Natural Solution for Acne

Acne No More Ebook

Acne is not only a patch to the beauty of a person but a painful and ever growing disease which has been common problem. Lots of chemical products are available in the market which not makes a big hole in pocket but hardly gives promising results. Acne no more is indeed a book that will permanently solve your all acne problems in the most holistic way without using any drugs or ointments. No matter whatever the age or sex of the person, it works on all. In addition to acne treatment it includes all the remedies for blackhead removal, scar marks and excessive oiliness. It includes all the step by step holistic process to get the best glowing and healthy without using any chemicals. Indeed the best in the market and written by Mike Warden who is certified Nutrition Specialist, Health Consultant, Medical Researcher and Author. The fastest and permanent results are guaranteed by the author and have been used and trusted by thousands of readers of this book. Within 2 months get prepared to get the glowing and clean skin that you have ever wished for. Continue reading...

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Growth Hormone And Insulinlike Growth Factors In Acne

Growth hormone is secreted by the pituitary gland. It acts on the liver and peripheral tissues to stimulate the production of IGFs, formerly known as somatomedians. There are two forms of IGF, termed IGF-1 and IGF-2. IGF-1 is the more prevalent growth factor. It has been hypothesized that growth hormone may be involved in the development of acne (29). Acne is most prevalent in adolescents during a time when growth hormone is maximally secreted and serum levels of IGF-1 are highest. In addition, IGF-1 can be produced locally within the skin, where it can interact with receptors on the sebaceous gland to stimulate its growth. Furthermore, conditions of growth hormone excess such as acromegaly are associated with sebor-rhea and the development of acne. In some tissues, the actions of IGF-1 can be mediated by androgens. It is possible that androgens may influence IGF-1 action in the sebaceous gland as well.

Clinical Presentation Of Adult Female Acne

For reasons that are not understood, the distribution of facial acne in many adult females differs from that seen in adolescents and in males. Many adult women note that acne localizes to the lateral face, chin, and neck (Fig. 2). Oftentimes, acne in these women is not necessarily widespread or severe, but rather it may be low-grade, persistent, and consist of a few isolated deep-seated tender nodules. Many women note flares of their acne just prior to their menstrual period with reports ranging from 27-60 to 70 of women (30-32). One study has been published that provides quantitative documentation of acne lesion counts over the menstrual period (33). In this study of women, who were followed over two menstrual cycles, 63 showed a 25 increase in inflammatory acne lesions prior to the menstrual period. Some women may feel that intermittent acne therapy prior to their menstrual period may be beneficial. There is no evidence for this approach. Since most acne therapy is designed to...

When To Suspect An Endocrine Disorder In Acne Patients

Although hormones influence acne, most acne patients do not have an endocrine disorder. Hyperandrogenism should be considered in female patients whose acne is severe, sudden in its onset, or is associated with hirsutism, or irregular menstrual periods. Additional clinical signs of hyperandrogenism include Cushinoid features, increased libido, clitoromegaly, deepening of the voice, acanthosis nigricans, or androgenetic alopecia. Women with hyperandrogenism may also have insulin resistance. They are at risk for the development of diabetes and cardiovascular disease. It is therefore important for the long-term health of these patients to identify hyperandrogenism so that they can receive appropriate therapy from an endo-crinologist or gynecologist.

Approach To Hormonal Therapy In Female Acne

Hormonal therapy is an excellent option for treatment of women whose acne is not responding to conventional therapy. If there are signs of hyperandrogenism, an endocrine evaluation is indicated, consisting of tests such as DHEAS, total- and free-testosterone, and an LH FSH ratio. Although hyperandrogenism is an indication for hormonal therapy, women with normal serum androgen levels also respond well to treatment. The mainstays of hormonal therapy include oral contraceptives and spironolactone. Other agents to choose from include cyproterone acetate, flutamide, and glucocorticoids. Hormonal agents work best as part of a combination regimen including topical retinoids or topical or oral antibiotics depending upon the severity of the acne. In some women, the additional of hormonal therapy has improved acne to the point where subsequent treatment with iso-tretinoin was no longer necessary. As more is learned about the hormones involved in acne, their source of production and the...

The Problem Of Antibiotic Overuse And A Philosophy For Acne Treatment

Overuse of antibiotics has received increased attention from public health experts and the lay press for some time. The increase in resistant organisms is a real and a significant phenomenon that results in greater illness and expense in treatment of acne and other diseases as well. Moreover, chronic antibiotic use has been implicated in increasing the risk of breast cancer (37,38) and increasing the incidence of upper respiratory infections (39), all in single studies that have yet to be confirmed. Whether or not this link to nonbacterial diseases proves to be real, there is sufficient reason to avoid long-term antibiotic therapy whenever possible. Acne, unfortunately, is neither a short-term disease nor one that is quickly controllable in many patients, and prolonged courses of antibiotics are often needed. Steps must be taken by the practitioner to minimize the need for chronic treatment by optimizing regimens so as to minimize antibiotic exposure. There are several methods that...

Overview of the Pathogenesis of Acne

Acne is an extremely complex disease with elements of pathogenesis involving defects in epidermal keratinization, androgen secretion, sebaceous function, bacterial growth, inflammation, and immunity. In the past 30 years, much has been worked out, and we now have a fairly detailed understanding of the events that result in an acne pimple, although there is also much left to be discovered. The initial event in acne is the formation of comedo, a plug in the follicle, which is termed open if a black tip is visible in the follicular orifice and closed if the opening has not distended enough to be visible without magnification. Patients (and their mothers) erroneously conclude that this black tip is due to dirt in the follicle. Rather, it represents oxidized melanin and perhaps certain sebaceous lipids (1,2). The earliest lesion is termed microcomedo and is clinically inapparent, but is the lesion that gives rise to inflammatory acne. Microcomedones are best visualized by harvesting them...

Oral Contraceptives Studied In Acne

Many oral contraceptives have been studied in the treatment of acne (Table 3). These include those containing ethinyl estradiol in combination with cyproter-one acetate (Diane, Dianette), ethynodiol diacetate (Demulen), levonorgestrel (TriPhasil, Alesse), norgestimate (Ortho Tri-Cyclen ), desogesterel (Desogen), and drosperinone (Yasmin, Yaz). Numerous studies point to the efficacy of ethinyl estradiol cyproterone acetate oral contraceptives (Diane and Dianette) in the treatment of acne. Reductions in inflammatory lesion count on the order of 50 to 75 have been reported (44,45). Two large studies involving a total of approximately 500 women with moderate acne were conducted with ethinyl estradiol 35 mg norgestimate (Ortho Tri-Cyclen). Improvement in inflammatory lesions, total lesions, and global assessment was noted with this oral contraceptive after six months of treatment (46,47). There was a 50 to 60 improvement in inflammatory lesions. Decreases in serum free testosterone and an...

