Hyperkeratosis, epidermolytic

A number of skin diseases, mainly characterized by blistering, have been found to be due to mutations in genes encoding various keratins. Three of these disorders are epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic pahnoplantar kerato-derma. The blistering probably reflects a diminished capacity of various layers of the skin to resist mechanical stresses due to abnormalities in microfilament strucmre. 

The two most severe types of ichthyosis, lamellar ichthyosis (LI) and epidermolytic hyperkeratosis (EHK), are distinct families of diseases with completely different etiologies (see Figure 8.1 and Table 8.3). Nevertheless, LI and EHK have several things in common they are rare, congenital diseases (prevalence <1/100,000) with more or less generalized hyperkeratosis and a defective skin barrier, and they usually demands vigorous therapy. 

Ichthyosis vulgaris X-Linked ichthyosis Lamellar ichthyosis (nonbullous ichthyosiform erythroderma) Epidermolytic hyperkeratosis (bullous ichthyosis)... 

FIGURE 8.6 Epidermolytic hyperkeratosis in a 10-year-old boy showing (a) extensive hyperkeratosis on the trank, (b) erosions and scaling around the ankle, and (c) verrucous hyperkeratosis in the axilla of a 25-year-old man carrying a spontaneous deletion in one of his K1 alleles (Vahlquist et al., unpubl. observ.). 

Virtanen, M., Gedde-Dahl, T., Mork, N.-J., Leigh, I., Bowden, P.E., and Vahlquist, A., Phenotypic/ genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression, Acta Derm. Venereol., 81, 163-170, 2001. 

Dillman et al. (2003) have recently shown that sulphur mustard causes keratin 14 and keratin 5 to clump into stable aggregates. These appear within 15 min of exposure to sulphur mustard. It was noted that a number of blistering disorders (epidermolysis bullosa simplex and epidermolytic hyperkeratosis) are associated with abnormalities of these keratin molecules (Fuchs et al, 1994). The role of keratin 14 in linking to plectin (another component of the hemidesmosomes) and to the bullous pemphigoid antigen le was also noted. Werrlein and Madren-Whalley (2000) demonstrated that sulphur mustard reduced expression of keratin 14... 

Fuchs E, Coulombe P, Cheng J et al. (1994). Genetic bases of epidermolysis bullosa simplex and epidermolytic hyperkeratosis. J Invest Dermatol, 103(Supplement 5), 25S-30S. 

Kempers S, Katz Hl.Wildnauer R, Green B.An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic hyperkeratosis, and ichthyosis. Cutis 1998 61 347-50. 

Unusual responses to therapy have been that palmoplantar blistering was enhanced by etretinate during therapy of patients with keratoderma palmaris et plantaris (epidermolytic type), epidermolytic hyperkeratosis, and pachyonychia congenita. Patients with Hailey-Hailey disease and atopic dermatitis have worsened with both retinoids. 

Figure 10.6 Epidermolytic hyperkeratosis, (a) Tonofibrillar clumps TQ and shells (TS) in the uppermost prickle cell layer (compare with Figures 10.4a and 10.7b) x4000. (b) Blister formation by acanthokeratolysis due to unilateral separation of desmosomes from one of their two neighbouring cells (open arrow) after loss of their inserting tonofilaments x8000. (c) Cytolytic blister formation without enlargement of intercellular spaces x4000...

Structural abnormalities are demonstrable in some dominant types, in keratohyalin (defective in autosomal dominant ichthyosis vulgaris), and tono-filaments (impaired or disturbed in their arrangement in hystrix-like ichthyoses clump formation in bullous ichthyosiform erythroderma or epidermolytic hyperkeratosis shell formation associated with high numbers of binucleate cells in ichthyosis hystrix type Curth-Macklin impairment in ichthyosis hystrix gravior type Rheydt). Keratohyalin and tonofilaments are both structural proteins of keratinizing tissues. 

Wilgram, G. F. and Caulfield, J. B. (1966). An electron microscopic study of epidermolytic hyperkeratosis. With a special note on the keratinosome as the fourth structural factor in the formation of the horny layer. Arch. Dermatol, 94,127... 

Epidermolytic hyperkeratosis Rare Autosomal dominant Birth lifelong Generalized accentuated skin markings bullae Increased epidermal kinetics reticulated granular layer... 

Figure 13.11 Woman with mixed form of gyrate erythema resembling erythrokeratodermia variabilis and epidermolytic hyperkeratosis. Histologic sections of skin specimens showed massive hyperkeratosis, but no epidermolytic features...

Klaus, S., Weinstein, G. D. and Frost, P. (1970). Localized epidermolytic hyperkeratosis. A form of keratoderma of the palms and soles. Arch. Dermatol, 101,272... 

Congenital epidermolytic hyperkeratosis, also called dominant congenital... 

Following the publications of Stiittgen and Beer on the use of vitamin A acid in the treatment of ichthyosiform erythroderma, Thomson and Milne reported the treatment of a seven-year-old girl with ichthyosiform erythroderma (epidermolytic hyperkeratosis) (Figure 21.1) by topical and systemic retinoic acid. 

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