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eISSN: 1643-3750

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Steroid sulfatase inhibitors as novel additions to the antipsoriatic armamentarium

Mohammad R. Namazi

Med Sci Monit 2005; 11(3): HY7-9

ID: 15365


Psoriasis is a clinical conundrum that affects an estimated 1–3% of the world’s population. The psoriatic disease process, characterized by a type 1 cytokine pattern, is supposed to be maintained by a continuing immune response in a “peripheral lymphoid tissue” that forms in lesional skin and is composed of T cells, dendritic cells, and vessels arranged like a T-dependent zone in lymph nodes. Dehydroepiandrosterone (DHEA), produced from dehydroepiandrosterone sulfate (DHEAS) through the enzymatic activity of DHEA-sulfatase, plays a pivotal role in the development
of the type 1 immune response generated in peripheral lymphoid organs. Taken together, it could be reasoned that DHEA-sulfatase inhibitors may have utility in the treatment of psoriasis. Furthermore, the addition of DHEA-sulfatase inhibitors to calcipotriol, which
encourages type 2 immune response, may provide an additive or synergistic inhibition of the type 1 immune response underlying psoriasis. It has been shown that topical application of cholesterol
sulfate in the hairless mouse causes epidermal hyperkeratosis, which can be prevented by co-application of topical cholesterol. Therefore, as the inhibition of conversion of cholesterol sulfate to cholesterol can induce epidermal hyperkeratosis and may thus abbreviate the benefi t obtained by inhibition of DHEAS to DHEA conversion, topical sulfatase inhibitors should preferably be co-applied with topical cholesterol, though it is also possible that the benefi cial immunological effects
of steroid sulfatase inhibitors outweigh their possible hyperkeratosis stimulation. Alternatively, the production of specifi c DHEA-sulfatase inhibitors can resolve the above concern. DHEA-sulfatase inhibitors may prove invaluable in the treatment of psoriasis.

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