Topical treatment of acne vulgaris: Retinoids and cutaneous irritation

Abstract

cles that involves a multifactored pathophysiology.1 Excessive sebum production, combined with abnormal desquamation of follicular epithelium, leads to an accumulation of these materials such that the lumina of sebaceous follicles become distended. This precursor, microscopic stage is known as a microcomedo. In this environment, Propionibacterium acnes proliferates and its production of proinflammatory chemotactic and cytokine factors is responsible for the inflammation of acne.2-4 Our therapeutic menu includes a variety of drugs, both topical and systemic, that can affect these areas of pathophysiology. The abnormal desquamation of follicular epithelium can be normalized by topical tretinoin and salicylic acid. These agents decrease the cohesion of corneocytes, minimize microcomedo formation and, in time, decrease both clinical noninflammatory and inflammatory lesions. The newer synthetic retinoid derivatives, adapalene and tazarotene, have also demonstrated effectiveness in the treatment of acne. Despite differences in physical characteristics and receptor affinity, their molecular and cellular mechanisms of action are thought to be similar to those of tretinoin.5 The major disadvantage of topical therapy for the treatment of acne is that many of the agents used cause tolerability problems. Significant erythema, dryness, peeling, scaling, and irritation may result in discontinuation of treatment,6 and in patients who continue treatment, irritation may lead to compliance problems.7 Tretinoin-induced irritation, for example, is generally doseand vehicle-related, and the level of irritation ranges from high to low with the solution, gel, and cream formulations, respectively.8 Unfortunately, efficacy is frequently dose-related as well, and some patients do not progress to an optimal tretinoin concentration because of tolerance problems.7 With this in mind, pharmaceutical research programs have focused on methods of minimizing the irritation caused by topical retinoids while preserving or improving their therapeutic benefits. The results of these programs have yielded several new developments. Modified tretinoin delivery systems, which minimize irritant effects and provide therapeutic benefit, are now available. These include complexes of tretinoin with polymer molecules and incorporation of tretinoin in microsponge particles. Two new agents, adapalene and tazarotene, bind with nuclear retinoid receptors and exert retinoid effects in a variety of systems. They have been found to be clinically effective in acne and have been approved by the FDA. From the Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia. Reprint requests: James J. Leyden, MD, Department of Dermatology, University of Pennsylvania Hospital, 3400 Spruce St., Philadelphia, PA 19104. J Am Acad Dermatol 1998;38:S1-4. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/0/88698 Topical treatment of acne vulgaris: Retinoids and cutaneous irritation