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Hailey-Hailey disease (benign familial pemphigus)

Author
Dean Morrell, MD
Section Editor
Jonathan A Dyer, MD
Deputy Editor
Rosamaria Corona, MD, DSc

INTRODUCTION

Hailey-Hailey disease (HHD) or "benign familial pemphigus" is a rare autosomal dominant disorder that affects the adhesion of epidermal keratinocytes. Initially described by the Hailey brothers in 1939 [1], this intraepidermal blistering disorder 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 pathological 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 [2]. 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.

PATHOGENESIS

Hailey-Hailey disease (HHD) is caused by loss-of-function mutations in the ATP2C1 gene at 3q22.1, which encodes the ATP-powered calcium pump protein hSPCA1that sequesters calcium into the Golgi apparatus [3]. About 100 different mutations, distributed throughout the ATP2C1 gene, have been described in patients with HHD [4]. These mutations, including nonsense, missense, frameshift, and splice-site mutations, are thought to lead to hSPCA1 haploinsufficiency.

              

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Literature review current through: Nov 2016. | This topic last updated: Tue Sep 06 00:00:00 GMT+00:00 2016.
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