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Hailey Hailey Disease Low Dose Naltrexone (LDN)

Hailey-Hailey Disease (HHD), also known as chronic benign familial pemphigus, is a rare (prevalence of 1 in 50,000) autosomal dominant genodermatosis characterized by painful vesicles and skin erosions primarily affecting the neck, axillae, and groin regions. 

There is currently no ability to cure HDD, with only limited, largely supportive treatment protocols available.  Antibiotics, antifungal agents, as well as systemic, topical and intralesional corticosteroids have been found to be useful in the management of HHD symptoms, as well as CO lasers in the treatment of recalcitrant plaques.

Two recent case studies have reported remarkable results involving 4 patients with intractable Hailey-Hailey disease, each given LDN as a solo treatment.  The first patient reported a dramatic improvement in clinical status, with a highly significant decrease in the adverse life quality index for dermatology patients from a level of 29 to 4 over the course of only seven months, in a patient previously unresponsive to all traditional treatment protocols.  The second case report described three patients who saw a greater than 80% reduction in the extent of their disease after only 3 months of LDN only therapy.  The frequency of flare-ups was dramatic, along with no adverse effects having been noted.

A third case report in April, 2019, described a 66 year old women with a 35 year history of pruritic recurring vesicles and erosions in both axillae and inguinal folds who had failed all traditional therapies including opical corticosteroids, antibiotics.  Phototherapy and even oral botulinum A therapy were attempted and failed as well.   6.25mg LDN nightly was initiated, with complete clearing observed 6 weeks later.  

Finally the 4th case study involved 3 additional patients, each recalcitrant to all therapies, beginning treatment of LDN with 3mg up to 4.5mg nightly.  Each obtained clinical resolution within 2 months. Interestingly upon stopping LDN therapies the patients would experience a flare of their symptoms, which would clear upon re-initiation of LDN.

The authors of the initial studies reported their recommendation that low-dose naltrexone may represent a low-cost and low-risk alternative or adjunct in the treatment of Hailey-Hailey disease.  The authors of the third case study state that "LDN is an effective and safe alternative for Hailey Hailey Disease, representing an important progress in the management of this disease with limited therapeutic options." The authors of the 4th study concluded that the success their patients enjoyed using LDN suggested that LDN represents a novel, highly effective treatment protocol for Hailey-Hailey disease.

"Low-Dose Naltrexone: A Novel Treatment for Hailey--Hailey Disease" (2018)

V Campbell, MD, C McGrath, MD
https://www.ncbi.nlm.nih.gov/pubmed/28991360 

"Low-Dose Naltrexone Treatment of Familial Benign Permphigus (Hailey-Hailey Disease)" (2017)

Omer Ibrahim, MD, Sara Hogan, MD
JAMA Dermatology  
Cleveland Clinic Foundation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817587

"Use of Low-Dose Naltrexone in the Treatment of Severe Hailey-Hailey Disease: One Case Report" (2019) 

Garagyay Cantero, MD, Canseco Martin, MD
https://www.ncbi.nlm.nih.gov/pubmed/30958613

"Treatment of Haily-Hailey Disease with Low-Dose Naltrexone" (2017)

Lauren Albers, BA, Jack ARviser, MD, PhD.
JAMA Dermatology
Emory University School of Medicine
https://www.ncbi.nlm.nih.gov/pubmed/28768313

Written by David Yeazel, MS, MPH