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The objective of this double-blind study was to compare the therapeutic effects of acitretin with those of etretinate in patients with Darier's disease. Twenty-six patients (10 males and 16 females) were included in the study. Patients were treated with 30 mg daily for the first 4 weeks and with an individually adjusted dose (10-50 mg/day) for the subsequent 12 weeks. Remission or marked improvement was obtained in 10 of the 13 acitretin-treated patients and in 8 of the 11 etretinate-treated patients who completed the 16-week treatment. The usual mucocutaneous adverse reactions of retinoids were observed in all but one patient. There were no significant differences between treatment groups with regard to the incidence of these reactions.

Six patients with persistent palmoplantar pustulosis were treated with acitretin, and the clinical response was compared with the effect on the intra-epidermal accumulation of polymorphonuclear PMN leukocytes. A prompt improvement of pustule formation and subsequently decreased scaling and erythema was seen in all patients. Following discontinuation of therapy, a relapse occurred within 2 weeks. With dosages of 45 or 55 mg/day, the clinical scores were only slightly better than with 25 or 35 mg/day. In patients using 25 mg acitretin a day, the leukotriene B4-induced intra-epidermal accumulation of polymorphonuclear leukocytes was not affected. However, a dosage of 35 mg/day resulted in a significant inhibition of PMN accumulation, dosages of 45 and 55 mg/day causing an even more pronounced inhibition of this process. Although the effect of different dosages of acitretin is not clearly expressed in the severity scores, the dose-dependent effect on PMN chemotaxis in vivo might be of relevance when combination therapies are considered, in order to achieve a complete clinical clearance.

Thirteen patients with Darier's disease with a mean extent of the lesions of 29.4 +/- 10% of the total skin area were treated with acitretin (the main metabolite of etretinate) for 16 weeks. The dose was 30 mg/day during the initial 8 weeks and was later adjusted individually to 10-30 mg/day in order to achieve optimal results. Three patients cleared completely, 7 patients showed marked improvement and 3 patients became slightly better during treatment. The mean extent of the lesions after the treatment was 7.3 +/- 8% of the skin area. Despite good clinical clearing, the improvement at the ultrastructural level was incomplete in the 3 patients studied by electron microscopy. Normal stratification did not develop and the size and number of desmosomes remained reduced. The main side effects during treatment were pruritus in 5 patients, diffuse alopecia in 2 patients and marked elevation in serum triglycerides in 4 patients. On the basis of this study, acitretin would seem to be a useful alternative to etretinate for the treatment of Darier's disease.

Thirty patients have been treated with either etretin, the main derivative of etretinate, or arotinoid Ro 13-6298, a polyaromatic retinoid, or isotretinoin. Sebum production was measured before and during the treatments. While no change was observed in the patients treated with etretin, a reduction of 33% of the sebum excretion rate was observed for those treated with arotinoid Ro 13-6298 but only after long treatment periods of 20 to 30 weeks. The sebum excretion rate decreased by 92% in the patients treated with isotretinoin. Four patients suffering from severe nodulocystic acne were treated with arotinoid Ro 13-6298 for 2-5 months without improvement. Substantial improvement, however, resulted after a subsequent treatment with isotretinoin; sebum production decreased markedly as well. This study suggests that neither etretin nor arotinoid Ro 13-6298 will replace isotretinoin in the treatment of severe nodulocystic acne.

The arotinoid ethyl ester Ro 13-6298 is a third generation retinoid shown to be thousand-fold more potent than etretinate (Tigason, Tegison) in animal testing and in human therapy. In an open uncontrolled trial, we treated 57 patients suffering from psoriasis (32) and various severe skin disorders (25) with daily doses ranging from 20 to 150 micrograms, during 1 to 130 weeks (mean = 12 weeks). Four patients were treated for 1 year or more. Given in micrograms per kg range, Ro 13-6298 showed a spectrum of clinical activity and mucocutaneous side effects similar to that of etretinate given in mg per kg range. One patient developed diffuse idiopathic skeletal hyperostosis after 2 years of continuous therapy. No increase in either serum triglycerides or cholesterol levels was observed, even in patients treated for 33 to 130 weeks. This might prove to be an advantage of this new retinoid. Furthermore, this series suggests that potent mucocutaneous (therapeutical and side) effects are not necessarily linked to all other signs of retinoid toxicity.

Acitretin, the free acid of etretinate, is less lipophilic and has a much shorter terminal half-life than the parent compound. The present double-blind, randomized study compared the therapeutic effectiveness and the tolerability of acitretin (n = 127) and etretinate (n = 41) in psoriasis. Patients were treated with 40 mg daily for the first 4 weeks and with an individually adjusted dose for the subsequent 8 weeks. The average daily doses of acitretin (0.54 mg/kg/day) and etretinate (0.65 mg/kg/day) were similar. The PASI (Psoriasis Area and Severity Index) scores improved in parallel in the 2 treatment groups. At the completion of the study, the PASI score improvement was 75.8% for acitretin and 70.8% for etretinate. Both acitretin and etretinate resulted in mucocutaneous side effects. Assessments of tolerability by investigators and patients showed a statistically significant difference in favour of etretinate. These results demonstrate that acitretin and etretinate have similar therapeutic effectiveness in psoriasis. Although the tolerance to acitretin was lower than to etretinate, acitretin offers the important advantage of a much shorter period of potential teratogenicity and is, therefore, to be preferred in women of childbearing potential.