F. William Danby

New developments in our understanding of acne pathogenesis and treatment

Abstract:  Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005–2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll‐like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR‐2, may stimulate the secretion of cytokines, such as interleukin (IL)‐6 and IL‐8 by follicular keratinocytes and IL‐8 and ‐12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL‐1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5α‐dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future.

Milk consumption and acne in teenaged boys

OBJECTIVE We sought to examine the association between dietary dairy intake and teenaged acne among boys. METHODS This was a prospective cohort study. We studied 4273 boys, members of a prospective cohort study of youths and of lifestyle factors, who reported dietary intake on up to 3 food frequency questionnaires from 1996 to 1998 and teenaged acne in 1999. We computed multivariate prevalence ratios and 95% confidence intervals for acne. RESULTS After adjusting for age at baseline, height, and energy intake, the multivariate prevalence ratios (95% confidence interval; P value for test of trend) for acne comparing highest (>2 servings/d) with lowest (<1/wk) intake categories in 1996 were 1.16 (1.01, 1.34; 0.77) for total milk, 1.10 (0.94, 1.28; 0.83) for whole/2% milk, 1.17 (0.99, 1.39; 0.08) for low-fat (1%) milk, and 1.19 (1.01, 1.40; 0.02) for skim milk. LIMITATIONS Not all members of the cohort responded to the questionnaire. Acne assessment was by self-report and boys whose symptoms might have been part of an underlying disorder were not excluded. We did not adjust for steroid use and other lifestyle factors that may affect occurrence of acne. CONCLUSION We found a positive association between intake of skim milk and acne. This finding suggests that skim milk contains hormonal constituents, or factors that influence endogenous hormones, in sufficient quantities to have biological effects in consumers.

A randomized, double-blind, placebo-controlled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of moderate to severe dandruff

BACKGROUND Ketoconazole is highly effective against the yeast Pityrosporum ovale, an organism believed to be involved in the pathogenesis of dandruff. OBJECTIVE Our purpose was to evaluate the safety and effectiveness of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo and placebo shampoo in patients with moderate to severe dandruff. METHODS Features assessed included adherent and loose dandruff scores, presence or absence of irritation, itching, yeast cells, and global improvement rating by the investigator. RESULTS A total of 246 patients were included. Mean total adherent dandruff score declined throughout the treatment period with both ketoconazole 2% and selenium sulfide 2.5% shampoos significantly better than placebo at all visits. Ketoconazole was statistically superior to selenium sulfide at day 8 only (p = 0.0026). Both medicated shampoos were significantly better than placebo for reducing irritation and itching. Of the nine adverse experiences reported during the treatment phase, all involved patients treated with selenium sulfide 2.5% shampoo. CONCLUSION Both ketoconazole 2% shampoo and selenium sulfide 2.5% shampoo are effective in the treatment of moderate to severe dandruff; however, ketoconazole 2% shampoo appears to be better tolerated.

Nutrition and acne

There are significant data supporting the role of diet in acne. Our Western diet includes many dairy sources containing hormones.. The natural function of milk being to stimulate growth, it contains anabolic steroids as well as true growth hormones and other growth factors. The presence of 5α-pregnanedione, 5α-androstanedione, and other precursors of 5α-dihydrotestosterone add to the potency of milk as a stimulant of acne. In addition, foods with significant sugar content and other carbohydrates yielding high glycemic loads affect serum insulin and insulin-like growth factor-1 levels, both of which promote increased production of available androgens and the subsequent development of acne.

Diet and acne

Acne is caused by the action of dihydrotestosterone, derived from endogenous and exogenous precursors, likely acting synergistically with insulin-like growth factor-1. These sources and interactions are discussed. Both a mechanism of action and recommended dietary changes that limit ingestion and production of these hormones are proposed.

New and traditional surgical approaches to hidradenitis suppurativa.

When the prevention of new lesions fails and when medical therapy of established and growing lesions is ineffective, surgery is the accepted method of dealing with hidradenitis suppurativa/acne inversa. The rationale and preferred techniques of mini-unroofing using a biopsy punch, deroofing using scissors, electrosurgery or laser, and classical wide excision and closure are discussed. The situation in which incision and drainage is considered for temporary pain relief would be best considered an opportunity for deroofing, as illustrated in the accompanying online videos.

Turning acne on/off via mTORC1

Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.

Diet in the prevention of hidradenitis suppurativa (acne inversa)

Full control of hidradenitis suppurativa requires the prevention of new lesions. These appear to be induced by a complex series of hormonally driven molecular activities that lead to obstruction of the follicular duct, rupture and destruction of the sebaceous glands, the development of deep dermal sinuses that subsequently rupture to the surface, and production of an invasive subcutaneous mass that is resistant to medical therapy. Preliminary observations suggest that the use of a healthy and fully natural zero dairy and low glycemic-load diet may provide relief from progression of the lesions and possibly prevention of new lesions, even when medications fail.

Acne: Diet and acnegenesis.

Acne is a manifestation of hormonal overstimulation of the pilosebaceous units of genetically susceptible individuals. Endogenous reproductive and growth hormones, exogenous reproductive hormones, insulin and endogenous insulin-like growth hormone-1, sourced from and stimulated by dairy and high glycemic load foods, all appear to contribute to this overstimulation. A postulated molecular mechanism linking food and acne is reported and integrated into the clinical picture.

Commentary: Unroofing for hidradenitis suppurativa, why and how

T raditional surgery for hidradenitis suppurativa (HS) consists of en bloc wide excision followed by primary closure or healing by secondary intent. A simpler technique consists of careful unroofing, exploration, and debridement of the scars, abscesses, cysts, and complex sinuses that characterize HS. Elsewhere in the Journal, van der Zee et al show us how. The following comments are directed at why this technique (which van der Zee et al refer to as ‘‘deroofing’’) succeeds when simple ‘‘incision and drainage’’ fails. The material caught beneath the epidermis in HS is not simple purulent inflammatory debris. HS is the product of genetic, mechanical, hormonal, and dietary influences. Failure of terminal differentiation of infundibular keratinocytes leads to accumulations of adherent keratinocytes plugging the duct, microcomedo development in the upper follicle, and tight occlusion of the acroinfundibulum. A genetic weakness of the glycoprotein glassy membrane support of the infrainfundibular wall is postulated as the physical defect that predisposes the pilosebaceous follicle, under the pressure of centrifugal expansion within the infundibular canal, to lose its structural integrity. Follicular contents leak out, stimulating the innate immune system. Inflammatory mediators multiply, the reaction is further inflamed, the