A sequential double immunoenzymic staining procedure was developed using the monoclonal antibody anti-BrdUrd and Ki67 in order to determine whether hyperproliferative skin disorders, such as psoriasis, are characterized by an increased growth fraction rather than a much shorter cell cycle time of all germinative cells. Ki67 binds to a proliferation-associated nuclear antigen in a variety of human cell types, and anti-BrdUrd can be used to identify DNA-synthesizing cells. Although in hyperproliferative epidermis the absolute numbers of BrdUrd-positive cells as well as Ki67-positive cells were grossly increased, the ratio of these values was not changed compared to the ratio found in the epidermis of the clinically uninvolved skin of psoriatic patients and in normal epidermis. This suggests an increased growth fraction in hyperproliferative epidermis. Our data show that immunohistochemical double-staining techniques can be a valuable tool in the study of cell cycle kinetics in epithelial tissues.

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To study the development of the psoriatic lesion, biopsies were taken from the margin of spreading plaques and acute pinpoint papules. Consecutive sections across the margin were stained using different monoclonal antibodies to characterize epidermal growth (Ki-67) and abnormal keratinization (Ks8.12, RKSE60). All three immunohistochemical markers showed pronounced changes in the lesional skin with a clear transition to the uninvolved skin. The suprabasal Ks8.12 binding was the earliest change found in the epidermis, and its localization high in the suprabasal compartment indicates that metabolic dysregulation in this cell population was not a consequence of the recruitment process in the basal layer.

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The relevance of salicylic acid in dithranol creams was evaluated in a double-blind study. Patients with chronic plaque psoriasis were treated using a short-contact schedule for dithranol on an outpatient basis. A left-right comparison was carried out between sites treated with either dithranol with 2 % salicylic acid (D+S) or dithranol in the same base without salicylic acid (D-S). Clinical results were evaluated once a week using the psoriasis area severity index. In order to quantify the improvement, flow cytometric measurements were done using the monoclonal antibody K_s8.12, recognizing keratin 16 in normal and lesional epidermis. Simultaneously, relative DNA content was quantified which previously was described as a useful method to monitor a therapeutic effect. Both PASI scores and K_s8.12 binding decreased after 6 weeks treatment with D+S and D-S. However, percentages of cells in SG₂M phases did not show a significant change. No significant difference was observed between sites treated with either D+S or D-S. Therefore we conclude that the addition of salicylic acid in a concentration of 2 % does not enhance the efficacy of dithranol creams and we confirm that K_s8.12 is a useful quantitative marker for therapeutic efficacy.