Alitretinoin vs Cyclosporine in Severe Recurrent Vesicular Hand Eczema

Inclusion Criteria: Age ≥ 18 years and ≤ 75 years * Severe or very severe recurrent vesicular hand eczema for a minimum duration of 3 months as defined by a Physician Global Assessment (PGA) using a validated Photoguide * Refractory to standard therapy, defined as: Patients received treatment with topical corticosteroids of class II or higher for at least 8 weeks within 3 months before enrolment, with either no response or a transient response. Patients had also received standard skin care, including emollients and barrier protection as appropriate, without significant improvement. Patients had avoided irritants and contact allergens, if identified, without significant improvement. * Women of childbearing potential are required to use at least two forms of contraception for at least 1 month before starting treatment, during treatment, and for at least 1 month after finishing treatment; these women are required to take monthly pregnancy tests * Able to provide written Informed Consent * Able to speak and read the Dutch language Exclusion Criteria: General criteria prior to randomization * Treated with alitretinoin or cyclosporine in the previous 3 months * Other morphologic types of hand eczema as defined by the Danish Contact Dermatitis Group * Patients with predominantly atopic dermatitis, in which the hands are also involved. (Patients with controlled atopic dermatitis, in which the hands are mainly affected, are eligible for inclusion.) * Psoriasis of the hands * Active bacterial, fungal, or viral infection of the hands * Pregnant/lactating or planning to become pregnant during the study period * Treatment with systemic medication or UV radiation within the previous 4 weeks * Mentally incompetent * Immunocompromised status * Uncontrolled arterial hypertension (minimally 3 measurements). Systolic pressure \> 160 mmHg or diastolic pressure \> 95 mmHg, despite starting anti-hypertensive medication (first choice amlodipine 5 mg/day) * Known or suspected allergy to ingredients in the study medications * Inclusion in a study of an investigational drug within 60 days prior to start of treatment * Current malignancy (other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and⁄or localized carcinoma in situ of the cervix) * Current active pancreatitis * Evidence of alcohol abuse or drug addiction * Malabsorption * Currently active gout * Recurring convulsions / epilepsy * Living vaccine (including bacillus Calmette-Guérin (BCG), varicella, measles, mumps, rubella, yellow fever, oral polio and oral typhoid) in the last 2 weeks or the planned application of such a vaccine during the study period * Chronic or recurrent infectious diseases * Contact sensitizations with clinical relevance to the hands, in which exposure to allergens is not avoided. * Hypervitaminosis A due to the use of vitamin A supplements containing \>2000 IU * Use of drugs with potential to change the effective dosis of study drugs within the previous 2 weeks Laboratory exclusion criteria post randomization * Alanine aminotransferase (ALAT) and ⁄or aspartate aminotransferase (ASAT) values \> 200% of the upper limit of normal * Impaired renal function as indicated by a clinically relevant abnormal creatinine value (to be determined by investigator or treating physician) * Anemia as indicated by a clinically relevant lowered hemoglobin value (to be determined by investigator or treating physician) Alitretinoin specific * Triglycerides \> 200% of the upper limit of normal, * Cholesterol or low density lipoprotein (LDL) cholesterol values \> 200% of the upper limit of normal * Uncontrolled hypothyroidism (to be determined by investigator or treating physician) Cyclosporine specific: * Impaired renal function as indicated by a clinically relevant abnormal creatinine value (to be determined by investigator or treating physician) * Uremia * Hyperkalemia * Hyperuricemia in patients with a medical history of gout