Causes of irritant contact dermatitis after occupational skin exposure: a systematic review.

PURPOSE: Irritant contact dermatitis (ICD) is a major cause of occupational disease. The aim was to review the relation between exposure to occupational irritants and ICD and the prognosis of ICD. METHODS: Through a systematic search, 1516 titles were identified, and 48 studies were included in the systematic review. RESULTS: We found that the evidence for an association between ICD and occupational irritants was strong for wet work, moderate for detergents and non-alcoholic disinfectants, and strong for a combination. The highest quality studies provided limited evidence for an association with use of occlusive gloves without other exposures and moderate evidence with simultaneous exposure to other wet work irritants. The evidence for an association between minor ICD and exposure to metalworking fluids was moderate. Regarding mechanical exposures, the literature was scarce and the evidence limited. We found that the prognosis for complete healing of ICD is poor, but improves after decrease of exposure through change of occupation or work tasks. There was no substantial evidence for an influence of gender, age, or household exposures. Inclusion of atopic dermatitis in the analysis did not alter the risk of ICD. Studies were at risk of bias, mainly due to selection and misclassification of exposure and outcome. This may have attenuated the results. CONCLUSION: This review reports strong evidence for an association between ICD and a combination of exposure to wet work and non-alcoholic disinfectants, moderate for metalworking fluids, limited for mechanical and glove exposure, and a strong evidence for a poor prognosis of ICD.

No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis.

BACKGROUND: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. OBJECTIVE: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. METHODS: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. RESULTS: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. LIMITATIONS: Observational prospective cohort study. CONCLUSION: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

Ingenol mebutate as topical treatment for actinic keratosis based on a prospective, non-interventional, multicentre study of real-life clinical practice in Germany: efficacy and quality of life.

BACKGROUND: The use of ingenol mebutate (IM) as a field-directed therapy over a short period of time has been shown to be effective and well tolerated in randomized Phase III trials. OBJECTIVES: To assess the efficacy and patient-reported outcomes for IM as treatment for actinic keratosis (AK) under daily "real-life" practice conditions. MATERIALS AND METHODS: A total of 826 adult patients with AK were enrolled by 292 dermatologists in Germany in a prospective, open, non-interventional, non-controlled, multicentre study. All patients were treated with IM and followed for eight weeks. RESULTS: The mean number of clinically visible AK lesions decreased significantly from 7.1±6.8 to 2.8±4.5 (p<0.0001). Most dermatologists (79.0%) rated global efficacy of IM as "very good"/"good" and 82.6% of the patients were "very satisfied" or "rather satisfied" with the efficacy of IM. Patient-reported outcomes showed greater efficacy and treatment comfort with IM compared to any last previous AK treatment with a comparable tolerability profile. Skin-related QoL data revealed a significant improvement of 50.2% after IM treatment (p<0.0001). Adverse events were reported in 7.0% of all patients, which were in most cases mild in intensity. CONCLUSION: Field-directed treatment with IM over a short period was associated with a high level of treatment satisfaction, as reported by dermatologists and patients. This observational study demonstrates the effectiveness and tolerability of IM in everyday clinical practice in addition to the known efficacy and safety obtained by randomized controlled clinical trials.

Interventions for hand eczema.

