(BQ) Part 2 book Dermatology acne presentation of content: The Vasculopathic pattern, panniculitis, fibrosing dermatitis, the depositional pattern, the melanocytic tumors, epithelial neoplasms, adnexal neoplasms, the mesenchymal tumors.
World Clin Dermatol 2013;1(1):128-43 Adult Acne *Alison M Layton MB ChB FRCP, Rebecca L Mawson MB ChB Bsc DRCOG Harrogate and District NHS Foundation Trust, Lancaster Park Road, Harrogate, HG2 7SX, London, UK ABSTRACT Acne remains as one of the commonest inflammatory dermatoses seen worldwide While teenage acne is still regarded as a ‘rite of passage’ by many, it is increasingly acknowledged that acne is a chronic disease extending beyond teenage years and in some cases, presents for the first time well after adolescence This article highlights key features of adult acne including debate around the definition, prevalence of the problem, underlying pathogenesis, and related epidemiological factors, as well as therapeutic options specific to management and related outcomes Introduction Acne represents a polymorphic inflammatory skin problem centered on the pilosebaceous unit It typically develops around adrenarche in association with an increase in androgen-mediated sebum production Over the last decade, it has been recognized that acne is a chronic condition.1 The peak age of onset for acne is 16–19 years in boys and 14–17 years in girls.2 Seventy percent of cases resolve after years of onset but in some cases, acne will either persist as a continuum until 20–30 years of age or present for the first time well after teenage years.3 DEFINING ADULT ACNE Defining a specific age for the onset of late-onset or adult acne is challenging, as it is dependent on individual maturity A classification based on age of onset greater *Corresponding author Email: alison.layton@hdft.nhs.uk © 2014 Jaypee Brothers Medical Publishers All rights reserved World Clinic Dermatology (Acne).indd 128 30-11-2013 17:04:57 Adult Acne Figure 1: Moderate inflammatory acne in a male of 26 years than 25 years, persistence beyond 21 years and/or relapse of acne post-adolescence has been suggested in the literature (Figure 1).3 Given adolescent acne is said to peak at the latest around 19 years for males and 17 years for females and the mean duration of adolescent acne is said to be 5 years, the age of 25 years lies outside the expected time of resolution for adolescent acne, so it is deemed a reasonable age to assume that the acne has presented as a part of adulthood However, it is acknowledged that each case needs to be judged on its own merit and this interpretation remains open to debate and in many cases, adult acne is a continuation from adolescence Implications Of Persistent Acne For The Patient Acne, at any age, can have a significant psychosocial impact, reducing self-esteem, leading to lower socioeconomic achievement, as well as affecting social functioning such as relationship formation and continuity The psychosocial impact of acne has been shown to be similar to other systemic diseases such as diabetes and epilepsy.4 Acne scarring correlates to the duration of acne5,6 and is also associated with significant psychological morbidity in many patients.7 The chronic nature of acne and resultant scarring increases the likelihood of psychological problems It has been shown that adults with acne, have a 40% prevalence of psychiatric co-morbidity.8 Effective therapy, started early in the course of the disease, improves acne in the majority of patients and may avoid resultant significant scarring.5 129 World Clinic Dermatology (Acne).indd 129 30-11-2013 17:04:57 Layton and Mawson PREVALENCE OF ADULT ACNE The prevalence of adult acne has been examined in many studies which have used different definitions and variable modes of assessment including surveys, clinical examination, patient-perceived assessment of acne, as well as community-based vs hospital-based evaluations Inconsistent approach makes it challenging to have a clear idea of the real prevalence of adult acne Table outlines the studies that have been published.9-15 Goulden et al.9 noted that the mean age of facial acne referred to the hospital department increased from 20.5 to 26.5 years over a period of 10 years from 1989 to 1999 They questioned whether this was related to an increased prevalence of acne in this age group or an increased awareness of the disorder and knowledge of improved therapies They conducted a survey of 749 randomly selected volunteers with facial acne Facial acne had persisted since childhood in most adults and clinical acne was noted in 3% of males and 12% of females (Table 2).9 The prevalence of acne, in this UK study, only declined significantly after 44 years of age This contrasts with an Indian study which showed that acne usually declines after 40 years of age but was still present in 2.1% of the studies’ population beyond 45 years.10 Other prevalence studies have also confirmed increased prevalence in females with adult acne compared to the males of the same age Table 1: Prevalence of Acne Reported by Age-group Author No of subjects Age (year)/Sex Country and year Study type Prevalence of acne Cunliffe et al.11 2,155 18–70 Males and females UK, 1979 Survey and clinical examination • 40–49 years: 3% males and 5% females • 50–59 years: 6% males and 8% females Stern12 20,749 15–44 