Steroid sulfatase inhibitors as novel additions to the antipsoriatic armamentarium.

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 benefit 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 beneficial immunological effects of steroid sulfatase inhibitors outweigh their possible hyperkeratosis stimulation. Alternatively, the production of specific DHEA-sulfatase inhibitors can resolve the above concern. DHEA-sulfatase inhibitors may prove invaluable in the treatment of psoriasis.