Ichthyosis: Mechanisms of Disease

Abstract: The disorders of cornification (Ichthyoses) comprise acquired and Inherited disorders characterized clinically by generalized sealing and histologically by hyperkeratosls. They may arise through defects In the production or maintenance of a normal cornmed cell compartment, or both. The stratum cornaum is composed of protein-enriched and llpid-depleted corneocytes (“bricks”) surrounded by an Intercellular domeln (“mortar”) composed of hydrophoblc, llpid-enriched membrane bllayers, and containing desmosomes and a limited array of hydrolytfc enzymes. Mechanisms whereby a genetic defect Involving either the bricks or the mortar may result In abnormal stratum comeum retention are diecussed using lehthyosls vulgaria and recessive X-linked ichthyosis as examples. In addition, epidermal hyperproliferation, which floods the cornfiled cell compartment with incompletely formed units, results In hyperkeratosis. To date, no primary disorders of epidermal hyperproliferation have been defined. Recent work, however, demonstrates that stratum corneum barrier function regulates epidermal DMA synthesis. For example, in essential fatty acid deficiency, barrier dysfunction Is responsible at least In part for the epidermal hyperprollferatlon. Defective barrier function due to detective lamellar body secretion may also underlbe the phenotypic changes after birth In harlequin Ichthyosis; that is, from the massive, constrictive hyperkeratosis of the newborn to an exfoliative erythroderma In survivors. The mechanisms whereby specific detects in cornlification result In generalized scaling disease are only beginning to be defined. Yet, even at this early stage, the view of the stratum corneum as a tightly organized structure whose function Is highly regulated is emerging. Hence, the disorders of comlflcation should provide Important insights into stratum comeum structure and function.