Males and females US, 1992 Survey of acne conglobata and acne of atleast a moderate degree with cysts and scars 15–44 years: 832,000 females and 1,319,000 males Male:female ratio for acne with cysts and scars 1.6:1 Poli et al.13 3,305 25–40 Females only France, 2001 Survey • 41% 17% clinical acne (mean 6.2 inflammatory lesions) || 24% physiologic acne (mean 1.3 inflammatory lesions) || Continued 130 World Clinic Dermatology (Acne).indd 130 30-11-2013 17:04:57 Adult Acne Continued Table 1: Prevalence of Acne Reported by Age-group Author No of subjects Age (year)/Sex Country and year Study type Prevalence of acne Goulden et al.9 200 25–55 Males and females UK, 1997 Clinical examination • >25 years:12% females and 3% males acne • Beyond 45 years: 12.5% Goulden et al.14 749 >25 Males and females UK, 1999 Communitybased study clinically examined >25 years: 54% females, 40% males Collier et al.15 1,013 >20 Males and females US, 2006 Survey Females vs males: • 20–29 years: 50.9% vs 42.5% • 30–39 years: 35.2% vs 20.1% • 40–49 years: 26.3% vs 12.0% • 50 years and older: 15.3% vs 7.3% Khunger et al.10 280 >25 Males and females India, 2008 Observational study • The mean age of the patients was 30.5 years • Persistent acne was observed in 73.2%, while late-onset was seen in 26.8% Table 2: Prevalence of Acne According to Grade and Age in a Group of Caucasian Volunteers Selected from University and Hospital Staff9 Type of acne Age (years) Prevalence male (%) Prevalence female (%) Clinical 18 35 23 29–39 10 40–49 18 10 25 29–39 30 29 40–49 Mild acne Perkins et al studied the variable pattern of acne among different ethnic groups, showing increased prevalence in African-American and Hispanic women compared to Indian, Caucasian, and Asian women.16 The prevalence of different subtypes of acne was similar through the ethnic groups, with the exception of Asian women, who had more inflammatory lesions and Caucasians demonstrated more 131 World Clinic Dermatology (Acne).indd 131 30-11-2013 17:04:57 Layton and Mawson comedonal acne Hyperpigmentation, dyspigmentation, and atrophic scarring was more common in African-American and Hispanic women Cunliffe et al reported that acne was more prevalent in female patients of age more than 23 years and that, men showed a gradual decline in their acne with age.11 An Indian study\reported 82.1% of adult women above 25 years of age were affected with acne when compared to 17.9% of men,10 and suggested, like Goulden et al.,9 that this might relate to greater awareness in this group of females A survey of 1,013 respondents reported that of them, 73.3% had acne at some point in their life Acne was more common in females than males at all ages after teenage years (p < 0.05).15 CLINICAL PRESENTATION OF ADULT ACNE Classification of Adult Acne Adult acne has been defined in the literature into the following suggested categories.3 • Late-onset, presenting for the first time over 25 years of age was found to occur in 34% of the cases in epidemiological study of adult females with acne.17 Within the context of this group, clinical subtypes have been described as || Chin acne either as a chronic inflammatory acne distributed on the chin and perioral region typically with deep-seated, long-lasting nodules, and cysts or Hyperseborrhea with retentional lesions, mostly small, closed comedones around the chin Significant flares have been described premenstrually3 || Sporadic acne occurring with no apparent reason or cause but may be associated with other systemic disease17 • Persistent acne This is a continuum of acne that begins in adolescence and may happen for a variety of reasons Patients might not have secured effective treatments; they might not have used treatments correctly, or might have failed to respond to treatments Acne is frequently present most of the time but there may be a significant premenstrual flare in women.18,19 A UK survey of adult acne patients showed most patients had acne since teenage years (71%)11 • Relapse of adolescent acne in adult age This can be difficult to identify from the history, as there is frequently no clarity around when the patient was free from acne; however, it may be easier to define when isotretinoin has been used successfully, as there will be a period of time post-therapy, when the patient was free from any acne A study by Collier et al suggested this might account for 4% of men and 13% of women.15 132 World Clinic Dermatology (Acne).indd 132 30-11-2013 17:04:57 Adult Acne DIFFERENCE IN CLINICAL PRESENTATION OF ADULT ACNE Some authors have identified distinct morphological differences in the characteristics of adult acne which may distinguish it from adolescent acne Unlike adolescent acne where males are affected more frequently than females, adult acne is more prevalent in females The classic presentation of adult acne is of inflammatory lesions (in particular, papules, pustules, and nodules) which are usually prominent over the lower chin, jawline, and neck (Figure 2).14,17,20 In contrast to this, an Indian study reported a predominance of lesions on the cheeks, which raises the question of variable distribution based on ethnicity.10 Comedonal activity is rare, but if present, it is usually in the form of closed comedones, retentional lesions, or microcysts around the lower face17 (Figure 3) A B Figure 2: A, Adult