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Indian Dermatol Online J. 2019 Aug 28;10(5):567-570. doi: 10.4103/idoj.IDOJ_453_18. eCollection 2019 Sep-Oct.

Low-Dose Naltrexone-Induced Remission in Hailey-Hailey Disease Maintained in Remission with Topical Combination of Ketamine and Diphenhydramine.

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Department of Dermatology and Dermatosurgery, Skinnocence: The Skin Clinic and Research Centre, Gurugram, Haryana, India.
Department of Dermatology and STD, LHMC and Associated Hospitals, New Delhi, India.
Department of Dermatology and STD, HIMS Institute, Safedabad, Uttar Pradesh, India.
Department of Dermatology, Mazandaran University of Medical Sciences, Sari, Iran.


Recent anecdotal evidence suggests that oral low-dose naltrexone (LDN) is effective for Hailey-Hailey disease (HHD) but suffers the limitation of immediate relapse following cessation of the medication. With lack of safety data on long-term administration of LDN, we explored the utility of a topical diphenhydramine/ketamine (DK) cream in maintaining the remission achieved with LDN. A 42-year-old male with treatment-refractory HHD remitted with 5 mg naltrexone/day but relapsed on stopping the drug. Symptoms abated after restarting LDN. The impact of regular twice-a-day application of a specially formulated DK cream containing diphenhydramine (2% w/w) and ketamine (1% w/w) over the affected areas on maintenance of remission was explored till the next relapse. Our approach enabled dose reduction of naltrexone to 3 mg/day without loss of treatment benefit. After 3-month overlap of naltrexone and DK cream, withdrawal of naltrexone maintained remission with only the topical regime with no adverse effects till 4 months of follow-up. The use of topical agents with anti-inflammatory, antipruritic, antinociceptive, and naltrexone-mimicking properties merits exploration as an option to provide short but significant period of naltrexone-free maintenance of remission to patients with HHD.


Benign familial pemphigus; Hailey–Hailey disease; diphenhydramine; ketamine; low-dose opioid; naltrexone

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