Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema

Inclusion Criteria: * Age ≥ 18 years and ≤ 75 years * Severe or very severe chronic non-hyperkeratotic 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 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 * Treatment with alitretinoin or azathioprine in the previous 3 months * Hyperkeratotic palmar eczema as defined by the Danish Contact Dermatitis Group * Patients with predominantly atopic dermatitis, in which the hands are also involved. Patients with mild atopic dermatitis, in which the hands are mainly affected are eligible for inclusion. * Psoriasis * 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 * 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 * 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 * Evidence of alcohol abuse or drug addiction * 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) Azathioprine specific • Patients with low or absent thiopurine methyltransferase (TPMT) activity (defined in our center as \<52 nmol/gHb/hour, combined with genotyping showing homozygous of compound heterozygous mutations) and a subsequent risk for life-threatening myelotoxicity