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CUTANEOUS DISORDERS OF CORNIFICATION

Ichthyoses

  • Group of disorders characterized by generalized scaling of the skin

  • Pathogenesis: increased cohesiveness of cells of the stratum corneum, abnormal keratinization, and abnormal proliferation

ICHTHYOSIS VULGARIS

  • Epidemiology: most common disorder of cornification; AD (Fig. 8-1)

  • Pathogenesis

    • Loss of function mutation in filaggrin (FLG) gene

    • Increased adherence of the stratum corneum and scale formation is thought to result from a lack of water-retaining amino acids that derive from filaggrin metabolism

  • Clinical features

    • Not present at birth; onset during infancy/childhood

    • Fine white, flaky scales develop on the extremities, especially the extensor surfaces with sparing of the groin and flexural areas due to increased humidity

    • Improves with advancing age

    • Associated with keratosis pilaris and atopic triad of asthma, hay fever, and eczema

  • Pathology

    • Thirty to fifty percent of affected individuals lack a granular layer on light microscopy and profilaggrin-containing keratohyalin granules by EM

  • Treatment

    • Emollients and humectants

    • Keratolytics—be careful with salicylic acid to avoid salicylism

    • Topical retinoids—can be irritating

FIGURE 8-1

Ichthyosis vulgaris. (Reprinted with permission from Freedberg IM et al: Fitzpatrick's Dermatology in General Medicine, 6th Ed. New York: McGraw-Hill; 2003, p. 487.)

LAMELLAR ICHTHYOSIS

  • Epidemiology: AR (Fig. 8-2)

  • Pathogenesis

    • In the majority of patients, it is caused by transglutaminase-1 deficiency due to deleterious mutations in the TGM1 gene

    • Has also been mapped to the ATP-binding cassette transporter gene (ABCA12) and the cytochrome P450 family 4, subfamily F, polypeptide 22 gene (CYP4F22)

  • Clinical features

    • Apparent at birth and persists throughout life

    • Collodion baby

    • Characterized by large, dark-brown, and plate-like scales that form a mosaic pattern with minimal to no erythroderma

    • Ectropion, eclabium, and significant hypoplasia of nasal and auricular cartilage due to tautness of facial skin

    • Variable palmoplantar keratoderma (PPK), may have alopecia and nail dystrophy

  • Treatment

    • Oral retinoids may be necessary from early childhood if severe

    • Keratolytics limited secondary to irritation and systemic absorption

    • Topical vitamin D3 derivatives, tazarotene, and formulations containing lactic acid and propylene glycol in a lipophilic cream base

    • Palliation for heat intolerance

    • Ophthalmologic evaluation

FIGURE 8-2

Lamellar ichthyosis. (Reprinted from Russell LJ et al. Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q. Am J Hum Genet 1994;55:1146.)

NON-BULLOUS CONGENITAL ICHTHYOSIFORM ERYTHRODERMA:

  • Epidemiology: AR

  • Pathogenesis

    • Mapped to 6 different genes: transglutaminase 1, ALOXE3, ALOX12B, ABCA12, CYP4F22, and NIPAL4.

    • 12-LOX and eLOX sequentially function to generate epoxy alcohol metabolites, which are necessary for formation of the epidermal lipid barrier

  • Clinical features

    • Presents at birth with a collodion membrane

    • Persists throughout life

    • Characterized by intense erythroderma, white small powdery scale, ...

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