Sebum Secretion and Acne

Saturated and monounsaturated fatty acids predominate in the sebaceous esters with only small proportions of dienes being present (4). Among the wax ester fatty acids, the saturated-to-monounsaturated fatty acid ratio is approximately 40 to 60 whereas in the cholesterol ester and triglyceride fractions this ratio is 65 35 and 70 30, respectively (13,16). The dienoic fatty acids include linoleic acid (C18 2 D9,12), derived from the diet, and an isomer thereof (C18 2 D5,8), which is synthesized in the gland (17). The proportion of C18 2 D9,12 relative to C18 2 D5,8 is decreased in acne. This is consistent with the suggestion that comedogenesis is initiated by a localized essential fatty acid deficiency (18).

Changes in the Pilosebaceous Unit in Acne

Production Sebum

There is no doubt that sebum plays an important etiological role in acne (99,168170). Patients with acne secrete more sebum than unaffected individuals and sebo-suppressive treatments alleviate acne the greater the inhibition the more profound the clinical response. In addition to elevated sebum excretion, it is well-established that acne is associated histologically and clinically with hypercornification of the duct epithelium (7,38,171). Ductal hypercornification results initially in the formation of microcomedones and eventually comedones, a process termed comedo-genesis. On the basis of a detailed histological study Kligman (7) concluded that comedogenesis began in the infrainfundibulum and was closely followed by hyper-keratosis of the sebaceous duct. This is now generally accepted to a reasonable description of what is likely to happen. Essentially, microcomedones are those follicles containing impactions, follicular casts, or sebaceous filaments of corneocytes, bacteria, sebum,...

Phototherapy and Laser Therapy of Acne

Light-based treatments for acne are not new. A tan has long been known to help teens with pimples, and it would not be surprising to find reports of acne phototherapy dating from the 1930s. In my youth, a local dermatologist was treating many of us with what must have been a cold quartz lamp along with various creams and oral antibiotics. He told me that he knew that the light was helpful, but could not say more than that about its mechanism. Since that time, there have been great advances in the understanding of acne and in laser and light technology, but the level of understanding of how light might help acne has not progressed much. In the past 10 years or so, there have been many reports of different light-based acne regimens (1), but all are small (or very small) studies and most can best be categorized as organized anecdote. The typical report describes a handful of patients who have treatment with light plus antibiotics plus other interventions (such as peels). Controls,...

Role Of Antimicrobial Peptides In Acne

The epidermis forms an effective barrier, however, the hair canal, the distal ORS of the hair follicle, and the pilosebaceous duct constitute major ports of entry for microbial invasion in humans and harbor a rich residential microflora such as P. acnes, Staphylococcus epidermidis, Demodex folliculorum, and Malassezia furfur. The distal ORS and the pilosebaceous duct are also characterized by many features of innate and adaptive immunological activity such as classical and nonclassical MHC class 1 expression, ICAM-1 expression, and the presence of intraepithelial Langerhans cells and perifollicular macrophages (28-30). It is of considerable interest, therefore, that this area of the pilosebaceous unit is also a hot spot in the development of acne vulgaris lesions. Acne, a disease of the pilosebaceous unit is characterized by hypercornifica-tion and hyperkeratosis of the ORS and sebaceous duct and perilesional infiltrate (PI). Lesions may be characterized as noninflammatory versus...

Dermatological Abnormalities Hirsutism Acne and Androgenic Alopecia

Acne has been reported to affect 12-14 of white PCOS patients (10,60), although the prevalence of this dermatological abnormality also varies with ethnicity. It is reportedly higher in Asian Indians (60) and lower in Pacific Islanders (58). Androgenic alopecia is a recognized sign of PCOS (61-63) however, in a study of 257 androgen excess patients undergoing treatment, only 12 (4.7 ) complained of hair loss only (10). Overall, acne and androgenic alopecia apparently have a low prevalence among patients with PCOS. Because studies quantifying and determining the prevalence of acne and androgenic alopecia in a significant number of unselected patients with PCOS are lacking, we did not include these disorders in our calculations of economic burden.

Androgens In Acne

Both clinical observation and experimental evidence confirm the importance of androgens in the pathophysiology of acne. The majority of circulating androgens are produced by the gonads and the adrenal gland. Androgens can also be produced locally within the sebaceous gland from the adrenal precursor hormone, DHEAS. The main androgens that interact with the androgen receptor are testosterone and DHT. Androgen receptors are found in the basal layer of the sebaceous gland and the outer root sheath keratinocytes of the hair follicle (1,2). DHT is approximately five to 10 times more potent than testosterone in its interaction with the androgen receptor. An essential role for androgens in stimulating sebum production is supported by several lines of evidence. For example, the development of acne in the prepuber-tal period has been associated with elevated serum levels of DHEAS, a precursor for testosterone (3,4). Androgen-insensitive subjects who lack functional androgen receptors do not...

Seborrhea andor Acne

The prevalence of androgen excess among acneic-only patients (excluding patients with hirsut-ism) is less than among hirsute women. In small studies, between 20 and 40 of patients with treatment-resistant acne and without menstrual disturbance, alopecia, or hirsutism are reported to have androgen excess, principally PCOS (30-33). Alternatively, data regarding the predictive ability of seborrhea for androgen excess is lacking. Large populational studies of acneic or hyperseborrheic patients, particularly those without other evidence of hyperandrogenism (e.g., hirsutism), are then still needed to better define this prevalence.

Acne

It affects up to 80 of young adults, in whom it can induce stress, depression, and anxiety, as determined by psychometric scoring (47,111,112). Acne is a disease of the infundibulum or pore of the human sebaceous pilosebaceous unit and of the gland itself. This unit develops at puberty, appears only at the site of acne lesions (the chest, back, and face), and seems to have no other function than to sometimes produce acne lesions. The earlier forms of acne are characterized by microcomedones, which represent an intrainfundibular scaling-like phenomenon. As the disease progresses in severity, comedogenesis develops, as does inflammation. Duct rupture is a late event in the development of most inflammatory lesions (47-50). Acne is generally accepted by clinicians to be a multifactorial disease and it is believed that acne is associated with seborrhea, the excess production of sebum by the sebaceous gland (49,113). Further, Propionibacferinm acnes is a...

