5 European countries. A random sample was drawn from the general population aged 18-74 years, based on electoral precincts. Socioeconomic status was estimated by combining net household income with the highest education of respondents. A total of 7,904 subjects were included in this analysis. The lifetime prevalence of "contact dermatitis" ranged from 13.1% (95% confidence interval (95% CI 11.8-14.4%) in subjects with low socioeconomic status, to 19.1% (95% CI 17.5-20.8%) in those with high socio-economic status. In younger subjects skin cancer was more prevalent in the middle or high socioeconomic status groups compared with the low socioeconomic status group (odds ratio 2.4; 95% CI 1.4-4.3); however, this effect was not found in elderly subjects. The lifetime prevalence for at least one atopic disease was 61.2% (95% CI 59.4-63.0%) in the low and 82.8% (95% CI 81.1-84.3%) in the high socioeconomic status group. Individuals with middle or high socioeconomic status reported an overall higher prevalence of skin and atopic diseases compared with those with low socioeconomic status. These findings may reflect differences in reporting, which are likely to result in an underdiagnoses, especially for skin cancer in the younger age groups with low socioeconomic status.

Allergy Alert Test for p-Phenylenediamine-Allergic Hair Dye Users.

BACKGROUND: Contact dermatitis to hair dyes remains a health concern. Regulations in many countries require consumer self-testing for hair dyes, but no standardized procedure exists. OBJECTIVE: The aim of this study was to develop a self-test protocol for an allergy alert test (AAT) that can elicit a self-noticeable alert signal in p-phenylenediamine (PPD)-allergic consumers. METHODS: Simulating consumer use conditions (open application for 45 minutes after mixing with a developer), PPD-positive hair dye-allergic subjects and PPD-negative control subjects were tested on the forearm and behind the ear with experimental products containing 0.05%, 0.25%, 0.75%, and 2% PPD. Reactions were self-evaluated by subjects and independently assessed by dermatologists. CONCLUSIONS: The AAT caused a reaction self-noticeable on the forearm in 90.5% (38/42) and behind the ear in 93% (39/42) of the PPD-positive subjects. This was objectified by a dermatological evaluation. The strength of the AAT response and the number of responding subjects increased with increasing PPD concentrations. Allergy alert test responses were also dependent on the reaction strength of the diagnostic patch test to PPD before the study; in subjects with (+++) patch test reactions, 19 of 19 were positive. All 48 control subjects were negative to the AAT. Therefore, the AAT protocol provides a signal indicative of an allergic reaction in PPD-allergic hair dye consumers.

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.

The feasibility of an allergy management support system (AMSS) for IgE-mediated allergy in primary care.

BACKGROUND: The allergy management support system (AMSS) was developed to assist general practitioners (GPs) to handle the increasing burden of allergic diseases and facilitates the diagnosis and management of allergy. The aim of this cluster-randomized controlled pilot study was to test the feasibility of this AMSS for primary care. METHODS: GPs received diagnostic and management recommendations generated by the AMSS in addition to sIgE-test results (intervention) or GPs received sIgE-test results only (control). The AMSS recommendations are based on the previously developed patient-completed AMSS questionnaire and sIgE-test results. The AMSS was considered feasible when > 70% of the AMSS recommendations were sent to the GP within ten working days of sIgE-testing. GPs completed a questionnaire on their diagnosis and management before (T1) and after (T2) receiving sIgE test results. Agreement and disagreement concerning diagnosis, medication and referrals between GPs and AMSS was investigated at T1 and T2. A total agreement score between GPs and AMSS was calculated. GPs in the intervention group completed a questionnaire to evaluate the utility of the AMSS. Semi-structured interviews were used to explore the motivation of GPs who did not include patients in this pilot study. RESULTS: Twenty-seven GPs included 101 patients. Forty-two patients (72%) completed the AMSS questionnaire in the intervention group. The majority of the AMSS recommendations (93%) were returned to the GP within 10 working days after sIgE-test results were known [mean (SD) 4.7 (4.0) working days]. GPs in the intervention group reported largely following the AMSS recommendations in 71% of cases. The total agreement scores concerning diagnosis were significantly higher (p < 0.001) in the intervention group than the control group [mean (SD); 0.9 (1.8) vs - 0.8 (1.0)]. The agreement concerning medication or referral between GPs and AMSS did not differ between the intervention and the control group. GPs in the intervention group were reasonably positive about the AMSS. Not enrolling patients was not caused by anticipated ineffectiveness of the AMSS. CONCLUSION: The AMSS can be considered to be feasible for primary care. GPs tend to follow the AMSS recommendations. The AMSS may contribute to the empowerment of GPs to better manage allergy patients in primary care.Trial registration ISRCTN ISRCTN36780877. Registered 23 November 2017 (retrospectively registered).

Interventions for preventing occupational irritant hand dermatitis.

