Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions

Abstract

IMPORTANCEDermatology 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 RELEVANCEThe 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.

Mechanisms and Management of Itch in Dry Skin

“…Dry skin-related itch in animal models was suppressed by μ-opioid receptor antagonists (26) and κ-opioid receptor agonists (85). Clinically, μ-opioid receptor antagonists and κ-opioid receptor agonists were found to inhibit itch in dry skin-related cutaneous or systemic diseases (106,107). Nalbuphine is a synthetic opioid analgesic, a mix of κ-opioid receptors agonist-μ-opioid receptors antagonist, clinically indicated for moderate to severe pain (108).…”

Use of low‐dose naltrexone in the treatment of severe Hailey–Hailey disease: One case report

“…Naltrexone is an opioid receptor antagonist approved by the UD Food and Drug Administration for the treatment of alcohol, heroin, and opioid addiction. LDN has been recently reported effective in three inflammatory skin diseases: HHD, lichen planopilaris, and scleroderma (Ekelem, Juhasz, Khera, & Mesinkovska, 2018).…”

“…These have effects on pain modulation and mood. Moreover, it has been proved that naloxone inhibits histamine release from basophils causing pruritus relief (Ekelem et al, 2018). LDN may also exert an anti-inflammatory action through its antagonist effect on toll-like receptor 4 found on macrophages such as microglia, decreasing the central production of proinflammatory cytokines: substance P, reactive oxygen species, and excitatory amino acids (Ibrahim, Hogan, Vij, & Fernandez, 2017).…”

Update on pharmacotherapy in psychodermatological disorders

“…[ 72 ] A systematic review evaluating 22 RCTs, case series, and reports for the utility of naltrexone in dermatology found it to be effective in intractable pruritus associated with inflammatory diseases. [ 73 ] Low dose naltrexone (1.5–4.5 mg/day) was more effective as an anti-inflammatory agent in dermatology than high dose naltrexone (12.5–50 mg/day). [ 73 ] A meta-analysis of RCTs on naltrexone in the treatment of broadly defined behavioral addictions, which included TTM and skin picking showed a beneficial effect.…”

“…[ 73 ] Low dose naltrexone (1.5–4.5 mg/day) was more effective as an anti-inflammatory agent in dermatology than high dose naltrexone (12.5–50 mg/day). [ 73 ] A meta-analysis of RCTs on naltrexone in the treatment of broadly defined behavioral addictions, which included TTM and skin picking showed a beneficial effect. [ 74 ] Dose adjustment is warranted in moderate to severe renal failure, and it is contraindicated in severe hepatic failure.…”