Treatment for Acne

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Treatment of Acne General Considerations

The exact classification and grading of acne is a fundamental requirement for the decision of the therapeutic regimen 1-4, 17-19 . In addition, acne at puberty needs subsequent prophylactic medication and care over several years after clinical healing. Infantile and pediatric acne, androgenization signs in female patients with acne tarda 20, 21 or patients with signs of acne inversa may necessitate an alternative treatment. The compliance of the patient is an additional important parameter for the therapeutic strategy to be considered and its success. Skin type (dark skin tends to postinflammatory hyperpigmentation) and, especially, the tendency for scar formation play a role in the selection of treatment 22 . Two to 7 of the patients with acne experience a severe course associated with considerable scarring. A severe course associated with the presence of potential generators of physical and psychotic scars may require a therapeutic regimen based on systemic drugs 3, 18 (table 1).

Mast Cells in Acne Inflammation

Human Inflammation Cells Pcr

Facilitate the local accumulation of blood leukocytes during the inflammatory response. Immunohistochemical study demonstrated that most of venules around the sebaceous glands not in normal subjects but in acne patients expressed E-selectin (data not shown). We have recently found using immunoelectron-microscopic method that SP is localized within specific granules of human skin MCs 31 . In addition to cutaneous sensory nerves, MC-derived SP may also affect the morphologic and immuno-logic alterations associated with the sebaceous glands and may contribute to the development of the inflammatory events in acne. The mechanisms of MC hyperplasia around the sebaceous glands in acne patients are unclear. The importance of stem cell factor (SCF), a potent fibroblast-derived MC growth factor, has been demonstrated using MC-deficient mutant mice 32 . SP upregulates the soluble form of SCF by human fibroblasts (fig. 3) in a dose-dependent manner (fig. 4) in monolayer culture, as measured by...

Introductionacne Vulgaris

Both clinical observation and experimental evidence confirm the importance of hormones in the pathophysiology of acne. Hormones are best known for their effects on sebum excretion. It has also been suggested that hormones may play a role in the follicular hyperkeratinization seen in follicles affected by acne 1-3 . From a therapeutic standpoint, the importance of the role of hormones in acne is supported by the clinical efficacy of hormonal therapy in women with acne. Although we know that hormones are important in the development of acne, many questions remain unanswered about the mechanism by which hormones exert their effects. For example, the specific hormones that are important in acne have not been definitively identified. Androgens such as dihydrotestosterone (DHT) and testosterone (T), the adrenal precursor dehydroepiandrosterone sulfate (DHEAS), estrogens such as estradiol and other hormones such as growth hormone may each be important in acne. It is not known if these...

Sebaceous Glands in Acne

Pathogenesis Acne

It is generally accepted that sebaceous glands were not innervated and the peripheral nervous system has no effect on the sebaceous biology. Indeed, nerve fibers, as documented immunohistochemically using the general neuronal marker PGP 9.5, were rarely observed around the sebaceous glands in normal facial skin. In contrast, facial skin from acne patients shows numerous fine nerve fibers not only around but also within sebaceous acini 19 . Numerous nerve endings were also observed in close apposition to the sebaceous glands ultrastructurally. Such increase in the number of nerve fibers, some of which are even invading into sebaceous acini, may result from increased expression of NGF on the sebaceous glands of acne-prone facial skin since NGF is essential for the survival, development, differentiation and function of peripheral sympathetic and sensory neurons, and acts as a neurotrophic molecule stimulating the sprouting of nerve fibers also in the skin 20 . Immunohistochemical study...

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.

Therapeutic Targets and Acne Drugs

Several clinical observations point to the importance of androgens in acne 23 . Androgens play an essential role in stimulating sebum production androgen-insensitive subjects who lack functional androgen receptors do not produce sebum and do not develop acne. Moreover, systemic administration of testosterone and dehydro-epiandrosterone increases the size and secretion of sebaceous glands 24-27 . Sebosuppression, i.e. suppression of sebaceous gland hyperactivity, can classically be achieved by systemic administration of anti-androgens or isotreti-noin 19, 24-26, 28, 29 (table 2). Abnormal keratinization of the infundibulum and the distal part of the sebaceous duct can be directly influenced through topical and systemic retinoids as well as through topical application of azelaic acid 30 . A number of further drugs can also secondarily induce keratolysis over their influence on other pathogenic factors 31 . Benzoyl peroxide and topical and systemic antibiotics primarily exhibit...

Growth Hormone Prolactin and Acne

IGF-1 is the more prevalent growth factor. It has been hypothesized that growth hormone may be involved in the development of acne 44 . Acne is most prevalent in adolescents during a time when growth hormone is maximally secreted and serum levels of IGF-1 are at their highest. In addition, IGF-1 can be locally produced 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 seborrhea and the development of acne. In some tissues, the actions of IGF-1 can be mediated by androgens. It is possible that andro-gens may influence IGF-1 action in the sebaceous gland as well. Acne can also be exacerbated by hyperprolactinemia 45, 46 .

Facial Acne in Adults

There are few studies about the prevalence and specificities of facial acne in the adult population. Several studies have been reported recently In England 9 , 749 employees of a hospital, a university and a large manufacturing firm in Leeds, older than 25 years, were examined. Facial acne was recorded in 231 women and 130 men giving an overall prevalence of 54 in women and 40 in men. It was mainly 'physiological acne' but clinical acne (grade > 0.75 on the Leeds scale) was recorded in 12 of the women and 3 of the men. Only 1 of the subjects with clinical acne had sought treatment. The majority believed that there was no effective therapy for acne. In Australia 10 , 1,457 subjects from central Victoria aged > 20 years were examined. The prevalence of acne was 12.8 (13.6 for women and 11.8 for men). There was a clear decrease with age from 42 in the age group 20-29 years to 1.4 in the 60-69 age group. Acne was classified as mild in 81.2 , moderate in 17 and severe Two recent...

