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November 28, 2018

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review

Author Affiliations
  • 1Department of Dermatology, University of California, Irvine
  • 2Department of Dermatology, Howard University Hospital, Washington, DC
JAMA Dermatol. 2019;155(2):229-236. doi:10.1001/jamadermatol.2018.4093
Key Points

Question  What are the dermatologic uses for naltrexone?

Findings  In this systematic review of 22 articles, naltrexone was used in low doses to treat lichen planopilarus, Hailey-Hailey disease, and pruritus associated with scleroderma. Naltrexone was used in high doses to treat pruritus of various systemic and cutaneous diseases.

Meaning  Naltrexone, particularly in low doses, has the potential for treating chronic inflammatory conditions of the skin; however, additional information about dosing and long-term treatment guidelines are needed.


Importance  Dermatology is encountering increasing rates of autoimmune disease manifesting in primary skin conditions that are difficult to treat without a risk of immunosuppression. Naltrexone is an orally active opioid antagonist that influences a variety of systemic pathways, including the immune system, in low doses of 1.5 to 4.0 mg/d. This phenomenon has piqued the interest of researchers and practitioners in regard to low-dose naltrexone’s potential in the treatment of several autoimmune conditions.

Objective  To review the existing literature on naltrexone treatment for dermatologic conditions.

Evidence Review  A primary literature search was conducted using PubMed in April 2018 for all articles published from 1971 to April 2018. Search terms consisted of naltrexone or low dose naltrexone or low-dose naltrexone and dermatology or skin or hair or nails. Reviews, animal studies, and nondermatologic and pharmacologic studies were excluded.

Findings  From 1037 articles, 22 were deemed to be appropriate for inclusion in this review for a qualitative synthesis. The 22 articles included randomized clinical trials, case reports, and series. There were 7 articles on low-dose naltexone, 1 on topical naltrexone, and 14 on high-dose naltrexone use in dermatology. In high, low, and topical doses, naltrexone was effective in treating pruritus attributable to atopic dermatitis, prurigo nodularis, cholestatsis, burn injury, systemic sclerosis, Hailey-Hailey disease, and lichen planopilaris. High-dose naltrexone was ineffective in treating flushing and uremic pruritus most likely because of the lack of opioid involvement in the pathophysiologic mechanisms of these conditions.

Conclusions and Relevance  The findings suggest that low-dose naltrexone is safe and effective in the treatment of Hailey-Hailey disease and lichen planopilaris and both low- and high-dose naltrexone successfully treat pruritus attributable to various pathologic conditions; however, more adverse effects occurred in those taking high doses. Low-dose naltrexone has the potential for the treatment of chronic inflammatory skin conditions; however, additional evidence is needed for dosing and long-term treatment guidelines.

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