J Cutan Med Surg 2018 May/Jun;22(3):362-364

1 Section of Dermatology, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Hailey-Hailey disease, or benign familial pemphigus, is a rare blistering disease originally described in 1939. The disease is due to an autosomal dominant mutation in the ATP2C1 gene on chromosome 3, which encodes for an adenosine triphosphate-dependent calcium pump in the Golgi apparatus whose function is to maintain intercellular calcium homeostasis. Common treatments for Hailey-Hailey disease involve calcineurin inhibitors, topical corticosteroids, topical or systemic antibiotics, topical antifungals, ablative lasers, or botulin toxin. Read More

JAMA 2018 Apr;319(14):1499-1500

Center for Clinical Studies, Webster, Texas.

Eur J Intern Med 2018 Jan 5. Epub 2018 Jan 5.

Dermatology Unit, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.

An Bras Dermatol 2017 May-Jun;92(3):439-440

Department of Pathology at Hospital Universitari Sagrat Cor - Grupo Quirónsalud - Barcelona, Spain.

Br J Dermatol 2018 May 23;178(5):1196-1198. Epub 2018 Feb 23.

Department of Dermatology, Wing D, Belfast City Hospital, Lisburn Rd, Belfast, BT9 7AB, U.K.

Hailey-Hailey disease (chronic benign familial pemphigus) is a rare inherited dermatosis typically characterized by erosions at intertriginous sites preceded by minor trauma or stress. We report a case of treatment-resistant Hailey-Hailey disease having failed topical and oral steroids, prophylactic aciclovir and doxycycline, and systemic therapies including dapsone, acitretin and ciclosporin. Low-dose naltrexone 4·5 mg once daily was commenced following an incidental benefit in this patient's similarly affected sister. Read More

Skin Res Technol 2018 Feb 7;24(1):85-92. Epub 2017 Aug 7.

Department of Dermatology, Hospital de Santa Maria, Lisbon, Portugal.

Background/purpose: Hailey-Hailey disease is a rare inherited acantholytic skin disorder characterized by heterogeneous clinical presentation. Its differential diagnosis might be wide, including other genodermatoses, inflammatory, and infectious skin diseases. Although histopathology remains as diagnostic gold standard, noninvasive techniques such as dermoscopy and reflectance confocal microscopy may assist clinical examination. Read More

JAMA Dermatol 2017 Oct;153(10):1015-1017

Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio.

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. Read More

JAMA Dermatol 2017 Oct;153(10):1018-1020

Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.

Importance: Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects.

Objective: To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease. Read More

Ann Dermatol Venereol 2017 Oct 29;144(10):599-606. Epub 2017 Jun 29.

Service de dermatologie, hôpital Saint-André, 1, rue Jean-Burguet, 33000 Bordeaux, France. Electronic address:

Background: Hailey-Hailey disease (HHD) is characterised by episodes of weeping erythematous lesions, particularly in areas subject to friction or maceration. Treatment is complex. The value of botulinum toxin has been demonstrated in several studies and in individual cases. Read More

Cell Mol Life Sci 2017 10 27;74(20):3687-3696. Epub 2017 May 27.

Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, 410013, Hunan, People's Republic of China.

Hailey-Hailey disease (HHD) is a rare autosomal dominant acantholytic dermatosis, characterized by a chronic course of repeated and exacerbated skin lesions in friction regions. The pathogenic gene of HHD was reported to be the ATPase calcium-transporting type 2C member 1 gene (ATP2C1) located on chromosome 3q21-q24. Its function is to maintain normal intracellular concentrations of Ca/Mn by transporting Ca/Mn into the Golgi apparatus. Read More

J Dermatolog Treat 2017 Nov 2;28(7):678-682. Epub 2017 Apr 2.

a Department of Dermatology and INSERM , University of Montpellier , Montpellier , France.

Introduction/background: Treatment of benign familial pemphigus or Hailey-Hailey disease (HHD), a rare inherited condition associated with a significant impairment of quality of life, is often challenging and disappointing with frequent relapses and infectious complications. Topical photodynamic therapy (PDT) may offer new perspectives in this difficult setting.

Material And Methods: Eight patients with long-lasting HHD lesions refractory to multiple treatments were treated on at least one involved site with PDT using methyl-amino levulinate with a standardized protocol of three sessions of irradiation separated by 3-week intervals. Read More

Indian J Dermatol Venereol Leprol 2017 Mar-Apr;83(2):259-262

Department of Skin and VD, Indira Gandhi Government Medical College, Nagpur, Maharashtra, India.