female inflammatory acne showing predilection to lower cheeks and chin B, Mixed inflammatory, non-inflammatory lesions at lower face and chin Figure 3: Adult female acne mixed inflammatory lesions and macrocomedones around lower cheeks and chin 133 World Clinic Dermatology (Acne).indd 133 30-11-2013 17:04:57 Layton and Mawson Adult acne is mainly mild-to-moderate in severity and may be refractory to treatment.3 However, cystic acne may occur and has been identified in up to 12% of adults.11,14 Studies show a variation in the site involved, depending on where the study has been conducted Observational studies of community samples show that persistent acne in women often involves non-facial skin, whereas studies looking at those referred to a dermatology department, found a predominance of facial distribution This may be in part due to the fact that pure truncal involvement is not deemed to be cosmetically distressing; hence, fewer patients present for treatment A survey of 942 adult females with acne in UK consulting dermatologists, aged between 25 and 40 years, found chest and back involvement in 28%.11 Underlying Pathogenesis And Associated Epidemiological Factors This area is extensively covered in other articles Although there is a limited evidence to suggest that the underlying pathophysiology of adult acne differs significantly from adolescent acne, it is important to rule out a number of factors as these may influence on-going management As a larger proportion of females suffer from adult acne, underlying hormonal imbalance should be considered where history or other clinical features indicate this as a possible underlying problem Hormonal Considerations Women with adult acne often show clinical features suggestive of hyperandrogenism such as hirsutism, premenstrual flare, and alopecia Very few of these women have raised laboratory markers of hyperandrogenism, but it raises the question of their having an end-organ hypersensitivity, rendering them more susceptible to circulating hormones Menstrual Cycle There is an extensive evidence that adult acne in females relates to hormonal aspects with flares occurring premenstrually.18,19 However, the prevalence varies A selfreported UK survey of 400 women found that 44% of women had premenstrual flares, with women older than 33 years were more likely to have flare than those between the age of 20 and 33 years.14 A smaller UK study found that 83% of women with persistent acne reported premenstrual flare.20 134 World Clinic Dermatology (Acne).indd 134 30-11-2013 17:04:58 Adult Acne Dihydroepiandrosteronesulfate Studies have looked at androgenic changes in women with acne A study examined women with adult-onset or hirsutism-associated acne compared with an age-matched control group.21 Luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), dihydroepiandrosteronesulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured and compared Results demonstrated that acne was associated with increased SHBG, free androgen index, and DHEAS in females with hirsutism, but only DHEAS was increased in women without hirsuitism.21 Androgens There is also a suggestion of target tissue androgens in the skin having a pathogenic role in women with adult acne.3,22 Androgens are produced locally in the sebaceous glands and keratinocytes via DHEAS metabolism Serum androgens, while within the normal range, may increase tissue-derived androgens in females with acne This may be due to local, more sensitive tissue enzyme activity and more sensitive receptors in the sebaceous gland and/or keratinocytes Other studies have confirmed that adrenal androgen secretion is only mildly elevated in patients with adult acne and patients without acne, have similar hormone levels.23,24 Endocrinopathies and Genetic Factors Late-onset Congenital Adrenal Hyperplasia There is a link between adult acne and late-onset congenital adrenal hyperplasia (CAH) One study identified 11.8% of patients with post-adolescent acne had reduced activity of the enzyme 21-hydroxylase, in keeping with late-onset CAH.25 Polycystic Ovarian Syndrome Symptoms of polycystic ovaries have been reported in 52–82% of patients with adult acne, although hormonal profiles were not in accordance with the classical polycystic ovary syndrome (PCOS).26 Genetic Factors Familial links with acne including adult acne that has been well-documented (Table 3).27 A large study of identical twins showed in 97.9% of individuals, both had acne.28 Other studies, around the world, have shown high rates of family members affected from 38 to 50%.13,16,28,29 Therefore, it seems that genetics might have a significant role to play in acne development, persistence, and response to treatment 135 World Clinic Dermatology (Acne).indd 135 30-11-2013 17:04:58 Layton and Mawson Table 3: High Frequency of Family History of Acne in Adult Women with Acne Father Acne history positive Acne history negative Responses 49 (71%) 20 (29%) N = 69 Mother 51 (74%) 18 (26%) N = 69 Sibling 37 (54%) 32 (46%) N = 69 At least one 47 (67%) 23 (33%) N = 69 External Factors Antibiotic Use There has been a developing understanding of the role of P acnes in adult acne and the impact of evolving antibiotic resistant bacteria.1 Many patients suffering from persistent acne have had many years of differing topical and/or oral antibiotic therapy, without