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The opioid-blocker naltrexone may be effective in managing a number of chronic inflammatory skin conditions, according to a systematic review of case series, reports, and randomized trials.

With varying degrees of evidence, low-dose oral naltrexone was effective in treating lichen planopilaris, Hailey-Hailey disease, and pruritus linked with scleroderma, reported Natasha Atanaskova Mesinkovska, MD, PhD, of the University of California Irvine, and colleagues.

"Naltrexone, particularly in low doses, has the potential to treat an array of primary skin lesions through inflammatory and immune-cell regulation and skin regeneration," the authors wrote in . "Potential future uses include the treatment of diabetic wounds, bullous diseases, scarring alopecia, alopecia areata, and psoriasis."

For lichen planopilaris, there was just one case series, but low-dose naltrexone (3 mg) resolved pruritus, decreased inflammation in the scalp, and slowed disease progression for all four patients treated. No adverse events were reported.

In Hailey-Hailey disease, the review looked at case reports and series on 11 naltrexone-treated patients. In one series assessing 3.0 to 4.5 mg oral doses, lesions completely cleared at 2 months in all three patients. There were flares when the drug was discontinued, but these resolved after restarting treatment.

High-dose naltrexone was effective for various forms of pruritus, but came with increased adverse events. In a 2016 prospective cohort study of 18 patients with pruritus from various causes treated with a 50-mg dose, the benefit as measured by a 50% improvement in the pruritus visual analog scale was observed in 13 patients. Adverse events included insomnia in two patients, as well as anorexia, fatigue, and constipation in one patient each.

Among 341 patients taking high doses in the studies that included such events, there were reports of nausea (n=46), gastrointestinal tract issues (n=30), dizziness (n=20), fatigue (n=18), and sleep disturbances (n=16).

High-dose treatment was also associated with worsening pruritus in studies of cholestatic and mycosis fungoides pruritus, and a prospective cohort study of 50 patients with pruritus of various causes. Only one study examined topical naltrexone -- in 38 patients with atopic dermatitis -- but showed benefit, with a response rate of 70%.

The patent for naltrexone expired about a year following its approval in 1984 for treating drug and alcohol addiction. Since then, there hasn't been much financial support to investigate the agent for other uses, according to the authors.

To address this consequential knowledge gap, "clinicians have diligently reported anecdotal successes of the treatment of multiple sclerosis, Crohn's disease, cancer, and HIV infection and AIDS," they wrote.

Notably, they emphasized, naltrexone is not approved for treating skin conditions. "However, research on animal models provides evidence that the medication may have several benefits on various aspects of skin disease. Among them are wound healing, anti-inflammatory effects, immunomodulation, and symptom control."

The investigators reviewed 22 articles, which included randomized clinical trials, and case reports and series. Of the papers evaluated, 14 involved high-dose naltrexone, seven involved low-dose naltrexone, and one was on a 1% topical formulation.

Using PubMed, the researchers conducted a primary literature search for papers published from 1971 to 2018, searching naltrexone, low-dose naltrexone, hair, skin, nails, and dermatology, or some variation of those terms. Search results that were reviews, animal studies, or non-dermatologic and pharmacologic were excluded.

"Reports of naltrexone use, the theories behind its efficacy, and thus far its low number of adverse effects are highly valued," the researchers concluded. "Future reporting is needed to determine appropriate conditions, dosing regimens, and long-term risks."