J Am Acad Dermatol 2017 Feb;76(2S1):S31-S33

Department of Dermatology, University Hospital Hassan II, Fes, Morocco.

Clin Pharmacokinet 2017 Aug;56(8):815-823

Stadtspital Triemli, Institute of Laboratory Medicine, Zurich, Switzerland.

Afamelanotide, the first α-melanocyte-stimulating hormone (MSH) analogue, synthesized in 1980, was broadly investigated in all aspects of pigmentation because its activity and stability were higher than the natural hormone. Afamelanotide binds to the melanocortin-1 receptor (MC1R), and MC1R signaling increases melanin synthesis, induces antioxidant activities, enhances DNA repair processes and modulates inflammation. The loss-of-function variants of the MC1R present in fair-skinned Caucasians are less effectively activated by the natural hormone. Read More

Hum Mutat 2017 Apr 15;38(4):343-356. Epub 2017 Feb 15.

Departments of Dermatology, Maastricht University Medical Centre, Maastricht, The Netherlands.

The two disorders of cornification associated with mutations in genes coding for intracellular calcium pumps are Darier disease (DD) and Hailey-Hailey disease (HHD). DD is caused by mutations in the ATP2A2 gene, whereas the ATP2C1 gene is associated with HHD. Both are inherited as autosomal-dominant traits. Read More

J Cutan Pathol 2016 Nov 22;43(11):1031-1035. Epub 2016 Aug 22.

Department of Dermatology, Yale School of Medicine, New Haven, CT, 06520-8059, USA.

We describe a 65-year-old Caucasian female with well-controlled Hailey-Hailey disease (HHD) who developed acute generalized exanthematous pustulosis (AGEP) with severe systemic symptoms. Despite sparing of the patient's intertriginous skin, histopathologic evidence of HHD was observed in all biopsies, suggestive of a unique koebernization phenomenon of HHD to areas of cutaneous drug eruption. While internal organ involvement is less commonly reported in AGEP, there are an increasing number of patients with signs and symptoms suggestive of an AGEP/drug reaction with eosinophilia and systemic symptoms (DRESS) spectrum of cutaneous drug disorders. Read More

J Am Acad Dermatol 2017 Mar 13;76(3):551-558.e3. Epub 2016 Oct 13.

Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.

Hailey-Hailey disease or familial benign chronic pemphigus is a rare blistering dermatosis that is characterized by recurrent erythematous plaques with a predilection for the skin folds. For extensive Hailey-Hailey disease that is recalcitrant to conventional therapy, laser ablation, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A, dermabrasion, glycopyrrolate, and afamelanotide have been reported as useful treatments, but comparative trials are lacking. This review discusses the various treatment modalities for Hailey-Hailey disease and a summary of the evidence for the most recommended treatments. Read More

Clin Cosmet Investig Dermatol 2016 14;9:281-290. Epub 2016 Sep 14.

Department of Dermatology and Cutaneous Surgery, University of Miami-Miller School of Medicine, Miami, FL, USA.

Benign familial chronic pemphigus or Hailey-Hailey disease is caused by an autosomal dominant mutation in the gene leading to suprabasilar acantholysis. The disease most commonly affects intertriginous areas symmetrically. The chronic nature of the disease and multiple recurrences make the disease bothersome for patients and a treatment challenge for physicians. Read More

Ear Nose Throat J 2016 Sep;95(9):370

Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, Woodland Hills, CA, USA.

Actas Dermosifiliogr 2017 Jan - Feb;108(1):78-79. Epub 2016 Sep 9.

Servicio de Dermatología, Hospital Clínic, Universitat de Barcelona, Barcelona, España.

Dermatol Online J 2016 Apr 18;22(4). Epub 2016 Apr 18.

Hospital Privado de Córdoba.

We present an atypical case of familial benign pemphigus (Hailey-Hailey disease), which presented as crusted, annular plaques limited to the back without intertriginous involvement. We could not find in the literature another patient with plaques located solely on the back without a prior history of classical disease. Read More

Biochim Biophys Acta 2016 11 11;1863(11):2650-2657. Epub 2016 Aug 11.

Department of Biology and Biotechnology "C. Darwin", Sapienza University of Rome, Rome, Italy. Electronic address:

Background: Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare, chronic and recurrent blistering disorder, histologically characterized by suprabasal acantholysis. HHD has been linked to mutations in ATP2C1, the gene encoding the human adenosine triphosphate (ATP)-powered calcium channel pump.