the adjuvant use of antimicrobials to prevent resistance Some adults with persistent acne may carry antibiotic resistant strains of P acnes which can contribute to or atleast result in some reduced efficacy to antibiotic therapies, although it is acknowledged that the correlation between carriage of antibiotic resistant P acnes and response to therapy is complex.30 However, the judicial use of antibiotics and concomitant use of an antimicrobial therapy alongside antibiotics, when required, is advocated.1 No differences in bacterial flora have been observed between adolescents and adults with acne; hence, it is unlikely that antibiotic resistant bacteria influence the course of adult acne per se.31 Drug-induced Acne A number of medications have been implicated in acne Studies have linked medications such as prednisolone, lithium, anabolic steroids, and phenytoin as possible causative agents.32 Exposure to Ultraviolet Light There is a suggestion that ultraviolet radiation may cause inflammation and generate squalene peroxides which are highly comedogenic.33,34 This may play a role in the persistence of acne in tropical countries, in addition to excessive perspiring and increased humidity.33,35 Climate There are various beliefs about the way that climate affects acne Traditionally, in the UK, it was thought that summer improved acne whereas winter aggravated 136 World Clinic Dermatology (Acne).indd 136 30-11-2013 17:04:58 Adult Acne it Indian studies found the opposite that sun exposure and summer seasons aggravate acne This may be explained by the relatively cool summers of the UK when compared to hot tropical climates.35 Obesity and Food Intake There is a suggestion of obesity and increased low-density lipoprotein (LDL) cholesterol being linked to acne.36 Food intake has been associated with adult acne in some studies.37 It is likely that this interplays with metabolic syndromes with increased serum levels of insulin-like growth factor (IGF) also being positively associated with acne lesions.38,39 Smoking Smoking may play a role in acne severity and has been significantly related in a dose-dependent manner to cigarette consumption.40,41 One variant common to smokers has been described in post-adolescent acne This embraces a paucity of inflammatory lesions, but large prominent cyst-like comedones homogeneously distributed on the whole face with a relative absence on the lower third of the face and the jawline.40 Cosmetics Cosmetics have been implicated in the development of acne in certain female population groups.42 Others have reported no clear link between acne and cosmetics, although there is thought to be an element of exacerbation by using oil or greasy products.10 Stress Chronic stress has been linked to adult acne and thought to be due to an increased androgen secretion in females.43 Studies have linked stress and acne in up to 71% cases.10,11,16 An association between increased levels of cortisol and emotional stress has been reported.44 A study of 13 patients with late-onset adult acne found no underlying abnormalities in levels of androgens but onset was related to stress.45 These patients did not respond to antibiotics or isotretinoin, but of the patients had clearance of acne with an antidepressant Pregnancy Pregnancy has a varied response on acne Some women find there is a flare in acne and some have improvement Goulden et al found a flare in 18%, improvement in 43%, and no effect in 39%.9 137 World Clinic Dermatology (Acne).indd 137 30-11-2013 17:04:58 – – – – – Benzoyl peroxide (4%-5%- 5.3%-6%9.8%-10%) Chlorhexidine gluconate (4%) Clay (% NS) + Jojoba (% NS) Salicylic acid (2%) Author In vitro studies Azelaic acid (1%) + Salicylic acid (1%) + Triclosan (0.04%) Agent Table 1: Cleansers for Acne World Clinic Dermatology (Acne).indd 237 • Level IB • High risk of bias • Level III Single-blind, crossover, RCT: 6% BPO foaming cloth cleanser switched to 6% BPO cleanser switched to 4% BPO washes (5’ single application) 1) Open, CT: 9.8% BPO foam “non leave-on” formulation (once daily for 2w); 2) Open, comparative, CT: 9.8% BPO foam “non leave-on” vs 5.3% BPO foam “leave-on” formulation (once daily for 2w) Del Rosso 20099 Leyden 201210 Shalita 198914 Bettley 197213 Meier 201212 Open, crossover, CT: 2% salicylic acid (SA) cleanser for 2w switched to 10% benzoyl peroxide (BPO) cleanser (once or twice daily for 2w) Placebo, RCT: 2% SA cream wash vs placebo (twice daily for m) Prospective, CT: clay jojoba facial mask (2–3 times/w for 6w) Stoughton 1) Comparative, RCT: 198711 4% chlorhexidine gluconate (CHG) cleanser vs 5% BPO cleanser (twice daily for 12w) 2) Double-blind, placebo, RCT: 4% CHG cleanser vs placebo (twice daily for 12w) • Level III • Level IB • Level III • Level IB • Level IIA Double-blind, placebo, CT: 5% BPO solution wash vs 10% BPO solution wash vs placebo (30s once daily for 4w) Choi 20107 Brummitt 19848 Comments • Level IB • Limited number of pts • Biopsy proven clinical results Study design Double-blind, placebo, RCT: 1% azelaic acid (AzA) +1% salicylic acid (SA) + 0.04% triclosan (TC) cleanser vs placebo (twice daily for 8w) Author In vivo studies The Role of Dermocosmetics in Modern Acne Treatment 237 30-11-2013 17:05:06 Micali et al SEBUM-CONTROLLING AGENTS Sebum is the results of androgen-driven secretion by sebaceous glands An overproduction