Interpretation of Significance

Several common blood isolates are almost always significant Staphylococcus aureus, Escherichia coli, and other members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Candida albicans. In contrast, common skin organisms, such as coagulase-negative staphylococci (CoNS), Coryneform bacilli, alpha-hemolytic streptococci, and Propionibacterium acne, are frequent contaminants. However, with many patients carrying an intravascular device that is prone to colonization and infection, each positive culture entails clinical correlation with other findings and sound judgment to make final assessment (Mirrett et al., 2001 Weinstein, 2003).

Effect of Iron Supplements

McGinley KJ, Webster GF, Ruggieri MR, Leyden JJ. Regional variation in density of cutaneous Propionibacterium correlation of Propionbacterium acnes populations with sebaceous secretions. J Clin Microbiol 1980 12 672-5. 7. Till AE, Goulden V, Cunliffe WJ, Holland KT. The cutaneous microflora of adolescent, persistent and late-onset acne patients does not differ. Br J Dermatol 2000 142 885-92. 8. Pawin H, Beylot C, Chivot M, et al. Physiopathology of acne vulgaris recent data, new understanding of the treatments. Eur J Dermatol 2004 14 4-12.

Movement Of Ctns Between Species Of Human Colonic Bacteroides Spp

The high number of strains in the post-1990 period that carry tetQ, even in the community isolates obtained from people who were not taking antibiotics, indicates that once acquired, tetQ is maintained very stably. Since, as already indicated, tetQ is found almost exclusively on a type of CTn exemplified by CTnDOT, a human Bacteroides CTn, this indicates that the CTn itself is also maintained very stably. It is interesting to note another characteristic of CTnDOT its excision and transfer are stimulated 100- to 1000-fold by exposure of the bacteria to tetracycline 33-35 . Tetracycline is used not only to treat acute human infections, but also in dermatology and agriculture. In the treatment of acne, tetracycline is administered orally in relatively low doses over a period that can extend from months to years 36,37 . In agriculture, tetracycline has been used to stimulate growth of some animals 38 . Thus, long dosage regimens for tetracycline have been widespread and could have been...

Growth Factors and Neuropeptides

EGF, TGF-a, basic FGF, and keratinocyte growth factor (KGF) all inhibit lipogenesis and with the exception of KGF are mitogenic in cultured hamster sebocytes (133,151). In organ culture of human sebaceous glands, EGF produced a dose-dependent inhibition of lipid synthesis and inhibited DNA synthesis (152), and removal of EGF from the medium caused an increase in the rate of lipogenesis without affecting cell turnover (113). In vivo, the presence of EGF inhibited the sebaceous gland differentiation in sheep (153), and in hamster ears, it stimulated the sebaceous glands to proliferate (154). Receptors for EGF are found in sebaceous glands (155). Based on this evidence, Kealey and colleagues proposed that EGF may be, in part, responsible for sebaceous gland atrophy observed during acne lesion formation (7,152). EGF can also induce changes in sebum composition. Ridden (156), reported that there was a fall in the amount of squalene and a corresponding rise in cholesterol, although this was...

Other modifications of established antibiotics classes

BAL19403 14 is a new macrolide that is highly potent against erythromycin-resistant and clindamycin-resistant propionibacteria 66,67 . Potent antiinflammatory activity and good pre-clinical safety make BAL19403 a good candidate for topical treatment of acne 68-70 . AR-709 15 is a new di-aminopyridine in Phase I clinical trials derived from a program aimed at optimizing dihydrofolate reductase (DHFR) inhibitors treating respiratory infections caused by multi-drug-resistant Streptococci, Pneumococci, and Staphylococci 71-73 . In enzyme assays using wild-type and mutant DHFR isolated from S. pneumoniae and S. aureus, the IC50 for AR-709 was 12 x-60 x lower than for trimethoprim (TMP) for the wild-type and 50-100 x lower for the mutant enzyme 74 . Accordingly, AR-709 has demonstrably more potent antibacterial activities than TMP against both TMP-S and TMP-R strains of S. pneumoniae and S. aureus. AR-709 is currently in a radiolabelled Human Microdose study where preliminary results...

Screening For An Endocrine Disorder

In the majority of women with acne, serum androgens are completely normal, yet these women will in fact respond if treated with hormonal therapy. Studies have shown that, as a group, women with acne may have higher levels of serum DHEAS, testosterone, and DHT than those without acne (7,34). However, although higher, these laboratory values may still be within the normal range. Serum levels of DHEAS, DHT, and IGF-1 are reported to correlate positively with acne lesion counts in women, whereas androstenedione and DHEAS correlate with lesion counts in men (35). Reduction of serum androgens or inhibition of their action, as obtained with oral contraceptives or antiandrogens, respectively, can lead to improvement in acne in women with normal serum androgen levels.

Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is recurrent inflammation of the apocrine sweat glands, particularly those of the axilla, genital, and perianal areas. It can result in obstruction and rupture of the duct and secondary infection. The lesions generally drain spontaneously, with formation of multiple sinus tracts and with hypertrophic scarring. Although not initially infected, the lesions frequently become secondarily infected. Often, patients with HS also are afflicted with acne, pilonidal cysts, and chronic scalp folliculitis thus, giving rise to the term follicular occlusion tetrad.

Summary of Predictive Value of Clinical Markers

Overall, between 50 and 75 of women with evidence of hirsutism or the complaint of unwanted hair growth will have androgen excess, notably PCOS. Alternatively, only 20 and 40 of patients with acne as their sole presenting complaint and only about 10 of women complaining of hair loss will have androgen excess. Between one-fourth and one-third of women with oligo- amenorrhea have androgen excess, and only about one-fifth of women with polycystic ovaries on ultrasonography will have androgen excess.

