eMedicine Specialties > Dermatology > Bullous Diseases

Familial Benign Pemphigus (Hailey-Hailey Disease)

Author: Thomas N Helm, MD, Clinical Associate Professor, Departments of Dermatology and Pathology, State University of New York at Buffalo; Director, Buffalo Medical Group Dermatopathology Laboratory
Coauthor(s): Thomas C Lee, MD, Intern, Department of Internal Medicine, New York University School of Medicine
Contributor Information and Disclosures

Updated: Aug 13, 2008

Introduction

Background

Familial benign pemphigus originally was described by the Hailey brothers in 1939.1 It is a chronic autosomal dominant disorder with incomplete penetrance. Approximately two thirds of patients 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.

Among the eMedicine articles on pemphigus are the following:

Additionally, the article Advances in Pemphigus Therapy, available from Medscape, may be of interest.

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

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.

Age

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

Clinical

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.

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 (see Media Files 1-6). 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.

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 3.4 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.

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.

More on Familial Benign Pemphigus (Hailey-Hailey Disease)

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Multimedia: Familial Benign Pemphigus (Hailey-Hailey Disease)
References
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References

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Further Reading

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Keywords

pemphigus, benign familial pemphigus, familial benign pemphigus, bullous disease, Hailey-Hailey disease

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Contributor Information and Disclosures

Author

Thomas N Helm, MD, Clinical Associate Professor, Departments of Dermatology and Pathology, State University of New York at Buffalo; 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, and American Society of Dermatopathology
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas C Lee, MD, Intern, Department of Internal Medicine, New York University School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

David Woodley, MD, Co-Chair, Professor, Department of Medicine, Division of Dermatology, University of Southern California
David Woodley, MD, Co-Chair is a member of the following medical societies: American Academy of Dermatology, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Physicians, American Federation for Medical Research, American Society for Clinical Investigation, New York Academy of Medicine, Society for Investigative Dermatology, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

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, and Women's Dermatologic Society
Disclosure: Johnson and Johnson stock holder dividends; Amgen stock holder dividends; Forest Lab, Inc stock holder dividends; Galaxo Smith Klein stock holder dividends; Covidien stock holder dividends; Novartis Grant/research funds Consulting; Biolex  sub-investigator

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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