Lipids in the pathogenesis of ichthyosis: topical cholesterol sulfate-induced scaling in hairless mice

Mary E. Maloney, University of Massachusetts Medical School
Mary L. Williams, University of California, San Francisco
Ervin H. Epstein Jr., University of California, San Francisco
Michael Y. Law, University of California, San Francisco
Peter O. Fritsch, University of California, San Francisco
Peter M. Elias, University of California, San Francisco

At the time of publication, Mary E. Maloney was not yet affiliated with the University of Massachusetts Medical School.

Abstract

Although several abnormalities of lipid metabolism have been associated with abnormal cornification in humans, evidence that these lipids directly provoke abnormal scale is lacking. One recently described example of a lipid abnormality in ichthyosis is absence of the enzyme steroid sulfatase in recessive X-linked ichthyosis (RXLI). This enzyme normally desulfates cholesterol sulfate (CS) and sulfated steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). As a result of this enzyme deficiency, patients with RXLI accumulate CS in their blood and skin. To determine whether sulfated sterols are the specific cause of increased scale, we applied CS, DHEAS, cholesterol, or vehicle alone to the backs of hairless mice. In animals treated with CS, but not with DHEAS or with vehicle, visible scale without erythema appeared after 1 week, peaked at 2 weeks, and then diminished. When the dose of CS was doubled, abnormal scale reappeared and then decreased again. CS-induced scale was reversible, clearing within 3 days of discontinuation of treatment. Because there was no acanthosis, dermal inflammation, abnormal transepidermal water loss, or increased labeling index, it appears that the 3-fold increase in thickness of the stratum corneum in CS-treated animals is due to a direct effect on this layer.