Microbiology and Pathogenesis

Bacterial factors are important in the pathogenesis of acne. Acne is believed to be associated with Propionibacterium acnes (18). The improvement in acne patients treated with systemic antibiotics effective against P. acnes, as well as other organisms, support this concept. The morphogenesis of acne lesions can be divided into two phases. The first phase is noninflammatory, during which keratin accumulates in affected follicles producing whiteheads (closed comedones), which have very small orifices, and blackheads (open comedones) which have distended orifices. The second is an inflammatory phase during which a variety of inflamed lesions may develop from a proportion of comedones. P. acnes is known to be related with the inflammatory process in acne lesions (18), Propionibacterium spp. possess immunostimulatory mechanisms such as complement activation, stimulation of lysosomal enzyme release from human neutrophils, and production of serum-independent neutrophil chemotactic factors...

Gonadotropin Releasing Agonists

Androgen production in the ovary can also be blocked by gonadotropin-releasing hormone agonists such as buserelin, nafarelin, or leuprolide. These gonadotropin-releasing agonists block ovulation by interrupting the cyclic release of FSH and LH from the pituitary. These drugs are efficacious in acne and hirsutism, and are available as injectable drugs or nasal spray. However, in addition to suppressing the production of ovarian androgens, these drugs also suppress the ovarian production of estrogens, thereby eliminating the function of the ovary. Thus, the patient could develop meno-pausal symptoms and suffer from hypoestrogenism. Headaches can also develop, as well as the occurrence of bone loss, due to the reduction in estrogen.

Are there any medications that I should adjust or stop taking while Im being treated for osteoporosis

That has been used for years to manufacture estrogen, progesterone, and testosterone. Because DHEA is a precursor of testosterone, sometimes high dosages of it cause male characteristic side effects such as facial hair and acne, although doses around 50 mg or less do not appear to cause these side effects. DHEA has been touted as an anti-aging miracle drug. Its claimed effects include increased energy and better sex drive. Although DHEA is available over the counter, you must discuss its pros and cons with your clinician before trying it. The dosage of DHEA being used in clinical trials is about 150 mg to 200 mg per day. A clinical trial looking at DHEA's effect on Crohn's disease is also being conducted.

Newer Forms Of Contraceptives

Recently, newer forms of contraceptives have been developed, such as contraceptive patches, vaginal rings, and injectable combination hormones. Each of these is designed to suppress ovulation and in this regard will lower the ovarian production of androgens. As of yet, these formulations have not been studied in the treatment of acne. The contraceptive patch (Ortho Evra) contains 20 mg of ethinyl estradiol and 150 mg of the progestin, norelgestromin. The patch is worn for three weeks and removed for one week, during which time menstrual bleeding will occur. The advantages of this formulation are better patient compliance, dosing that is not affected by gastrointestinal disturbances, and more consistent serum levels of estrogen serum levels compared to oral dosing (56). The vaginal ring (NuvaRing) is a contraceptive vaginal ring that releases 15 mg of ethinyl estradiol and 120 mg of the progestin, etonogestrel. It is placed within the vagina for three weeks and removed for one week. In...

Introduction Bioptron Phototherapy

For all its aforementioned effects, Bioptron polarized light has also found wide application in cosmetology, most frequently in skins with expanded pores, energy-weakened parts of skin, wrinkles, scalp and hair problems, cellulite, acne, and herpes. Wound healing time is reduced by one third to half the normal healing time 12, 13 . Macrophages might play the central role in the wound healing process, for the polarized light might stimulate them to secrete growth factors 14 . It was also noticed in vital capil-laroscopy that local circulation was improved within the area treated with polarized light 15-17 . With po-larized-light biotherapy, the healing effect is also evident on the wounds resistant to all other forms of therapy (ulcers of various etiologies, pressure sores, burns, surgical wounds, wounds of various etiologies) 4, 18, 19 .

Regulation of Pilosebaceous Unit Activity

Androgen sensitivity of pilosebaceous units has been confirmed by the positive detection of androgen receptors in pilosebaceous units by immunohistochem-istry (Fig. 4) (95-97) and by their isolation from sebaceous gland cells (98). However, it has not been possible to demonstrate differences in receptor levels that explain androgen dependent dermatoses, such as acne or the different rates of sebum production in different individuals. There is a strong correlation between sebum excretion rate and acne grade (99,100), but it has not been possible to relate the rate of sebum production to differences in androgen receptor levels in different acne patients. Clinically, 13-cis-RA is given orally for severe acne at doses of 1 mg kg day for four months and produces a rapid reduction in sebum excretion, for example, down to 20 of its former level within four weeks (127). This is due to sebaceous gland atrophy as demonstrated by histological methods (128) but the mechanism involved is unknown....

Cell Biology of the Pilosebaceous Unit

Follicular Duct

This chapter reviews the structure and function of the pilosebaceous unit and the controlling influences on the pilosebaceous unit and sebum secretion. The chapter is divided into three sections. Section I gives an account of the structure and function of the normal pilosebaceous unit Section II describes the biochemistry and regulation of pilosebaceous unit biology and finally, Section III deals briefly with the biochemical changes occurring in the pilosebaceous duct in acne.

Fusobacterium Species

Mourelatos K, Eady EA, Cunliffe WJ, Clark SM, Cove JH. Temporal changes in sebum excretion and propionibacterial colonization in preadolescent children with and without acne. Br J Dermatol 2007 156 22-31. 52. Beeler BA, Crowder JG, Smith JW, White A. Propionibacterium acnes pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulo-nephritis. Am J Med 1976 61 935-8. 53. Purdy S, deBerker D. Acnes. BMJ 2006 333 949-53.

Mechanism Of Retinoid Action

Images Retinoid Mechanism Action

Retinoids are a class of chemical compounds that include active metabolites of vitamin A (retinol) as well as a diverse array of synthetic derivatives. Vitamin A is required for normal embryonic development, epithelial homeostasis, maintainance of reproductive capacity, and functioning of the visual cycle (1). Additionally, retinoids have been shown to modulate a wide variety of cellular processes, including proliferation, differentiation, homeostasis, and malignant transformation (for reviews see refs. 2-5). Retinoids also act pharmacologically to restore regulation of differentiation and growth in certain prema-lignant and malignant cells in vitro and in vivo (6,7). Consequently, retinoids are under study as therapeutic and chemopreventive agents for a variety of cancers (see refs. 8-10 for reviews). Retinoids are also potent drugs for the treatment of severe cystic acne, psoriasis, and several other dermatologic disorders (11).

