The in vitro effect of hydroxychloroquine on skin morphology in psoriasis.
BACKGROUND
In earlier papers, we suggested that the aggravation of psoriasis by antimalarial drugs (analogous to hypolipidemic drugs) could be initiated by a break in the epidermal barrier. We suggested that these drugs exerted their effect by inhibiting epidermal transglutaminase activity, and supported this hypothesis by demonstrating the effect of hydroxychloroquine sulfate (HCQS) on the morphology of cultured skin and on liver transglutaminase activity. In the present article, we describe, for the first time, the morphologic 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 experiment was repeated twice.


RESULTS
Significant changes in the epidermal morphology of psoriatic skin cultured in the presence of HCQS, compared with skin cultured without the presence of the drug, were observed. The most striking changes were enhanced and irregular keratinization and dermo-epidermal detachment and cleft formation. No parakeratosis or other characteristics of psoriasis were observed.


CONCLUSIONS
The first changes caused by HCQS on the cultured skin of psoriatic patients are not characteristic of psoriasis, and include hyperproliferation and enhanced and irregular keratinization. The present experimental study gives further support to the hypothesis that HCQS causes an initial break in the barrier function of the epidermis (probably by inhibiting transglutaminase activity), which is followed by a physiologic response of the epidermis aimed at barrier restoration. This rather nonspecific stimulus to epidermal proliferation is probably sufficient to trigger psoriasis, in vivo, among genetically predisposed patients.
Wolf
R
R
Macabbi Health Care Outpatient Clinic, and the Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Schiavo
A L
AL
Lombardi
M L
ML
de Angelis
F
F
Ruocco
V
V
D000962:Antimalarials / Q000494:pharmacology*; D046508:Culture Techniques; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007633:Keratins / Q000187:drug effects / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D011565:Psoriasis / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D000962:Antimalarials; D008543:Melanins; D006886:Hydroxychloroquine; D007633:Keratins