Double-Blind, Placebo-Controlled Study of Onabotulinumtoxin A for the Treatment of Hailey-Hailey Disease

April 2023 | Volume 22 | Issue 4 | 339 | Copyright © April 2023


Published online March 21, 2023

Ryan Saal BSa, Charlene Oldfield MDa, James Bota MDa, Robert Pariser MDb, David Pariser MDb

aEastern Virginia Medical School, Norfolk, VA
bDepartment of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA

Abstract
Background: Hailey-Hailey disease (HHD) can be treated with topical steroids, antibiotics, and invasive surgical procedures. Since sweating often exacerbates HHD lesions, the use of onabotulinumtoxin A could serve as an adjunctive treatment.
Objective: The goal of this study was to evaluate the safety and efficacy of onabotulinumtoxin A for the treatment of HHD.
Methods: A double-blind, placebo-controlled single center study was conducted. Six HHD patients who successfully completed this trial in addition to 1 patient who exited early are reported and discussed. Four of these patients received an initial injection of Btx-A and 3 received the placebo initially.
Results: All patients except 1 who received an initial or reinjection of Btx-A decreased 2 levels on a 4-point clinical severity scale at weeks 8 or 12 after treatment. Patient 6 received an initial placebo injection and maintained clearance for 6 months, while patients 5 and 7 did not have any improvement in their target lesions after a placebo injection. All patients who received a reinjection of Btx-A at the week 4 follow-up decreased by at least 1 level on the HHD severity scale.
Conclusion: Btx-A is a safe treatment that is effective for most cases of HHD. The most severe cases of HHD may not respond to Btx-A as sole treatment.

J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6857

Citation: Saal R, Oldfield C, Bota J, et al. Double-blind, placebo-controlled study of Onabotulinumtoxin A for the treatment of Hailey-Hailey disease. J Drugs Dermatol. 2023;22(4):339-343. doi:10.36849/JDD.6857

INTRODUCTION

Hzailey-Hailey disease (HHD), or benign familial pemphigus, is an uncommon blistering disorder that presents as recurrent vesicles and erosions. These lesions often appear in the third to fourth decade of life,1 mostly in the axillae, neck, groin, or inframammary folds, where sweat, moisture, and friction likely play important roles in the development of the disease.2 The condition is typically worse in the summer.3 In affected individuals, skin trauma, bacterial infections, fungal infections, or sunburn may trigger lesions. HHD is an autosomal dominant disease due to mutation in a calcium ATPase (ATP2C1) on chromosome 3q21.3 This disease has variable penetrance, with 70% of patients showing a definite family history.2

Treatments for HHD include nonsurgical approaches such as topical4 and oral antimicrobial agents, topical antifungals, short courses of topical and oral corticosteroids,5 oral retinoids,6 methotrexate, dapsone, and cyclosporine.7 In addition, surgical methods have been used for the treatment of HHD. These treatments include surgical excision with healing by secondary intent,8 primary closure,9 grafting,10-12 dermabrasion,13-14 CO2 laser vaporization,15-18 and Er:YAG laser ablation.19

Onabotulinumtoxin A (Botox® Allergan) is a purified neurotoxin. Several published case reports have supported the use of onabotulinumtoxin A in treatment of HHD.1,20-23 This 6-month randomized, double-blind, placebo-controlled cross-over study was designed to test the hypothesis that treatment with onabotulinumtoxin A (BtxA) is safe and effective for subjects with HHD in individuals aged 12 years and older.

MATERIALS AND METHODS

This was a single-center study, registered with clinicaltrials.gov (ID:100817). Enrolled patients had biopsy-proven HHD and/or a compelling family history of HHD. Patients were also at least 12 years of age and had a negative pregnancy test, if applicable, prior to injection. All treatments for HHD were discontinued for at least 14 days before their initial injection. After randomization, patients were treated with the placebo (saline) or Btx-A on day 1. Injections were prepared by a blinded third party. The investigator was blinded as to which study drug the subject received. Patients were seen for in-office visits at weeks 4, 8, 12, and at any point between week 12 and month 6 for relapse of the disease. If the subject did not achieve improvement of HHD by week 4, they were deemed to be non-responders and
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