Adolescent Acne

The evaluation of the prevalence of adolescent acne is submitted to important variations directly related to the definition of 'acne' used in different studies, which is very variable. Indeed, in some studies one closed or opened comedone is sufficient to consider the subject as a 'patient with acne' and in other studies such as the Daniel study 2 , more than 20 inflammatory and retentional lesions were necessary to consider the subject as having acne. Thus, in Bloch's study 1 , realized among 4,191 subjects and in which one comedone was sufficient to classify the patient as having acne, the prevalence of acne was 68.5 in boys and 59.6 in girls. On the contrary, in Daniel's study 2 , performed in 914 patients, only 27.9 of the boys and 20.8 of the girls had acne lesions. Review of different studies in the literature shows a mean prevalence of between 70 and 87 without significant differences according to country. Acne The frequency of acne in the population increases with age. Thus,...

Seborrhea andor Acne

The prevalence of androgen excess among acneic-only patients (excluding patients with hirsutism) 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.

What is acne

Acne lesions develop from the sebaceous glands associated with hair follicles on the face, external auditory meatus, back, chest, and anogenital area. (Sebaceous glands are also found on the eyelids and mucosa, prepuce and cervix, where they are not associated with hair follicles.) The sebaceous gland contains holocrine cells that secrete triglycerides, fatty acids, wax esters, and sterols as sebum. The main changes in acne are thickening of the keratin lining of the sebaceous duct, to produce blackheads or comedones the colour of blackheads is due to melanin, not dirt an increase in Propionibacterium acnes bacteria in the duct Androgenic hormones increase the size of sebaceous glands and the amount of sebum in both male and female adolescents. Oestrogens have the opposite effect in prepubertal boys and eunuchs. In some women with acne there is lowering of the concentration of sex hormone binding globulin and a consequent increase in free testosterone concentrations. There is probably...

Acne Genetics

The genetic influence on pathogenesis of acne is well documented in twins 30 and genealogic studies. In some types of acne, such as acne conglobata, hereditary factors are more apparent, and a correlation has been suggested between neonatal acne and familial hyperandrogenism 4 . Nodulocystic IA is often observed in relatives of patients with extensive steatocystoma, adolescent and postadolescent acne 31 . Fifty percent of postadolescent acne patients have at least one first-degree relative with the condition 32 . Sebum excretion also correlates with acne susceptibility, and sebum excretion rates are similar in identical twins 33 . Several chromosomal abnormalities, including 46XYY genotype 34 , 46XY+ (4p+ 14q-) 35 , and partial trisomy 13 36 have been reported to be associated with nodulocystic acne. The relationship of acne and various genes has been investigated. An HLA antigen study was negative for acne conglobata 37 , but HLA phenotypes were identical in siblings affected with...

Mid Childhood Acne

This type of acne occurs between 1 and 7 years of age. Acne is very rare in this group and when it occurs should be evaluated for hyperandrogenemia. done with a bone age measurement, growth chart and laboratory tests that include serum total and free testosterone, DHEA, DHEAS, LH, FSH, prolactin and 17a-hydroxyprogesterone. Occasional reports of acne at this age because of .D-actinomycin are available in the literature. Mid-childhood acne can be confused sometimes with keratosis pilaris of the cheeks and with keratin cysts (mil-ia) particularly when they get inflamed. Both lesions are common in atopics 3, 16 . The therapy is identical to that of infantile acne.

Prepubertal Acne

Increasing number of early onset acne before obvious signs of puberty is a recognized phenomenon associated more with pubertal development than with age. There is apparently a genetic predisposition. Adrenarche presents with high levels of DHEA and DHEAS that start rising at 6-7 years in girls and 7-8 years in boys and follow increasing during mid puberty. Excessive androgen production may result due to adrenal hyperandrogenism (exaggerated adrenarche, exuberant production of adrenal androgens relative to cortisol), congenital adrenal hyperplasia, Cushing's disease, 21-hyroxy-lase deficiency, and more rarely androgen producing tumors. Ovarian contribution to androgens can be through tumors (malignant and benign), but most commonly due to polycystic ovarian disease associated very often with obesity, persistent or resistant acne and insulin resistance 3, 12 . Acne could be the first sign of pubertal maturation and associated with increase in sebum and urinary excretion of androgenic...

Infantile Acne

Infantile acne (IA) usually starts later than neonatal acne, generally between 6 and 9 months (range 6-16 months) 16 . It also presents a male predominance. Lesions are localized on the face with the cheeks being the area most affected. A large survey on IA has been recently published showing that IA was mainly moderate in 62 of cases and mild and severe in 24 and 17 of cases, respectively. In addition to open and closed comedones, there were 59 of cases with inflammatory lesions and 17 with scars 17 . Occasional cases of conglobate acne can be seen they occur primarily on the face and the clinical picture is exactly like the adult version. Infantile acne, especially conglobate infantile acne, may be related with severe forms of the disease in adolescence. A family history of severe acne can be present 18 . In severe cases of IA or persistent neonatal acne an infantile hyperandrogenemia should be excluded 16 . Physical examination looking for precocious puberty, bone age measurements...