BACKGROUND: Hand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social stigma, and impairment in employment. Many different interventions of unknown effectiveness are used to treat hand eczema. OBJECTIVES: To assess the effects of topical and systemic interventions for hand eczema in adults and children. SEARCH METHODS: We searched the following up to April 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, GREAT, and four trials registries. We checked the reference lists of included studies for further references to relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared interventions for hand eczema, regardless of hand eczema type and other affected sites, versus no treatment, placebo, vehicle, or active treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were participant- and investigator-rated good/excellent control of symptoms, and adverse events. MAIN RESULTS: We included 60 RCTs, conducted in secondary care (5469 participants with mild to severe chronic hand eczema). Most participants were over 18 years old. The duration of treatment was short, generally up to four months. Only 24 studies included a follow-up period. Clinical heterogeneity in treatments and outcome measures was evident. Few studies performed head-to-head comparisons of different interventions. Risk of bias varied considerably, with only five studies at low risk in all domains. Twenty-two studies were industry-funded.Eighteen trials studied topical corticosteroids or calcineurin inhibitors; 10 studies, phototherapy; three studies, systemic immunosuppressives; and five studies, oral retinoids. Most studies compared an active intervention against no treatment, variants of the same medication, or placebo (or vehicle). Below, we present results from the main comparisons.Corticosteroid creams/ointments: when assessed 15 days after the start of treatment, clobetasol propionate 0.05% foam probably improves participant-rated control of symptoms compared to vehicle (risk ratio (RR) 2.32, 95% confidence interval (CI) 1.38 to 3.91; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 8; 1 study, 125 participants); the effect of clobetasol compared to vehicle for investigator-rated improvement is less clear (RR 1.43, 95% CI 0.86 to 2.40). More participants had at least one adverse event with clobetasol (11/62 versus 5/63; RR 2.24, 95% CI 0.82 to 6.06), including application site burning/pruritus. This evidence was rated as moderate certainty.When assessed 36 weeks after the start of treatment, mometasone furoate cream used thrice weekly may slightly improve investigator-rated symptom control compared to twice weekly (RR 1.23, 95% CI 0.94 to 1.61; 1 study, 72 participants) after remission is reached. Participant-rated symptoms were not measured. Some mild atrophy was reported in both groups (RR 1.76, 95% CI 0.45 to 6.83; 5/35 versus 3/37). This evidence was rated as low certainty.Irradiation with ultraviolet (UV) light: local combination ultraviolet light therapy (PUVA) may lead to improvement in investigator-rated symptom control when compared to local narrow-band UVB after 12 weeks of treatment (RR 0.50, 95% CI 0.22 to 1.16; 1 study, 60 participants). However, the 95% CI indicates that PUVA might make little or no difference. Participant-rated symptoms were not measured. Adverse events (mainly erythema) were reported by 9/30 participants in the narrow-band UVB group versus none in the PUVA group. This evidence was rated as moderate certainty.Topical calcineurin inhibitors: tacrolimus 0.1% over two weeks probably improves investigator-rated symptom control measured after three weeks compared to vehicle (14/14 tacrolimus versus 0/14 vehicle; 1 study). Participant-rated symptoms were not measured. Four of 14 people in the tacrolimus group versus zero in the vehicle group had well-tolerated application site burning/itching.A within-participant study in 16 participants compared 0.1% tacrolimus to 0.1% mometasone furoate but did not measure investigator- or participant-rated symptoms. Both treatments were well tolerated when assessed at two weeks during four weeks of treatment.Evidence from these studies was rated as moderate certainty.Oral interventions: oral cyclosporin 3 mg/kg/d probably slightly improves investigator-rated (RR 1.88, 95% CI 0.88 to 3.99; 1 study, 34 participants) or participant-rated (RR 1.25, 95% CI 0.69 to 2.27) control of symptoms compared to topical betamethasone dipropionate 0.05% after six weeks of treatment. The risk of adverse events such as dizziness was similar between groups (up to 36 weeks; RR 1.22, 95% CI 0.80 to 1.86, n = 55; 15/27 betamethasone versus 19/28 cyclosporin). The evidence was rated as moderate certainty.Alitretinoin 10 mg improves investigator-rated symptom control compared with placebo (RR 1.58, 95% CI 1.20 to 2.07; NNTB 11, 95% CI 6.3 to 26.5; 2 studies, n = 781) and alitretinoin 30 mg also improves this outcome compared with placebo (RR 2.75, 95% CI 2.20 to 3.43; NNTB 4, 95% CI 3 to 5; 2 studies, n = 1210). Similar results were found for participant-rated symptom control: alitretinoin 10 mg RR 1.73 (95% CI 1.25 to 2.40) and 30 mg RR 2.75 (95% CI 2.18 to 3.48). Evidence was rated as high certainty. The number of adverse events (including headache) probably did not differ between alitretinoin 10 mg and placebo (RR 1.01, 95% CI 0.66 to 1.55; 1 study, n = 158; moderate-certainty evidence), but the risk of headache increased with alitretinoin 30 mg (RR 3.43, 95% CI 2.45 to 4.81; 2 studies, n = 1210; high-certainty evidence). Outcomes were assessed between 48 and 72 weeks. AUTHORS' CONCLUSIONS: Most findings were from single studies with low precision, so they should be interpreted with caution. Topical corticosteroids and UV phototherapy were two of the major standard treatments, but evidence is insufficient to support one specific treatment over another. The effect of topical calcineurin inhibitors is not certain. Alitretinoin is more effective than placebo in controlling symptoms, but advantages over other treatments need evaluating.Well-designed and well-reported, long-term (more than three months), head-to-head studies comparing different treatments are needed. Consensus is required regarding the definition of hand eczema and its subtypes, and a standard severity scale should be established.The main limitation was heterogeneity between studies. Small sample size impacted our ability to detect differences between treatments.

The significance of batch and patch test method in establishing contact allergy to fragrance mix I-EDEN Fragrance Study Group.

