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Familial Benign Pemphigus (Hailey-Hailey Disease)

  • Author: Thomas N Helm, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Apr 09, 2015
 

Background

Familial benign pemphigus (Hailey-Hailey disease) originally was described by the Hailey brothers in 1939.[1] Familial benign pemphigus is a chronic autosomal dominant disorder with incomplete penetrance. Approximately two thirds of patients with familial benign pemphigus have a family history of the disorder. A history of multiple relapses and remissions is characteristic. Decreased numbers of desmosomes have been implicated in the pathogenesis of benign familial pemphigus. Therapeutic options are limited.

Medscape Drugs & Diseases articles on pemphigus include Pemphigus Erythematosus, Pemphigus Foliaceus, Pemphigus Herpetiformis, and Pemphigus Vulgaris.

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Pathophysiology

Keratinocytes are held together through desmosomes and adherens junctions. These junctions consist of calcium-binding transmembrane glycoproteins, which contribute to cellular adhesion. Many hypotheses exist concerning the pathogenesis of familial benign pemphigus, but the cause remains uncertain. An overall defect in keratinocyte adhesion appears to be secondary to a primary defect in a calcium pump protein, ATP2C1.

ATP2C1 encodes the secretory pathway Ca2+/Mn2 ATPase (hSPCA1). Mutant proteins in familial benign pemphigus create a loss of sensitivity to Ca2+ and Mn2+ ion binding and transport. Low levels of Ca2+ within Golgi bodies impair protein processing. Gene expression may be affected in benign familial pemphigus, as may phosphorylation of adhesion molecules. Localized postzygotic mutation has caused segmental manifestations of familial benign pemphigus.[2, 3]

A 2009 study has shown that the calcium content of basal keratinocytes is lower than in normal skin and that transition of keratin 14 to 10 is abnormal.[4]

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Epidemiology

Frequency

United States

No precise data are available on the incidence of familial benign pemphigus.

Mortality/Morbidity

Familial benign pemphigus causes discomfort but is not life threatening. Benign familial pemphigus lesions often begin during the teenage years and manifest as itchy and malodorous plaques.

Sex

Both sexes are affected equally by familial benign pemphigus.

Age

Familial benign pemphigus often manifests in the late teenage years or in adulthood (30s and 40s).

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Contributor Information and Disclosures
Author

Thomas N Helm, MD Clinical Professor of Dermatology and Pathology, University of Buffalo, State University of New York School of Medicine and Biomedical Sciences; Director, Buffalo Medical Group Dermatopathology Laboratory

Thomas N Helm, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society of Dermatopathology

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas C Lee, MD Associated Gastroenterologists of Central New York, St Joseph’s Hospital

Thomas C Lee, MD is a member of the following medical societies: American College of Gastroenterology, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Julia R Nunley, MD Professor, Program Director, Dermatology Residency, Department of Dermatology, Virginia Commonwealth University Medical Center

Julia R Nunley, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Dermatology Society, Medical Society of Virginia, National Kidney Foundation, Phi Beta Kappa, Women's Dermatologic Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Board of Dermatology<br/>Co-Editor for the text Dermatological Manifestations of Kidney Disease .

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Harry Dao, Jr, MD Assistant Professor, Department of Dermatology, Baylor College of Medicine

Harry Dao, Jr, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References
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  2. Fairclough RJ, Dode L, Vanoevelen J, et al. Effect of Hailey-Hailey Disease mutations on the function of a new variant of human secretory pathway Ca2+/Mn2+-ATPase (hSPCA1). J Biol Chem. 2003 Jul 4. 278(27):24721-30. [Medline].

  3. Foggia L, Aronchik I, Aberg K, Brown B, Hovnanian A, Mauro TM. Activity of the hSPCA1 Golgi Ca2+ pump is essential for Ca2+-mediated Ca2+ response and cell viability in Darier disease. J Cell Sci. 2006 Feb 15. 119:671-9. [Medline].

  4. Leinonen PT, Hagg PM, Peltonen S, et al. Reevaluation of the normal epidermal calcium gradient, and analysis of calcium levels and ATP receptors in Hailey-Hailey and Darier epidermis. J Invest Dermatol. 2009 Jun. 129(6):1379-87. [Medline].

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  9. Ruiz-Rodriguez R, Alvarez JG, Jaen P, Acevedo A, Cordoba S. Photodynamic therapy with 5-aminolevulinic acid for recalcitrant familial benign pemphigus (Hailey-Hailey disease). J Am Acad Dermatol. 2002 Nov. 47(5):740-2. [Medline].

  10. Konrad H, Karamfilov T, Wollina U. Intracutaneous botulinum toxin A versus ablative therapy of Hailey-Hailey disease--a case report. J Cosmet Laser Ther. 2001 Dec. 3(4):181-4. [Medline].

  11. Lapiere JC, Hirsh A, Gordon KB, Cook B, Montalvo A. Botulinum toxin type A for the treatment of axillary Hailey-Hailey disease. Dermatol Surg. 2000 Apr. 26(4):371-4. [Medline].

  12. Lopez-Ferrer A, Alomar A. Botulinum toxin A for the treatment of familial benign pemphigus. Actas Dermosifiliogr. 2012 Aug 8.

  13. Kaniszewska M, Rovner R, Arshanapalli A, Tung R. Oral glycopyrrolate for the treatment of hailey-hailey disease. JAMA Dermatol. 2015 Mar 1. 151(3):328-9. [Medline].

  14. Berger EM, Galadari HI, Gottlieb AB. Successful treatment of Hailey-Hailey disease with acitretin. J Drugs Dermatol. 2007 Jul. 6(7):734-6. [Medline].

  15. Hurd DS, Johnston C, Bevins A. A case report of Hailey-Hailey disease treated with alefacept (Amevive). Br J Dermatol. 2008 Feb. 158(2):399-401. [Medline].

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  17. Hamada T, Umemura H, Aoyama Y, Iwatsuki K. Successful therapeutic use of targeted narrow-band ultraviolet B therapy for refractory hailey-hailey disease. Acta Derm Venereol. 2012 Jun 27.

  18. Awadalla F, Rosenbach A. Effective treatment of hailey-hailey disease with a long-pulsed (5 ms) alexandrite laser. J Cosmet Laser Ther. 2011/08. 13(4):191-2.

  19. Don PC, Carney PS, Lynch WS, Zaim MT, Hassan MO. Carbon dioxide laserabrasion: a new approach to management of familial benign chronic pemphigus (Hailey-Hailey disease). J Dermatol Surg Oncol. 1987 Nov. 13(11):1187-94. [Medline].

  20. Fisher GH, Geronemus RG. Improvement of familial benign pemphigus after treatment with pulsed-dye laser: a case report. Dermatol Surg. 2006 Jul. 32(7):966-8. [Medline].

  21. Kartamaa M, Reitamo S. Familial benign chronic pemphigus (Hailey-Hailey disease). Treatment with carbon dioxide laser vaporization. Arch Dermatol. 1992 May. 128(5):646-8. [Medline].

  22. Fernandez Guarino M, Ryan AM, et al. Experience with photodynamic therapy in Hailey-Hailey disease. J Dermatolog Treat. 2008. 19(5):288-90. [Medline].

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  24. Fisher BK, Margesson LJ. Hailey-Hailey disease (familial benign chronic pemphigus). Genital Skin Disorders: Diagnosis and Treatment. St. Louis, Mo: Mosby-Year Book; 1998. 68, 117.

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