Variable response to low-dose naltrexone in patients with Darier disease: a case series

Background: Darier disease is a rare autosomal-dominant genodermatosis with a loss of function of a Ca ²⁺ -ATPase pump (SERCA2-pump). Clinically, the disease is characterized by red–brown keratotic papules mainly in seborrhoeic areas and has only limited and unsatisfactory treatment options. Previously, low-dose naltrexone was described as a successful treatment option in Hailey–Hailey disease, a genodermatosis with a genetic mutation coding for a similar loss of function of a Ca ²⁺ -ATPase pump (hSPCA1-pump). Objective: To assess the efficacy of low-dose naltrexone as a treatment option in Darier disease. Methods: Six patients with biopsy-proven Darier disease (four had severe, one had moderate and one mild clinical manifestations). The patients received off-label therapy with naltrexone [5 mg per os (p.o.)] and magnesium [200 mg p.o.]. Patients were followed up every 4 weeks for minimally 12 weeks. Upon clinical presentation, the disease severity and subjective pain and itch scores were assessed, and standardized photographs were obtained. Results: The clinical response to naltrexone varied after 12 weeks. The four patients with severe Darier disease showed worsening after initial improvement during the first 4 weeks, whereas the two patients with a mild to moderate clinical manifestation clearly improved, showing almost full remission after 12 weeks with complete flattening of the keratotic papules. Conclusion: Low-dose naltrexone did not have an effect on severe Darier disease compared to Hailey–Hailey disease, but it was beneficial in mild to moderate forms of the disease. Further studies are needed to confirm these observations of variable responses.