Unmet Needs in Darier's Disease from a Patient's Perspective: Lessons Learnt from the German Registry.

The MDHHgermany registry was initiated to characterize the "real-life" situation of affected individuals with Darier's disease (DD; Morbus Darier, MD) and Hailey-Hailey disease (HH), including their treatment and healthcare. To gain deeper insights into medical care of patients with DD, various aspects such as demographics, subjective symptoms, patient satisfaction with medical care, past and current therapies were explored. Patients with diagnosed DD were included. Subjective symptoms such as itch, pain and burning sensation were assessed. Individual therapy goals were recorded and patients assessed previous/current therapies along with satisfaction of medical care and treatment. A total of 55 patients were recruited; 47 patients were eligible for the analysis. Pruritus was rated the most bothersome symptom. Some 42.6% had not received systemic treatment so far or systemic therapies were rated ineffective (32.6%). Most commonly oral retinoids were prescribed, followed by corticosteroids. Patient satisfaction with medical care and treatment proved to be mediocre. This "real-life" data show an alarming unmet need regarding patients' satisfaction with medical care and treatment, evidenced by the reported lack of disease control. Further studies and interventions are needed to improve the spectrum of available therapies. MDHHgermany provides a foundational platform for future clinical trials, epidemiological studies, and pathophysiological analyses.

Patients' perspective, quality of life and treatment goals in Hailey-Hailey disease: Lessons learned from the German National Registry.

BACKGROUND: Hailey-Hailey disease (HHD) remains a difficult-to-treat dermatosis and little is known about the patient's perception of the disease activity, the treatment success and its impact on quality-of-life (QoL). OBJECTIVE: To obtain better understanding of HHD patients' needs regarding their medical condition, financial burden, QoL, subjective well-being and treatment thereof as well as satisfaction to evaluate common treatments' 'real-life' relevance. METHODS: With initiation of the national registry for Darier's disease (DD; Morbus Darier, MD) and Hailey-Hailey disease (HH) MDHHgermany, patients with HHD diagnosis were included starting June 2020. To assess subjective symptoms, patients filled out questionnaires such as the DLQI (dermatological life quality index), numeric rating scale (NRS) for itch, pain and burning sensation, as well as the SWLS (satisfaction with life scale) questionnaire to quantify overall satisfaction in life. Additionally, data on therapies were collected along with the patients' satisfaction of those and their medical care. Furthermore, patients assessed financial aspects and work ability. RESULTS: One hundred and two patients were recruited from dermatology clinics, office-based dermatologists and self-help platforms across Germany between June 2020 and February 2023, 90 were eligible and analysed (mean: 49.91 years, 73.33% females, 26.67% males). 39.77% stated according to the DLQI their life is severely/very severely affected. Satisfaction with life was mediocre. Burning sensation was most pronounced among subjective symptoms (NRS 5.85 ± 2.80). Systemic treatments were rated as ineffective according to 56.92%, 25.56% had never received one. Most prescribed systemic treatments were corticosteroids (73.8%), followed by low-dose naltrexone (LDN) (26.2%), retinoids (15.4%) and antibiotics (13.8%). Satisfaction with medical care was generally low. CONCLUSION: Our 'real-life' data state a major disease burden and impact on the QoL for affected individuals, as well as limited disease control due to inadequate therapies. MDHHgermany can provide insights into improvement of healthcare support with this debilitating disease and improve QoL. In the long term, it aims to provide basis for further clinical trials, epidemiological studies and immunological investigations.

Generalized Hailey-Hailey disease associated with c.2395C>T ATP2C1 gene mutation and fatal outcome.

Hailey-Hailey disease (HHD) is a rare, autosomal dominant genodermatosis caused by a mutation of the ATP2C1 gene and presenting as an erosive dermatosis, particularly in the intertriginous areas. Generalized HHD is a rare variant. We present a case of widespread, recalcitrant HHD in a middle-aged woman with a fatal outcome. No other underlying dermatosis was identified, with the possible exception of drug sensitivity to carbamazepine. Diagnosis of HHD was confirmed by histology and genetic studies which showed a c.2395C>T mutation in the ATP2C1 gene. Concurrent pemphigus was excluded. Cases of generalized HHD are extremely rare and present a challenge in diagnosis and management. Increased awareness of this severe clinical variant is needed to improve quality of care for patients with this form of HHD.