Proposed Hybrid Method

Hormonal control of sebaceous gland activity (Thiboutot) and the etiology of acne (Strauss) are discussed at length in later chapters of this book. SEBUM SECRETION AND ACNE It has long been established that elevated rates of sebum secretion are associated with acne, and treatments that lower sebaceous gland activity are therapeutic (34). It should be noted that with the bentonite method for measurement of sebum secretion, the mean sebum secretion rates for nonacne control subjects, mild-to-moderate acne, and severe acne are significantly different with higher secretion rates, occurring with more severe disease (35). The role of sebum in come-dogenesis and initiation of acne and the available therapies are discussed in later chapters of this book. In general, any treatment that significantly reduces sebum secretion is therapeutic for acne. It has been demonstrated that sebaceous lipids can increase the permeability of the skin (36). This was first demonstrated after application of...

The Central Nervous System

Setting Sun Sign

Setting sun sign in a normal newborn infant. The setting sun sign means that conjugate upward deviation is decreased. The upper eyelids are retracted and the irides are partly covered by the lower eyelid giving the appearance of a sunset. This is rarely observed as an isolated finding in an otherwise normal newborn infant. It may be normal if it is transient, but if it persists, it must be investigated. Note associated neonatal acne in this infant. Figure 3.1. Setting sun sign in a normal newborn infant. The setting sun sign means that conjugate upward deviation is decreased. The upper eyelids are retracted and the irides are partly covered by the lower eyelid giving the appearance of a sunset. This is rarely observed as an isolated finding in an otherwise normal newborn infant. It may be normal if it is transient, but if it persists, it must be investigated. Note associated neonatal acne in this infant.

Clinically Studied Inhibitors 31 5LO and FLAP inhibitors

Reduce Corneum

Zileuton (1) is the only marketed 5-LO inhibitor and is approved for the treatment of asthma 44 . The treatment of mild asthmatics with zileuton (600 mg qid, 2 weeks) resulted in a 96 increase in plasma thromboxane B2 from baseline levels and a corresponding 62 increase in spontaneous platelet aggregation, suggesting a shunting of arachidonic acid metabolism to the cyclooxygenase pathway 45 . In a small clinical trial, zileuton provided a magnitude of prophylaxis in exercise-induced asthma (as measured by FEV1) equivalent in magnitude but considerably shorter in duration than salmeterol, montelukast and zafirlukast 46 . Zileuton inhibited bronchoalveolar lavage (BAL) fluid eosinophil counts by 68 upon antigen challenge in a sub-population of allergic asthmatics who exhibited a significant increase in BAL leukotrienes and inflammatory cytokines, but not in those patients where leukotriene levels were unchanged upon antigen challenge 47 . Zileuton provided minimal efficacy 48 or no...

The Molecular Biology of Retinoids and Their Receptors

Pml Rar Alfa Acido Retinoico

Acne vulgaris is a multifactorial disease of the skin in areas rich in sebaceous follicles. It is characterized by seborrhea, hypercornification of the infundibulum (the neck of the sebaceous gland), and the presence of comedones and inflammatory lesions such as papules and pustules. The inflammatory pathway is mediated by antigenic and inflammatory products of Propionibacterium acnes (1). Although acne is mostly associated with puberty, persistent or late onset acne may be similar in physiology to pubertal acne, with hyperandrogenicity and increased sebogenesis, being the key factors (2). The hyperproliferation of the infundibulum keratinocytes, characterized by the expression of the hyperproliferative marker proteins, Ki67 and K6 16, and the resulting immature stratum corneum does not desquamate efficiently, leading to clumps of squames that attach to the hair follicle causing a blockage to sebum flow. Hypercornification of the infrainfundibulum is an early feature of the...

Why should I take drugs that have side effects

Weight gain and altered body habitus Steroids and ACTH result in an increased appetite. Their use can result in tremendous weight gain, even as high as 70 pounds in a few days. There is also a redistribution of body fat that women in particular do not like. Fat is deposited over the face and upper part of the chest and neck, abdomen, and buttocks. As easy as it is to gain the weight, it is difficult to take it off. When caloric intake is managed (restricted), the deposition of fat over the upper back, abdomen, and buttocks is minimized, but not eliminated. The alteration of body image may be traumatic, particularly to women. Acne often accompanies the use of steroids and ACTH. It can be easily managed with use of low doses of tetracy-cline antibiotics.

Androgen Metabolism Within the Skin

Acne may be mediated by serum androgens, locally produced androgens, or a combination of both. Insights have been gained regarding the local metabolism of androgens within sebaceous glands (9). Such insights may be of benefit in the design of new acne therapies. The skin and sebaceous gland are capable of producing and metabolizing androgens (9). DHEAS is the major adrenal androgen precursor. It circulates in the blood stream in relatively high levels compared with other hormones with the exception of cortisol. In fact, in for review, see Ref. postmenopausal women, all sex steroids made in the skin are from adrenal steroid precursors, especially DHEA. Secretion of this precursor steroid by the adrenals decreases progressively from age 30 to less than 50 of its maximal value at age 60 (10). The enzyme 3 -hydroxysteroid dehydrogenase (3 -HSD) acts on DHEA to convert it to androstenedione (Fig. 1). This conversion may take place in the adrenal gland and tissues such as the sebaceous...

Tenascin X Deficiency Pcos

To confirm the diagnosis of 11-OH-deficient NCAH and potentially develop diagnostic criteria, we genotyped five patients with presumed 11-OH-deficient NCAH (21). Three were children (two females and one male) who presented with advanced bone age, accelerated growth, acne, and precocious adrenarche. Two of these were found to have mutations of both CYP11B1 alleles, defects that affected enzymatic expression in vitro. One of these two individuals had an 11-deoxycortisol level after ACTH stimulation of 41 ng mL (upper normal limit of controls was < 8 ng mL), the other had a urinary tetrahydro-11-deoxycortisol level of 1690 g 24 hours (upper normal limit of controls was less than 50 g 24 hours). No mutations of the coding regions or intron exon boundaries of the CYP11B1 genes in the third child could be detected. In addition, we studied two adult hyperandrogenic women with presumed 11-OH-deficient NCAH, neither of which had mutations of their CYP11B1 genes (21). These last two patients...