Types of acne

Acne vulgaris Acne vulgaris, the common type of acne, occurs during puberty and affects the comedogenic areas of the face, back, and chest. There may be a familial tendency to acne. Acne vulgaris is slightly more common in boys, 30-40 of whom have acne between the ages of 18 and 19. In girls the peak incidence is between 16 and 18 years. Adult acne is a variant affecting 1 of men and 5 of women aged 40. Acne keloidalis is a type of scarring acne seen on the neck in men. Patients with acne often complain of excessive greasiness of the skin, with blackheads, pimples, or plukes developing. These may be associated with inflammatory papules and pustules developing into larger cysts and nodules. Resolving lesions leave inflammatory macules and scarring. Scars may be atrophic, sometimes with ice pick lesions or keloid formation. Keloids consist of hypertrophic scar tissue and occur predominantly on the neck, upper back, and shoulders and over the sternum. Acne excoree The changes of acne are...

Treatment of acne

In most adolescents acne clears spontaneously with minimal scarring. Reassurance and explanation along the following lines helps greatly (3) The less patients are self conscious and worry about their appearance the less other people will take any notice of their acne. Patients with acne should be advised to hold a hot wet flannel on the face (a much simpler alternative to the commercial Facial saunas), followed by gentle rubbing in of a plain soap. Savlon solution, diluted 10 times with water, is an excellent alternative for controlling greasy skin. There are many proprietary preparations, most of which act as keratolytics, dissolving the keratin plug of the comedone. They can also cause considerable dryness and scaling of the skin. Ultraviolet light therapy is less effective than natural sunlight but is helpful for extensive acne. It is a helpful additional treatment in the winter months. Synthetic retinoids. For severe cases resistant to other treatments these drugs, which can be...

Neonatal Acne

Neonatal acne is present at birth or appears shortly after. It is more common than fully appreciated if the diagnosis is based in a few comedones more than 20 of newborns are affected 1 . The most common lesions are comedones, papules and pustules. They are few in number and usually localized on the face, more often cheeks and forehead. Involvement of the chest, back or groins has been reported. Most cases are mild and transient. Lesions appear mainly at 2-4 weeks healing spontaneously, without scarring, in 4 weeks to 3-6 months. Neonatal acne has been suggested to be more frequent in male infants 2, 3 . The pathogenetic mechanisms of neonatal acne are still unclear. A positive family history of acne supports the importance of genetic factors. Familial hyperandroge-nism including acne and hirsutism give the evidence that maternal androgens may play a role through transplacen-tal stimulation of sebaceous glands 4 . There is a considerable sebum excretion rate during the neonatal period...

Glands in Acne

Immunohistochemical staining for NEP in normal facial skin was negative within the sebaceous glands. On the other hand, NEP was highly expressed in the sebaceous glands of acne patients in which immunoreactivity for NEP in the sebaceous glands were restricted to the germi-native cells. There was a statistically significant difference in the percentage of NEP-positive sebaceous acini to all acini between acne patients and controls 26 . We next examined effects of SP on NEP expression in the sebaceous glands using organ-cultured skin in vitro. Although normal facial skin specimens supplemented with medium alone showed no expression of NEP in sebaceous cells, skin specimens stimulated with SP revealed prominent NEP staining in the germinative cells of the sebaceous acini, which appeared to be analogous to the staining pattern of the sebaceous glands in acne patients. In addition, SP induced NEP expression in sebaceous glands in a dose-dependent manner 26 . Taking into account the lack of...

Brigitte Drenoa Florence Polib

Acne vulgaris is a distressing condition related to the pilo sebaceous follicle and which is considered as an 'adolescent' disorder. It is characterized by spontaneous resolution in the late teens or early twenties in the majority of cases. The first publication about the epidemiology of acne was in 1931 by Bloch 1 . Already at this time, the onset of acne was noted slightly earlier in girls (12.1 1.5) compared to boys (12.8 1.7 years), retentional lesions being the earliest lesions (13 at 6 years and 32 at 7 years of age). Since this publication, no significant evolution has been noted concerning the age of onset of acne. According to different studies of the literature performed in different countries in the world, the mean onset of acne is 11 years in girls and 12 years in boys, remaining earlier in girls (1 or 2 years) with mainly retentional lesions (open and closed comedones). However, adult acne has also been described recently.

Dr Christos Zouboulis

Prof Christos Zouboulis

4 Editorial Current and Future Aspects on Acne 7 Epidemiology of Acne 17 New Aspects in Acne Inflammation 24 Acne in Infancy and Acne Genetics 29 Topical Treatment in Acne. Current Status and Future Aspects 37 Update and Future of Systemic Acne Treatment 54 Propionibacterium acnes Resistance A Worldwide Problem 57 Update and Future of Hormonal Therapy in Acne 68 Less Common Methods to Treat Acne Editorial Current and Future Aspects on Acne It is a great pleasure to present the Proceedings of the Symposium on Acne held at the 20th World Congress of Dermatology, July 1-5, 2002 in Paris. The topics discussed have been selected to address current and future aspects of research, clinical entities and treatment of the most common human disease. The manuscripts represent a cooperative effort of 20 experts on acne from literally all around the globe. They are state-of-the-art reports including data on the increasing evidence of acne occurrence in a considerable amount of adults, especially...

