Evidence is emerging that naltrexone, a medicine used to treat opioid and alcohol abuse, can also control a genetic skin disease that causes painful, itchy rashes and blisters.
Two separate brief reports last week in JAMA Dermatology, from Emory and Cleveland Clinic investigators, describe the treatment of six patients with Hailey-Hailey disease.
Dermatologist Ron Feldman, MD, PhD is the senior author on the Emory report, which says:
“Low-dose naltrexone has been widely touted on social media platforms, including multiple YouTube videos, as an anecdotal treatment for patients with HHD, with surprisingly no published evidence until this year.”
Feldman tells Lab Land: “We decided to try it based on the patients; we had no clue about low-dose naltrexone until we met one of the patients with Hailey-Hailey disease, who came in asking for this therapy based on social media.”
At Emory, each of the three patients had tried at least four prior treatments, such as antibiotics and corticosteroids, but all were unsuccessful in controlling the disease.
Skin lesion improvement occurred as early as a week after starting oral naltrexone, and the lesions were cleared within a few months. When they stopped taking the medicine, their skins flared up again.
Hailey-Hailey disease is caused by a mutation in the gene ATP2C1, which causes skin cells to have defects in adhering to each other. The disease is inherited in a dominant fashion, meaning that receiving a mutated copy from just one parent causes trouble. ATP2C1 is thought to encode a calcium pump, but a 2016 Scientific Reports paper on the disorder says:
“It remains an enigma why individuals with defects in the ATP2C1 gene develop a skin-specific disease…”
Feldman adds:
“The gene defect is known, although there are many mutations that can lead to the same clinical findings. We don’t typically send off for gene testing if strong family history and histology are suggestive. The most interesting aspect of this, besides the patients driving their therapy, is why would naltrexone work on this disease and can this mechanism provide insight into other calcium dependent pathways/diseases.”
In the context of opioid abuse, naltrexone blocks opioid receptors. The authors write that in the skin, naltrexone may be promoting wound healing or have anti-inflammatory effects.
Low-dose naltrexone has also been studied for autoimmune diseases such as Crohn’s disease and multiple sclerosis. And a cautionary note: commenters such as the blog Science Based Medicine have criticized the promotion of low-dose naltrexone for a wide variety of conditions. Update: This site (Low Dose Naltrexone) is a good illustration.
First author Lauren Daugherty (previously Albers), MD was a medical student who is scheduled to start her dermatology residency at Emory next year. Jack Arbiser, MD, PhD is a co-author.
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