Familial Benign Pemphigus (Hailey-Hailey Disease) Clinical Presentation: History, Physical, Causes
Familial Benign Pemphigus (Hailey-Hailey Disease) Clinical Presentation: History, Physical, Causes
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.
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.
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.
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.
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.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.
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.
Differential Diagnoses
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
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
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, National Kidney Foundation, Phi Beta Kappa, Women's Dermatologic Society, Medical Dermatology Society, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Society of Virginia
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
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
References
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).
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, as shown in the images below.
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.
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.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.
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.
Differential Diagnoses
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
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
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, National Kidney Foundation, Phi Beta Kappa, Women's Dermatologic Society, Medical Dermatology Society, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Society of Virginia
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
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
References
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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).
