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BACKGROUND: Numerous therapeutic schemes recommend topical administration of emollients immediately prior to ultraviolet (UV) B therapy. The rationale behind the clinical improvement is a presumed enhancement of UV transmission through the epidermis. Originating from this clinical observation, there has been some concern as to whether a well-hydrated skin in general might be more susceptible to actinic damage. OBJECTIVES: To investigate whether rehydration of healthy skin causes an altered UVB sensitivity in vivo. METHODS: We determined minimal erythema doses (MEDs) and erythema sum scores (ESSs) after differential rehydration of the skin in 10 healthy volunteers. In each subject six UVB phototests were performed after pretreatment with five different emulsifying ointments (unguentum emulsificans and dilutions with 30, 50, 70 and 90% aqua purificans) plus a negative control. In vivo evaluation of stratum corneum hydration was performed by measurement of electrical capacitance. RESULTS: The results of this randomized, double-blind in vivo study indicated that rehydration of normal stratum corneum with the emulsifying ointments tested did not result in a significantly altered sensitivity to the erythematous effects of UVB irradiation (no significant differences in MED and ESS). Furthermore, there was no correlation between measured stratum corneum hydration and the erythema response of healthy skin. CONCLUSIONS: Although many schemes recommend the administration of emollients prior to UV therapy, there have also been calls for caution, as an uncritical application may interfere with such treatment. We showed that the emulsifying ointments tested exhibited no photoprotective potential and thus are suitable for the pretreatment of psoriasis prior to phototherapy. It has long been discussed whether the effects of emollient pretreatment on response to UV occur only in psoriatic skin or also in healthy skin. Our results indicated that stratum corneum rehydration did not result in a significantly increased erythema response of healthy skin to UVB exposure. With regard to the use of rehydrating cosmetics in everyday life, the outcome of our pilot study is reassuring, as we could not confirm with our experimental design that well-hydrated healthy skin is more prone to actinic damage.

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Chronic cutaneous lesions in eight of 15 survivors of the Chernobyl nuclear energy plant accident presenting with clinical features of cutaneous radiation fibrosis were examined 6 years after exposure using high-frequency ultrasound. In all patients, lesional skin was examined using both the B- and A-modes. Similar phenomena were found in all patients. The corium was increased in thickness as well as density compared to normal skin. The increase in density was seen not only in the medium strata but also particularly at the border between corium and subcutaneous tissue. Within the subcutaneous tissue proper, isles of echo-rich spots were prominent. The number and width of echo signals in the subcutaneous tissue were increased, representing the sonographic correlate of subcutaneous fibrotic trabeculae. The thickness of epidermis plus corium was increased by more than 50% and was even doubled in some cases. According to the present findings obtained from patients with very severe exposure to ionising radiation, ultrasound analysis of cutaneous and subcutaneous radiation fibrosis shows a characteristic picture. Moreover, it was demonstrated that quantitative assessment of skin thickness is possible. As the method is simple and noninvasive, repeated examinations are possible. This provides the basis for monitoring possible treatment effects and efficient follow-up in these chronically progressive clinical conditions after exposure to ionising radiation.

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Repeated open application of clobetasol 17-propionate cream and ointment to normal skin over a period of 6 weeks induced an increase in skin surface roughness as assessed by profilometry (p < 0.05), while 6 weeks' application of triamcinolone acetonide cream and ointment did not. The increase in skin roughness with clobetasol 17-propionate cream turned out to be greater than with ointment containing identical amounts of clobetasol 17-propionate (p < 0.05). A clear-cut correlation between increase of skin surface roughness and skin thickness as assessed by high-frequency ultrasound could be demonstrated only with clobetasol 17-propionate cream and ointment.

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Topical glucocorticoids still belong to the most important medications available in dermatotherapy. The clinical use of topical glucocorticoids, however, nowadays is limited by the fear of side-effects both systemic and local, especially skin atrophy. The purpose of this study was to assess the atrophogenicity potential of newly developed topical glucocorticoids which were said to show an increased benefit-risk ratio. The test preparations comprised mometasone furoate, the corresponding vehicle, prednicarbate and hydrocortisone. They were applied once or twice daily for 6 weeks in healthy volunteers. Skin thickness was assessed weekly by using high frequency pulsed ultrasound. Clinically, none of the volunteers showed any sign of overt skin atrophy. Skin thickness, however, was reduced to a certain extent with all trial preparations including the base preparation. As to be expected from previous experiments the results for hydrocortisone and prednicarbate did not differ significantly from the ones for the base preparation. Interestingly, the same applied to mometasone furoate. These findings, together with the other available data, give evidence of an increased benefit-risk ratio as compared to previous medium potent topical glucocorticoids. This might be of particular interest facing psoriasis vulgaris where an antiproliferative activity of a drug is needed.

