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.     

Tacalcitol ointment in the treatment of psoriasis vulgaris:a multicentre, placebo-controlled, double-blind study on efficacy and safety

Summary Tacalcitol is a vitamin D analogue which has been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2μg/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 μg/g tacalcitol ointment in Caucasian psoriatics.
The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P<0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12·3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1α,24-dihydroxyvitamin D₃ and 25- hydroxyvitamin D₃ did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 μg/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.     

Simultaneous assessment of inflammation and epidermal proliferation in psoriatic plaques during long-term treatment with the vitamin D3 analogue MC903: modulations and interrelations

The influence of topical application of MC903, an analogue of 1 alpha,25-dihydroxyvitamin D3, on psoriatic plaques was investigated during a long-term treatment study. The parameters for epidermal growth and for inflammation were assessed on frozen sections using immunohistochemical methods to elucidate their modulations in time and the interrelations between the different cell types involved during treatment with MC903. Biopsies were taken before and after 1, 2, 4 and 12 weeks of treatment. Monoclonal antibodies against the hyperproliferation-associated keratin 16, against cycling nuclei, and against T lymphocytes, B lymphocytes, Langerhans cells and CD14-positive cells were used in combination with a polyclonal antibody against polymorphonuclear leucocyte (PMN)-elastase. The earliest change was a statistically significant decrease in PMN after 1 week of treatment followed by a decline of cycling nuclei after 2 weeks. These changes preceded a decrease of T lymphocytes which occurred after 4 weeks. Keratin 16 content tended to diminish after 4 weeks of treatment. CD14+ cells decreased slightly during the observation period, whereas Langerhans cells tended to increase. No B lymphocytes were found. These results suggest that MC903 influences the number of PMN and epidermal growth rather than the number of T lymphocytes.     

Methotrexate inhibits the leukotriene B4 induced intraepidermal accumulation of polymorphonuclear leukocytes

The penetration of polymorphonuclear leukocytes (PMNs) into the epidermis following topical application of leukotriene B4 was assessed in the clinically uninvolved skin of psoriatic patients treated with methotrexate and of psoriatic patients without treatment, and in normal controls. Inhibition of PMN infiltration was observed in those patients treated with methotrexate while there was no significant difference between untreated psoriatic patients and normal controls.     

The hereditary palmoplantar keratoses: an updated review and classification

The palmoplantar keratoses (PPKs) comprise a heterogeneous group of disorders of keratinization, which can be subdivided into hereditary and acquired forms. Many authors have attempted to classify the hereditary forms,^1–5 and most classifications have been based on the morphology, distribution, associated symptoms and mode of inheritance. Subsequently, many new forms have been recognized, and what were previously considered to be distinct types have been shown to be variants of a single type, both of which limit the usefulness of previous classifications. Hence, we propose a new, updated classification, which enables accurate diagnosis of these disorders.     

Epidermal cell DNA content and intermediate filaments keratin 10 and vimentin after treatment of psoriasis with calcipotriol cream once daily, twice daily and in combination with clobetasone 17-butyrate cream or betamethasone 17-valerate cream: a comparative flow cytometric study

Calcipotriol and corticosteroids, two therapy modalities frequently prescribed in the treatment of psoriasis, are often used in combination. The aim of the present study was to determine whether the cell biological response pattern of concurrent use of calcipotriol and corticosteroids is different from calcipotriol monotherapy. Forty patients with chronic plaque psoriasis were divided at random in four parallel groups and treated for 8 weeks with: (1) calcipotriol cream (50 μg/g once daily); (2) calcipotriol cream twice daily; (3) calcipotriol and clobetasone 17-butyrate (0.5 μg/g) creams; and (4) calcipotriol and betamethasone 17-valerate (1 mg/g) creams. Before and after treatment keratotome biopsies were taken and single cell suspensions prepared for flow cytometric analysis. Flow cytometric multiparameter quantification of markers for proliferation (TO-PRO-3), differentiation (antikeratin 10) and inflammation (antivimentin) was used to evaluate all four therapy modalities. A statistically significant decrease of the percentage of basal cells in S- and G₂M-phase (proliferation)was obtained with all therapy modalities, except for calcipotriol monotherapy applied once daily. A significant reduction of the number of vimentin-positive cells (non-keratinocytes) was observed following combined treatment with calcipotriol and clobetasone butyrate. In contrast, monotherapy with calcipotriol had virtually no effect on the number of vimentin-positive cells. It can be concluded that: (i) calcipotriol monotherapy, applied once daily was less antiproliferative compared with twice daily applications of calcipotriol or the combined treatment with corticosteroids and that (ii) the combination of calcipotriol and corticosteroids proved to have a marked effect on the percentage of non-keratinocytes, in contrast to the modest effect of calcipotriol.     

Effect of topical calcipotriol on congenital ichthyoses

We investigated the clinical efficacy of topically applied calcipotriol in six patients with congenital ichthyosis, using a double-blind, bilaterally paired, comparative approach. Unilateral improvement, in favour of the calcipotriol-treated side, was observed in three patients with lamellar ichthyosis. A beneficial response was also observed in a patient with bullous ichthyotic erythroderma of Brocq. No clinical side-effects or laboratory anomalies were observed. This study indicates that calcipotriol constitutes a new and promising approach in alleviating disorders of keratinization characterized by hyperproliferation, other than psoriasis.