Skin-nontumor / Clinical dermatology
Blistering disorders
Epidermolytic hyperkeratosis

Author: Erin M. Carlquist, M.D. (see Authors page)
Editor: Lauren Stuart, M.D.
Editorial Board Member review: Jerad Gardner, M.D.

Revised: 14 June 2016, last major update December 2014

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Epidermolytic hyperkeratosis

Cite this page: Epidermolytic hyperkeratosis. PathologyOutlines.com website. http://pathologyoutlines.com/topic/skinnontumorepidermolytichyperkeratosis.html. Accessed December 7th, 2016.
Definition / General
  • Keratinization disorder which presents at birth with generalized erythema, widespread bullae and desquamation resulting in denuded skin
  • Form of ichthyosis, an abnormality of epidermal maturation resulting in skin fragility

  • "Epidermolytic hyperkeratosis" is a descriptive term which refers to specific microscopic features (i.e. vacuolar degeneration of the spinous layer, keratin filament clumping and hyperkeratosis), but these findings may be seen in various entities, not just this disease (Int J Dermatol 2005;44:1):
    • Generalized: bullous ichthyosis
    • Systematized or linear: epidermal nevus variant
    • Palmoplantar: palmoplantar keratoderma variant (Vorner type)
    • Solitary: epidermolytic acanthoma
    • Multiple discrete: disseminated epidermolytic acanthoma
    • Incidental: focal epidermolytic hyperkeratosis
    • Solar keratosis related: a rare variant of solar keratosis
    • Follicular: nevoid follicular epidermolytic hyperkeratosis
    • Mucosal: epidermolytic leukoplakia
Terminology
  • Other names:
    • Epidermolytic ichthyosis
    • Bullous congenital ichthyosiform erythroderma
    • Bullous ichthysosis
    • Bullous erythroderma ichthyosiformis congenita of Brocq
    • Disorder of cornification type 3
    • Vorner's syndrome
Epidemiology
Sites
Pathophysiology
  • Defects in keratin genes (KRT1 and KRT10) cause excessive and abnormal keratinization
  • Mutations occur in carboxy-terminal of rod domain of keratin 1 (K1) and in amino-terminal of rod domain of keratin 10 (K10)
Clinical Features
  • Presents at birth with generalized erythema, followed by development of thick verrucous scaling on flexor surfaces
  • Distinct foul odor due to secondary bacterial colonization of thickened skin (Dermatol Online J 2014;20:21248)
  • Complications include infection, sepsis, dehydration and electrolyte imbalances due to compromised skin barrier (Dermatol Online J 2014;20:21248)
  • Palmar and plantar involvement occurs in 60% of patients, most commonly in those with K1 mutations (Dermatol Online J 2014;20:21248)

  • Linear epidermolytic hyperkeratosis is associated with genetic mosaicism (Dermatol Online J 2014;20:21248)
    • Linear hyperkeratosis in streaks along Blaschko lines
    • Unilateral or bilateral, localized or generalized
    • Absence of blistering (unlike classical epidermolytic hyperkeratosis)
Diagnosis
  • Characteristic histological and ultrastructural findings (see below)
  • Immunofluorescence to determine which keratin type is involved (Hum Mol Genet 2006;15:1133)
Case Reports
Treatment
  • Symptom management only (Int J Dermatol 2005;44:1):
    • Daily bathing and moisturizing twice daily
    • Alpha hydroxy acids to reduce xerosis
    • Antibiotic ointment applied to fissures
    • Retinoids in severe cases, but use with caution as may exacerbate blistering (An Bras Dermatol 2011;86:S72)
Clinical Images

Images hosted on other servers:

"Corrugated cardboard" like

Palms

Anterior ankles

Close-up of ankle

Presenting as erythroderma and blistering

Generalized epidermolytic hyperkeratosis



Hyperkeratotic papules

Papules in proximal thigh

Left palmar hyperkeratosis

Plantar hyperkeratosis

Thickened red hyperkeratotic corrugated plaques

Plaques distributed over neck, back and flexural surfaces

Gross Description
  • Varies based on age
    • Infants have generalized erythema accompanied by erosions and bullae
    • In a few years, lesions evolve into verrucous plaques and scales
Micro Description
  • Epidermolytic hyperkeratosis (characteristic feature disease is named for), also called granular degeneration, is seen in upper epidermis
    • Granular and vacuolar degeneration of spinous and granular cell layers
    • Microscopically this appears as cleared spaces of variable size around nuclei in upper layers of nucleated epidermis

  • Granular layer contains an increased number of irregularly shaped keratohyaline granules
  • Overlying hyperkeratosis
  • Bullae form due to separation of edematous keratinocytes; keratinocytes fall apart (epidermolysis) due to lack of normal cytoplasmic keratin filament infrastructure that normally gives keratinocytes their strength
  • Mild lymphocytic inflammatory infiltrate in upper epidermis
  • Many more mitoses are present than in normal epidermis
Micro Images

Images hosted on other servers:

Diagram

1 yr old with hyperkeratotic lesions in axilla and thighs



Systematized linear epidermolytic hyperkeratosis

Focal epidermolytic hyperkeratosis

Continuous epidermolytic hyperkeratosis

Mosaic

Epidermolytic ichthyosis



Parakeratosis, hypergranulosisand vacuolar degenerationof granular and spinous layer

Positive Stains
  • Suprabasal epithelium shows increased expression of keratin 14
Electron Microscopy Description
  • Increase and clumping of tonofilaments
  • Increased and premature formation of keratohyaline granules of variable size
  • At periphery of cells are numerous keratohyaline granules embedded in thick shells of irregularly-clumped tonofilaments
  • Desmosome attachment to keratinocytes is abnormal due to disturbed desmosome-tonofilament associations, which leads to blister formation
Differential Diagnosis