Retinaldehyde and Retinylp Glucuronide

Retinoyl-P-glucuronide is a naturally occurring, biologically active metabolite of vitamin A. A 0.16 retinoyl-P-glucuronide cream was shown to be effective against inflammatory and non-inflammatory acne lesions in Asian-Indian patients 37 as well as in patients in the US, with comparable efficacy to tretinoin, but without the irritation potential or other side effects of tretinoin 38 . The percutaneous absorption, metabolism and excretion of topically applied radioactive retinoyl-P-glucuronide and tretinoin were similar in the rat and thus not of relevance for the differences in local tolerance 39 . Retinaldehyde was shown to have a significant comedo-lytic activity in the rhino mouse model 40 . After topical application in acne patients of retinaldehyde 0.1 gel or its vehicle every morning and erythromycin 4 lotion every evening for 8 weeks, comedones and microcysts were significantly improved with retinaldehyde combined with erythromycin, but not with erythromycin alone. In both...

Topical Antimicrobials

Topical antimicrobial agents have been in use for more than 30 years in acne. Indication is acne papulo-pustulosa grade I-II or in combination with retinoids in grade III or with oral antibiotics in grade IV (assessment score according to Plewig and Kligman). The most commonly used topical antimicrobials are benzoylperoxide, erythromycin, clindamycin and azelaic acid. Topical tetracyclines and topical chloramphenicol are less commonly used due to lower efficacy or specific side effects.

Implication and Strategies for the Future

It is now clear that antibiotic resistant strains of P. acnes are found worldwide. The level of resistance is greatest to erythromycin but tetracycline resistance including minocycline is also occurring, as is reduced sensitivity to clindamycin. The evidence points to an evolving problem. The common practice of long-term use of antibiotics, years in many instances, is now hard to defend unless one prescribes some form of benzoyl peroxide which suppresses emergence of resistant strains 18 . In this regard, the potential usefulness of benzoyl peroxide washes, which deposit benzoyl peroxide which resists rinsing off, are particularly interesting. Another strategy is the use of topical retinoids to maintain clearing once antibiotic therapy has suppressed the inflammatory phase of acne and possibly to consider systemic isotretinoin as an option for those in whom inflammation cannot be controlled without prolonged antibiotic use (table 4).

Estrogens and Sebum Production

Very little is known about the role of estrogens in modulating sebum production. Any estrogen given sys-temically in sufficient amounts will decrease sebum production. The dose of estrogen required to suppress sebum production however is greater than the dose required to suppress ovulation. Although some patients acne will respond well to lower-dose agents containing 0.035-0.050 mg of ethinyl estradiol or its esters, higher doses of estrogen are often required to demonstrate a reduction in sebum secretion 39 . The major active estrogen is estra-diol which is produced from testosterone by the action of the enzyme aromatase. Aromatase is active in the ovary, adipose tissue and other peripheral tissues. Estradiol can be converted to the less potent estrogen, estrone by the action of the 17P-HSD enzyme. Both aromatase and 17 P- HSD are present in the skin 26, 40 . As in the case of androgens, it is not known if circulating estrogens or locally-produced estrogens are important in...

Options for Hormonal Therapy

Within the class of androgen receptor blockers, the drug options are spironolactone, cyproterone acetate, and flutamide. In the United States, spironolactone is the drug most commonly used. Oral spironolactone decreases sebum excretion rate and inhibits the type 2 17P-HSD 48, 49 . Recommended doses for the treatment of acne are 50-100 mg, taken with meals 50 . However, many women respond well to 25 mg twice daily, and some even respond to just 25 mg a day. These low doses in healthy young women are well tolerated. However, if this drug is used in older women with other possible medical problems, or if higher doses are used for conditions such as hirsutism or androgenic alopecia, serum electrolytes should be monitored. Side effects to be aware of include breast tenderness and menstrual irregularities. Flutamide, a very potent antiandrogen that is also used to treat prostate cancer, can be used in the treatment of acne, hirsutism, and androgenic alopecia 52 . It can be given in doses of...

New Developments and Future Trends

Leukotrienes Inflammatory Mediators

After decades of stagnation, research on systemic acne treatment has expanded markedly in the last several years. The results of numerous studies have greatly increased our understanding of both the pathophysiology of the disease and the mechanisms of action for current therapies. New developments occurred including the low-dose long-term isotretinoin regimen, new isotretinoin formulations, understanding of isotretinoin's anti-sebotropic action, new antibiotics, and combination treatments to reduce toxicity and bacterial resistance, and new oral contraceptives. Future trends represent new anti-inflammatory agents, such as 5-lipoxygenase inhibitors, insulin-sen Low-dose isotretinoin (0.1-0.3 mg ml day daily or intermittent use) can effectively control acne, also being cost-effective. Nevertheless, the daily dose is too low for the cumulative dose obtained to be definitively curative. Although studies have been centered on the use of low doses only in older patients with exceptionally...

Androgens and Sebum Production

Acne Vulgaris

An essential role for androgens in stimulating sebum production is supported by the following clinical evidence (1) androgen-insensitive subjects who lack functional androgen receptors do not produce sebum and do not develop acne 7 , and (2) systemic administration of testosterone and dehydroepiandrosterone increases the size and secretion of sebaceous glands 8 . Several clinical observations point to the importance of androgens in acne. The development of early acne in the prepubertal period has been associated with elevated serum levels of dehydroepiandrosterone sulfate (DHEAS), a precursor of testosterone 9, 10 . For example, acne occurs near the time of puberty. In fact, investigators have demonstrated that acne begins to develop at the time of adrenarche when the adrenal gland begins to produce large quantities of DHEAS 9, 10 . This hormone can serve as a precursor to the production of more potent androgens within the sebaceous gland. The rise in serum DHEAS in prepubescent...

