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An exceptionally diverse group of disorders that are both heterogeneous in their genetic or acquired pathophysiologic bases and pleiotropic in their phenotypic expressions can be assembled under the general category of alterations of the stratum corneum and epidermis. These disorders reflect a wide range of acquired and hereditary pathologic processes. Two distinct themes, however, unite many of the entities described here. One common pathophysiologic feature reflects defects in the cornification process that manifest clinicopathologically as ichthyoses; the other involves molecular defects in keratin genes and other genes yet to be determined that confer defective epidermal integrity and that present clinically as the mechanobullous disorders.

Many of the disorders collated here, particularly the ichthyoses, have similar microscopic features, complicating the histopathologic differential diagnosis and highlighting the importance of clinical correlation and ancillary testing, including immunocytochemistry. Indeed, for the hereditary cytolytic (mechanobullous) disorders, immunolabeling of basement membrane components to delineate the level of the separation within the tissue is necessary for adequate diagnosis. The histopathologic algorithms offered here, therefore, only serve in many situations to refine the differential diagnosis to a limited level, beyond which one must resort to supplemental strategies.

The organization of this chapter follows the 2 major schemata comprising defects in the process of keratinization and defective epidermal integrity, the latter often due to mutations in keratin genes creating defective structural proteins. Pathways for differential diagnosis of the nonbullous ichthyoses are discussed first followed by disorders with epidermolytic changes. As in prior editions of this textbook, the organization follows from recognizable patterns of disease effects at the histological level, thereby allowing generation of differential diagnoses for resolution by more refined strategies.


The designation “ichthyosis” is a descriptive term covering a variety of keratinization disorders that are usually genetic in nature. Although their genetic bases are heterogeneous, all of them share the common feature of scaling skin, which is often generalized, but as in the instances of the palmoplantar keratodermas and the erythrokeratodermas, may also be localized. This section covers disorders with significant hyperkeratosis due to defective keratinization but with no cytolytic (epidermolytic) alterations. The organization of these hyperkeratotic disorders, which was originally adapted in prior editions of this textbook from the work of Traupe,1 follows the diagnostic algorithm of Fig. 14-1. This schema focuses on whether the predominant mode of keratinization is ortho- or parakeratotic and secondarily on the status of the stratum granulosum. Table 14-1 summarizes the features that assist with the differential diagnosis of the entities.

TABLE 14-1Differential Diagnosis of Nonbullous Ichthyoses and Related Disorders

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