A. Breathnach, M. Nazzaro-porro, S. Passi
Apr 1, 1989
Citations
0
Influential Citations
48
Citations
Journal
Clinics in dermatology
Abstract
Abstract Azelaic acid (COOH(CH 2 ) 7 COOH), is a medium chain-length saturated, 9-carbon atom dicarboxylic acid, which has recently been shown to have important biologic activities and some useful practical therapeutic applications. It can be obtained by oxidation of fatty acids, such as oleic acid, which are unsaturated in the 9-C position, and in humans it has been reported present in the urine of noncompensated diabetics and of patients with congenital inability to oxidize monocarboxylic acids. 1 During investigations on the causation of the hypochromia in pityriasis versicolor, dicarboxylic acids of chain-length C 6 –C 12 were found to be formed in cultures of Pityrosporum to which unsaturated fatty acids with double bonds in the 6 to 12 positions were added. 2,3 An ascending gradient of competitive anti-tyrosinase activity of the diacids was demonstrated and in another study, 4 damage to melanocytes. Because of these findings, it seemed possible the diacids might be involved in the hypochromia of pityriasis versicolor, and perhaps useful in the topical treatment of hyperpigmentary disorders as an alternative to phenolic compounds, such as monobenzoyl ester of hydroquinone, which are alternative substrates of tyrosinase. These latter often produce residual hypochromia of both hyperpigmented and adjacent uninvolved normal skin, which is a disadvantage of their use. The final choice of dicarboxylic acid for original application and investigation fell upon azelaic acid, mainly because it occupies the middle range of anti-tyrosinase activity, is relatively cheap, and more easily soluble and capable of being incorporated into a base cream than those at the higher level of activity. A 15% cream was originally employed, but a 20% one is now standard; occasionally, we have studied the effects of a 35% cream. Early limited open trials established a beneficial effect of the cream on some hyperpigmentary disorders and showed that it had no clinical depigmenting effect on normal skin. 2,5 These preliminary results encouraged further clinical studies extending over the years, and initiated parallel laboratory investigations aimed at elucidating the mechanism of action of azelaic acid. An outline of these will be given first because they provide a background and rationale (often post hoc ) for the clinical use of the diacid.