Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

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)(2006)(2007)(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 5a-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. Biology of sebaceous glandsThe sebaceous gland is a holocrine gland, and its secretion is formed by the complete disintegration of the glandular cells. Excreting sebum is the major function of sebaceous glands (1), and increased sebum excretion is a major concurrent event that parallels the development of acne lesions. With the development of human sebaceous gland experimental models for in vitro studies (2-5), considerable progress has been made in our understanding of many new

Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have been developed during the last years. It is the intention of this article to review the most important anti-aging strategies that dermatologists have nowadays in hand, including including preventive measurements, cosmetological strategies, topical and systemic therapeutic agents and invasive procedures.

No abstract

Abbott Laboratories.

Human facial sebaceous gland cells were transfected with a PBR-322-based plasmid containing the coding region for the Simian virus-40 large T antigen. The resulting proliferating cell cultures have been passaged over 50 times to date, have been cloned, and show no signs of senescence after 4&DF;1 2 y in vitro, whereas normal human sebocytes can only be grown for three to six passages. The immortalized transfected cells, termed SZ95, expressed the Simian virus-40 large T antigen and presented an hyper-diploid-aneuploid karyotype with a modal chromosome number of 64.5. The SZ95 cell line exhibited epithelial, polymorphous characteristics with different cell sizes of up to 3.25-fold during proliferation and 6-fold at confluence, showing numerous cytoplasmic lipid droplets. The cells showed large cytoplasm profiles with abundant organelles, including vacuoles and myelin figures which indicated lipid synthesis. Lack of or only few desmosomal areas were observed. SZ95 cells expressed molecules typically associated with human sebocytes, such as keratins 7, 13, and 19, and several proteins of the polymorphous epithelial mucin family. Functional studies revealed synthesis of the sebaceous lipids squalene and wax esters as well as of triglycerides and free fatty acids, even after 25-40 passages; active lipid secretion; population doubling times of 52.4 +/- 1.6 h; reduced growth but maintenance of lipid synthesis under serum-free conditions; and retrieval of cell proliferation after addition of 5alpha-dihydrotestosterone. Retinoids significantly inhibited proliferation of certain SZ95 cell clones in the expected magnitude 13-cis-retinoic acid > all-trans-retinoic acid > > acitretin. Thus SZ95 is an immortalized human sebaceous gland cell line that shows the morphologic, phenotypic and functional characteristics of normal human sebocytes.

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases.

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. To date, an evidence-based therapeutic approach has not been the standard of care and this is likely due to the lack of evidence based treatment guidelines. The purpose of this study was to promote a holistic evidence-based approach which implemented Level of Evidence and Strength of Recommendation for the treatment of HS. Based upon the European Dermatology Forumguidelines for the management of HS, evidence-based approach was explored for the treatment of HS. The diagnosis of HS should be made by a dermatologist or other healthcare professional with expert knowledge in HS. All patients should be offered adjuvant therapy as needed (pain management, weight loss, tobacco cessation, treatment of super infections, and application of appropriate dressings). The treating physician should be familiar with disease severity scores, especially Hurley staging, physician global assessment and others. The routine use of patient’reported outcomesincluding DLQI, itch and pain assessment (Visual Analogue Scale) is strongly recommended. The need for surgical intervention should be assessed in all patients depending upon type and extent of scarring, and an evidence-based surgical approach should be implemented. Evidence-based medical treatment of mild disease consists of topical Clindamycin 1 % solution/gel b.i.d. for 12 weeks or Tetracycline 500 p.o. b.i.d. for 4 months (LOE IIb, SOR B), for more widespread disease. If patient fails to exhibit response to treatment or for a PGA of moderate-to-severe disease, Clindamycin 300 p.o. b.i.d. with Rifampicin 600 p.o. o.d. for 10 weeks (LOE III, SOR C) should be considered. If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present. If the patient fails to exhibit response, then consideration of second or third line therapy is required. A growing body of evidence is being published to guide the treatment of HS. HS therapy should be based upon the evaluation of the inflammatory components as well as the scarring and should be directed by evidence-based guidelines. Treatment should include surgery as well as medical treatment. Future studies should include benefit risk ratio analysis and long term assessment of efficacy and safety, in order to facilitate long term evidence based treatment and rational pharmacotherapy.