Hailey-Hailey disease (benign familial pemphigus)
- Dean Morrell, MD
Dean Morrell, MD
- Associate Professor, Department of Dermatology
- University of North Carolina Chapel Hill
Hailey-Hailey disease (HHD, MIM #169600), also called benign familial pemphigus or benign chronic pemphigus, is a rare autosomal dominant disorder that affects the adhesion of epidermal keratinocytes. Initially described by the Hailey brothers in 1939 , this intraepidermal blistering disorder is characterized by blistering, erosions, maceration, and frequent secondary infection in the flexural areas. HHD is a chronic condition with multiple recurrences and limited therapeutic options.
This topic will discuss the pathogenesis, clinical manifestations, diagnosis, and treatment of HHD. Darier disease, a condition that shares many clinical and pathologic features with HHD, is discussed separately. (See "Darier disease".)
EPIDEMIOLOGY AND GENETICS
Hailey-Hailey disease (HHD) is a rare disorder. Its prevalence is unknown, since many patients lack an accurate diagnosis or do not seek treatment. The age of onset and clinical manifestations of HHD can vary widely within families, but presentation during childhood is uncommon . There is no apparent difference in prevalence among different ethnic groups.
Genetics — HHD (MIM #169600) is inherited in an autosomal dominant manner with complete penetrance and variable expressivity. Only two-thirds of patients have a family history of HHD; de novo mutations or lack of phenotypic expression in affected family members account for the absence of family history in the remainder. Interfamilial phenotypic variations and the lack of clear genotype-phenotype correlations indicate that environmental and/or other genetic factors may modify the clinical presentation.
Hailey-Hailey disease (HHD) is caused by loss-of-function mutations in the ATP2C1 gene at 3q22.1, which encodes the adenosine triphosphate (ATP)-powered, magnesium-dependent calcium pump protein hSPCA1; its function is to maintain normal intracellular concentrations of free calcium (Ca2+) by sequestering Ca2+ into the Golgi apparatus .
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- EPIDEMIOLOGY AND GENETICS
- CLINICAL PRESENTATION AND COURSE
- Clinical course
- Risk of squamous cell carcinoma
- Molecular diagnosis
- DIFFERENTIAL DIAGNOSIS
- APPROACH TO MANAGEMENT
- General measures
- First-line therapies
- Second-line therapies
- THERAPEUTIC OPTIONS
- Topical and intralesional therapies
- Systemic therapies
- Surgical or destructive therapies
- Emerging medical therapies
- GENETIC COUNSELING
- SUMMARY AND RECOMMENDATIONS