Clinical, ultrastructural and biochemical effects of an aromatic retinoid (etretinate) on psoriasis and Darier's disease
Lauharanta, J.
Acta Dermato-Venereologica. Supplementum 101: 1-29
1982
ISSN/ISBN: 0365-8341 PMID: 6954822 Document Number: 190832
Patients (90) with psoriasis and 8 with Dairer's disease were studied clinically before and during treatment with an oral aromatic retinoid (etretinate, Ro 10-9359). In the treatment of psoriasis, 2 different combinations of etretinate and PUVA were used and patients treated with PUVA alone served as controls. Ultrastructural examination of the skin lesions was performed in 8 patients with psoriasis and in 5 patients with Darier's disease. The biochemical studies consisted of monitoring of skin polyamine levls in 8 psoriatics during etretinate treatment and in 7 psoriatics during PUVA treatment and monitoring of serum levels of vitamin A, retinol-binding protein and prealbumin in 22 etretinate-treated patients. Clinical results were good. During a 10-wk treatment period with etretinate, 3 of the 20 psoriatic patients showed complete clearing and marked improvement was achieved in 13 (65%) patients. By combining etretinate with PUVA therapy the clearing rate was increased, and the total UVA dose needed was .apprx. 1/3 of that in PUVA treatment alone. In Dairer's disease etretinate cleared 6 of 8 patients in 4-6 wk. Partial clearing was achieved in 2 patients. According to the grade of severity of the disease, intermittent or continuous treatment proved necessary. Both in psoriasis and Darier's disease etretinate was rather well tolerated when used at an initial dose of 0.7-0.9 mg/kd per day with reduction during treatment according to the clinical response. Dryness of the lips or cheilitis was the most frequent side effect seen in the majority of patients. Alopecia occurred in 16% of the patients treated with etretinate for > 4 wk. Ultrastructural examination revealed granular material in the enlarged intercellular space in the epidermis of untreated psoriatic lesions. This material was increased during the initial (2-4 wk) phase of etretinate treatment, which preceded normalization of the intercellular space. Similar material was observed during PVUA treatment. No evidence of its mucoid nature was obtained in light microscopy using various stainings with affinity to mucosubstances. In Darier's disease the suprabasal acantholysis was the 1st pathological sign to disappear during etretinate treatment. This was followed by normalization of various signs of abnormal keratinization. The elongation of rete ridges was the last pathological feature to remain. No uniform changes were observed in intercellular material in Darier's disease. Polyamine levels were significantly elevated in untreated psoriatic skin lesions as compared with the healthy controls. During etretinate treatment the putrescine level was normalized, whereas the spermidine and spermine levels, despite marked reduction, remained somewhat above the controls at remission. The reduction in polyamines during etretinate and PUVA treatments ran roughly parallel, but the initial drop in putrescine was more rapid during etretinate treatment. Vitamin A and transport protein levels in blood remained practically unchanged even during long-term (up to 15 mo.) treatment with etretinate, indicating that this drug does not interfere with vitamin A transport in blood. Psoriasis and Darier's disease evidently can be effectively treated with etretinate. The clearing rate in psoriasis can be increased by combining etretinate with PUVA therapy. Associated with clinical improvement, the light microscopical and EM picture in psoriasis and Darier's disease and the lesional polyamine levels in psoriasis are shifted towards normal.