Methods: In this work, the genetically tractable yeast Kluyveromyces lactis has been used to study the molecular basis of Hailey-Hailey disease. Read More

J Cutan Med Surg 2016 Nov 12;20(6):589-591. Epub 2016 Jul 12.

Department of Dermatology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.

Background: Darier's disease is an autosomal dominant genodermatosis typified by hyperkeratotic papules and plaques in a predominately seborrheic distribution. The vesiculo-bullous variant of Darier's disease is rare. Several previously reported cases have demonstrated clinical and microscopic features resembling familial benign chronic pemphigus or Hailey-Hailey disease. Read More

Indian J Dermatol Venereol Leprol 2016 Jul-Aug;82(4):429-31

Department of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu 210042; Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu 210042, China.

Cell Death Dis 2016 06 9;7(6):e2259. Epub 2016 Jun 9.

Aging Research Center (Ce.S.I.), University 'G. D'Annunzio' of Chieti-Pescara, Chieti 66100, Italy.

ATP2C1 gene codes for the secretory pathway Ca(2+)/Mn(2+)-ATPase pump type 1 (SPCA1) localizing at the golgi apparatus. Mutations on the human ATP2C1 gene, causing decreased levels of the SPCA1 expression, have been identified as the cause of the Hailey-Hailey disease, a rare skin disorder. In the last few years, several mutations have been described, and here we summarize how they are distributed along the gene and how missense mutations affect protein expression. Read More

JAAD Case Rep 2016 Mar 16;2(2):159-61. Epub 2016 Apr 16.

Department of Dermatology, St. Joseph Mercy Hospital, Ann Arbor, Michigan.

J Dermatol 2016 Oct;43(10):1197-1200

Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hailey-Hailey disease (HHD) is a kind of autosomal dominant dermatosis. The ATP2C1 gene has been identified as the pathogenic gene of HHD since 2000. In this study, direct DNA sequencing was used to identify ATP2C1 gene mutations in four Chinese families and two sporadic cases with HHD. Read More

Indian J Dermatol Venereol Leprol 2016 May-Jun;82(3):306-7

School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, China.

Clin Exp Dermatol 2016 07 15;41(5):558-9. Epub 2016 Apr 15.

School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.

Clin Exp Dermatol 2016 Aug 30;41(6):628-31. Epub 2016 Mar 30.

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA.

Papular acantholytic dyskeratosis (PAD) of the vulva is a rare, chronic disorder first described in 1984. It presents in young women as white to skin-coloured smooth papules over the vulva, which are persistent but asymptomatic. Histologically, there is hyperkeratosis and focal parakeratosis with acantholytic and dyskeratotic cells forming corps ronds and grains, placing PAD within Ackerman's spectrum of focal acantholytic dyskeratoses with Hailey-Hailey disease (HHD) and Darier disease. Read More

Dermatol Ther 2016 Nov 11;29(6):394-395. Epub 2016 Mar 11.

Department of Dermatology, University of Rochester, School of Medicine and Dentistry, Rochester, New York.

Actas Dermosifiliogr 2016 Jul-Aug;107(6):537-9. Epub 2016 Jan 23.

Servicio de Dermatología, Hospital General Universitario de Ciudad Real, Ciudad Real, España.

Genet Mol Res 2015 Dec 29;14(4):19349-59. Epub 2015 Dec 29.

Department of Phototherapy, Shanghai Skin Disease Hospital, Shanghai, China.

Hailey-Hailey disease (HHD) is an autosomal dominant disorder in which the ATP2C1 gene has been implicated. Many mutations of this gene have been detected in HHD patients. To analyze such mutations in HHD and summarize all those identified in Chinese patients with this disease, we examined four familial and two sporadic cases and searched for case reports and papers by using the Chinese Biological Medicine Database and PubMed. Read More

Cutis 2015 Dec;96(6):E14-6

Florida State University College of Medicine, Tallahassee, USA.

Int J Dermatol 2016 Mar 31;55(3):e170-1. Epub 2015 Oct 31.

Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.

Int J Dermatol 2016 Mar 31;55(3):e169-70. Epub 2015 Oct 31.

Section of Pediatric Gastroenterology, Department of Pediatrics, Baylor College of Medicine, Texas Childrens Hospital, USDA/ARS Childrens Nutrition Research Center, Houston, TX, USA.

Actas Dermosifiliogr 2015 Dec 18;106(10):852-4. Epub 2015 Sep 18.

Departamento de Dermatología, Hospital Universitario Severo Ochoa, Leganés, Madrid, España.

Int J Dermatol 2015 Nov 4;54(11):1309-14. Epub 2015 Sep 4.

Department of Dermatology, Mayo Clinic, Rochester, MN, USA.

