Low-Dose Naltrexone Treatment of Familial Benign Pemphigus (Hailey-Hailey Disease)

Abstract

amilial benign pemphigus, or Hailey-Hailey disease (HHD), is a rare autosomal dominant genetic dermatosis characterized by chronic, recurrent vesicles, erosions, and maceration in flexural areas. It results from mutations in the ATP2C1 gene (UniProt P98194) that lead to defective calcium homeostasis in the Golgi apparatus and ultimately loss of adhesion between keratinocytes. 1 Hailey-Hailey disease is often challenging to treat. Herein, we present a novel treatment option for HHD. MethodsPatients with biopsy-proven recalcitrant HHD were evaluated in the outpatient dermatology clinic at the Cleveland Clinic and treated with low-dose naltrexone hydrochloride (1.5-3.0 mg/d).Because reported dosages in the literature for low-dose naltrexone hydrochloride range from 1.5 to 4.5 mg per day, 1,2 patients were started on 1.5 mg/d and titrated monthly as needed; concomitant topical and systemic medications were ceased. The same physician (one of us, A.P.F.) administered all treatments to all patients and assessed response. Patients were followed up every 2 to 3 months. Clinical response, adverse effects, and subjective quality of life were monitored throughout the treatment. The study dates were January 2016 to January 2017. Because no standardized rating scale exists for HHD to date, response was judged and quantified by taking into account healing of areas of cutaneous breakdown, improvement in erythema, and decrease in patients' reported symptoms or pain and discomfort. No laboratory monitoring was necessary.The department of dermatology determined that institutional review board approval was not necessary for the IMPORTANCE Familial benign pemphigus, or Hailey-Hailey disease (HHD), is a rare and debilitating genetic dermatosis characterized by chronic, recurrent vesicles, erosions, and maceration in flexural areas. Despite the reported therapeutic modalities, such as topical and systemic corticosteroids, systemic immunomodulators, topical and systemic retinoids, and laser, HHD can still be markedly difficult to control. OBJECTIVE To assess low-dose naltrexone hydrochloride in the treatment of recalcitrant HHD. DESIGN, SETTING, AND PARTICIPANTSIn this case series, 3 patients with biopsy-proven recalcitrant HHD were evaluated in the outpatient dermatology clinic at the Cleveland Clinic. Each patient was treated with low-dose naltrexone hydrochloride at a dosage of 1.5 to 3.0 mg per day. No laboratory monitoring was necessary. Clinical response (healing of erosions, improvement in erythema, and alleviation of pain), adverse effects, and subjective quality of life were monitored throughout the treatment. The study dates were January 2016 to January 2017. MAIN OUTCOMES AND MEASURESObjective clinical response as assessed by the treating dermatologist, subjective quality of life as reported by the patient, and recorded adverse effects were monitored throughout the treatment at intervals of 2 to 3 months. RESULTSThe 3 patients included a woman in her 40s and 2 men in their 60s. Each patient exhibited at least an 80% improveme...

Variable response to low‐dose naltrexone in patients with Darier disease: a case series

“…Previously, however, several studies reported success with lowdose naltrexone in treating refractory patients with Hailey-Hailey disease. [6][7][8][9] This prompted us to evaluate low-dose naltrexone (LDN) as a treatment option in Darier disease. The dosage in the published cases was very heterogeneous ranging from 3.5 to 50 mg. As LDN is dosed at 5 mg [p.o.]…”

Use of low‐dose naltrexone in the treatment of severe Hailey–Hailey disease: One case report

“…Three to fifty millgrams doses have been safely reported for an adequate response (Cao, Lilly, & Chen, ; Ibrahim et al, ), to our knowledge this is the first case treated with naltrexone 6.25 mg per day. If required, adjunctive agents such as acitretin and systemic antibiotics could be added (Cao et al, ; Kollman & Bass, ).…”

“…Three to fifty millgrams doses have been safely reported for an adequate response (Cao, Lilly, & Chen, 2018;Ibrahim et al, 2017), to our knowledge this is the first case treated with naltrexone 6.25 mg per day. If required, adjunctive agents such as acitretin and systemic F I G U R E 1 Erythematous, fissured, macerated, symmetrical, and well-defined plaques were found involving both axillae F I G U R E 2 Three weeks after, erosions began to heal and improvement of erythema was observed F I G U R E 3 Complete resolution of the lesions 8 months after initiating treatment with low-dose naltrexone…”

“…Moreover, it has been proved that naloxone inhibits histamine release from basophils causing pruritus relief (Ekelem et al, 2018). LDN may also exert an anti-inflammatory action through its antagonist effect on toll-like receptor 4 found on macrophages such as microglia, decreasing the central production of proinflammatory cytokines: substance P, reactive oxygen species, and excitatory amino acids (Ibrahim, Hogan, Vij, & Fernandez, 2017).…”

“…Low-dose naltrexone has been used in multiple diseases and its safety has been established. Patients may experience minor adverse effects, such as headache, gastrointestinal tract symptoms, and vivid dreams (Ibrahim et al, 2017). Contraindications for its use include opiate addiction, acute hepatitis, or liver failure (Campbell, McGrath, & Corry, 2018).…”