The Use of Naltrexone to Successfully Treat Severe Hailey-Hailey Disease

A 65-year-old gentleman presented with a three-year history of burning, itching, and splitting of the scrotal skin. He had previously been treated with topical corticosteroids, emollients, antifungals, and multiple short and long courses of antibiotics, with limited response. A biopsy was performed, which confirmed a diagnosis of Hailey-Hailey disease (HHD). HHD is an autosomal dominant genodermatosis characterised by vesicles that form eroded, erythematous plaques with painful rhagades in flexural areas. Oral naltrexone has been used to treat alcohol use disorder and opioid use disorder for many years. Naltrexone is known to block opioid receptors and indirectly antagonize toll-like receptor 4 in the microglial cells of the central nervous system and peripheral macrophages. This potentially reduces inflammation due to a decrease in the production of substance P, tumour necrosis factor, interleukin-6 (IL-6), and other pro-inflammatory cytokines. In 2022, acitretin was commenced and uptitrated to 25 mg once daily. Unfortunately, his condition deteriorated, with extensive erosions affecting the groin and scrotum, and the patient also developed side effects from the medication. A surgical opinion was sought, but surgery was not considered suitable. Courses of prednisolone did not help. Other immunosuppressive agents, such as methotrexate, cyclosporine, and azathioprine, have been described in the literature with varying efficacy. After two years, the pain from his erosions had reduced his ability to walk. Naltrexone 2.5 mg was commenced and subsequently uptitrated to 5 mg. Six weeks later, the patient had an 80% improvement in his condition. The patient experienced no side effects from the treatment and required no blood monitoring. This gentleman with severe HHD predominantly affecting the scrotum was commenced on oral naltrexone. Naltrexone is postulated to work due to its analgesic and anti-inflammatory effects. It is a well-tolerated treatment for severe HHD that has drastically improved both our patient's skin and his quality of life.