Screening for an Endocrine Disorder

In the majority of cases of women with acne, serum androgens are completely normal, yet it may nonetheless seem clear that there is a hormonal component to the acne. That is, the acne becomes worse prior to menstruation, for example, and it does in fact respond if treated with hormonal therapy. This dilemma has led to studies that have found that, as a group, women with acne will have higher levels of serum DHEAS, testosterone, and DHT, than those without acne 11, 47 . However, the laboratory values may still be within the normal range. Worth noting is that these values are at the high end of the normal range and that clinical and laboratory data support the use of hormonal therapy in this group in that their acne does respond to the therapy 47 .

Aetiology of Comedogenesis

Hybridization Vitro Technique

Comedogenesis is due to the accumulation of corneo-cytes in the pilosebaceous duct 5 . This could be due to hyperproliferation of ductal keratinocytes, inadequate separation of the ductal corneocytes or a combination of both factors 6 . There is reasonable evidence to support the hyperproliferation of ductal keratinocytes 7 . This has been demonstrated immunohistochemically using a monoclonal antibody to Ki67, a nuclear marker expressed by actively cycling cells, which labels increased numbers of basal keratinocytes of the follicle wall of both comedones and microcomedones compared with normal control follicles (fig. 1) 7 . Similarly, suprabasal immunola-belling of keratin 16 (K16), a phenotypic marker of hyper-proliferating and abnormally differentiating keratino-cytes, is found in ductal keratinocytes of acne lesions (fig. 2) 8 . These data are further supported by the finding, using in situ hybridization, that transcripts of K6, the N. control N. acne Comedone Fig. 1. Ductal...

New Topical Retinoids

Comedonal Acne Anatomy

New topical anti-acne therapies are required for several reasons. There is no topical anti-acne therapy which reduces lesions by over 60 in contrast to, for example, oral isotretinoin which can suppress lesions by 100 . This may simply be a measure of penetration of the drug. Most topical therapies frequently produce an irritant dermatitis, and this will reduce compliance. Many antibiotics have been shown to produce resistant P. acnes, and this is associated in some patients with clinical failure. New reti-noid molecules such as adapalene 17, 18 have been developed, while old retinoids have been redeveloped Fig. 6. Pomade acne. Fig. 7. Chloracne. Fig. 8. Naevoid acne. Fig. 6. Pomade acne. Fig. 7. Chloracne. Fig. 8. Naevoid acne.

Tamibaroten Palmitate

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was ad-apalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance....

Effects of SP on the Sebaceous Glands

Testosterone and lipogenesis were examined in sebaceous glands of Syrian hamsters, and demonstrated that immobilization-induced stress lowered the levels of testosterone in plasma as well as in the skin, which resulted in decreased lipogenesis in the skin 22 . Although these data suggest that psychological or physiological stress can influence sebaceous gland function by inducing changes in the neuroendocrine system, they provide no appropriate explanation for the effects of stress-induced exacerbation of acne. Taking into account that stress can elicit SP release from peripheral nerves 17 , it is tempting to speculate that SP should be partially involved in stress-induced exacerbation of the disease.

John S Strauss

Acne Vulgar

The acne symposium held at the 20th World Congress in Paris in July 2002 was an opportunity for some of those working in the field to present their findings on a wide selection of topics related to the pathogenesis and treatment of acne. The presentations were indeed world-wide, including investigators from Argentina, Chile, France, Germany, Japan, Taiwan, United Kingdom, United States, and Venezuela. As is appropriate for the World Congress which is held every 5 years, these papers are a comprehensive review of the past, present, and future. The publication of these nine papers as a unit in this journal covers varying points of view, and is an excellent reference source for all those interested in acne. There is a need to focus our attention on acne, as it should not be forgotten that in developed countries, it is still responsible for more visits to the dermatologist than any other skin disease. A basic theme that runs throughout the nine papers is the importance of the four...

Systemic Treatment

Oral prednisone 0.5-1.0 mg kg daily should be prescribed to patients with severe inflammatory acne vulga-ris, acne fulminans and pyoderma faciale. Prednisone must be administered for 4-6 weeks and then reduced gradually. In acne fulminans and pyoderma faciale it is preferable to prescribe the steroids for 3-4 weeks before prescribing the isotretinoin. Similar oral doses are also indicated in patients whose acne flares badly while taking isotretinoin 13 . Many times the worsening of acne observed between the third and the sixth week may be very severe and even trigger genuine manifestations of acne fulminans, although they should, more appropriately, be called 'pseudo' acne fulminans, since systemic features are minimal or almost absent and no pyrexia is noted. Baseline hematology and biochemistry parameters are within normal ranges. As this was observed in our department in 18 of 590 patients between 1983 and 1990, we decided to use isotretinoin and corticosteroids simultaneously and...

Benzoylperoxide

Currently, benzoylperoxide is still the gold standard for mild-to-moderate acne. Bacterial resistances have not been detected yet. Fixed combination preparations are available with erythromycin, and those with clindamycin are in preparation. They are more efficacious and better tolerated then benzoylperoxide alone. BPO is available as a solution, washing gel or cream 1-5 concentration. 10 concentrations are not significantly more efficacious but more irritative 2, 46, 51, 52 . The side effect profile of BPO depends on the galenic formulation of i.p. dryness of the skin and exsiccation eczema. It can bleach the hair and clothes. The following recommendations can be given ideal for mild-to-moderate inflammatory acne papulo-pustulosa optimal combi The common induction of an irritant dermatitis can be avoided by less frequent application making the incidence of true contact sensitivity low 55 . A water-based benzoyl peroxide preparation was found to cause significantly less skin...

Patients

Although hormones influence acne, it is clear that the majority of 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, acanthosis nigricans or a deepening of the voice. 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 endocrinologist or gynecologist.

