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

Itching in patients with chronic hand eczema: Data from the CARPE registry

BACKGROUND Itching is a leading symptom of chronic hand eczema (CHE) having a great impact on patients. The determinants of itching in CHE are unclear. OBJECTIVE We performed a cross-sectional analysis investigating factors associated with the presence and severity of itch in CHE patients from the CARPE registry. METHODS We present baseline data on itch in relationship with sociodemographic factors, severity of CHE, atopy, contact allergy, treatment and patient- reported outcomes including health-related quality of life (HRQoL). RESULTS Of 1,051 patients with CHE, 78.1% reported itching. Significant positive associations with itching were observed for younger age groups (17-25 and 26-45 years), for moderate, severe and very severe CHE and for small/moderate impairment in HRQoL. Atopic skin diathesis, hardly being able to realize treatment recommendations and very or extremely large impairments in HRQoL were associated with itch severity. CONCLUSION Taking the identified variables into account may help identify vulnerable groups most affected by (severe) itch

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

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