BACKGROUND: A fragrance mix consisting of eight separate fragrance ingredients (fragrance mix I [FM I]) is present in most baseline patch test series. Patch testing with the TRUE Test technique is considered to detect less contact allergy to FM I than testing with the Finn Chamber technique. OBJECTIVE: To investigate the possible significance of batch and patch test method in establishing contact allergy to FM I. METHODS: Three thousand one hundred and nineteen individuals representing a sample of the general population were patch tested with two batches of FM I with two patch test techniques at six dermatology clinics in five European countries. The TRUE Test technique and the Finn Chamber technique with pet. preparations were used. McNemar's test was used for statistical calculations. RESULTS: The contact allergy prevalences varied between 0.7% and 2.6%. The patch tests with the mixes containing Evernia prunastri (oak moss) with a high content of chloratranol/atranol resulted in substantially more positive reactions than the corresponding tests with the mixes containing oak moss with a low content of chloratranol/atranol. The Finn Chamber technique detected significantly more contact allergic reactions than the TRUE Test technique (P < 0.001). CONCLUSION: The Finn Chamber technique detects more contact allergy to FM I than the TRUE Test technique.

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.

Chronic hand eczema in Germany: 5-year follow-up data from the CARPE registry.

BACKGROUND: The CARPE registry was set up in 2009 to prospectively investigate the management of patients with chronic hand eczema (CHE). OBJECTIVES: To report comprehensive follow-up data from the CARPE registry. PATIENTS AND METHODS: We investigated sociodemographic and clinical characteristics, provision of medical care, physician-assessed outcomes, and patient-reported outcomes (PROs). Data were collected between 2009 and 2016, with up to 5 years of follow-up, and are reported descriptively. RESULTS: Overall, 1281 patients were included in the registry (53.7% female). Mean age was 47.0 years. Of the patients, 793 and 231 completed the 2-year follow-up and 5-year follow-up, respectively. At baseline, 5.4% had changed or given up their job because of CHE, the average duration of CHE was 6.1 years, and, in 22.4%, the CHE was severe according to physician global assessment. Systemic treatment (alitretinoin, acitretin, and methotrexate) was prescribed at least once to 39.0% of the patients during the course of the follow-up. Disease severity, quality of life and treatment satisfaction improved over time, and the proportion of patients receiving systemic treatments decreased. CONCLUSIONS: Under continued dermatological care, substantial improvements in disease severity and PROs over time was achieved during the course of the CARPE registry, even in patients with long-standing and severe hand eczema.

Quality of Life in Hand Eczema Questionnaire: Validation of the Japanese version of a disease-specific measure of quality of life for hand eczema patients.

Hand eczema (HE) is a common skin disease that impairs health-related quality of life (HRQOL). Impairments in HRQOL have already been reported in Japanese HE patients using the Skindex-16. Recently, an instrument to measure disease-specific HRQOL in HE patients was developed by an international expert group, consisting of domains for: (i) symptoms; (ii) emotions; (iii) functioning; and (iv) treatment and prevention. The objective of this study is to translate the English-language version of the Quality of Life Hand Eczema Questionnaire (QOLHEQ) to Japanese and then to validate the Japanese version. The Japanese version of the QOLHEQ, the Dermatological Life Quality Index (DLQI) and a questionnaire regarding basic demographic information, including patient ratings of HE severity, were distributed to Japanese HE patients. Additionally, a dermatologist evaluated patients' HE severity using the Physician Global Assessment. A total of 124 patients with a mean age of 43.7 years were included in the analysis, and 78% of the sample was female. Cronbach's alphas for the domains symptoms, emotions, functioning, and treatment and prevention were 0.76, 0.89, 0.88 and 0.81, respectively. The total QOLHEQ score showed a strong correlation with the DLQI, a moderate correlation with patient-rated severity and weak correlations with dermatologist-rated severity and the number of consultations. The Japanese version of the QOLHEQ showed excellent reliability and high validity. The Japanese version of the QOLHEQ is ready for use in epidemiological studies to evaluate HRQOL impairments in HE patients.

Chronic hand eczema: A prospective analysis of the Swiss CARPE registry focusing on factors associated with clinical and quality of life improvement.

BACKGROUND: Hand eczema (HE) is common and may follow a chronic disease course. So far, prospective studies investigating the risk factors for disease progression as a prerequisite for targeted prevention are scarce. OBJECTIVE: To evaluate the overall association of HE-associated factors with clinical and quality of life (QoL) improvement during a follow-up of 2 years. METHODS: Data of the prospective patient cohort (N = 199) followed by the Swiss chronic HE (CHE) registry on long-term patient management (CARPE-CH) were analysed by means of both classic regression and semantic map analyses. RESULTS: Both severity of HE and QoL significantly improved over the period of 2 years (P < .001). However, 20% of patients had moderate to severe HE after 2 years of follow-up. As factors associated with an unfavourable CHE clinical course and QoL, environmental exposures, male sex, occupational skin disease, job loss or change at baseline, allergic contact dermatitis, a chronic disease course, palmar localization and widespread eczema were identified. CONCLUSIONS: Analysis of prospective data from CARPE-CH shows a complex pattern of associations among variables as shown by semantic map and classic statistical analyses. Factors related to occupational exposure had the highest impact on CHE.