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.

Strategies used for measuring long-term control in atopic dermatitis trials: A systematic review.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD. OBJECTIVE: We sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. METHODS: We conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English. RESULTS: In all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application. LIMITATIONS: We included RCT data only. CONCLUSION: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes.

Alitretinoin and acitretin in severe chronic hand eczema; results from a retrospective daily practice study.

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events.

The optimal patch test concentration for ascaridole as a sensitizing component of tea tree oil.

BACKGROUND: Tea tree oil is used as a natural remedy, but is also a popular ingredient in household and cosmetic products. Oxidation of tea tree oil results in degradation products, such as ascaridole, which may cause allergic contact dermatitis. OBJECTIVES: To identify the optimal patch test concentration for ascaridole, and to investigate the relationship between a positive reaction to ascaridole and a positive reaction to oxidized tea tree oil. PATIENTS/MATERIALS/METHODS: Three hundred and nineteen patients with eczema were patch tested with ascaridole 1%, 2%, and 5%, and 250 patients were patch tested with oxidized tea tree oil 5%. Readings were performed on D3 and D7 according to a patch test calibration protocol. RESULTS: With an increasing ascaridole test concentration, the frequency of positive reactions increased: ascaridole 1%, 1.4%; ascaridole 2%, 5.5%; and ascaridole 5%, 7.2%. However, the frequencies of irritant and doubtful reactions also increased, especially for ascaridole 5%. A positive reaction to ascaridole was related to a positive reaction to tea tree oil. CONCLUSIONS: This study is in support of ascaridole being a sensitizer. We recommend patch testing with ascaridole at 2%. The finding that every positive reaction to oxidized tea tree oil is accompanied by a positive reaction to ascaridole suggests that ascaridole might be a contact allergen in oxidized tea tree oil.

Anaphylaxis and severe systemic reactions caused by skin contact with persulfates in hair-bleaching products.

BACKGROUND: Persulfates have been reported to cause both delayed-type and immediate skin reactions. They may also cause immediate reactions of the mucous membranes of the bronchial system through inhalation, leading to asthma and rhinitis. Anaphylactic reactions caused by contact with persulfates are rare. The mechanism of immediate reactions caused by persulfates is unclear. OBJECTIVES: To report 2 cases with systemic reactions after skin contact with persulfates, and to propose a test protocol for diagnosing immediate reactions caused by persulfates. METHODS: Prick tests with serial dilutions of ammonium and potassium persulfate were performed. Patch tests were also performed with the two agents. Persulfate-specific IgE was detected with two different IgE immunoblotting techniques. RESULTS: Prick tests were positive with ammonium and potassium persufate, but no specific IgE was detected in the serum. Patch tests showed early positive reactions to both persulfates in 1 patient. CONCLUSIONS: Prick tests and patch tests can be valuable in the testing of patients with a suspicion of an immediate-type reaction caused by persulfates. The mechanism of these reactions remains unclear.