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Hand eczema is a common condition in the general population. The pathogenesis is largely unknown. The first part of this thesis studied the pathogenesis of hyperkeratotic hand eczema. This subtype has a typical presentation with thick hyperkeratosis of the palms and differs from other subtypes of hand eczema. Immunofluorescence showed that multiple proteins (e.g. filaggrin) had different staining patterns. It is still questionable if hyperkeratotic hand eczema is a subtype of hand eczema or an own entity and future research is necessary. Part two focuses on different systemic treatments in severe hand eczema by drug survival studies. Drug survival is an outcome measure to evaluate long term potency of a treatment. Daily practice data of alitretinoin, acitretin, cyclosporine, methotrexate and azathioprine was retrospectively collected. Cyclosporine was, besides alitretinoin, the most valuable treatment option in severe chronic hand eczema. Furthermore showed these data that current systemic treatments are often limited by side effects and ineffectiveness. Part three explores the burden of disease in terms of health-related quality of life, treatment satisfaction and treatment adherence in chronic vesicular hand eczema. Severity affected both, quality of live as treatment satisfaction. Patients with systemic treatment had a higher treatment satisfaction compared with those using only topical treatment. Systemic treatment should therefore be more accessible in severe vesicular hand eczema. The last chapter of this thesis is a review about cost of illness. Total costs in hand eczema varies between €1311-€9742 per patient per year. Occupational costs formed the largest component of total costs.

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoine 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.

Background: The efficacy and safety of methotrexate has been reported in a few clinical studies. The aim of this study was to identify the course of treatment with methotrexate in daily practice in patients with severe atopic dermatitis, with respect to reasons for discontinuation of treatment and side-effects. In addition we evaluated the effectiveness. Methods: Patient data (UMCG/UMCU, January 1997 - October 2013) were recorded in an Access database: patient characteristics; start/stop dates; subjective side-effects; objective side-effects (laboratory assessment); reasons to stop; retrospective Physician's Global Assessment (patients treated for at least 8 weeks). Results: A total of 46 patients (UMCG n=34; UMCU n=12) were treated with methotrexate (mean age 48.2 years). Eighteen patients still use methotrexate. The median treatment duration was 188.5 (11.0-1382.0) days, with a mean maintenance dose of 12.9 mg/week. The main reason for discontinuation of treatment was side-effects in 14/28 (50.0%) patients: 3 patients with objective side-effects (increased liver enzymes); 11 patients with subjective sideeffects. Other reasons for discontinuation were nonresponsiveness 6/28 (21.4%) and remission 2/28 (7.1%). Overall, gastrointestinal symptoms were the most common side-effects in 13/46 patients. A good clinical response to treatment was found in 20/38 (52.6%) patients; moderate response in 11/38 (29.0%) patients; no response in 7/38 (18.4%) patients. Conclusion: Results of methotrexate therapy in daily practice are not as good as the results from clinical trials. A substantial percentage of patients discontinued treatment, mainly due to side-effects. More results from daily practice are needed to appoint risk factors for discontinuation and treatment failure.

Hand eczema is a prevalent skin disease, which can significantly impact several aspects of life in terms of daily activities, social activities, psychological well-being, work-related aspects, and quality of life. This thesis was divided into three parts, with a focus on the pathogenesis of hyperkeratotic hand eczema in the first part, followed by the prevalence, severity and risk factors for hand eczema in the second part. It was found that among the Dutch general population, the lifetime prevalence of hand eczema was 15.0% and the 1-year prevalence 7.3%. The prevalence of severe to very severe hand eczema at worst ever was 1.9%. It was found that the majority of subjects with hand eczema in the past year had chronic hand eczema. Several lifestyle factors, such as smoking, obesity and stress, were associated with hand eczema. The last part of this thesis included different aspects of patient care with some first promising results of the use of dupilumab (biologic) and the use of baricitinib (JAK inhibitor) as treatment for hand eczema. Besides focusing on the treatment, it is also important to focus on its impact on the patient according to patients with hand eczema. Lastly, a substantial proportion of subjects with hand eczema reported limited health literacy. This emphasizes the need for more awareness of limited health literacy among clinicians treating this patient population. The three parts together encompass very diverse aspects of hand eczema, resulting in a thesis with a broad vision on hand eczema, which is hopefully also what you, as reader of my thesis, will remember; keep a broad vision when counseling patients with hand eczema to cover all related aspects that are necessary to provide optimal personalized care.