of sebum is frequently seen in acne patients Drugs such as systemic retinoids, birth-control pills and spironolactone are indicated to regulate the overproduction of sebum Topical sebum-controlling agents are cosmetic products, which are used to absorb and retain sebum Their action seems mostly due to the presence of so-called “matifiant” agents like methacrylate copolymer microsphere.1 Their role on 5a-reductase or on sebaceous glands activity has been claimed, but this issue still needs to be confirmed.15 Among the various sebum controlling agents, two studies in vitro and nine CTs (Level IB = 5; Level IIA = 2; Level III = 2) listed in Table have been identified.15-24 ANTIMICROBIAL AGENT Topical antibiotic are commonly used for the management of moderate-tosevere acne vulgaris In order to optimize efficacy and to reduce the emergence of Propionibacterium acnes resistance, topical antibiotics are most commonly used in combination with antimicrobial-controlling agents Five studies in vitro and four CTs (Level IB = 3; Level IIA = 1) are listed in Table 3.25-31 ANTIINFLAMMATORY AGENTS Recent understanding in the pathogenesis of acne has suggested a pilot role of inflammatory (IF) events in the development of acne lesions Most of topical or systemic pharmacological therapies for acne have also an antiinflammatory action and the use of cosmetics with antiinflammatory properties may seems reasonable Ten studies in vitro and 19 CTs (Level IB = 10; Level II4 = 5; Level III = 4) listed in Table have been identified.20,23,24,28,32-53 CORNEOLYTICS Corneolytics are cosmetics that cause intercorneocyte cell detachment so as to induce a comedolytic effects They include a-hydroxyacids such as glycolic acid (GA), lactic acid (LA) and citric acid; b hydroxyacids like salicylic acid (SA) and a-ketoacids such as pyruvic acid in concentrations varying from 2% to 7% and up with GA as well as retinaldehyde (RAL) and retinol, at concentration of 1% or less.4 This group of cosmetics is particularly indicated for comedonal acne, making comedones more superficial and at the same time smoothing the skin They 238 World Clinic Dermatology (Acne).indd 238 30-11-2013 17:05:06 Mahmood 201016 – – Raynaud 200715 – – – – Nicotinamide (2%) + Panthenol (1%) Retinaldehyde (0.1%) + Glycolic acid (6%) Serenoa repens (2%) Silicic acid (%NS) Tetranoic acid (TA) (2%) Triethyl citrate (% NS) + Ethyl linoleate (% NS) + Salicylic acid (0.5%) Zinc pyrrolidone (0.1%) + Laminaria digitata (% NS) Author In vitro studies Green tea (3%) Agent Table 2: Sebum Controlling Agents World Clinic Dermatology (Acne).indd 239 Open CT: 2% Serenoa repens cream-gel (twice daily for 4w) Dobrev 200719 Capitanio 201224 Charakida 200723 • Level IB • Biophysical only assessment • Level IIA assessment evaluation • Level IB • Biophysical, clinical and self- • Level IIA Double-blind, placebo, RCT: • Level IB 0.1% zinc pyrrolidone + seaweed Laminaria digitata • Biophysical only assessment extract cream vs placebo (twice daily for 8w) Double-blind, placebo, RCT: triethyl citrate + ethyl linoleate + 0.5% salicylic acid (TES) lotion vs placebo (twice daily for 12w Controlled, CT 2% TA solution vs no treatment (twice daily for w) Double-blind, placebo, RCT: silicic acid emulsion vs placebo (twice daily for 8w) Fernandez 200521 Burton 197022 Double-blind, placebo, CT: Silicic acid gel vs placebo (20m twice daily for 6w) Lassus 199620 • Level III • Level IB • Biophysical only assessment Multicentre, double-blind, placebo, RCT: 0.1% retinaldehyde (RAL) + 6% glycolic acid (GA) (RALGA) emulsion vs placebo (once daily for 12w) Draelos 200617 Poli 200518 • Level III Comments • Level IB • Biophysical only assessment Open, CT: 3% tea emulsion (twice daily for 8w) Study design Multicentre, double-blind, placebo, RCT: 2% nicotinamide + 1% panthenol gel (NP) vs placebo (twice daily for 4w) Mahmood 201016 Author In vivo studies The Role of Dermocosmetics in Modern Acne Treatment 239 30-11-2013 17:05:06 World Clinic Dermatology (Acne).indd 240 Enshaieh 200728 Franz 197831 Raman 199527 Lee 200329 DominguezDelgado 201130 Tea tree oil (5%) Triclosan (0.1%) Pavicic 200726 Pavicic 200726 Phytosphingosine (0.2%) Prottey 198425 Author Prottey 198425 Author In vitro studies Ethyl lactate (10%) Agent Table 3: Antimicrobials Agents In vivo studies Double-blind, placebo, CT: 0.1% triclosan (TC) cream vs 0.1% TC + 0.75% propylene phenoxetol cream vs placebo (twice daily for 8w) Double-blind, placebo, RCT: 5% tea tree oil gel vs placebo (twice daily for 6w) Placebo, RCT: 0.2% phytosphingosine (PS) emulsion vs 0.2% PS-hydrochloride salt (HCL) vs triclosan (NS % and formulation) vs placebo (twice daily for 8w) Placebo, RCT: 10% ethyl lactate alcohol lotion vs placebo (twice daily for 2w) Study design • Level IIA • Level IB assessment • Level IB • Limited number of patients • In vitro and in vivo study • Microbiologic only assessment • Level IB • Limited number of patients • In vitro and in vivo study • Microbiologic and biophysical Comments Micali et al 240 30-11-2013 17:05:06 World Clinic Dermatology (Acne).indd 241 Multicenter, prospective, placebo, CT: 0.2% myrtacine + 4% nicotinamide (MN) emulsion vs placebo (twice daily for 4w) Multicentre, double-blind, comparative, RCT: 4% nicotinamide (N) gel vs 1% clindamycin gel (twice daily for 8w) Fiorini-Puybaret Veraldi 