Hailey-Hailey Disease and Review of Management
October 2014 | Volume 13 | Issue 10 | Original Article | 1254 | Copyright © October 2014
Anthony Chiaravalloti MDa and Michael Payette MD MBAb
aSUNY Upstate Medical University Syracuse, NY
bUniversity of Connecticut Farmington, CT
IMPORTANCE: Hailey-Hailey disease, or familial benign chronic pemphigus, is a rare genodermatosis that can be challenging for both patients and dermatologists as the disease can significantly impact patients’ quality of life and is often difficult to control. In recalcitrant cases, multiple treatment modalities are often needed to obtain benefit. Unfortunately, most of the available evidence pertaining to treatment is scattered across case reports and retrospective analyses.
OBJECTIVE: To review successful treatments of Hailey-Hailey, synthesize the evidence, and provide recommendations for therapy.
Findings: The best evidence exists for treatment with topical steroids and topical antimicrobials. Refractory disease has shown the most benefit with addition of oral antibiotics, excisional procedures and botulinum toxin A. Other therapies are described but with much less supporting evidence.
CONCLUSIONS: Herein we review the literature to identify successful treatments for Hailey-Hailey disease. We have outlined the treatments with the most evidence. The difficult nature of treating this disease requires that clinicians approach each patient differently. The literature shows that no one regiment works for all patients. J Drugs Dermatol
Hailey-Hailey disease, or familial benign chronic pemphigus was first described by the Hailey brothers in 1939. It is a rare genodermatosis inherited in an autosomal dominant manner with variable expressivity. The incidence has been estimated at 1/50,0001 with equal predilection for males and females.2 The actual prevalence is likely higher due to mislabeling of the diagnosis and patients not seeking treatment for milder variants.2 The disease is not usually clinically apparent until the second-fourth decades of life highlighting the importance of environmental factors1.
Hailey-Hailey results from a mutation of the ATP2C1 gene1 which encodes a calcium- dependent ATPase (hSPCA1).1 Numerous types of mutations in varying locations have been reported showing there is no universal mutation or location in the gene that causes this disease.1 This protein functions to regulate the sequestration of calcium in Golgi apparatuses.1 Although the hSPCA1 protein is ubiquitous throughout the body, the human keratinocyte has been shown to be especially dependent on it for its calcium homeostasis compared with other human cells.1 This deregulation of calcium metabolism causes impaired desmosome function leading to acantholysis of the suprabasilar epidermis in skin.1
Classic clinical features consist of vesicles, erosions, weeping plaques, fissures, and scale crust symmetrically distributed in intertriginous areas, with the most common areas being the axillae, groin, neck, inframammary folds and perineum.1,2 Rare variants with mucosal or vulvar involvement have also been reported, as have unusual variants due to somatic mutations that present with unilateral or linear distributions.1,2 Up to 71% of patients also have asymptomatic linear, white bands in the nail plates. This has been the presenting feature in many cases.1,2 Patients usually present with itching, pain and a malodorous smell from secondary polymicrobial infection with different species of bacteria and fungi.2 These symptoms can be debilitating and often interfere with physical activity, employment and acts of intimacy. Symptoms are commonly reported to be exacerbated by sweat, heat, friction from clothes and minor trauma. 1-3 The natural progression of the disease is characterized by a chronic waxing and waning course that dramatically affects quality of life.2 Long term, these patients may have an increased risk of squamous cell carcinoma.4,5
The diagnosis is made clinically and confirmed with histologic exam. Characteristic pathologic features include intraepidermal vesicles and bullae with suprabasalar acantholysis.6 This has been likened to a “dilapidated brick wall.”1 There can be mild dyskeratosis and neutrophils can be found within the vesicles. The dermis is relatively normal, though sometimes it shows a mild lymphocytic perivascular inflammatory infiltrate.6 DIF should be negative and should not show any linear complement or immunoglobulin, findings that can differentiate Hailey-Hailey from other intraepidermal blistering disorders.1-3,6
Hailey-Hailey is a difficult disease for patients and for physicians. Patients are discouraged by the frequent flares and debilitating morbidity while physicians struggle with refractory cases. The difficulty of treating recalcitrant disease is evidenced by the wide spectrum of treatments reported. A literature search was conducted to collect evidence-based data on the treatment of