RESUMEN
Treatment of psoriasis with dithranol as monotherapy or dithranol in combination with UVB phototherapy is an effective and safe approach for the management of psoriasis. Recently a new formulation of dithranol embedded in crystalline monoglycerides (Micanol) has become available. It was shown that this formulation combines adequate efficacy with low irritation and staining properties. The aim of the present study was to compare and contrast three treatment schedules with respect to clinical efficacy and tolerability: Micanol monotherapy, Micanol in combination with UVB phototherapy and placebo combined with UVB phototherapy. The study design was a partly open, partly double-blind, randomized, left-right comparison. In total 36 patients were included and 24 body halves were available for each of the three treatments. The combination of Micanol with UVB resulted in clearance of lesions in 54% of the patients (body halves). Combination therapies with Micanol and either of the two other therapies were highly effective. However, with the number of patients investigated, a statistically significant difference between the three therapeutic approaches with respect to efficacy could not be shown. The three treatments resulted in a grosso modo comparable clinical improvement. Severe irritation was observed in 8% and staining of the skin in 29% of the patients treated with the combination therapy Micanol/UVB, which is far less compared to the irritation and staining by the conventional short contact approaches. The efficacy and tolerability of Micanol make this active substance an important tool in the management of psoriasis.
Asunto(s)
Antralina/administración & dosificación , Antiinflamatorios/administración & dosificación , Psoriasis/tratamiento farmacológico , Psoriasis/radioterapia , Terapia Ultravioleta , Administración Tópica , Adulto , Anciano , Antralina/efectos adversos , Antiinflamatorios/efectos adversos , Distribución de Chi-Cuadrado , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , PomadasRESUMEN
The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16.
Asunto(s)
Proteínas de Filamentos Intermediarios/análisis , Precursores de Proteínas/análisis , Psoriasis/patología , Piel/química , Tenascina/análisis , Adulto , Anciano , Biopsia , División Celular/fisiología , Células Epidérmicas , Epidermis/química , Epidermis/patología , Femenino , Proteínas Filagrina , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/metabolismo , Queratinas/análisis , Queratinas/genética , Queratinas/metabolismo , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Psoriasis/metabolismo , Psoriasis/fisiopatología , Piel/patología , Piel/fisiopatología , Tenascina/genética , Tenascina/metabolismoRESUMEN
The clinical efficacy and tolerability of the vitamin D3 analogues calcitriol, calcipotriol and 1 alpha, 24 dihydroxyvitamin D3 in the treatment of psoriasis have been assessed in various clinical studies. In vitro and in vivo investigations have shown interference of these compounds with epidermal growth, keratinisation and inflammation. In this study we quantified the in vivo cell biological effects during treatment of psoriatic plaques with 1 alpha, 24 dihydroxyvitamin D3. By using a flow cytometric triple labelling procedure, we could discriminate different epidermal subpopulations, permitting precise assessment of epidermal cell cycle kinetics. Twenty patients with plaque-type psoriasis were treated in a double-blind placebo-controlled left-right comparative study with 1 alpha, 24 dihydroxyvitamin D3 ointment (4 micrograms/g applied once daily) for 8 weeks. Epidermal cell suspensions prepared from keratotome biopsies taken before and after treatment were stained with TO-PRO-3 iodide (a new DNA fluorochrome) and monoclonal antibodies against keratin 10 (as a marker for differentiation) and vimentin (as a marker for inflammation), simultaneously. The flow cytometric analyses showed a significant decrease of proliferating basal keratinocytes in verum-treated lesions, whereas such a decrease was not observed in placebo-treated lesions. The amount of keratin 10-positive keratinocytes increased and the presence of vimentin-positive cells decreased in cell suspensions derived from both verum- and placebo-treated lesions, but these effects were not significant. We conclude that multiparameter flow cytometry promises to be an adequate approach to assess the interference of antipsoriatic treatments with cutaneous inflammation, epidermal proliferation and keratinisation. Topical 1 alpha, 24 dihydroxyvitamin D3 seems to exert its in vivo antipsoriatic effect mainly through an inhibition of epidermal growth.
Asunto(s)
Fármacos Dermatológicos/uso terapéutico , Dihidroxicolecalciferoles/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Biopsia , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , ADN/análisis , Fármacos Dermatológicos/administración & dosificación , Dihidroxicolecalciferoles/administración & dosificación , Método Doble Ciego , Epidermis/efectos de los fármacos , Epidermis/patología , Femenino , Citometría de Flujo , Colorantes Fluorescentes , Humanos , Inflamación , Queratinas/análisis , Masculino , Persona de Mediana Edad , Placebos , Psoriasis/patología , Vimentina/análisisRESUMEN
Platelet-activating factor (PAF) is considered to be one of the most potent lipid mediators in allergic and inflammatory reactions. Suggestions that PAF is produced by cutaneous cells, and cells infiltrating the skin from the blood, have been reported. PAF has been identified in allergic cutaneous reactions and also in psoriatic lesions. The biological activity of PAF is thought to be mediated by cell membrane receptors. Studies revealed that PAF-antagonists can be active in animal models of cutaneous inflammation. In humans PAF-antagonists showed minimal therapeutic improvement in studies of antigen-induced cutaneous responses in atopic subjects. No data are available on the effects of PAF-antagonists in psoriasis. The objective of this study was to investigate the effect of a potent PAF-antagonist (Ro 24-0238, 10% solution in diethylene glycol monoethyl ether) in 10 patients with chronic plaque psoriasis, a placebo-controlled double-blind study. Clinical response was evaluated and markers of inflammation, differentiation and proliferation were studied immunohistochemically on punch biopsies taken from actively treated and placebo-treated lesions, before and after treatment. This study demonstrated that a 10% solution of the PAF-antagonist Ro 24-0238 was not effective at the clinical or cell biological level after a 4-week treatment period. The most likely explanation for these negative observations is that PAF is not a significant factor in the pathogenesis of psoriasis.