201136 201237 Emanuele 201242 Fabbrocini 201144 Pasricha 197934 Grange 200938 Padula 201039 – – Gao 200343 Myrtacine (0.2%) + Nicotinamide (4%) Nicotinamide (4%) Nicotinamide (4%) + Linoleic acid - rich phophatidylcoline (4%) Nicotinamide (4%) + Retinol (1%) + Dehydrocholesterol (0,5%) Resveratrol (0.01%) Morganti 201141 Shalita 199540 Garg 200235 Single-blind, placebo, CT: 0.01 mg/ml resveratrol hydrogel vs placebo (daily for 8w) Prospective, CT: 4% Nicotinamide + 1% retinol + 0.5% dehydrocholesterol (DHC) in a moisturized base (twice daily for w) Multicentre, double-blind, placebo RCT: 4% Nicotinamide + linoleic acid- rich phoshatidylcoline (N-PHCL) emulsion vs 1% clindamycin phosphate emulsion + placebo (once daily for 12w) Open, uncontrolled, CT: 5% lactic acid (LA) solution (twice daily for 48w) Open, uncontrolled, CT: 2% tea lotion (twice daily for w) Lactic acid (5%) Elsaie 200933 – Double blind, placebo CT: 1) 2.5% BPO gel vs placebo (twice daily for w) 2) 2.5% BPO gel vs 5% BPO gel (twice daily for w) 3) 2.5% BPO gel vs 10% BPO gel (twice daily for w) Study design Green tea (2%) Mills 198632 Author In vivo studies – Author In vitro studies Benzoyl peroxide (2.5%-5%-10%) Agent Table 4: Antinflammatory Agents results Continued • Level IIA • Biopsy proven clinical results • Level III • Biopsy proven clinical evaluation • Level IB • Biophysical and clinical • Level IB • Level IIA • Level III • Level III • Level IIA Comments The Role of Dermocosmetics in Modern Acne Treatment 241 30-11-2013 17:05:06 World Clinic Dermatology (Acne).indd 242 Chen 201246 – Khalil 200449 Koh 200250 – – Jarrousse 2007 52 Silicic acid (% NS) Tea (2%) Tea tree oil (5%) Triethyl citrate (NS %) + Ethyl linoleate (NS %) + Salicylic acid (0.5%) Zinc pyrrolidone (0.1%) + Laminaria digitata (NS %) Zinc sulphate (2%) 39 Padula 2010 Author In vitro studies Salicylic acid (0.5%) Agent Table 4: Antinflammatory Agents Continued Double-blind, placebo CT: 2% zinc sulphate solution vs placebo (three time daily for 12w Single-blind, comparative, RCT: 2% tea lotion vs 5% zinc sulphate solution (twice daily for 8w) Sharquie 200848 Double-blind, placebo, RCT: 0.1% zinc pyrrolidone cream vs placebo (twice daily for 8w) Cochran 198553 Capitanio 201224 Double-blind, placebo, RCT: 0.5% TES lotion vs placebo (twice daily for 12w) Double-blind, placebo, RCT: 5% tea tree oil gel vs placebo (twice daily for 6.4w) Enshaieh 200728 Charakida 200723 Single blind, RCT: 5% tea tree oil gel vs 5% BPO lotion (once daily for ) • Level IB • Level IIA • Level IB • Level IB • Level IB • Level IB • Level IB Single-blind, comparative, RCT: 2% tea lotion vs 5% zinc sulphate solution (twice daily for 8w) Sharquie 200848 Bassett 199051 • Level IB • Level IIA • Level IB Comments Single-blind, placebo, RCT: 2% tea lotion vs placebo (twice daily for 8w) Double-blind, placebo, CT: Silicic acid gel vs placebo (20m twice daily for 6w) Double-blind, placebo, RCT: 0.5% salicylic acid (SA) in alcohol-solution vs placebo (twice-daily for 12w) Study design Sharquie 200647 Lassus 199620 Shalita 198145 Author In vivo studies Micali et al 242 30-11-2013 17:05:06 The Role of Dermocosmetics in Modern Acne Treatment represent a valid and useful option for patients that not tolerate prescription topical retinoids and during maintenance therapy.5 There are three studies in vitro and 11 CTs on corneolytic agents (Level IB = 7; Level IIA = 1; Level III = 3) listed in Table 5.18,25,45,51,54-63 MOISTURIZERS Moisturizers are cosmetics designed to hydrate the stratum corneum and make the skin soft and sooth The hydration is an important issue in acne patients considering that many treatments, such as topical and systemic retinoids as well as BPO, may cause skin xerosis Moisturizers for acne patients are mostly humectants and emollients.2 Specific lines of moisturizers indicated for patients receiving oral isotretinoin are available Some of them are designed to improve cheilitis, dry eyes or nose bleeding There are four CTs (Level IB = 1; Level III = 3) that have been listed in Table 6.52-55 SUNSCREEN PRODUCTS Ultraviolet (UV) radiation may have a mild antiinflammatory effect, but it also promotes infundibular hyperkeratosis For these reasons acne tends to get worse after returning from summer holidays.56 Therefore, it is important to educate patients to avoid lengthy midday sun exposure and the use of products containing vegetables oils, considered as comedogenic.57 Photoprotection is strongly recommended in all acne patients, especially in those taking oral/topical retinoids, oral antibiotics and oral contraceptive pill (OCP) or birth-control pills as a combination of an estrogen and a progestin A wide range of products are specifically designed for acne; all oil free as evanescent emulsions O/A, gels and spray, some of them also containing sebum-controlling agents is available No in vitro or in vivo studies in acne patients are available for this product category SHAVING PRODUCTS In male patients with inflammatory acne, daily shaving should not be recommended Specific nonirritating foams or gels enhanced by antibacterial agents such as triclosan (TC) and zinc, along with the use of noncomedogenic and soothing after shave products should be suggested,56 in order to prevent or minimize irritations or infections No in vitro or in vivo specific studies have