The Sebaceous Gland Is a Steroidogenic Tissue

The skin and sebaceous glands are capable of synthesizing cholesterol de novo from acetate (22-24). Although this cholesterol is utilized in cell membranes, in the formation of the epidermal barrier, and is secreted in sebum, its use as a substrate for steroid hormone synthesis had not been established until recently. In order for steroid synthesis to occur, cholesterol needs to be translocated from the outer to the inner mitochondrial membrane. This process is regulated by the steroidogenic acute regulatory protein (25). Additional enzymes and cofactors needed to convert cholesterol into a steroid include P450 cholesterol side chain cleavage, adrenodoxin reductase, cytochrome P450c17, and steroidogenic factor-1. Expression of each of these proteins was found in human facial skin, sebocytes, and in a recently developed simian virus (SV) 40-immortalized human sebocyte cell line (SEB-1) (26). These data demonstrate that the skin is in fact a steroidogenic tissue. The clinical...

Medical History and Physical Examination in Patients With Possible Androgen Excess

Polycystic Appearing Ovaries

The timing and pace of pubertal development and its relation to complaints of unwanted hair growth, hair loss, acne, and or obesity should be established. The onset and progression of these complaints should also be established. Drug or medication use and exposure or use of skin irritants should be elicited. A detailed menstrual history should be obtained, with an emphasis on determining whether evidence of ovulatory function (e.g., premenstrual molimina) is present. Change in skin pigmentation or texture, extremity or head size, and changes in facial contour should be noted. A detailed family history of endocrine, reproductive, or metabolic disorders should be obtained. A family history of similar hyperandrogenic signs and symptoms is a powerful clue to the inherited basis of the disorder, although a familial association can be noted for PCOS, HAIR-AN syndrome, NCAH, and IH patients. Clinicians should note that the etiology of hirsutism can often be suspected from the history alone....

Disorders Affecting Pilosebaceous Unit Biology

Various disorders affect pilosebaceous units, although these diseases are rarely life threatening. Three types of skin cysts exist epidermoid cysts result from squamous metaplasia of a damaged sebaceous gland, while trichilemmal cysts and steatocys-toma are both genetically determined structural aberrations of the pilosebaceous duct. Accumulation of material in the follicular lumen results in distension of the follicle, leading to the formation of noninflamed lesions that are typical of acne, which is the most common follicular disease. In terminal follicles, plugging of the pilosebaceous duct may occur and result in keratosis pilaris. Inflammation around follicles is often seen at the skin surface, for example in folliculitis or acne. In folliculitis, there is extensive colonization of the follicular lumen by microflora.

Biochemical Changes in the Infundibulum During Comedogenesis

The process of comedogenesis is thought to be due to hyperproliferation of ductal keratinocytes, inadequate separation of the ductal corneocytes, or a combination of both factors, resulting in microcomedones. Hyperproliferation of basal keratino-cytes in acne has been demonstrated (180,181) and correlates with keratin 16 expression, a marker for hyperproliferation suprabasally (182). Aldana et al. (183) proposed a cycling of normal follicles through different levels of expression of Ki-67 (a proliferation marker) and keratin 16 and that these represent different stages of development of the microcomedone. The point at which both Ki-67 and keratin 16 are coexpressed by the follicle is when the follicle is susceptible to comedogenic changes (184). A more extensive investigation of adhesion in follicles is required. In epidermis, intercellular adhesion is mediated by lipids, cellular adhesion molecules, and desmosomes. At the present time, the relative importance of follicular...

Corticosteroids

But are more comfortable to some patients. Except in mild cases, ointments should be used because of their higher penetrance and potency. The lowest strength that gives adequate results should be used. Halogenated corticosteroid preparations, such as 0.1 betamethasone (Valisone), 0.025 fluocinolone (Synalar), and 0.1 or 0.025 triamcinolone (Aristocort, Kenalog), have potent anti-inflammatory properties and can be used sparingly on affected body lesions. These preparations should not be used on the face and neck. Hydrocortisone cream or ointment, 1 , can be used sparingly on the face and neck, but stronger preparations should be avoided. Topical steroids should be applied twice daily after application of lubricating creams or ointments as discussed. These preparations will penetrate the lubricant and reach the affected skin. Although generally safe from systemic absorption, diffuse application of topical steroids over long periods can have the adverse effects of striae, atrophic...

Conclusions

The study of PPAR expression profiles and the identification of target genes and ligands in the skin and its appendages as well as the utilization of PPAR mouse mutant models have unveiled distinct physiological functions of the PPARs (Table 3). In particular, activation of PPARs regulates differentiation and proliferation, lipid metabolism, inflammation, and apoptosis. However, the molecular mechanisms by which PPARs coordinate the regulation of these processes remain largely unknown, and thus PPARs represent a major research target for the understanding and treatment of many skin diseases including acne. The research reviewed here focused on PPAR activity in human epidermis and its appendages. The data demonstrates that PPARs regulate many of the physiological processes that are involved in acne. However, it is also apparent that there is some discrepancies with regard to the physiological effects of PPAR ligands on sebaceous lipogenesis, which may be attributed to the different...

Cyproterone Acetate

Cyproterone acetate is available in many parts of the world, but not in the United States. It possesses dual activity in that it serves as a progestogen in oral contraceptives in addition to its direct inhibition of the androgen receptor. It can be given in doses of 2 to 100 mg per day as a single agent, in which case there can be improvement in 75 to 90 of women with acne. Cyproterone acetate, however, is most commonly used in the form of an oral contraceptive combined with ethinyl estra-diol in varying doses (38). Numerous clinical studies support the efficacy of these oral contraceptive preparations in women with acne.

Flutamide

Flutamide is a potent nonsteroidal antagonist of the androgen receptor. Although most commonly used to treat prostate cancer, flutamide has been reported to be efficacious in the treatment of acne, hirsutism, and androgenic alopecia (39). It can be given in doses of 250 mg twice daily in combination with an oral contraceptive. Fatal hepatitis has been reported with this drug. Liver function tests should be monitored and serious consideration should be given to the risk benefit ratio of its use in acne (40). Additionally, because it is an antiandrogen, pregnancy issues are a concern.

Progestins

The progestins contained in oral contraceptives include estranges and gonanes, which are derivatives of 19-nortestosterone, cyprotereone acetate, and a novel progestin, drosperinone. Members of the estrane and gonane class of progestins (Table 2) can cross-react with the androgen receptor, which can lead to increased androgenic effects and could aggravate acne, hirsutism, or androgenic alopecia. These progestins can also cause changes in lipid metabolism and can increase serum glucose, leading to glucose intolerance, as well as possibly interfering with the beneficial effect of estrogen on the sex hormone-binding globulin. However, the third generation progestins, including norgestimate, desogestrel, and gesto-dene, are more selective for the progesterone receptor rather than the androgen receptor. The biological relevance of these differences, however, is uncertain. For years, it has been known that almost all oral contraceptives are beneficial in the treatment of acne (42). It is...