Loss of ATP2C1 function promotes trafficking and degradation of NOTCH1: Implications for Hailey-Hailey disease.

Hailey-Hailey disease (HHD) is a rare autosomal dominantly inherited disorder caused by mutations in the ATP2C1 gene that encodes an adenosine triphosphate (ATP)-powered calcium channel pump. HHD is characterized by impaired epidermal cell-to-cell adhesion and defective keratinocyte growth/differentiation. The mechanism by which mutant ATP2C1 causes HHD is unknown and current treatments for affected individuals do not address the underlying defects and are ineffective. Notch signalling is a direct determinant of keratinocyte growth and differentiation. We found that loss of ATP2C1 leads to impaired Notch1 signalling, thus deregulation of the Notch signalling response is therefore likely to contribute to HHD manifestation. NOTCH1 is a transmembrane receptor and upon ligand binding, the intracellular domain (NICD) translocates to the nucleus activating its target genes. In the context of HHD, we found that loss of ATP2C1 function promotes upregulation of the active NOTCH1 protein (NICD-Val1744). Here, deeply exploring this aspect, we observed that NOTCH1 activation is not associated with the transcriptional enhancement of its targets. Moreover, in agreement with these results, we found a cytoplasmic localization of NICD-Val1744. We have also observed that ATP2C1-loss is associated with the degradation of NICD-Val1744 through the lysosomal/proteasome pathway. These results show that ATP2C1-loss could promote a mechanism by which NOTCH1 is endocytosed and degraded by the cell membrane. The deregulation of this phenomenon, finely regulated in physiological conditions, could in HHD lead to the deregulation of NOTCH1 with alteration of skin homeostasis and disease manifestation.

Acute generalized exanthematous pustulosis associated with clindamycin in a patient with Hailey-Hailey disease.

A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.

Hailey-Hailey Disease is Associated with Diabetes: A Population-based Cohort Study, Clinical Cohort Study, and Pedigree Analysis.

Hailey-Hailey disease is a rare hereditary skin disease caused by mutations in the ATP2C1 gene encoding the secretory pathway Ca2+/Mn2+-ATPase 1 (SPCA1) protein. Extracutaneous manifestations of Hailey-Hailey disease are plausible but still largely unknown. The aim of this study was to explore the association between Hailey-Hailey disease and diabetes. A population-based cohort study of 347 individuals with Hailey-Hailey  disease was performed to assess the risks of type 1  diabetes and type 2 diabetes, using Swedish nationwide registries. Pedigrees from 2 Swedish families with Hailey-Hailey disease were also investigated: 1 with concurrent type 1 diabetes and HLA-DQ3, the other with type 2 diabetes. Lastly, a clinical cohort with 23 individuals with Hailey-Hailey disease and matched healthy controls was evaluated regarding diabetes. In the register data males with Hailey-Hailey disease had a 70% elevated risk of type 2 diabetes, whereas no  excess risk among women could be confirmed. In both pedigrees an unusually high inheritance for diabetes was observed. In the clinical cohort, individuals with Hailey-Hailey disease displayed a metabolic phenotype indicative of type 2 diabetes. Hailey-Hailey disease seems to act as a synergistic risk factor for diabetes. This study indicates, for the first time, an association between Hailey-Hailey disease and diabetes and represents human evidence that SPCA1 and the Golgi apparatus may be implicated in diabetes pathophysiology.

Interleukin-17A immune pattern across genetic acantholytic and blistering disorders.