been performed 243 World Clinic Dermatology (Acne).indd 243 30-11-2013 17:05:06 World Clinic Dermatology (Acne).indd 244 Multicentre, double-blind, placebo, RCT: 0.1% RAL + 6% GA emulsion (RALGA) vs placebo (once daily for 12w) Multicentre, CT: 0.1% retinaldehyde (RAL) + 6% glycolic acid (GA) (RALGA) emulsion (once daily for 12w) Multicenter, CT: 0.1% RAL + 6% GA (RALGA) emulsion (once daily for 12w) Baldo 201059 Poli 200518 Dréno 200562 Dréno 200963 – – – Tran 200560 Bordat 200561 Lactic acid (2%) Malic acid (2%) Retinaldehyde (0.1%) + Glycolic acid (6%) Scherdin 200458 Hunt 199257 • Level III Multicentre, comparative, CT: 2% malic acid (MA) cream vs MA cream + topic antibiotics or retinoids or BPO (twice daily for 8w) • Level III • Level III Continued assessment evaluation • Level IB • Clinical and self- • Level IB • Biopsy proven results assessment evaluation • Level IB • Clinical and self- assessment evaluation • Level IB • Clinical and self- • Level IIA Comments Placebo, RCT: 1) 2% lactic acid (LA) cream-gel vs 2% salicylic acid (SA) cream-gel vs placebo (twice daily for 6w) 2) 2% LA cleansing gel vs 2% LA cleansing gel + 2% SA cream-gel vs 2% LA cleansing gel + 2% LA tonic + 2% SA cream-gel (twice daily for 6w) Double-blind, placebo, RCT: 14% gluconolactone lotion vs 5% benzoyl peroxide lotion vs placebo (NS application number for 12w) Double-blind, placebo, RCT: 10% glycolic acid (GA) emulsion vs placebo (once daily for 12w) Gluconolactone (14%) Abels 201156 XhauflaireUhoda 200855 In vivo studies Double-blind, placebo, CT: 5% acetycysteine gel vs placebo (twice day for w) Study design Glycolic acid (10%) Montes 201254 Author - Author In vitro studies Acetylcysteine (5%) Agent Table 5: Corneolityc Agents Micali et al 244 30-11-2013 17:05:06 – – – Silicic acid (% NS) Tea tree oil (5%) Author In vitro studies Salycilic acid (0.5%-2%) Agent Table 5: Corneolityc Agents Continued World Clinic Dermatology (Acne).indd 245 Bassett 199051 Fernandez 200525 Shalita 198145 Author Single blind, RCT: 5% tea tree oil gel vs 5% BPO lotion (once daily for 8w) Double-blind, placebo, RCT: silicic acid emulsion vs placebo (twice daily for 8w) Double-blind, placebo, RCT: 0.5% salicylic acid (SA) in alcohol-solution vs placebo (twice-daily for 12w) Study design In vivo studies • Level IB • Level IB • Level IB Comments The Role of Dermocosmetics in Modern Acne Treatment 245 30-11-2013 17:05:06 World Clinic Dermatology (Acne).indd 246 – – – – Glycerin (% NS) Urea (10%) in Benzoyl peroxide (4.5%/8.5%) Witch hazel (% NS) + Glycerin (NS %) Author In vitro studies Ceramide (%NS) Agent Table 6: Moisturizer Agents Bartenjev 201155 Gold 200654 Laquieze 200653 Zeichner 201252 Author In vivo studies Open, uncontrolled, CT: glycerin and witch hazel extracts emulsion (twice daily for 8w) Multicenter, comparative, CT: 10% urea in 4.5% BPO or 8.5% BPO cleanser/ cream/gel vs 10% urea in 4.5% BPO or 8.5% BPO cleanser/cream/gel + minocycline vs 10% urea in 4.5% BPO or 8.5% BPO cleanser/cream/gel + systemic doxycycline (once daily for 4w) Controlled, RCT: 1) glycerin cream (on one half of the face) and systemic isotretinoin (10 to 20 mg daily) vs systemic isotretinoin (twice daily for 2m) 2) glycerin cream (on one half of the face) and topic 0.05% tretinoin cream vs topic 0.05% tretinoin cream (daily for 2w) Open, CT; ceramide lotion + 2.5% BPO gel (morning) + ceramide lotion + 0.05% tretinoin (evening) vs ceramide lotion + 1.2% CP/2.5%BPO (morning) + ceramide lotion + 0.05% tretinoin (evening) (for 12 w) Study design • Level III • Level III self-assessment evaluation • Level IB • Clinical, biophysical, and • Level III Comments Micali et al 246 30-11-2013 17:05:06 The Role of Dermocosmetics in Modern Acne Treatment CAMOUFLAGE Camouflage, or corrective maquillage, is a makeup technique able to minimize some unaesthetic postinflammatory disorders such as hyperpigmentations typical of acne.5,6 The benefit of covering inflammatory lesions with designed corrective cosmetics has scientifically been proven Generic and commercial cosmetic makeup is not indicated for acne patients because of its potential comedogenic role The approach to corrective cover cosmetics (CCC) consists of two steps The first one is a preliminary clinical evaluation, in order to evaluate need and realistic expectations for CCC.2 The second one consists in the application of green or yellow undercover, used, respectively to minimize inflammatory lesions and brownish hyperpigmented spots The most appropriate foundation color (liquid or creamy formulations) is then applied and after this a powder is gently pressed.2,51,64 Lastly, additional colored facial cosmetics, including eye shadow, eyeliner and mascara may be applied to improve final appearance No in vitro or in vivo CTs are available, although several studies confirm the beneficial cosmetic and psychological improvement of camouflage technique in acne patients.64-68 DISCUSSION The use of cosmetics plays an important role in the management of acne, and there are a growing number of scientific papers suggesting their in vitro and/ or in vivo efficacy Although, preliminary investigational in vitro results have seldom been confirmed in vivo and for many substances active in vitro, there is a stringent need for CTs Moreover, a major pitfall is that cosmetics usually contain multiple