The in vitro effect of hydroxychloroquine on skin morphology in psoriasis

Background In earlier papers, we suggested that the aggravation of psoriasi s by antimalarial drugs (analogous to hypolipidemic drugs) could be initiat ed by a break in the epidermal barrier. We suggested that these drugs exert ed their effect by inhibiting epidermal transglutaminase activity and suppo rted this hypothesis by demonstrating the effect of hydroxychloroquine sulf ate (HCQS) on the morphology of cultured skin and on liver transglutaminase activity. In the present article, we describe, for the first time, the mor phologic changes induced by HCQS on cultured skin of psoriatic patients. Methods Uninvolved (apparently normal) skin explanted from the back of two psoriatic patients was cultured in the presence of 9.2 and 13.8 mM of HCQS for 3 days. The morphologic changes were evaluated in a blind manner. The e xperiment was repeated twice. Results Significant changes in the epidermal morphology of psoriatic skin c ultured in the presence of HCQS, compared with skin cultured without the pr esence of the drug, were observed. The most striking changes were enhanced and irregular keratinization and dermo-epidermal detachment and cleft forma tion. No parakeratosis or other characteristics of psoriasis were observed. Conclusions The first changes caused by HCQS on the cultured skin of psoria tic patients are not characteristic of psoriasis, and include hyperprolifer ation and enhanced and irregular keratinization. The present experimental s tudy gives further support to the hypothesis that HCQS causes an initial br eak in the barrier function of the epidermis (probably by inhibiting transg lutaminase activity), which is followed by a physiologic response of the ep idermis aimed at barrier restoration. This rather nonspecific stimulus to e pidermal proliferation is probably sufficient to trigger psoriasis, in vivo , among genetically predisposed patients.