There is a high therapeutic need in acantholytic and blistering genodermatoses. Cutaneous inflammation is a reasonable therapeutic target, although the patterns are not yet fully elucidated. Here we investigated by immunohistochemistry whether interleukin (IL)-17A is expressed in the inflammatory infiltrate in 34 patients with Hailey-Hailey disease, Darier disease, and junctional and dystrophic epidermolysis bullosa. There was a 5-7-fold increase in the number of IL-17A-positive cells in all patients' samples as compared with normal skin. IL-17A cells were present in epidermal acantholytic areas and dermal inflammatory infiltrates in Hailey-Hailey and Darier disease. In epidermolysis bullosa samples, positive cells were present at the dermoepidermal junction zone. The IL-17A inflammatory pattern was validated by observing upregulation of downstream genes/proteins, S100A7, S100A8 and S100A9 (S100 calcium-binding proteins). These results suggest that IL-17A contributes to skin inflammation and could be a therapeutic target during inflammatory flares in these disorders.

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

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.

Dupilumab in the treatment of genodermatosis: A systematic review.

Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper-IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including "dupilumab," "genodermatosis", "Netherton syndrome", "ichthyosis", "epidermolysis bullosa" and "hyper-IgE syndrome". The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with some genetic disorders.

Weak immunohistochemical expression of galectin-3 near blisters in Hailey-Hailey disease.

BACKGROUND: Hailey-Hailey disease (HHD) is an uncommon hereditary and benign skin condition characterized by blisters and erosions on intertriginous areas. It is related to a mutation of the ATP2C1 gene, which encodes a Ca2+ pump. It is characterized by multiple foci of skin acantholysis in the epidermis, with dyskeratosis and suprabasilar clefting. Galectin-3 is a beta-galactoside-binding protein that has an essential role in cell-to-cell and cell-to-matrix adhesion. We assessed galectin-3 immunohistochemical expression in HHD to explore its impact on the pathogenesis of this hereditary blistering disorder. METHOD: In a retrospective study, seven specimens from seven patients diagnosed with HHD were stained with antibodies to galectin-3. We evaluated the nuclear and cytoplasmic expression of galectin-3, as well as the staining intensity around blisters and distant normal skin. RESULTS: We observed a significant decrease in cytoplasmic and nuclear expression of galectin-3 as well as stain intensity around blisters compared with distant normal skin. CONCLUSIONS: While the acantholysis process in HHD is related to abnormality in cadherin expression caused by altered Ca2+ pump concentration, lower expression of galectin-3 may cause the extension of blisters by initiating cell-to-cell disassembly in the epidermis.

Sequential treatments of Hailey-Hailey disease with photodynamic therapy, botulinum toxin type A and dapsone: A case report.

Hailey-Hailey disease is a rare autosomal dominant chronic recalcitrant blistering genodermatosis involving the intertriginous areas. Therapeutic options are various, depending on the type and size of the lesion, and include topical and systemic corticosteroids, topical and systemic retinoids, and DMARDs, but the only true curative approach is represented by the destruction of the affected areas through different techniques like carbon dioxide laser, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A. We report a case of Hailey-Hailey disease successfully treated with a consequential regimen of PDT, botulinum toxin type A and dapsone.

Subcellular compartmentalization of STIM1 for the distinction of Darier disease from Hailey-Hailey disease.

BACKGROUND AND OBJECTIVES: Darier disease (DD) and Hailey-Hailey disease (HHD) are rare disorders caused by mutations in the ATPase, Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2 (ATP2A2) and ATPase Ca2+ Transporting Type 2C, Member 1 (ATP2C1) gene, respectively, which lead to a disturbance of calcium metabolism in keratinocytes. Clinically, this is reflected by an impairment of keratinization. Histologically, acantholysis with variable degrees of dyskeratosis and parakeratosis is observed. Both diseases can usually be differentiated clinically, histopathologically and genetically. However, their routine distinction might be challenging since some patients do not harbor ATP2A2 or ATP2C1 mutations. To solve this diagnostic challenge, we studied the differential expression of two proteins of store-operated calcium entry (SOCE), stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (ORAI1), by immunohistochemistry. PATIENTS AND METHODS: Five individuals with ambiguous diagnostic findings and eight controls with an unambiguous diagnosis were studied clinically, histologically, genetically, and by immunohistochemistry for STIM1 and ORAI1. RESULTS: DD patients consistently showed a cytoplasmic STIM1 expression while patients with HHD revealed a membrane-associated staining pattern. In contrast, ORAI1 did not show a differential expression pattern. CONCLUSIONS: Our data suggest subcellular compartmentalization of STIM1 as novel biomarker for the distinction of the two disorders.

