Vitamin A Acid

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Abstract
Synopsis: Vitamin A acid (retinoic acid; tretinoin) is a vitamin A derivative used in the topical treatment of acne. It acts by ‘unseating’ comedones, improvement developing slowly over a period of 2 to 3 or more months, and is also said to prevent the formation of new lesions. About three-quarters of patients with acne vulgaris benefit from treatment. In controlled studies, results achieved after a 3 to 4 months course of treatment were superior to those with sulphur-resorcinol-salicylic acid. When compared with benzoyl peroxide, results were variable and appear to depend on the length of treatment, the types of formulations used, and the concentrations compared. Application of vitamin A acid should, be continued until the patient has been free of new lesions for several months. Further continued application at a less frequent interval or using a less active dosage form may help to prevent exacerbations of acne. A systemic antibacterial agent such as tetracycline can be given as well in patients with moderate to severe lesions. Vitamin A acid is used in conjunction with gentle washing (to remove surface oil) but should be applied to a dry skin to avoid unnecessary irritation. Patient education and encouragement are crucial during the initial phase of treatment when microcomedones may be converted to pustules prior to desquamation. In animal studies 0.05 to 0.1 % vitamin A acid applied topically for 1 to 2 months resulted in stimulation of epidermal cell proliferation with the development of epidermal hyperplasia. Serum transaminases were increased on a dose-related basis after topical or oral administration, and serum alkaline phosphatase and bone resorption increased in rats after receiving oral doses for several months. Human pharmacodynamic studies in normal volunteers showed temporary erythema, increased skin permeability and a thickened epidermis after topical administration. In acne patients a dose related increase in the proliferation rate of epidermal cells occurs and the stratum corneum becomes loosened and disrupted. Topical vitamin A acid has marked comedolytic activity against coal tar- and steroid-induced acne lesions. Both topical and oral administration have increased serum bilirubin, alkaline phosphatase, transaminases and thymol turbidity and flocculation test values, but all liver function test values reverted to normal on withdrawal of treatment. These changes do not appear to be clinically significant. Pharmacokinetic studies in rats indicate that systemically-administered vitamin A acid is rapidly metabolised in the presence of vitamin A deficiency with only small amounts being stored in skeletal tissue and body organs. Excretion in the rat occurs primarily via the bile and to a lesser extent in the urine. Studies in man have demonstrated urinary excretion of small amounts of vitamin A acid and metabolites after topical administration. In therapeutic trials in patients with acne vulgaris, topical application of vitamin A acid has produced a very good or good improvement in about three-quarters of the patients. The most marked improvement occurs in the numbers of comedones, papules or pustules with a lesser effect on nodules or cysts. Controlled studies have demonstrated that vitamin A acid is superior to placebo and to sulphur-resorcinol-salicylic acid. Its relative efficacy compared with benzoyl peroxide has varied and appears to depend on the duration of treatment, since the effect of vitamin A acid develops more slowly (over a period of 2 to 3 or more months), and the concentration and types of formulations compared. Thus, when results were evaluated after 3 months, 0.1 % vitamin A acid solution was superior to 5 % benzoyl peroxide lotion in 1 study, but when results were assessed at less than 3 months in other studies 5 to 10% benzoyl peroxide gel was superior to 0.05 % vitamin A acid solution or 0.1 % cream. ‘Longer-term’ studies using several concentrations and formulations of both agents are needed to clarify their comparative effectiveness. Combined treatment with systemic antibiotics (e.g. a tetracycline) may increase the proportion of patients showing good to excellent response over that achieved with either treatment alone. Erythema and peeling occur frequently and are dose-related, but do not appear to be necessary for therapeutic benefit. Although their occurrence may hasten the onset of improvement, final therapeutic results are not affected if sub-peeling doses are used. The severity of erythema and peeling can therefore be minimised by adjusting the concentration of the preparation used and the frequency of application according to the reactivity of the patients skin to the drug. Side-effects: Allergic contact dermatitis has been reported in isolated instances and depigmentation and increased susceptibility to sunburn have also occurred. Dosage: Vitamin A acid is available as cream, solution or gel and is used in conjunction with gentle washing (with conventional soap) to remove surface oil, but should be applied to a dry skin (at least 15 minutes after washing) to avoid unnecessary irritation. Application should be continued until the patient has been free of new lesions for several months. Further continued application at less frequent intervals or with a less active preparation of vitamin A acid may help to prevent exacerbations of acne, although this has not been tested in controlled studies. Patients with a dark complexion should apply vitamin A acid once or twice daily to the entire area where lesions occur. Those with fairer skin may be more easily irritated, and thus may require less frequent application or a less concentrated preparation. There appears to be little over-all benefit in producing more than a slight erythema or peeling. During...