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Brief Report
October 2017

Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone

Author Affiliations
  • 1Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia
  • 2Atlanta Veterans Administration Medical Center, Decatur, Georgia
JAMA Dermatol. 2017;153(10):1018-1020. doi:10.1001/jamadermatol.2017.2446
Key Points

Question  Can low-dose naltrexone be used to successfully treat Hailey-Hailey disease?

Findings  In this case series of 3 patients with severe Hailey-Hailey disease recalcitrant to multiple therapies, treatment with low-dose naltrexone at 3 mg and, in 2 of the patients, titrated to 4.5 mg nightly, was attempted and resulted in clinical resolution within 2 months. Lesions flared when stopping low-dose naltrexone and cleared within a few days on rechallenge.

Meaning  The success of these cases of Hailey-Hailey disease treated with low-dose naltrexone along with the medication’s low adverse effect profile suggest low-dose naltrexone as a novel therapy for Hailey-Hailey disease.

Abstract

Importance  Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects.

Objective  To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease.

Design, Setting, and Participants  This study was a case series performed at a dermatology outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to at least 4 therapies.

Interventions  Low-dose naltrexone, 3 mg nightly, titrated to 4.5 mg nightly in 2 patients.

Main Outcomes and Measures  Reduction in size of lesions as well as subjective improvement of symptoms.

Results  All 3 patients noted significant healing of erosions and plaques starting from the peripheral aspect within 1 to 2 weeks of treatment, and clinical resolution of lesions within 2 months. Discontinuation of low-dose naltrexone resulted in flaring of symptoms, which cleared within 2 to 3 days on rechallenge with low-dose naltrexone.

Conclusions and Relevance  We present herein 3 cases of patients with severe Hailey-Hailey disease treated with low-dose naltrexone who achieved clinical resolution of symptoms. The success of these cases suggests low-dose naltrexone as a novel therapy for Hailey-Hailey disease. The possible mechanism may involve low-dose naltrexone influencing opioid or toll-like receptor signaling to improve calcium mobilization and improve keratinocyte differentiation and wound healing. Future studies are needed to clarify the mechanism and to define the role of low-dose naltrexone for treatment of Hailey-Hailey disease.

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