Downregulation of involucrin in psoriatic lesions following therapy with propylthiouracil, an anti‐thyroid thioureylene: immunohistochemistry and gene expression analysis

Background Propylthiouracil ( PTU ), an anti‐thyroid thioureylene, has been shown to be effective in chronic plaque psoriasis. Involucrin is a precursor protein that is upregulated in psoriasis. Objectives This study evaluated the expression of involucrin in the epidermis of skin in psoriatic plaques before and after treatment with PTU . Methods This was an open‐label, prospective study in which 25 psoriasis patients underwent skin biopsies prior to treatment with oral PTU 100 mg three times per day for 12 weeks. Patients were assessed at 2, 6, and 12 weeks. Skin biopsies were repeated at the same sites at 12 weeks. Pre‐ and post‐treatment specimens were subjected to immunohistochemical staining and real‐time polymerase chain reaction for involucrin. Results Mean ± standard deviation ( SD ) scores on the P soriasis A rea and S everity I ndex reduced significantly from 17.86 ± 9.9 at baseline to 4.63 ± 4.1 at week 12 ( P  < 0.001). Histomorphometric analysis revealed marked decreases in numbers of positively stained cells and intensity of staining. Staining became localized to the upper granular layers after therapy. Immunohistochemical scoring for involucrin reduced from a mean ±  SD of 9.00 ± 0.67 at baseline to 3.90 ± 0.88 at week 12 ( P  < 0.0001). Conclusions In psoriasis, there is increased expression of involucrin, which leads to abnormal keratinocyte differentiation and hence to the formation of psoriatic plaques. The therapeutic effect of PTU in psoriasis may be attributable to the downregulation of involucrin. Larger trials should further elucidate the mechanism and therapeutic potential of PTU in psoriasis.