A three-year follow-up study of psoriasis patients treated with low dosages of etretinate orally and corticosteroids topically.

Etretinate 0.5 mg/kg body weight combined with 0.1% triamcinolone acetonide and 5% salicylic acid in an O/W cream gave more than 70% improvement in 62% of 75 patients. Of this satisfactorily improved group, at least 41% were still in the same condition after 3 years on a maintenance dose of, on average, 0.3 mg/kg body weight etretinate daily and 20 g weekly of a relatively strong corticosteroid cream. The side effects were acceptable and the convenience for the patients is great as compared with other treatment.

Combined treatment of psoriasis with a new aromatic retinoid (Tigason) in low dosage orally and triamcinolone acetonide cream topically: a double-blind trial.

In a multicentre double-blind trial the effect of three therapy regimens was studied for 6 weeks in ninety psoriasis patients: (1) aromatic retinoid (Ro 10-9359) orally (0.50-0.66 mg/kg body weight) and placebo cream topically; (2) aromatic retinoid (Ro 10-9359) (same dosage) with 0.1% triamcinolone acetonide and 5% salicylic acid in lanette wax cream; (3) placebo capsules with 0.1% triamcinolone acetonide and 5% salicylic acid in lanette wax cream. Regimen 1 had virtually no effect and regimen 2 gave better results than regimen 3 for almost all parameters, although statistical significance was reached for only some of them. The 6 week double-blind period was followed by an open study in which all patients were treated according to regimen 2. The clinical result could be maintained up to the end of the study (18 weeks), when more than 60% of the patients showed good to excellant (80-100%) improvement. Most of the side-effects of retinoid were mild and relatively rare. It is concluded that the combination of the aromatic retinoid (Ro 10-9359) given in low dosage orally with corticosteroids topically is as effective as therapy with the retinoid in high dosage alone, but with markedly less side-effects.

Is the use of Ro 10-9359 (Tigason) in children justified?

In 5 children ranging in age from 8 to 12 years, treatment with Ro 10-9359 for either psoriasis or erythrokeratodermia variabilis for periods of between 11 and 17 months did not cause marked growth retardation and gave excellent therapeutic results.

Xanthomatosis and other clinical findings in patients with elevated levels of very low density lipoproteins.

Forty-six patients with xanthomatosis and elevated very low density lipoproteins (VLDL) levels (in different types of hyperlipoproteinaemia) were classified on the basis of the WHO criteria and the cholesterol/triglyceride ratio in VLDL. A large majority (31/46) of the patients referred to the Department of Dermatology could be classified as hyperlipoproteinaemia type III, only 8/46 as type IIB and 7/46 as type IV/V. This distinction seems to be relevant as the xanthomatous lesions differed distinctly between these three types of hyperlipoproteinaemia. Xanthochromia striata palmaris was present in 29/31 cases of hyperlipoproteinaemia type III and was not found in type IV/V patients, who had distinctive papuloeruptive xanthomas. During a follow-up in 35/46 patients all xanthomas disappeared within 2 years except the xanthelasma palpebrarum and tendinous xanthomas. All type IV/V patients (7/7) but only one type III patient (1/31) had abnormal glucose tolerance. Only 2/18 type III patients less than 45 years showed claudication and none of the young type III patients had angina pectoris. In contrast, all four type IIB patients less than 45 years had clinical signs of atherosclerosis. However, angina pectoris and/or claudication were present in 5/13 type III patients over 45 years old. The mean serum cholesterol level was equally elevated in both groups but the cholesterol was mainly present in VLDL in type III and in low density lipoproteins (LDL) in type IIB. In 9/31 type III patients the LDL level was also elevated but was easily normalized by a diet low in carbohydrate, whereas the elevated LDL level in type IIB was therapy-resistant. The recognition of xanthomatous lesions, specifically xanthochromia striata palmaris, as an early sign of type III hyperlipoproteinaemia, can lead to the early diagnosis and successful treatment of these patients, and thus possibly prevent the development of premature atherosclerosis.

Effects of glucocorticosteroids on cultured human skin fibroblasts. III. Transient inhibition of cell proliferation in the early growth stages and reduced susceptibility in later growth stages.

An immediate depression of the rate of cell proliferation occurred upon addition of glucocorticosteroids to cultures of human skin fibroblasts in the early growth stages. A reduced sensitivity or even insensitivity of the fibroblasts to growth inhibition inhibition was found upon the addition of the steroids at later stages of cell growth, when the cell density has increased. The inhibition in the early growth stages is transient and is most pronounced if the cultured medium is not renewed. This transient inhibition is not due to the development of steroid-resistant cell lines, and resembles the effect called tachyphylaxis, as is also observed in vasoconstriction tests.

Penetration of various corticosteroids through epidermis in vitro.

The penetration through the epidermis in vitro of various topically used corticosteroids was compared. The amount penetrating through the epidermis from an ethanolic solution showed good correlation with the polarity of the corticosteroids under study. Hydrocortisone, the most polar corticosteroid, penetrates the epidermis the most rapidly; clobetasone butyrate, the least polar, the slowest. Other corticosteroids, i.e., hydrocortisone-17-butyrate, triamcinolone acetonide, and clobetasol-17-propionate, form an intermediate group whose penetration rates and polarities decrease in the indicated sequence. The corticosteroid generally accepted as having greater clinical efficacy in creams or ointments did not permeate better from an ethanolic solution in vitro.

Effects of glucocorticosteroids on primary human skin fibroblasts. I. Inhibition of the proliferation of cultured primary human skin and mouse L929 fibroblasts.

Various glucocorticosteroids were added to logarithmically growing cultures of primary human skin fibroblasts and of mouse L929 fibroblasts. These steroids inhibited proliferation of the human fibroblasts at concentrations which fall in a range expected to occur during the topical treatment of skin disorders. In terms of the concentrations required for the inhibition hydrocortisone was least and clobetasol-17-propionate most effective. All other steroids studied (hydrocortisone-17-butyrate, triamcinolone acetonide, betamethasone-17-valerate and hydrocortisone-21-acetate) showed medium effectiveness. Fluorination as such may not enhance the inhibitory effect. The inhibition was independent of the source (baby foreskin or adult arm skin) and passage number (7th to 13th or 15th and 16th passage, respectively) of the cells. The possible relationship between the inhibition of cell proliferation by such steroids and their therapeutic effect in psoriasis and their atrophic side effects is discussed. Mouse L929 fibroblasts were affected at 10(3)--10(4)-fold lower steroid concentrations and the range of the effective concentrations was 10(4)--10(5) times as wide as that for the primary human skin fibroblasts. It was concluded that these mouse fibroblasts are a poor model system for the study of in vivo effects of glucocorticosteroids in man.