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Low-dose naltrexone as treatment for epidermolysis bullosa pruriginosa-associated refractory pruritus
Case Reports; JAAD Case Rep
19 June 2023
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339115/
A rare subtype of epidermolysis bullosa, epidermolysis bullosa pruriginosa (EBP) is characterized by severely pruritic lichenified and hypertrophic prurigo-like nodules and plaques secondary to chronic itching. No standard first-line therapy currently exists. Reported is a case of EBP pruritus which could not be managed with dupilumab, due to persistent pruritus and intolerable side effects, subsequently successfully treated with low-dose naltrexone.
Naltrexone, an opioid antagonist, is an alternative therapy that has gained increased use in dermatology. Opioid receptors, particularly the μ-opioid receptor, are found throughout the skin affecting various aspects of cell adhesion, migration, and proliferation. Naltrexone exerts a dual effect through blockade of morphine-induced itch via the μ-opioid receptor, while also reducing inflammatory mediators including tumor necrosis factor-α, interleukin 6, and nitric oxide. Prior studies have demonstrated that naltrexone yields symptomatic improvement of pruritus associated with atopic dermatitis, psoriasis, systemic sclerosis, lichen planopilaris, benign chronic pemphigus (Hailey-Hailey disease), and even nondermatologic conditions including cholestasis.
Low doses of naltrexone (1-5 mg) bind opioid receptors intermittently, increasing expression of both ligands and receptors to restore neuroepidermal homeostasis. Therefore, intermittent binding of low-dose naltrexone may potentiate its efficacy in reducing pruritus.
Low-dose naltrexone may be used as a relatively inexpensive therapy that is very well-tolerated with a minimal risk profile. Further studies may evaluate the effect of low-dose naltrexone when used in conjunction with other therapeutics, such as JAK inhibitors,6 for improved symptomatic and clinical management of EBP-associated pruritus.
Keywords: COL7A1; blistering disorders; dupilumab; epidermolysis bullosa pruriginosa; naltrexone; pruritus.