Abstract

There is ample clinical evidence suggesting that the nervous system such as emotional stress can influence the course of acne. We examined possible participation of cutaneous neurogenic factors including neuropeptides, neuropeptide-degrading enzymes and neurotrophic factors, in association with inflammation in the pathogenesis of acne. Immunohistochemical studies revealed that substance P (SP)-immunoreactive nerve fibers were in close apposition to the sebaceous glands, and that neutral endopeptidase (NEP) was expressed in the germina-tive cells of the sebaceous glands in the skin from acne patients. Nerve growth factor showed immunoreactivity only within the germinative cells. In addition, an increase in the number of mast cells and a strong expression of endothelial leukocyte adhesion molecule-1 on the postcapillary venules were observed in adjacent areas to the sebaceous glands. In vitro, the levels and the expression of stem cell factor by fibroblasts were upregulated by SP. When...

Azelaic Acid

Azelaic acid is a 9-dicarbonic acid with efficacy on fol-licular keratinization and on P. acnes. It seems to have some inflammatory efficacy via effects on neutrophilic granulocytes. In clinical studies, a similar efficacy as tre-tinoin in comedonal acne has been demonstrated. The efficacy in papular-pustular acne in comparison to BPO is lower, but after 12-16 weeks similar results could be achieved. No bacterial resistance has yet been detected. Currently, azelaic acid is available in a 20 cream formulation. Clinical trials for a new formulation as a lotion have been performed which should be better tolerated in patients with more greasy skin 58 .

Tazarotene

Besides psoriasis, tazarotene is currently also available for acne treatment in the US market as a 0.5 and 0.1 gel or cream. The efficacy is comparable to adapalene, but its local tolerance by daily application is quite unfavorable and similar to tretinoin. Therefore, tazarotene was recently studied for its efficacy in a so-called short contact application manner similar to dithranol short time application from 30 s up to 5 min. In this study, three arms where compared twice daily, once daily, and vehicle. The once daily application was nearly equivalent to the twice daily and both where highly significantly better than vehicle 34-36 . The irritative potential was reduced.

Conclusion

Despite the interest on the development of topical treatments for acne in the last decades 30 , systemic treatment is still a milestone, especially in the treatment of moderate-to-severe scarring types of the disease. The establishment of new systemic drugs for acne is based on the consideration of successes and pitfalls of the past and the emerging knowledge of the future 125 . Among all pathogenetic factors of acne, inflammation seems to be rediscovered 13 and anti-inflammatory concepts seem to become the new trend of systemic and topical acne treatment. 1 Gollnick H, Zouboulis ChC, Akamatsu H, Ku-rokawa I, Schulte A Pathogenesis and pathogenesis related treatment of acne. J Dermatol 1991 18 489-499. 2 Brown SK, Shalita AR Acne vulgaris. Lancet 1998 351 1871-1876. 3 Zouboulis ChC Acne Current aspects on pathology and treatment. Dermatol Experiences 1999 1 6-37. 5 Cunliffe WJ, Eady EA A reappraisal and update on the pathogenesis and treatment of acne. Cur Opin Infect Dis 1992 5...

Comedonal Types

Submarine Comedones

Biopsy sections of normal-looking skin in an acne-prone individual with comedonal acne will frequently (28 ) show histological features of microcomedones. Biopsies of papules taken at up to 72 h of development will reveal a microcomedone in 52 of subjects, a whitehead in 22 and a blackhead in 10 22 , confirming even further the practical need to apply topical therapies to apparently non-involved skin. This term refers to blackheads and whiteheads which are > 1 mm in size. Whiteheads are the most common. They need to be treated for two reasons. They are a cosmetic problem and may flare into inflamed lesions (fig. 5), especially in patients treated with oral isotretinoin. In such patients, they are the major reason for a severe flare of the acne and surprisingly are easily missed unless adequate lighting and examination techniques, i.e. stretching the skin, are used. The optimum therapy is gentle cautery 26-28 . This is performed under topical local anaesthesia using an anaesthetic...

Conclusions

Hormonal therapy is an option for treatment when acne is not responding to conventional therapy. If there are signs of hyperandrogenism, an endocrine evaluation is indicated, consisting of an assessment of DHEAS, total and free-testosterone levels and an LH FSH ratio. Although an indication for hormonal therapy is hyperandro-genism, women with normal serum androgen levels also respond well to treatment. Hormonal therapy choices consist of androgen-receptor blockers, androgen-produc-tion blockers, and, potentially in the future, androgen-metabolizing enzyme inhibitors. The mainstays of hormonal therapy include oral contraceptives and spirono-lactone. Other agents to choose from are cyproterone, flu-tamide, and glucocorticoids. As more is learned about the hormones involved in acne, their source of production and the mechanisms by which they influence sebaceous gland growth and sebum production, new opportunities will arise for the development of novel therapies aimed at the hormonal...

Adapalene

Adapalene is a third-generation retinoid available as cream, gel or solution in 0.1 concentration. Currently, clinical studies comparing 0.1-0.3 adapalene are being performed. In a survey on nearly 1,000 patients, it could be demonstrated that adapalene 0.1 gel has the same efficacy as tretinoin gel 0.025 . The number of acne lesions was reduced by between 49 and 62 . The compar

Physical Treatment

The beneficial effects derived from the use of low temperatures in the treatment of different dermatological conditions have long been known. In that respect, cold compresses, to relieve inflammatory acne, as well as car The introduction of isotretinoin and a better management of its usage successfully solve nearly all cases of acne. Radiation therapy is being reserved at present for the most recalcitrant cases and should be administered only by highly skilled people who are fully aware of its risks. Ultraviolet light is scarcely used. Yet, it is well known that acne often improves clinically after exposure to sunlight or artificially produced solar radiation and more than 70 of patients report definite improvement after exposure to the sun during the summer. Reddening, as well as ultraviolet light-induced tan, produce a camouflage effect. Its therapeutic action might be linked to a biologic effect of the sunlight on the pilose-baceous system. It may have an anti-inflammatory action...