Patients with Darier Disease Exhibit Cognitive Impairment while Patients with Hailey-Hailey Disease Do Not: An Experimental, Matched Case-control Study.

Darier disease and Hailey-Hailey disease are severe, monogenetic dermatological disorders with mutations affecting all cells, making them liable to exhibit extra-dermal symptoms. The aim of this study is to assess broad cognitive function in individuals with these diseases, using an experimental, case-control set-up comparing cognition in patients with that in healthy controls matched for age, sex and level of education. Cognition was assessed with the Cambridge Neuropsycho-logical Test Automated Battery. Patients with Darier disease (n = 29) performed significantly poorer on 5 of the 10 key cognitive measurements, while patients with Hailey-Hailey disease (n = 25) did not perform differently from controls. The main conclusion is that patients with Darier disease exhibit significant impairment in cognitive function, which reinforces the view that Darier disease should be regarded as a disorder affecting multiple organs, and should therefore be given medical consideration, and possibly treat-ment, as such.

Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination.

is missing (Short communication).

Darier and Hailey-Hailey disease: update 2021.

The autosomal-dominant genodermatoses Darier disease and Hailey-Hailey disease present special challenges to dermatologists. Despite their similar pathogenesis featuring impaired adhesion of suprabasal keratinocytes as a result of defective ATPases in epidermal calcium channels, the two diseases differ considerably in clinical presentation and therapeutic options. Darier disease is characterized by reddish brown, keratotic papules in seborrheic and intertriginous areas, which may coalesce into extensive lesions. Individuals affected with Hailey-Hailey disease primarily develop intertriginous papulovesicles and small blisters, which often evolve into erythematous plaques with erosions and painful fissures. Quality of life is significantly reduced because of complaints (itch, burning sensation, pain), body malodor and chronicity. Therapeutic options remain limited. Antiseptics and intermittent topical corticosteroids are a cornerstone of therapy, and systemic anti-infective treatment is often required in cases of superinfection. Ablative surgical interventions such as dermabrasion and CO2 laser surgery can lead to long-term remissions in intertriginous Hailey-Hailey disease, while temporary relief may also be achieved by intralesional injections of botulinum toxin. Of the systemic medications available for Darier disease, acitretin, which is approved for this purpose, has the best supporting evidence. The efficacy of immunosuppressants and immune modulators is inconsistent. Low-dose naltrexone produces more satisfactory results in Hailey-Hailey than Darier disease. The present CME article summarizes current knowledge of the two dermatoses, taking recent developments into account.

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease.

BACKGROUND: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKII proteins in the skin lesions of HHD patients. METHODS: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. RESULTS: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels. CONCLUSION: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKII levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

Mosaic variant in ATP2C1 presenting as relapsing linear acantholytic dermatosis.

