Interventions for hand eczema

BackgroundHand 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.ObjectivesTo assess the effects of topical and systemic interventions for hand eczema in adults and children.Search methodsWe 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 criteriaWe 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 analysisWe used standard methodological procedures expected by Cochrane. Primary outcomes were participant‐ and investigator‐rated good/excellent control of symptoms, and adverse events.Main resultsWe 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' conclusionsMost 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

Validation of a questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix I

Background In a European study on contact allergy in the general population, it was hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure, and thereafter subsequent avoidance of scented products, implied a diagnosis of allergic contact dermatitis. Objectives The primary aim of this study was to validate this hypothesis and algorithm. The secondary aim was to investigate whether there was any association between the outcome of the repeated open application test (ROAT) and the patch test reactivity. Methods In total, 109 patients with and without contact allergy to fragrance mix (FM) I were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. Results Positive ROAT reactions were noted in 26 of the 44 volunteers with contact allergy to FM I. None of the volunteers reacted to the vehicle (P <0 center dot 001). More individuals with a positive algorithm had positive ROATs than those with a negative algorithm. However, the difference was not statistically significant. The lower the patch test concentration eliciting a positive test reaction, the more likely a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. Conclusions The algorithm used in this study was not substantiated in this ROAT set-up. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period. What's already known about this topic? To the best of our knowledge, a scientifically designed and conducted repeated open application test (ROAT) has never been performed before to validate a diagnosis of allergic contact dermatitis partly based on a questionnaire. What does this study add? This is the largest controlled, randomized and blinded ROAT performed to date. Higher patch test reactivity to fragrance mix I indicated a greater likelihood of a positive ROAT

Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema - a long-term analysis from a Swiss perspective

BACKGROUND: The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. METHODS: A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. RESULTS: Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions. CONCLUSION: The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland

Virus-Induced Cancers of the Skin and Mucosa:Are We Dealing with "Smoking Guns" or "Smoke and Mirrors" in the Operating Theatre?

Introduction: Human papillomavirus (HPV) alone is thought to cause ~610,000 cases of cancer per year, and is the dominant aetiological agent for ano-genital (esp. cervical) and head and neck cancers (esp. oropharyngeal). Merkel cell polyomavirus (MCV) is a more recently discovered virus which causes Merkel cell carcinoma, a rare but highly aggressive skin malignancy. Methods: We explored the available published evidence to see if transmission of live HPV or MCV virus in smoke generated by laser or diathermy was feasible, and would pose an infection risk. Long-term infection with such carcinogenic viruses would then pose an increased risk for the development of virus-induced cancers in medical personnel. Results: The morphological structures of both HPV and MCV are very similar, and the size, external capsids and genomic structures show striking similarity. Both viruses have a non-enveloped external protein capsid consisting of 72 capsomeres, and a double-stranded DNA core. Sizes of both viruses range from 50 to 60 nm. There are now recent data demonstrating live and infectious HPV in smoke, and that these viruses can be used to infect cells in vitro. Further, anecdotal reports of virus transmission leading to disease causation in the production of respiratory airway viral warts (benign disease), and, finally, reports of HPV-induced oropharyngeal carcinoma (malignant disease) in two gynaecological surgeons as an occupational health hazard have been published recently. Conclusion: There is now sufficient evidence to support the hypotheses that live infectious carcinogenic viruses can be transmitted via smoke generated from surgical procedures, and, in rare instances, actually cause significant disease. Protective measures such as smoke extraction and airway protection should be instituted for all healthcare personnel, particularly those with multiple repeated exposures such as gynaecological surgeons

Personal solar ultraviolet radiation dosimetry in an\ua0occupational setting across Europe

Background: Work-related solar ultraviolet radiation (UVR) is an important factor in the pathogenesis of non-melanoma skin cancer (NMSC). The World Health Organization, through the International Agency for Research on Cancer, has classified solar UVR as a group 1 carcinogen since 2012. The main problems encountered so far in the study of occupationally induced skin cancer include the lack of accurate occupational UVR dosimetry as well as insufficient distinction between occupational and leisure UVR exposure and underreporting of NMSC. Objectives: The aim of this study was to collect long-term individual UVR measurements in outdoor workers across European countries. Methods: A prospective study was initiated through the European Academy of Dermatology and Venereology, Healthy Skin@Work Campaign, measuring UVR exposure doses at occupational settings of masons from five European countries. Measurements were performed for several consecutive months using the GENESIS-UV measurement system. Results: The results identified alarming UVR exposure data. Average daily UVR doses ranged 148.40–680.48&nbsp;J/m2 in Romania, 342.4–640.8&nbsp;J/m2 in Italy, 165.5–466.2&nbsp;J/m2 in Croatia, 41.8–473.8&nbsp;J/m2 in Denmark and 88.15–400.22&nbsp;J/m2 in Germany. Results showed an expected latitude dependence with increasing UVR yearly dosage from the north to the south of Europe. Conclusions: This study shows that outdoor workers from EU countries included in this study are exposed to high levels of occupational solar UVR, vastly exceeding the occupational exposure limits for solar UVR exposure, considered to be 1–1.33 SED/day in the period from May to September. This finding may serve as an evidence-based recommendation to authorities on implementing occupational skin cancer prevention strategies

Report drawn up on behalf of the Committee on Energy, Research and Technology on the development of advanced reactors, Part A: Motion for a resolution. Working Documents 1984-85, Document 1-224/84/A, 8 May 1984

Background Population/based studies about contact allergy are scarce. Objectives To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. Methods A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. Results In total, 27.0% [95% confidence interval (CI) 25.5-28.5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (>= 1%) were found for nickel (14.5%, 95% CI 13.2-15.8), thiomersal (5.0%, 95% CI 4.2-5.8), cobalt (2.2%, 95% CI 1.7-2.7), FM II (1.9%, 95% CI 1.5-2.5), FM I (1.8%, 95% CI 1.4-2.3), HICC (1.4%, 95% CI 1.0-1.9), p-tert-butylphenol formaldehyde resin (1.3%, 95% CI 0.9-1.7) and para-phenylenediamine (1.0%, 95% CI 0.6-1.3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15.1%, 95% CI 13.8-16.3) had an increased risk for contact allergy (odds ratio 1.9, 95% CI 1.5-2.5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7.6%, 95% CI 6.7-8.6; odds ratio 1.0, 95% CI 0.7-1.4). Conclusions Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced

Computer-aided dermoscopy for diagnosis of melanoma

BACKGROUND: Computer-aided dermoscopy using artificial neural networks has been reported to be an accurate tool for the evaluation of pigmented skin lesions. We set out to determine the sensitivity and specificity of a computer-aided dermoscopy system for diagnosis of melanoma in Iranian patients. METHODS: We studied 122 pigmented skin lesions which were referred for diagnostic evaluation or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes and all of their clinical diagnostic considerations were recorded. The lesions were analyzed using a microDERM(® )dermoscopy unit. The output value of the software for each lesion was a score between 0 and 10. All of the lesions were excised and examined histologically. RESULTS: Histopathological examination revealed melanoma in six lesions. Considering only the most likely clinical diagnosis, sensitivity and specificity of clinical examination for diagnosis of melanoma were 83% and 96%, respectively. Considering all clinical diagnostic considerations, the sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88 for dermoscopy score, the sensitivity and specificity of the score for diagnosis of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34, the sensitivity and specificity were 100% and 90%. CONCLUSION: The diagnostic accuracy of the dermoscopy system was at the level of clinical examination by dermatologists with naked eyes. This system may represent a useful tool for screening of melanoma, particularly at centers not experienced in the field of pigmented skin lesions

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