The epidermal phenotype during initiation of the psoriatic lesion in the symptomless margin of relapsing psoriasis

Background: The mature psoriatic lesion does not necessarily demonstrate ch anges relevant to early phases of the lesion. Objective: In a model for relapsing psoriasis we examined the epidermal phe notype by means of a panel of immunohistochemical parameters: keratins 14 a nd 16, epidermal growth factor receptor (EGFR), Ki-67 antigen, and Tdt-medi ated Unscheduled Nick End Labeling to detect apoptosis. Methods: In 9 patients, we cleared psoriatic plaques by topical treatment w ith clobetasol-17-propionate under hydrocolloid occlusion. Relapse (defined as a clinical sum score greater than or equal to 6) was awaited. Biopsy sp ecimens of the psoriatic lesion, the cleared skin, the relapsed plaque, and its clinically normal margin were assessed. Results: Psoriasis recurred after 19 +/- 6 weeks (mean +/- SEM). During tre atment all parameters improved considerably; however, the number of apoptot ic cells was not affected. Ki-67 values decreased well below the normal ran ge. At initial relapse, the symptomless skin adjacent to the relapsing lesi on (margin) showed a marked expression of keratin 16 and EGFR. Ki-67 expres sion was increasing in the margin but was below values of the mature lesion . The localization of cycling cells in the first suprabasal layers was a re markable feature. Keratin 14 expression was increased in the recurrent lesi on itself, but not in the symptomless margin. Conclusion: Keratin 16 and EGFR expression are early phenomena in the evolu tion of the lesion, and they anticipate epidermal proliferation. The expres sion of keratin 14 follows overt epidermal hyperproliferation. The present observation in incipient psoriasis lends support to the hypothesis that the basal cell compartment does not have a primary involvement in the initiati on of epidermal abnormalities in psoriasis, but that a coordinated sequence of events involving proliferation and differentiation markers in the first suprabasal layers of the epidermis could be the key to the pathogenesis of this puzzling disease.