Epidermal differentiation characteristics of the psoriatic plaque during short contact treatment with dithranol cream

Dithranol has been used successfully in the treatment of psoriasis for more than 75 years, and much in vitro anti in vivo research has been done on the elucidation of the mode of action of this potent and safe antipsoriatic therapy. In vivo research has research major effects of dithranol on epidermal proliferation and inflammation- Information on the in vivo effects on epidermal differentiation is limited. Therefore, the dynamics of a set of differentiation markers (keratin 16, filaggrin, keratinocyte transglutaminase, involucrin) and markers for proliferation and inflammation (Ki-67, T lymphocytes, polymorphonuclear leucocytes) were studied in skin biopsies of six patients with psoriasis during 4 weeks of dithranol therapy. The treatment regimen involved a short contact protocol at our out-patient day treatment centre with an easily washed off cream. Treatment resulted in a decrease of the PASI score of 48° in 4 weeks. Immunohistochemically, a major decrease of keratin 16 content and virtually complete restoration of the filaggrin positive cell layer were seen. These changes proved to be significant by comparison of the markers over the group of six patients. Although many other topical treatments for psoriasis (occlusive therapy and vitamin D₃ analogues) result in a prominent reduction in the amount of transglutaminase and involucrin positive cell layers, the effect of dirhranol on these markers is minimal.     

Distribution of skin-derived antileucoproteases (SKALP) in the marginal zone of the spreading psoriatic lesion

Two new elastase inhibitors (SKALP, skin-derived antileucoproteases) were recently described in the lesional skin in psoriasis. The present study investigated the distribution of SKALP activity in the marginal zone of spreading psoriatic plaques. In a 4-mm zone immediately adjacent to the erythemato-squamous plaques, SKALP activity was slightly increased compared to distant uninvolved skin. Within the lesion the anti-elastase activity was pronounced, but was significantly higher in the central zone of the plaque compared to the periphery. The appearance of SKALP in the psoriatic lesion appears to be a late event compared to endothelial involvement, intraepidermal accumulation of PMNs, epidermal proliferation and abnormal keratinization. This observation lends further support for the hypothesis that the induction of anti-elastase activity is associated with the off-switch of cutaneous inflammation.     

Skin manifestations in congenital deficiency of leucocyte-adherence glycoproteins (CDLG)

In congenital deficiency of leucocyte-adherence glycoproteins (CDLG) there is an immunodeficiency with impaired leucocyte function and cutaneous and extracutaneous infections occur. In more than 30% of cases the condition has a fatal course. We report the skin manifestations of three siblings with CDLG in which areas of skin necrosis occurred that resembled pyoderma gangrenosum.     

Leukotriene B4 fails to induce penetration of lymorphonuclear leukocytes into psoriatic lesions

The intraepidermal accumulation of polymorphonuclear leukocytes following the epicutaneous application of leukotriene B4 (LTB4) was studied in lesional and clinically uninvolved skin of five patients with chronic stable plaque psoriasis. The lesions were found to be wholly unresponsive to LTB4, doses of 100 ng failing to produce either micropustules or exocytosis. This phenomenon was sharply localized; the response immediately adjacent to the lesion being identical to that in more distant uninvolved skin. We speculate that both the reduced response to LTB4 in the psoriatic patient and also the tolerance to LTB4 seen after repeated applications, result from the induction of a P450-linked hydroxylase.