Benzoyl Peroxide

Benzoyl peroxide (BP) is a topical disinfectant that was originally used as a peeling agent for acne. Its mechanism of action is through lowering P. acnes populations by oxidative killing, and the drug is extremely effective as a topical agent. When applied to the skin, BP breaks down into benzoic acid and hydrogen peroxide (1,2). It assumed that the peroxide accounts for the majority of bactericidal activity, but no studies have been performed to assess the activity of benzoic acid in acne. The major side effect of BP is irritation, which usually is easily managed with moisturizers. However, BP has been reported as a contact sensitizer in as many as 4 of patients and can reach nearly 75 when applied to leg ulcers (3), but in clinical acne practice actual contact allergy is rarely noted. As a heavy prescriber of the drug, I see, at most, a case every few years. Various concentrations of BP are available, but there is no convincing data to prove that high concentrations are more...

Macrolides

Topical and oral erythromycin and topical clindamycin have been well-established acne treatments for decades, but have become much less effective in the past 15 years or so due to the acquisition of resistance by P. acnes. Resistant bacteria are now induced quickly by macrolide therapy because most patients have a portion of their normal skin flora that is genetically resistant, and that subgroup expands under the selective pressure of therapy (8-11). Resistant bacteria make for acne that resists therapy and erythromycin resistant strains are typically resistant to clin-damycin and vice versa. Resistance can be combated by the addition of BP to topical macrolide regimens. It has been clearly shown that such combination products are not only more effective than monotherapy with macrolides, but also do not permit the survival of resistant populations of P. acnes (6). Other macrolides for example, azithromycin have been reported in small studies to be of value in acne (12), but no data...

Tetracyclines

The tetracycline family of antibiotics are extremely useful in acne because they have multiple modes of action, functioning as antibiotics that reduce bacterial populations, and as anti-inflammatory drugs that attack acne from a second front. Tetracyclines, especially doxycycline and minocycline are highly anti-inflammatory in many cell systems (Table 1). Neutrophil and monocyte chemotaxis is inhibited through calcium chelation, blunting the migration of cells to the follicle (13). Granuloma formation in vitro (14) and in vivo (15) is inhibited with minocycline and doxycycline roughly 10-fold more active than tetracycline. In this model, macrolides and cephalosporines were inactive. Protein kinase C is inhibited (15), perhaps interfering with signal transduction. Generation of reactive oxygen species and the oxidative burst in neutrophils is decreased (16). Nitric oxide production is modulated (17). Matrix metalloprotease and collagenase activity is inhibited (18-20). In vivo,...

Treatment Regimens

Because acne is a multifactorial disease, and because most acne treatments (isotre-tinoin excepted) are not completely effective, typical treatment regimens involve one or more medications. Multidrug treatment schemes are an undesirable fact of acne therapy. They make compliance difficult in a patient population that is TABLE 3 Acne Treatment Regimens Mild-to-moderate inflammatory acne Benzoyl peroxide-clindamycin gel q.d. or b.i.d. Topical clindamycin foam q.d. + benzoyl peroxide wash q.d. Benzoyl peroxide-clindamycin gel q.d. + topical retinoid q.d. Moderate-to-severe inflammatory acne Doxycycline 75-100 mg b.i.d. + topical retinoid q.d. Minocycline 75-100 mg b.i.d. + topical retinoid fundamentally noncompliant, and add expense. Therefore, regimens should be as streamlined as possible. Table 3 presents useful antibiotic treatment plans for acne of varying severites.

Use And Side Effects

Dispensed and equally divided over two index fingers, which then dab the medication evenly onto opposite sides of the face and spread the medication into a thin layer until no visible product remains (21). Hands should be washed afterwards to avoid retinoid dermatitis (21). Application should first occur every other night for one to two weeks depending on the skin type so as to minimize the initial irritation that may otherwise discourage adherence to the treatment regimen (1,21). Oily skin is better able to tolerate the potential irritating effects of the retinoids and, as such, a shorter introductory period may be utilized (21). Non-comedogenic moisturizers can be used to minimize xerosis, erythema, and stinging (2). Patients should be instructed that as long as four to six weeks of use may be required before the onset of efficacy and that an initial flare in acne may occur following two to four weeks of use due to an accelerated evolution of preexisting microcomedones (3). Periodic...

Efficacy

Acne vulgaris is an almost ubiquitous condition. When antimicrobials are used alone, there is a risk of creating widespread, multidrug resistance of P. acnes as well as other skin flora such as Staphylococcus aureus (2,5,30). This potential resistance can be limited by combining agents that act on different steps in the mechanism of acne pathogenesis. When topical retinoids are used in combination with oral or topical antimicrobials, excessive ductal cornification, P. acnes proliferation, and inflammation can be simultaneously targeted for increased efficacy, faster onset of effects, decreased total antibiotic use and risk of resistance, and shorter overall duration of treatment (2). The combination tretinoin with topical or oral antibiotics has been shown to be superior to either alone in decreasing lesion count, increasing rate of improvement, and decreasing levels of P. acnes and free fatty acids (8,14). Similarly, the combination of adapalene with topical doxycycline or...

Nimotuzumab

Overexpression of epidermal growth factor receptor (EGFR), a transmembrane receptor tyrosine kinase, is prevalent in malignant tumors of epithelial origin and is especially common in breast, head and neck, colon, and lung cancer. With EGFR overexpression, prognosis is poor due to associated tumor invasion, metastasis, enhanced angiogenesis, and resistance to chemotherapy thus, modulation of EGFR-mediated signaling is an attractive target for intervention. Small-molecule kinase inhibitors (gefitinib and erlotinib) and a monoclonal antibody (cetuximab) specific for EGFR are in clinical evaluation, but treatment cessation due to development of severe acne-like rash is common with these EGFR antagonists. Notably, nimotuzumab, a humanized form of the murine IgG2a monoclonal antibody that has been launched in India for treatment of head and neck cancers overexpressing EGFR, demonstrates clinical efficacy devoid of the rash toxicity. Presumably, humanization of the antibody sequence...

