Skin nontumor
Blistering disorders
Hailey-Hailey disease (HHD)

Author: Narina Grove, M.D., M.A. (see Authors page)

Revised: 19 July 2017, last major update July 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Hailey-Hailey disease[title]
Cite this page: Hailey-Hailey disease. PathologyOutlines.com website. http://pathologyoutlines.com/topic/skinnontumorhaileyhailey.html. Accessed July 21st, 2017.
Definition / general
  • Autosomal dominant genodermatosis characterized by intraepidermal vesicles located predominately in intertriginous area
  • Vesicles may progress to bullae, then rupture, forming a crust
  • Histology shows intraepidermal acantholysis due to nonfunctional desmosomal protein complexes
Essential features
  • Genodermatosis with autosomal dominant inheritance pattern (mutation in ATPC1 gene), 1/3 of cases are sporadic
  • Presents in second to forth decades, improves with age
  • Vesicles / bullae in intertriginous areas (axillae, groin, perianal and inframammary areas). exacerbated by perspiration
  • Rarely involves other areas
  • Relapsing remitting clinical course
  • Secondary infection (bacterial, herpetic) can be problematic and serious
  • Main treatment is topical steroids and topical antimicrobials
Terminology
  • Also called benign familial pemphigus
  • Papular acantholytic dermatosis in genitocrural region may be a localized form of H-H disease
ICD-10 coding
  • Q82.8
Epidemiology
Sites
  • Axillae, groin, perianal and inframammary areas
  • Rarely involves other sites
Pathophysiology
  • Mutation in ATP2C1, a calcium pump important in normal function of desmosomal protein complex
  • Dissociation of intracellular and extracellular domains of desmosomal cadherin and E-cadherin (adherens junction associated protein)
  • Faulty calcium pump action leads to disorganized function of desmogleins, which are calcium dependent adherence proteins (cadherins) (Indian Dermatol Online J 2016;7:147)
  • Hailey-Hailey and Darier disease share similar pathogenesis, as opposed to pemphigus vulgaris, in which autoantibodies develop against desmosomal proteins
Etiology
  • Blistering lesions in affected individuals may be induced by trauma, heat, UV light, perspiration
  • May be complicated by secondary infection with scabies, bacteria, herpes or yeast
Clinical features
  • Pruritic / burning, often malodorous lesions
  • Papular, verrucous, annular and vesiculopustular variants are rare
  • Nikolski sign may be positive
  • 1/3 of cases are sporadic
  • Healing accompanied by hyperpigmentation, but scarring is rare
  • Longitudinal leukonychia (asymptomatic white longitudinal bands on the fingernails in 70% of patients)
  • Superinfection by Candida albicans, herpes virus and Staphylococcus aureus are frequent complications
  • Cases of complication by squamous cell carcinoma have been reported
  • Symptoms worsen during summer, often disappear during winter
Case reports
Treatment
  • Topical steroids and topical antimicrobials are the first line treatments
  • Botulinum toxin A injections
  • Cryotherapy
  • Photodynamic therapy
  • Oral magnesium chloride
  • Laser ablation
  • Electron beam radiotherapy
  • Dermabrasion
  • Glycopyrrolate
  • Afamelanotide
Clinical images

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Hailey-Hailey in right axilla

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Hailey-Hailey under breast

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Hyperpigmented plaques over groin

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Hailey-Hailey lesions on left groin

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Figure 2b. Showing
longitudinal leukonychia
and ridging
Microscopic (histologic) description
  • Suprabasilar and intraepidermal clefting
  • Acantholysis of keratinocytes resembling dilapidated brick wall
  • Epidermal hyperplasia
  • No pronounced dyskeratosis but dyskeratotic keratinocytes have well defined nucleus and preserved cytoplasm (unlike pemphigus vulgaris)
  • Corps ronds and grains are rare
  • Adnexal structures are spared
  • Dermis shows variable chronic inflammatory infiltrate
  • Parakeratotic crust may contain neutrophils and bacteria
  • Immunofluorescence negative
Microscopic (histologic) images

Images hosted on Pathout server:
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Broad intraepidermal vesicles with “dilapidated brick appearance”
Contributed by Savita Ries, M.D., Long Beach Memorial Medical Center, Long Beach, CA



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Image 3: Hailey-Hailey disease

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Figure 1: HHD on
right sole, groin
and trunk
Molecular / cytogenetics description
  • Autosomal dominant condition with incomplete penetrance
  • ATPase calcium transporting type 2C member 1 gene (ATP2C1) on chromosome 3q21-q24 encodes a CA2+/ Mn2+ ATPase channel pump SPCA1
Differential diagnosis
  • Darier Disease
    • ATP2A2 mutation
    • Less acantholysis, more dyskeratosis
    • Involves "seborrheic" areas of the body, including scalp, face, upper chest, back
    • Acantholytic zones involve adnexal structures (particularly hair follicles)
    • Numerous corps ronds and grains
  • Grover disease
    • Narrow vesicles involving only a few rete ridges but may be histologically identical to Hailey-Hailey disease
    • Different clinical distribution of lesions
    • Acquired rather than inherited (no family history)
  • Papular acantholytic dermatosis of the genitocrural region
    • Localized variant of Hailey-Hailey or Darier disease involving only the perigenital areas
  • Pemphigus vulgaris
    • No predilection for intertriginous areas
    • Intact epithelium in adjacent epidermis
    • Involvement of adnexal structures
    • Eosinophils on histology
    • Less acantholysis, more dyskeratosis
    • Autoimmune mediated direct immunofluorescence is positive
  • Relapsing linear acantholytic dermatosis
    • Vesicles follow the lines of Blaschko
Additional references