Effect of Iron Supplements

McGinley KJ, Webster GF, Ruggieri MR, Leyden JJ. Regional variation in density of cutaneous Propionibacterium correlation of Propionibacterium 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.

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...

Mechanism Of Retinoid 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).

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 ultrasonogra-phy will have androgen excess.

Preoperative abnormalities

A review of 31 patients with Cushing's disease showed that the commonest clinical features, in order of frequency, were weakness, thin skin, obesity, easy bruising, hypertension, menstrual disorders, hirsutism, impotence, striae, proximal muscle weakness, oedema, osteoporosis, mental disorders, diabetic GTT, backache, acne, hypokalaemia and fasting hyperglycaemia (Urbanic & George 1981). Fractures occur, and wound healing is poor.

Treatment of eczema and inflammatory dermatoses

Steroid ointments are effective in relieving inflammation and itching but are not always used effectively. Advise patients to use a strong steroid (such as betamethasone or fluocinolone acetonide) frequently for a few days to bring the condition under control then change to a weaker steroid (dilute betamethasone, fluocinolone, clobetasone, hydrocortisone) less frequently. Strong steroids should not be continued for long periods, and, as a rule, do not prescribe any steroid stronger than hydrocortisone for the face. Strong steroids can cause atrophy of the skin if used for long periods, particularly when applied under occlusive dressings. On the face they may lead to florid telangiectasia and acne-like pustules. Avoid using steroids on ulcerated areas. Prolonged use of topical steroids may mask an underlying bacterial or fungal infection.

Mild Moderate Acute Crohns Colitis

Corticosteroids are effective inductive therapies for patients with moderate-severe Crohn's colitis or for patients with mild-moderate disease that has not responded to amino-salicylates and or antibiotics. Controlled release budesonide formulations are also efficacious for mild-moderate CD involving the right colon, but are not effective for more distal colonic disease. Doses of 40 to 60 mg daily of prednisone (or up to 1 mg kg d) are initiated until a clinical response has been established. Subsequent tapering is individualized according to the rate of response. Generally, the dosage is gradually reduced by 5 mg week until the drug can be ceased or symptoms flare. In the NCCDS, 78 of patients responded to steroids given in this way. The response to budesonide is somewhat less and neither systemic nor nonsystemic steroids are efficacious at preventing relapse. Indeed, after a course of corticosteroids, approximately 75 of patients will either have a flare of disease activity or...

Developmental View Of Womens Health And The Menstrual Cycle

Puberty marks the beginning of adolescence, bringing with it a number of dramatic physical changes such as breast development, growth of pubic and axillary hair, hip widening, and acne. Menarche normally occurs between the ages of 10 and 16, approximately 2 years after the onset of puberty. Of all of the pubertal changes, the start of menstruation is perhaps the most meaningful event, in that it represents a clear passage into womanhood physically and psychologically. Menarche may be exciting, affirming, frightening, awkward, or all of these and other feelings simultaneously. Although menarche does not itself indicate reproductive maturity, it does signify its future prom- Physical changes associated with puberty, including breast development, growth of pubic and axillary hair, menarche (ages 10-18), hip widening, vaginal discharge, and acne

The Central Nervous System

Lowes Syndrome

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.

Medical History and Physical Examination in Patients With Possible Androgen Excess

Modified Ferriman Gallwey Score

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....

Anovulation Is A Characteristic Feature Of Pcos. It Manifests As Menstrual Disturbance 80 Amenorrhoea Oligoamenorrhea

Patient With Hyperandrogenism

Patients with PCOS may present complaining of irregular or unpredictable menstrual cycles, unwanted hair growth, acne or scalp hair loss, or unexplained weight gain or overweight (see Section 2.1.4.). Another frequent presenting complaint of PCOS may be infertility, possibly associated with recurrent first trimester miscarriages. Approximately 30-50 of PCOS patients will complain of infertility at the time they are seen for their first visit (1,2). The timing of the development of symptoms is important in assessing the etiology of hyperandrogenism. As such it is helpful to have the patient's mother present for at least initial part of the evaluation. A history of perimenarcheal changes in skin quality, such as the development of seborrhea or acne, the darkening and coarsening of hairs, or the appearance of new unwanted hairs, is common in patients with PCOS. A history of premature adrenarche or early pubarche may also be elicited (3) as well as a history of low birthweight (4,5)....

Do Mutations Cause Crime

Testicular Atrophy Picture

The report generated intense interest and spirited (sometimes bitter) debate in the scientific and forensic community. As clinical geneticists found and studied more men with XYY syndrome, they learned that in addition to being tall, some of them had coarse facial features, scars from severe acne, and low intelligence. In a word, many of them looked much like Hollywood's portrayal of a hulking criminal. On the other hand, most men with XYY syndrome looked normal, were clearly of normal intelligence, and were leading ordinary lives. A number of researchers argued that the reason that persons with an extra Y chromosome were more likely to turn up in prison populations was because if they committed petty crimes they were more likely to get caught, and if they were tried before a jury they were, because of their criminal look, more likely to be convicted.

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 tetracycline antibiotics.