BACKGROUND: Occupational irritant hand dermatitis (OIHD) causes significant functional impairment, disruption of work, and discomfort in the working population. Different preventive measures such as protective gloves, barrier creams and moisturisers can be used, but it is not clear how effective these are. This is an update of a Cochrane review which was previously published in 2010. OBJECTIVES: To assess the effects of primary preventive interventions and strategies (physical and behavioural) for preventing OIHD in healthy people (who have no hand dermatitis) who work in occupations where the skin is at risk of damage due to contact with water, detergents, chemicals or other irritants, or from wearing gloves. SEARCH METHODS: We updated our searches of the following databases to January 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLlNE, and Embase. We also searched five trials registers and checked the bibliographies of included studies for further references to relevant trials. We handsearched two sets of conference proceedings. SELECTION CRITERIA: We included parallel and cross-over randomised controlled trials (RCTs) which examined the effectiveness of barrier creams, moisturisers, gloves, or educational interventions compared to no intervention for the primary prevention of OIHD under field conditions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were signs and symptoms of OIHD developed during the trials, and the frequency of treatment discontinuation due to adverse effects. MAIN RESULTS: We included nine RCTs involving 2888 participants without occupational irritant hand dermatitis (OIHD) at baseline. Six studies, including 1533 participants, investigated the effects of barrier creams, moisturisers, or both. Three studies, including 1355 participants, assessed the effectiveness of skin protection education on the prevention of OIHD. No studies were eligible that investigated the effects of protective gloves. Among each type of intervention, there was heterogeneity concerning the criteria for assessing signs and symptoms of OIHD, the products, and the occupations. Selection bias, performance bias, and reporting bias were generally unclear across all studies. The risk of detection bias was low in five studies and high in one study. The risk of other biases was low in four studies and high in two studies.The eligible trials involved a variety of participants, including: metal workers exposed to cutting fluids, dye and print factory workers, gut cleaners in swine slaughterhouses, cleaners and kitchen workers, nurse apprentices, hospital employees handling irritants, and hairdressing apprentices. All studies were undertaken at the respective work places. Study duration ranged from four weeks to three years. The participants' ages ranged from 16 to 67 years.Meta-analyses for barrier creams, moisturisers, a combination of both barrier creams and moisturisers, or skin protection education showed imprecise effects favouring the intervention. Twenty-nine per cent of participants who applied barrier creams developed signs of OIHD, compared to 33% of the controls, so the risk may be slightly reduced with this measure (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.06; 999 participants; 4 studies; low-quality evidence). However, this risk reduction may not be clinically important. There may be a clinically important protective effect with the use of moisturisers: in the intervention groups, 13% of participants developed symptoms of OIHD compared to 19% of the controls (RR 0.71, 95% CI 0.46 to 1.09; 507 participants; 3 studies; low-quality evidence). Likewise, there may be a clinically important protective effect from using a combination of barrier creams and moisturisers: 8% of participants in the intervention group developed signs of OIHD, compared to 13% of the controls (RR 0.68, 95% CI 0.33 to 1.42; 474 participants; 2 studies; low-quality evidence). We are uncertain whether skin protection education reduces the risk of developing signs of OIHD (RR 0.76, 95% CI 0.54 to 1.08; 1355 participants; 3 studies; very low-quality evidence). Twenty-one per cent of participants who received skin protection education developed signs of OIHD, compared to 28% of the controls.None of the studies addressed the frequency of treatment discontinuation due to adverse effects of the products directly. However, in three studies of barrier creams, the reasons for withdrawal from the studies were unrelated to adverse effects. Likewise, in one study of moisturisers plus barrier creams, and in one study of skin protection education, reasons for dropout were unrelated to adverse effects. The remaining studies (one to two in each comparison) reported dropouts without stating how many of them may have been due to adverse reactions to the interventions. We judged the quality of this evidence as moderate, due to the indirectness of the results. The investigated interventions to prevent OIHD probably cause few or no serious adverse effects. AUTHORS' CONCLUSIONS: Moisturisers used alone or in combination with barrier creams may result in a clinically important protective effect, either in the long- or short-term, for the primary prevention of OIHD. Barrier creams alone may have slight protective effect, but this does not appear to be clinically important. The results for all of these comparisons were imprecise, and the low quality of the evidence means that our confidence in the effect estimates is limited. For skin protection education, the results varied substantially across the trials, the effect was imprecise, and the pooled risk reduction was not large enough to be clinically important. The very low quality of the evidence means that we are unsure as to whether skin protection education reduces the risk of developing OIHD. The interventions probably cause few or no serious adverse effects.We conclude that at present there is insufficient evidence to confidently assess the effectiveness of interventions used in the primary prevention of OIHD. This does not necessarily mean that current measures are ineffective. Even though the update of this review included larger studies of reasonable quality, there is still a need for trials which apply standardised measures for the detection of OIHD in order to determine the effectiveness of the different prevention strategies.