Relapsing linear acantholytic dermatosis (RLAD) is a rare disease that manifests as recurring episodes of crusted and vesicular lesions distributed in a Blaschkoid pattern with histology resembling Hailey-Hailey disease. RLAD, in the presence of generalized disease, has been shown to be a type 2 mosaic form of Hailey-Hailey disease. RLAD, without systemic disease, has been hypothesized to be type 1 mosaic Hailey-Hailey disease, but this assertion has lacked genetic conformation. To determine the genetic abnormalities causing RLAD, we performed exome sequencing of affected tissue and blood in one patient. Exome sequencing of a punch biopsy revealed a c.238A>T, p.(Lys80*) variant in ATP2C1 found in 26% of the reads from lesional skin but absent in germline DNA. This somatic variant causes a truncated protein that would likely result in loss of function. Our findings indicate that, in this patient, RLAD is a clinical presentation of type 1 segmental Hailey-Hailey disease. What's already known about this topic? Relapsing linear acantholytic dermatosis (RLAD) is postulated to be a mosaic form of Hailey-Hailey disease. This hypothesis has remained unproven for type 1 disease and the putative gene and driving genetic variants have remained unknown. What does this study add? Exome sequencing, performed on lesional skin and matched blood, found RLAD lesions to be mosaic for variants causing a premature stop codon in ATP2C1. Our findings support the hypothesis that RLAD is a type 1 segmental form of Hailey-Hailey disease caused by postzygotic variants in ATP2C1.

An enhanced transcutaneous delivery of botulinum toxin for the treatment of Hailey-Hailey disease.

Successful treatment of Hailey-Hailey disease with intradermal botulinum toxin injections has been previously reported. The main disadvantages of this treatment are the excruciating pain and the risk of infections due to the numerous injections. We sought to evaluate the clinical effectiveness and safety profile of a novel approach using an energy-based device (Tixel, Novoxel, and Israel), followed by the topical application of botulinum toxin Type A for the treatment of Hailey-Hailey disease. A retrospective study of all cases of histologically diagnosed cases of Hailey-Hailey disease treated with Tixel device followed by topical application of botulinum toxin between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. The study included eight patients, of whom seven patients (87.5%) showed good or partial response. No systemic or local adverse effects were reported. There was no difference in effectivity between different body areas. Response to treatment ranged between patients with an average duration of 7.125 months after the second treatment. Tixel treatment followed by topical application of botulinum toxin can be considered in the treatment of Hailey-Hailey disease. This approach is less invasive, less painful, and yet effective as well as safe.

Incidental Acantholysis in Hailey-Hailey Disease (Microscopic Nikolsky Sign): An Underappreciated Histologic Sign.

Identification of subtle disease-specific histologic changes may be of significant help in early diagnosis of acantholytic skin diseases. Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis characterized by vesiculoerosive lesions favoring the intertriginous areas. Histologically, HHD is characterized by full-thickness acantholysis of the spinous layer in association with dyskeratosis of individual keratinocytes; a pemphigus vulgaris-like suprabasal pattern of acantholysis may be observed in the earliest stages of disease. HHD is characterized by highly variable expressivity regarding the age at onset and severity of the disease. Patients may present with late-onset and/or only mild disease. We report the recurrent presence of incidental foci of variably extensive, subclinical acantholysis in multiple bioptic specimens taken from a patient with known HHD for dermatologic conditions other than HHD. Such histologic finding has gone underappreciated in the literature, despite being a likely frequent occurrence in skin biopsies from HHD patients; recognition of this finding might represent a valuable diagnostic clue in selected cases of HHD.

Vulvar Hailey-Hailey disease treated with low-dose naltrexone: case report and literature review.

PURPOSE: To report a case of vulvar familial benign pemphigus, or Hailey-Hailey disease, treated successfully with low-dose naltrexone and to review the current literature. METHODS: We report a case of a 71-year-old white woman with vulvar Hailey-Hailey disease recalcitrant to topical corticosteroids. After treatment with low-dose naltrexone, 3 mg nightly was initiated, the lesions began to heal and 5 months later her skin showed no lesions. A literature review on the use of low-dose naltrexone for Hailey-Hailey disease was performed. We searched the PubMed/MEDLINE databases for previous case reports using the key words ''Pemphigus, Benign Familial'' and ''naltrexone". RESULTS: We found 35 more cases of Hailey-Hailey disease treated with naltrexone, showing promising results, reported until January 2020, with no major adverse effects. CONCLUSION: Low-dose naltrexone may represent a cost-effective and successful treatment modality in nongeneralized Hailey-Hailey disease without serious adverse effects. Future prospective studies are needed to investigate this interesting therapeutic option.