Hydroxy Acids

Environ Quel Before After

Fig. 62.4. a Acne-scarred skin with photoageing prior to topical vitamin A, vitamin C and antioxidants. b After 52 treatments of iontophoresis and low-frequency sonophoresis (The Environ DF IONZYME machine for pulsed iontophoresis and low-frequency sonophoresis was used. The products used were Environ Crystal Masque and Environ C-Quel. Home skin care was with Environ) of vitamin A, vitamin C and continuous home skin care. No surgery was between the a and b

Mechanism Of Action

Topical retinoids act to clear and prevent the formation of the microcomedo, the precursor to acneiform lesions. The microcomedo is formed from the occlusion of the follicular ostium by the androgen-induced production of sebum and the accumulation of stratum corneum cells (5). In normal skin, the corneocytes of the hair follicle's infrainfundibular region are small and form a noncontinuous, incoherent layer of cells that easily desquamate individually into the follicular canal (1,2,6). They then travel to the surface of the skin through the secretion of lipid-rich sebum (6). In contrast, the follicular epithelium of the microcomedo demonstrates abnormal, hyperactive keratinization, resulting in hypergranulosis and hyperkeratosis (2,5). Corneocytes are more cohesive and less able to migrate to the skin surface and instead become lodged within the follicle, occluding the expulsion of sebum, distending the follicular ostia, and thus forming the comedo (1,6). The anaerobic environment...

Cytokines

Upregulated mRNA and protein synthesis of vascular endothelial growth factor (VEGF) (165). Thus in follicular diseases, liberation of IL-1 into the dermis may contribute toward inflammation and increased levels of VEGF by follicular kerati-nocytes can stimulate angiogenesis. In acne, high levels of IL-1 a bioactivity existed in comedonal contents (166).

Retinoid Types

Similarly, novel vehicles can allow controlled release of topical retinoids. Polyolprepolymer-2 is a material designed to help retain drug molecules in and on the skin when applied topically and has been shown to distribute tretinoin over time with equivalent efficacy to vehicle-free analogous formulations (16). The incorporation of tretinoin into this vehicle prevents rapid and excess percutaneous absorption of tretinoin, decreasing irritation (16). In vitro absorption studies, guinea pig irritation models, human patch test studies, and acne clinical trials of tre-tinoin gel and cream containing polyolprepolymer-2 demonstrate that the absorption of tretinoin during the first six hours of delivery is significantly less than that of standard preparations of tretinoin, but becomes similar after this time (16). Additionally, the total penetration of polyolprepolymer-impregnated tretinoin is less than vehicle-free tretinoin (16). Human patch tests demonstrated that both tre-tinoin gel and...

Organizations

Acinetobacter A bacterium that infects the upper respiratory tract and that has been hypothesized to be a causative factor in MS by some researchers in England. Acne A skin condition common in young people with increased secretion from oil glands in the skin, accompanied by formation of comedos (blackheads). These glands tend to become infected with organisms living in or on the skin making the skin raised and red.

Effects Of Retinoids

Hypovitaminosis has been related to the expression of acne (25), and so its addition to skin should alleviate the condition. All-trans-RA was the first retinoid used, but it was ineffectual on acne when used systemically. 13-cis-RA (isotretinoin), however, is an extremely effective oral anti-acne drug by causing marked sebosuppression (26). 13-cis-RA has been shown to inhibit significantly sebocyte proliferation, differentiation, and lipid synthesis in vivo. Despite its potent biological effects, 13-cis-RA exhibits only low-binding affinity for CRABP and nuclear receptors (27). This unique antisebotrophic activity results from a selective isomerization to all-trans-RA intracellularly in sebocytes, reduces all-trans-RA inactivation compared with all-trans-RA, and mediates inhibition of sebocyte proliferation (28). The synthesis of CRABP II, which facilitates the degradation of intracellular all-trans-RA, was delayed and induced lesser by 13-cis-RA when compared with all-trans-RA, in...

Free Fatty Acids

Sebum contains numerous fatty acids and many are quite unique in structure, including a wide variety of straight, branched, saturated, and unsaturated fatty acids (77). In human sebum, about 27 of fatty acids chains are saturated, with the greatest proportion being unsaturated (68 ). The vast majority of these are monounsaturated (64 ) and about 4 are diunsaturated, with the remainder being composed of fatty acid chains longer than 22 carbons (78). Monounsaturated fatty acids of sebum have a double bond usually inserted at position A9. However, in human sebum there is an unusual placing of the double bond at A6 to produce sapienic acid. Sapienic acid is a very abundant and important monounsaturated fatty acid with 16-carbons and a cis double bond located at the sixth carbon from the carboxyl terminal. This fatty acid has been implicated in acne and is produced by an enzyme unique to sebaceous glands, the A6 desaturase, which has recently been isolated from human skin, and its...

Sebutape

More recently, Sebutape (Cuderm Corporation, Dallas, Texas, U.S.A.) has been introduced for assessment of pore patterns and sebum secretion (22,23). This adsor-bant polymeric tape is white but turns transparent at the points where sebum is adsorbed. This tape is used after clearing sebum from the surface, but not depletion of the follicular reservoir, although there is no fundamental reason why this could notbe done. Typically, the Sebutape is removed from the forehead after three hours, although it has been suggested that one hour would be adequate (24), and placed on a black background. The pore pattern then appears as black dots on a white background, and the total black area determined by image analysis is proportional to the amount of sebum secreted (25). One can qualitatively assign the pore pattern to one of five categories, referring to images provided by the manufacturer prepubertal, pubertal, acne, mature, or senescent (26). It is also possible to extract lipids from the...

Distribution

As mentioned earlier, all skin areas excluding the glabrous skin, that is, the palmar (palms) and plantar (soles), possess pilosebaceous units. Although the number of secreting follicles, and consequently sebum output, varies greatly between individuals, the distribution and shape of follicles tend to follow the same pattern over the human body (19). The highest density of sebaceous and vellus follicles is found on the face, especially on the forehead, where there may be as many as 900 glands cm2 in some areas (20), but the number varies according to the study Blume et al. (21) determined a density of 423 follicles cm2, Pagnoni et al. (22) found 455 follicles cm2 on the lateral forehead and up to 1220 follicles cm2 in the nose area, and most recently, Otberg et al. (23) determined a number of 292 follicles cm2 on the forehead. Nevertheless, there is agreement that sebum output is maximal on the forehead, nose, and chin, the so-called t-zone and decreases toward the outer edges of the...

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