Response of psoriasis to a new topical retinoid, AGN 190168.
BACKGROUND
Oral retinoids have been widely used in psoriasis, but topical forms have been ineffective or irritating.


OBJECTIVE
Our purpose was to determine the clinical and molecular effects of a new topical retinoid, AGN 190168, on psoriasis.


METHODS
Seven patients with psoriasis were treated for 2 weeks with topical retinoid and 2 weeks with vehicle. Two control subjects with psoriasis were treated for 2 weeks with vehicle alone. Biopsy specimens from normal skin as well as from untreated and treated psoriatic lesions were compared by immunohistochemical analysis. Differentiation and inflammatory markers were studied.


RESULTS
Clinical improvement was seen in all seven patients after 2 weeks of treatment. Improvement was still present, but not significant, after 2 additional weeks of vehicle application. Histologic examination showed a return to a more normal morphology in four of seven biopsy specimens, which correlated with filaggrin expression. There was a diminution in the precocious expression of keratinocyte transglutaminase, keratin 16, and involucrin, as well as a decrease in epidermal growth factor receptor and in the number of cells expressing intercellular adhesion molecule type 1 and HLA-DR.


CONCLUSIONS
Clinical and histologic improvements were seen in psoriasis in association with the topical application of AGN 190168 at 2 weeks, including decreased inflammation and restoration of normal epidermal differentiation. Small patient numbers and the possibility that the changes were related to clinical improvement alone and not the topical agent preclude definitive conclusions.
Esgleyes-Ribot
T
T
Department of Dermatology, University of Texas Medical School at Houston 77030.
Chandraratna
R A
RA
Lew-Kaya
D A
DA
Sefton
J
J
Duvic
M
M
D000279:Administration, Cutaneous; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D004311:Double-Blind Method; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000096:biosynthesis; D008297:Male; D009539:Nicotinic Acids; D010865:Pilot Projects; D011446:Prospective Studies; D011498:Protein Precursors / Q000096:biosynthesis; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012176:Retinoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011503:Transglutaminases / Q000096:biosynthesis
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006684:HLA-DR Antigens; D007381:Intermediate Filament Proteins; D009539:Nicotinic Acids; D011498:Protein Precursors; D012176:Retinoids; D018799:Intercellular Adhesion Molecule-1; C032253:involucrin; D007633:Keratins; C086827:tazarotene; D011503:Transglutaminases; D066246:ErbB Receptors