Background: Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis that leads to skin breakdown and blister formation, usually in intertriginous areas. Laser ablation is a known surgical treatment for HHD.

Objectives: We report outcomes in a series of patients with HHD treated with carbon dioxide (CO2 ) laser ablation. Read More

Eur J Dermatol 2016 Aug;26(4):414-6

Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.

Exp Dermatol 2015 Oct 18;24(10):788-9. Epub 2015 Aug 18.

Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.

Clin Dermatol 2015 Jul-Aug;33(4):452-5. Epub 2015 Apr 8.

Department of Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, Fatih, Istanbul 34098, Turkey.

Hailey-Hailey disease, also called benign familial pemphigus, is a late-onset blistering disorder that affects the flexures. There are typically painful erosions and cracks in affected areas. Lesions generally begin between 20 and 40 years of age. Read More

J Cutan Pathol 2015 Aug 26;42(8):574-7. Epub 2015 May 26.

Department of Dermatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Atypical acquired melanocytic nevi in patients with epidermolysis bullosa (EB) have been referred to as EB nevi and are considered to be a type of recurrent nevus with atypical but distinctive histopathologic findings. Herein, we describe an atypical nevus in a patient with Hailey-Hailey disease with different histopathologic findings from EB nevi because of presumably different pathogenesis. It is important to be aware that the recurrent nevi phenomenon can be seen in acantholytic conditions as well as blistering disorders, given these lesions may clinically resemble melanoma. Read More

J Eur Acad Dermatol Venereol 2016 Jun 6;30(6):1057-9. Epub 2015 Apr 6.

The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.

PLoS One 2015 2;10(4):e0121253. Epub 2015 Apr 2.

Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.

The autosomal dominant Hailey Hailey disease (HHD) is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1) in the Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly in the intertrigines. Here we report an exome next generation sequencing (NGS) based analysis of ATPase genes in a Greek family with 3 HHD patients presenting with clinically atypical lesions mainly localized on the neck and shoulders. Read More

J Cutan Med Surg 2015 Mar-Apr;19(2):163-6. Epub 2015 Mar 5.

Department of Dermatology, Tufts Medical Center, Boston, MA, and private practice, Chelmsford, MA.

Background: Benign chronic familial pemphigus (BFCP) is an autosomal dominant dermatosis characterized by flares of painful and often debilitating blistering lesions in high friction areas of the body such as the groin, axillae, lateral neck, and intergluteal cleft. Limited knowledge of its pathophysiology has made treatment of BFCP a considerable challenge and efficacy with current first line therapies, topical corticosteroids and antibiotics, is variable.

Case Report: We present a case of this disease in a 52 year old woman that has responded dramatically to the addition of oral cyclosporine to her existing regimen of oral acitretin, with significant improvement of skin lesions, mobility, and quality of life. Read More

J Am Acad Dermatol 2015 Apr;72(4):735-7

Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.

Dermatol Ther 2015 May-Jun;28(3):158-65. Epub 2015 Mar 3.

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

Tumor necrosis factor-alpha (TNF)-alpha inhibitors are licensed for patients with severe refractory psoriasis and psoriatic arthritis. However, TNF-alpha inhibitors have also been used off-label for various recalcitrant mucocutaneous diseases. This study aimed to evaluate the efficacy and safety of TNF-alpha inhibitors used for off-label dermatological indications. Read More

PLoS One 2015 6;10(2):e0115530. Epub 2015 Feb 6.

Department of Dermatology, American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon; Department of Dermatology, Columbia University, New York, New York, United States of America.

Background: Hailey-Hailey disease (HHD) is an inherited blistering dermatosis characterized by recurrent erosions and erythematous plaques that generally manifest in intertriginous areas. Genetically, HHD is an autosomal dominant disease, resulting from heterozygous mutations in ATP2C1, which encodes a Ca2+/Mn2+ATPase. In this study, we aimed at identifying and analyzing mutations in five patients from unrelated families diagnosed with HHD and study the underlying molecular pathogenesis. Read More

JAMA Dermatol 2015 Mar;151(3):328-9

Division of Dermatology, Loyola University, Stritch School of Medicine, Maywood, Illinois.

J Drugs Dermatol 2015 Jan;14(1):68-70

Hailey-Hailey disease is a genetic disorder that affects flexural skin with scale, blisters, and maceration. Botulinum toxins have been previously used to treat Hailey-Hailey disease. Here, we present a patient who underwent one treatment of onabotulinumtoxinA and achieved excellent improvement that was sustained for three months post initial treatment. Read More