hoe-777 and Atrophy

Topics: Administration, Cutaneous; Adult; Atrophy; Betamethasone Valerate; Biopsy; Cell Count; Clobetasol; Drug Evaluation; Female; Glucocorticoids; Humans; Hydrocortisone; Keratinocytes; Male; Middle Aged; Occlusive Dressings; Pharmaceutical Vehicles; Prednisolone; Skin; Telangiectasis; Ultrasonography

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.

Topics: Administration, Topical; Anti-Inflammatory Agents; Atrophy; Betamethasone Valerate; Dermatitis, Atopic; Glucocorticoids; Humans; Mometasone Furoate; Odds Ratio; Prednisolone; Pregnadienediols; Psoriasis; Skin

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.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Atrophy; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Mometasone Furoate; Ointments; Prednisolone; Pregnadienediols; Skin

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Atrophy; Calcitriol; Clobetasol; Dermatitis, Contact; Dermatologic Agents; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Prednisolone; Skin; Ultrasonography

Topics: Administration, Cutaneous; Adolescent; Adult; Atrophy; Betamethasone Valerate; Double-Blind Method; Drug Evaluation; Epidermis; Female; Humans; Male; Middle Aged; Photomicrography; Prednisolone; Severity of Illness Index; Telangiectasis

Topics: Administration, Cutaneous; Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Atrophy; Betamethasone Valerate; Clobetasol; Dermatitis, Phototoxic; Double-Blind Method; Drug Tolerance; Female; Humans; Irritants; Male; Methylprednisolone; Occlusive Dressings; Ointments; Prednisolone; Skin; Skin Tests

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.

Topics: Administration, Topical; Anti-Inflammatory Agents; Atrophy; Betamethasone Valerate; Double-Blind Method; Humans; Hydrocortisone; Ointments; Prednisolone; Skin; Ultrasonography

The atrophogenic potential of medium-potent topical glucocorticoids is still controversial. In a double-blind controlled trial 24 healthy volunteers either applied 0.25% prednicarbate cream or the corresponding vehicle to one and 0.1% betamethasone-17-valerate cream or 0.05% clobetasol-17-propionate cream to the other forearm twice daily. Skin thickness was regularly assessed during the six week period of application and for further three weeks thereafter, using both the B- and A-mode of a 20 MHz ultrasound scanner. Both betamethasone-17-valerate and clobetasol-17-propionate cream significantly reduced skin thickness as compared to cream base while prednicarbate cream did not. Given that 0.1% betamethasone-17-valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect.

Topics: Adult; Anti-Inflammatory Agents; Atrophy; Betamethasone Valerate; Clobetasol; Double-Blind Method; Female; Humans; Male; Ointments; Pharmaceutical Vehicles; Prednisolone; Skin

Topics: Anti-Inflammatory Agents; Atrophy; Cortisone; Glucocorticoids; Humans; Methylprednisolone; Mometasone Furoate; Ointments; Pituitary-Adrenal System; Prednisolone; Pregnadienediols; Skin Diseases; Time Factors

Topics: Administration, Topical; Anti-Inflammatory Agents; Atrophy; Humans; Hydrocortisone; Prednisolone; Risk Factors; Skin

Topics: Administration, Cutaneous; Adult; Atrophy; Betamethasone Valerate; Clobetasol; Double-Blind Method; Glucocorticoids; Humans; Hydrocortisone; Pharmaceutical Vehicles; Prednisolone; Skin; Ultrasonography