Familial Benign Pemphigus (Hailey-Hailey Disease) Clinical Presentation
- Author: Thomas N Helm, MD; Chief Editor: Dirk M Elston, MD more...
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.
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.
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