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BACKGROUND: Nonhalogenated double esters of prednisolone or hydrocortisone applied topically to the skin have a low atrophogenic potential. However, activity and benefit/risk ratio and therefore the superiority over conventional topical glucocorticoids are not well defined. METHODS: The activities of cream preparations with prednicarbate (0.025% to 0.25%), hydrocortisone aceponate, and hydrocortisone buteprate (0.1%) are compared to the effects of betamethasone 17-valerate (0.1%), hydrocortisone (1%), and two drug-free vehicles in 60 healthy volunteers. Test models are the skin blanching assay (occluded and nonoccluded mode), ultraviolet-induced erythema, and an irritant (sodium dodecyl sulfate) dermatitis. The benefit/risk ratio is derived from the activity in the former models and the reduction of skin thickness as determined previously. RESULTS: Prednicarbate activity increases in a dose-dependent manner. Prednicarbate, 0.25%, and the hydrocortisone double esters appear to be equipotent to betamethasone 17-valerate in the skin blanching test and the ultraviolet-erythema test, but superior to hydrocortisone and the vehicles. Prednicarbate and its vehicle, however, do not reverse irritant dermatitis. The benefit/risk ratios of prednicarbate and hydrocortisone aceponate exceed those with betamethasone 17-valerate. CONCLUSIONS: Prednicarbate and hydrocortisone aceponate are intermediate potent glucocorticoids that are superior to betamethasone 17-valerate because of the improved benefit/risk ratio. Patients with severe atopic dermatitis and those who relapse frequently should profit from the treatment with these newer glucocorticoids.

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Topical glucocorticoids are still among the dermatologicals most frequently used. This is due to their undebatable potency in inflammatory skin disease. Their use is limited by the fear of side effects both systemic and topical, especially skin atrophy. Hence, congeners with an increased benefit-risk ratio are urgently needed and research on new drugs no longer focuses on more active drugs but safer ones. Only recently, evidence has been forwarded that the goal is realistic. Some new glucocorticoids, especially the nonfluorinated double-ester type such as prednicarbate, appear promising. In fact, they seem to affect fibroblast growth in vitro as well as skin thickness in vivo less than equipotent conventional glucocorticoids. Pertinent findings in humans have been obtained with the use of ultrasound equipment. The relevant aspects of chemistry, pharmacology, clinical benefits, and toxicology of the various glucocorticoids old and new are reviewed, as are potential future alternatives.

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Recently a defect in the function of the enzyme delta-6-desaturase has been discussed as a major factor in the development of atopic eczema. Delta-6-desaturase is responsible for the conversion of linoleic acid to gamma linolenic acid. Several plants, including evening primrose, are known to be fairly rich in gamma linolenic acid. Hence, substitution of gamma linolenic acid in patients prone to developing atopic eczema seems like a feasible concept. During the last few years different clinical trials have been performed. Controlled trials following a parallel study design showed marked improvement in atopic eczema. Patients treated with the drug showed less inflammation, dryness, scaling and overall severity compared to controls. Although these findings have been supported by meta-analysis, there is still conflicting evidence in trials based on a crossover design alone, demonstrating a decrease in itching. At present, evening primrose oil in doses used for the treatment of atopic eczema is considered safe. However, still more trials addressing both efficacy and safety are needed to make a final decision.

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24 healthy volunteers with no history of skin disease were entered in a 6-week double-blind randomized study to compare the atrophogenicity potentials of both cream and ointment forms of triamcinolone acetonide and clobetasol propionate. The atrophogenicity potential of cream preparations turned out to be greater than that of ointment preparations containing identical amounts of the same glucocorticoid. This result proves both the reproducibility of the assay and the general character of the phenomenon in view of the limited previous evidence.

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With the advent of non-fluorinated double esters the spectrum of topical dermatotherapy with glucocorticoids seems to have broadened to include safer congeners. To assess the atrophogenicity potential of glucocorticoids, high-frequency ultrasound has been proposed. In a comparative trial using the DUB 20 system, 24 healthy volunteers applied hydrocortisone aceponate, the corresponding vehicle, prednicarbate ointment and betamethasone-17-valerate ointment over a period of 6 weeks. While both hydrocortisone aceponate and prednicarbate ointment induced no significant reduction in skin thickness, the onset of epidermal-dermal thinning with betamethasone-17-valerate was early and the extent marked. These findings imply an increased therapeutic index with the non-fluorinated double esters.

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