13-cis-Retinoic Acid in Acne — Mechanism of Action

Abstract

13-cis-retinoic acid is of undoubted value in the treatment of patients with nodular cystic acne and in the treatment of patients with moderately severe acne, particularly if the patient has failed to respond adequately to the more conventional treatments.^1–3 The drug has such a dramatic effect since it influences most of the major factors involved in the aetiology of acne. Although opinion differs on both sides of the Atlantic as to which is the prime reason for acne, most Europeans with a few exceptions favour the view that the main drive to acne is the increased androgen effect on the sebaceous gland resulting in seborrhoea, a phenomenon which correlates well with the clinical severity.⁴ Kligman and colleagues and others support the view that hyperkeratinization of the pilosebaceous duct is the main reason for acne.⁵ However it is likely that most opinions favour the view that bacteria, especially Propionibacterium acnes (P. acnes), are not the prime role for the development of acne but are important as a secondary contributing role particularly to the development of inflammation and possibly with the later development of some of the non-inflamed lesions.^6,7 The fourth factor in the development of acne is the production of inflammation. Some data suggest that inflammatory lesions arise exclusively from non-inflamed lesions⁸ but recent histological data in our own laboratory would support the idea that some inflammatory lesions may arise from follicles showing no evidence of hyperkeratinization. The inflammation is undoubtedly due to the diffusion of low molecular weight biological potent factors which diffuse from the pilosebaceous duct and in turn trigger both complement activation and Chemotaxis.^9,10 This chapter will consider the effect of 13-cis-retinoic acid on these four factors: sebum production, ductal hyperkeratinization, cutaneous and ductal bacteria and inflammation.