644 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The Pathogenesis of Acne Vulgaris JOHN S. STRAUSS, M.D., and PETER E. POCHI, M.D.* In a short presentation it is not possible to discuss fully all the fac- tors involved in the pathogenesis of acne vulgaris. However, we will pose and attempt to answer two questions concerning the etiology of ache, and having addressed ourselves to these two issues, relate them to thera- peutic approaches which may be of interest to the cosmetic industry. The two questions are. (1) What is the cause of inflammatory acne? and (2) Is ache a hormonal disease? In discussing the cause of inflammatory acne we are specifically excluding comedo formation, and we will be concerned with the inflam- matory pustules, papules, and nodules of ache. The initial changes that are seen histologically in inflammatory acne are small areas of edema of the follicular wall or partial rupture of the follicular wall, there being no clinical evidence of inflammation with these early ruptures (1). These breaks in the follicular structure may occur with or without pre- ceding comedo formation the former is more common. In the imme- diate area of the dermis surrounding these breaks there is a lymphocytic infiltrate. Why rupture occurs is open to conjecture. However, it is unlikely that it is due to pressure alone, since rupture may occur without prior comedo formation. While the cause of rupture is unknown, there is evidence bearing upon factors which may induce the inflammatory response. The follicle contains bacteria, keratinous material, and lipid. Can any of these excite the inflammatory reaction observed ? It is unlikely that the rupture and the accompanying inflammation are the direct result of bacterial in- vasion. There is no polymorphonuclear leukocytic response, as might be expected with invasion of the dermis by pyogenic organisms, and bacterial stains do not demonstrate the presence of any bacteria in the * Department of Dermatology and Evans Memorial Department of Clinical Research, University Hospital, and the Department of Dermatology, Boston University School of Medicine, Boston University Medical Center, Boston, Mass. This investigation was supported in part by Research Grants AM 07388 and AM 03084, National Institute of Arthritis and Metabolic Disease, United States Public Health Service.

PATHOGENESiS OF ACNE VULGARIS 645 immediate region of the follicular disruption. It is also unlikely that the reaction is due to the escape of keratinous material since the area of rupture is initially quite small. Furthermore, experimental in- j eetions of defatted eomedones promote a foreign-body giant cell re- action (1) such changes are not observed in early follieular rupture. The experimental intradermal injection of surface lipids, most of which is sebum, induces a lymphoeytie infiltrate (1, 2) and it is probable that sebum itself causes the early inflammation of aene. Sebum is a complex lipid mixture. Freshly secreted sebum contains no free fatty adds (3). However, surface collections ordinarily contain approxi- mately one-third free fatty adds, one-third triglyeerides, and one-third nonsaponifiable components (4). When the various fractions of sebum are injected into human skin, the greatest amount of inflammation fol- lows the injection of the free fatty adds, the response being similar to that produced by whole sebum (1, 2). Much less inflammation is pro- dueed by the other components including triglyeerides, wax alcohols, squalene, and cholesterol. Therefore, the fatty adds are the most ir- ritating compounds in sebum. Another line of evidence lending support to the importance of sebum in the inflammatory response was a study of sebum production in a large group of 17- to 21-year-old males (5). Sebum production was found to be higher in those subjects with aene as compared to normal individuals. Moreover, within the group of individuals with aene, sebum production was proportional to the degree of aene, although within the individual groups (i.e., mild, moderate, severe aene) considerable variation in sebum production was observed. More direct evidence of a role for sebum in the etiology of inflamma- tory aene is provided by the therapeutic effect of estrogens and antibio- tics. Estrogens suppress sebaceous gland secretion (6, 7). Accompany- ing this decrease in sebum production there is concomitant improvement in aene. Thus, decreasing the output of sebum lessens the severity of inflammatory aene. This relationship is discussed in more detail sub- sequently. Broad-spectrum antibiotics are also of use in aene. For in- stance, small dosages of tetraeyeline (i.e., 250-500 rag/day) will benefit most eases of inflammatory aene. Tetraeyeline in these doses will de- erease the free fatty adds in sebum (8). The esterified fatty add frae- tion is increased under these circumstances, but the total content of fatty adds is unchanged. When antibiotics are stopped, the free fatty add fraction increases again. Thus, it would appear that by altering the composition of sebum and reducing the concentration of free fatty