Cushings Syndrome

Physical characteristics of Cushing's syndrome. A, Side profile of a patient with Cushing's syndrome demonstrating an increased cervical fat pad (so-called buffalo hump), abdominal obesity, and thin extremities and petechiae (on the wrist). The round (so-called moon) facial appearance, plethora, and acne cannot be seen readily here. B, Violescent abdominal striae in a patient with Cushing's syndrome. Such striae also can be observed on the inner parts of the legs in some patients.

Retinoids

These vitamin A derivatives have proved very effective in the treatment of psoriasis and acne but are not without risk of side effects. The most serious is that they are teratogenic and must be discontinued for at least three months after stopping treatment in the case of isotretinoin and five years after taking acitretin. This drug is used for severe acne vulgaris that has not responded to antibiotics or other treatments. It is therefore often used in adolescence and it is important to be aware of the musculoskeletal effects and possible mood changes.

Epidermal Cysts

Two cystic conditions may be encountered externally, each in a different location. Epidermal inclusion cysts, traditionally known as sebaceous cysts, are usually located low in the postauricular crease. They represent backed-up oil glands and occur in individuals with oily skin and acne. These patients tend to have them behind both auricles and in other facial areas as well. Their usual content is cheesy sebum, but at times they may swell up and abscess, often infected with staph. If they are infected, the treatment is an antistaphylococcal antibiotic. Often the infection will resolve, but incision and drainage may be necessary. Troublesome recurrences can be surgically excised, when not infected, taking care to remove the entire cyst lining. Even then, they may reappear.

Antiaging Medicine

Indeed, it is the cosmetics industry that is at the center of this controversy, for it is quick to market any compound that may be used as an antiwrinkle cream or skin exfoliant for what they call the vibrant, youthful look. Whether they have the right to do so is up to governmental agencies, such as the Food and Drug Administration (FDA) in the United States, which oversees the marketing of any compound that claim to have medicinal properties.

Cyproterone Acetate

Cyproterone acetate is an effective treatment for hirsutism and acne and is widely used throughout the world for this indication. However, it is not available in the United States. Doses of the drug used for treatment of hirsutism range widely, between 2 and 100 mg day (2 mg are contained in the previously mentioned contraceptive pill).

Epidemiology

Absence of these promoters is potentially useful in providing a less cluttered view of the disease. The fact remains that in the majority of men or women, no special risk feature is evident other than age. Avoiding potential mammary carcinogens and aspiring to a low-risk profile are some lessons in prevention derived from studies of breast cancer in males. Fortunately, ionizing radiation is no longer used to treat pubertal gynecomastia, acne, and other benign conditions of youth. Hormonal stimulation of the male breast and obesity are avoidable. Identification of individuals with an inherited high risk for breast cancer through genetic testing can permit more informed decisions about prophylactic mastectomy for men.41

Congenital Anomalies

Down Syndrome Multiple Births

Teratogens13 are viruses, chemicals, and other agents that cause anatomical deformities in the fetus. Perhaps the most notorious teratogenic drug is thalidomide, a sedative first marketed in 1957. Thalidomide was taken by women in early pregnancy, often before they knew they were pregnant, and caused over 5,000 babies to be born with unformed arms or legs (fig. 29.13) and often with defects of the ears, heart, and intestines. It was taken off the market in 1961 but has recently been reintroduced for limited purposes. Many teratogens produce less obvious effects, including physical or mental retardation, hyperirritability, inattention, strokes, seizures, respiratory arrest, crib death, and cancer. A general lesson to be learned from the thalidomide tragedy and other cases is that pregnant women should avoid all sedatives, barbiturates, and opiates. Even the acne medicine Acutane has caused severe birth defects.

Topical steroids

Topical steroids provide effective anti-inflammatory treatment but have the disadvantage of causing atrophy (due to decreased fibrin formation) and telangiectasis. They are readily absorbed by thin skin around the eyes and in flexures. On the face the halogenated steroids produce considerable telangiectasia, so nothing stronger than hydrocortisone should be used (except in lupus erythematosus). They can cause hirsutism and folliculitis or acne. Infection of the skin may be concealed (tinea incognita, for example) or made worse.

Info

Clinical manifestations of PCOS are different in obese women with PCOS compared with lean women with PCOS (8) (Table 1). Obese women with PCOS report more menstrual irregularities and more oligo- amenorrhea than their lean counterparts. Obesity is also associated with an increased prevalence of infertility in PCOS and in the general population as well. The risk of miscarriage is also increased in obese women, whether or not they have PCOS. Moreover, obesity increases the risk of complications during pregnancy, such as gestational diabetes and pre-eclampsia (9). Finally, obese women with PCOS tend to have higher hirsutism and acne scores than lean PCOS women.

Flutamide

Some studies reported that this drug is more effective than spironolactone or finasteride in the treatment of hirsutism. However, differences were small, and all these medications gave similar results in a controlled comparative trial (18). Anecdotal evidence suggests that flutamide is more effective than other drugs in treating androgen-dependent acne, although no controlled study has been specifically designed to assess this aspect. Some studies reported that this drug might have favorable effects on visceral fat and on the lipid profile in patients with PCOS (22,23). These effects are of great interest in subjects who frequently show abdominal obesity, insulin resistance, and multiple metabolic abnormalities.

The Natural Acne Remedy

The Natural Acne Remedy

Download this Guide and Discover 50 Ways To Treat Acne Using Only Natural Remedies. About Time You Got Rid of Your Acne? Inside this guide, you'll discover: 50 ways to treat acne using natural remedies. The benefits of treating acne using natural remedies. Natural acne remedies to treat acne scarring. The side effects of popular acne medicines and treatments plus much, much more.

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