Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Familial Benign Pemphigus (Hailey-Hailey Disease) Clinical Presentation

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

History

A family history of benign familial pemphigus usually is present. Commonly, patients may not have symptoms until ages 30-49 years. Delayed diagnosis of familial benign pemphigus also is common, especially if the patient's lesions respond to topical corticosteroids, antibiotics, or antifungals.

Next

Physical

With familial benign pemphigus, vesicles and erythematous plaques with overlying crusts typically occur in the genital area, as well as the chest, neck, and axillary areas, as shown in the images below.

Right axilla with erosive erythematous plaques. Right axilla with erosive erythematous plaques.
Lumbar back with erythematous plaques with impetigLumbar back with erythematous plaques with impetiginized crust.
Left axilla with tender erythematous plaques. Left axilla with tender erythematous plaques.
Eroded and crusted plaques in right groin at base Eroded and crusted plaques in right groin at base of penis.
Erythema of scrotum and erosive plaques in left grErythema of scrotum and erosive plaques in left groin (simulated intertrigo).
Central groin with yellow crust over cleaned plaquCentral groin with yellow crust over cleaned plaques.

Burning and itching accompany the eruption, and a malodorous drainage occurs in some cases as a result of secondary infection. Symptoms related to staphylococcal and candidal overgrowth are common in familial benign pemphigus. Multiple asymptomatic longitudinal white bands on the fingernails also have been described. Involvement of mucosa is rare. The characteristic clinical appearance of familial benign pemphigus, as well as biopsy findings, readily confirms the diagnosis.

Previous
Next

Causes

Hailey-Hailey disease, or familial benign pemphigus, is hypothesized to result from a genetic defect in a calcium pump protein. The pump mutation is in ATP2C1, a gene localized on chromosome 3.[5] This gene defect is similar to the genetic defect in Darier disease, which also is a calcium pump defect, ATP2A2. The gene ATP2C1 encodes the human secretory pathway Ca++ -ATPase hSPCA1, which is dysfunctional and causes abnormal calcium release from the Golgi apparatus and endoplasmic reticulum. Acantholytic dermatosis of the crural folds may be a variant of Hailey-Hailey disease (familial benign pemphigus) and is also associated with ATP2C1 mutation.[6]

In addition to the primary gene defect in Hailey-Hailey disease (familial benign pemphigus), contributing factors are known that exacerbate the disease. These include heat, friction, and infection, resulting in separation of keratinocytes, especially in the intertriginous areas. Through ultrastructural studies of familial benign pemphigus lesions, characteristic changes in keratinocyte morphology have been described, including retracted tonofilaments, elongated membrane microvilli, and reduced numbers of desmosomes.

Previous
 
 
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
  1. Hailey H, Hailey H. Familial benign chronic pemphigus. Arch Dermatol. 1939. 39:679-85.

  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].

  5. Zhu YG, Yang S, Gao M, et al. Two novel mutations of the ATP2C1 gene in Chinese families with Hailey-Hailey disease. J Dermatol Sci. 2006 May. 42(2):125-7. [Medline].

  6. Lipoff JB, Mudgil AV, Young S, Chu P, Cohen SR. Acantholytic dermatosis of the crural folds with ATP2C1 mutation is a possible variant of Hailey-Hailey Disease. J Cutan Med Surg. 2009 May-Jun. 13(3):151-4. [Medline].

  7. Hunt MJ, Salisbury EL, Painter DM, Lee S. Vesiculobullous Hailey-Hailey disease: successful treatment with oral retinoids. Australas J Dermatol. 1996 Nov. 37(4):196-8. [Medline].

  8. Rabeni EJ, Cunningham NM. Effective treatment of Hailey-Hailey disease with topical tacrolimus. J Am Acad Dermatol. 2002 Nov. 47(5):797-8. [Medline].

  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].

  16. Tang MB, Tan ES. Hailey-Hailey disease: effective treatment with topical cadexomer iodine. J Dermatolog Treat. 2011 Oct. 22(5):304-5. [Medline].

  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].

  23. Pagliarello C, Paradisi A, Dianzani C, Paradisi M, Persichetti P. Topical tacrolimus and 50% zinc oxide paste for Hailey-Hailey disease: less is more. Acta Derm Venereol. 2012 Jul. 92(4):437-8. [Medline].

  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.

Previous
Next
 
Right axilla with erosive erythematous plaques.
Lumbar back with erythematous plaques with impetiginized crust.
Left axilla with tender erythematous plaques.
Eroded and crusted plaques in right groin at base of penis.
Erythema of scrotum and erosive plaques in left groin (simulated intertrigo).
Central groin with yellow crust over cleaned plaques.
Acantholysis at all levels of the epidermis (hematoxylin and eosin stain, original magnification X20).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.