different active principles, whose efficacy should be tested both as single ingredients and as combination treatment In fact, positive clinical results are likely to be due to a synergistic action of multiple agents, or even depend on the vehicle used Yet, only a few agents fulfill the concept of evidence-based medicine In particular, for cleansers, a double-blind, placebo-controlled RCT has shown that the use of a cleanser containing a mixture of 1% azelaic acid (AzA), 1% SA and 0.04% TC decreases inflammatory lesions (evaluated by facial photographs and skin biopsy), and also downsizes the rebound effect at the end of treatment.7 Some studies also confirmed that in inflammatory acne, concurrently treated with topical antibiotics, the use of a BPO cleanser should be encouraged because this agent is able to reduce the development and the proliferation of P acnes-resistant strains69 even when used in short-contact therapy.10 Among the various sebum-controlling agents, nicotinamide has shown the best efficacy profile, according to one placebo-controlled RCT, in reducing the sebum excretion rate (SER) of facial acne skin after weeks of treatment (21.85% vs 10.7% in placebo group) As regards antimicrobial agents, ethyl lactate and phytosphingosine 247 World Clinic Dermatology (Acne).indd 247 30-11-2013 17:05:06 Micali et al (PS) have been proven to effectively reduce P acnes growth both in vitro and in vivo.25,26 In particular, the antimicrobial action of PS, previously investigated in vitro by evaluating the inhibitory effect of PS on growth of Gram-positive and negative bacteria, was then confirmed in vivo by a test on unwashed hands calculating the total microbial count, and in a placebo-controlled RCT on acne patients.26 Among the antiinflammatory agents, the use of nicotinamide and resveratrol should be encouraged, according to studies that have shown their efficacy evaluated by skin biopsy at the beginning and end of treatment.42,44 Corneolytic agents have shown to be effective in preventing and treating postacne scarring70 and/or include improve postinflammatory hyperpigmentation without causing any overt blanching effect, and are thus suitable for extensive use in dark skin patients.70,71 Available studies on moisturizers for acne confirm that they can be used in affected patients without inducing a comedogenetic effect CONCLUSION Cosmetics are part of the therapeutic armamentarium in dermatology and many patients along with an appropriate pharmacologic treatment ask for cosmetological advices If not provided, and patients left free to choose the cosmetics they like, the risk of compromising the ongoing prescription treatment is high and the onset of irritant/allergic contact dermatitis, photodermatitis and/or xerosis should be taken into consideration A cosmetics correct choice may enhance the therapeutic outcome as well as patient’s compliance Editor’s Comment Cosmetics are part of the therapeutic armamentarium in the management of acne and many a pretty handsome face marred by acne has benefitted dramatically with clever use of cosmetics On the flip side, the incorrect use of inappropriate cosmetics is known to aggravate the disease, largely due to presence of comedogenic ingredients in many cosmetics In this article, Drs Micali, Dall’Oglio and Tedeschi have discussed the use of cosmetics in patients with acne Based on extensive literature search and their personal experience, they have highlighted the use of appropriate cleansers, sebum controlling agents, corneolytics, antimicrobial products, antiinflammatory and moisturizing agents specifically designed for acne patients They also emphasize the importance of using appropriate photoprotective agents and shaving products Finally, they discuss personalized camouflage makeup techniques using noncomedogenic products so as to minimize the esthetic problem associated with acne and improve patients’ self-esteem and adherence to treatment Neena Khanna 248 World Clinic Dermatology (Acne).indd 248 30-11-2013 17:05:06 The Role of Dermocosmetics in Modern Acne Treatment REFERENCES Poli F [Cosmetic treatments and acne] Rev Prat 2002;52:859-62 Schwartz RA, Micali G (Eds) Acne New Delhi, India: Macmillan Publishers; 2013 Lavrijsen AP, Vermeer BJ Cosmetics and drugs Is there a need for a third group: cosmeceutics? Br J Dermatol 1991;124:503-4 Solomon BA, Shalita AR Effects of detergents on acne Clin Dermatol 1996;14:95-9 Toombs EL Cosmetics in the treatment of acne vulgaris Dermatol Clin 2005;23:575-81 Draelos ZD Cosmetics in acne and rosacea Semin Cutan Med Surg 2001;20:209-14 Choi YS, Suh HS, Yoon MY, Min SU, Kim JS, Jung JY, et al A study of the efficacy of cleansers for acne vulgaris J Dermatol Treat 2010;21:201-5 Brummitt LC, Cunliffe WJ A dose-response investigation of a benzoyl peroxide wash in the treatment of acne a laboratory study Br J Clin Pract 1984;38:139-40 Del Rosso JQ A 6% benzoyl peroxide foaming cloth cleanser used in the treatment of acne vulgaris: aesthetic characteristics, patients preference considerations, and impact on compliance with treatment J Clin Aesthet Dermatol 2009;2:26-9 10 Leyden JJ, Del Rosso JQ The effect of benzoyl peroxide 9.8% emollient foam on reduction of Propionibacterium acnes on the back using a short contact therapy approach J Drugs Dermatol 2012;11:830-3 11 Stoughton RB, Leyden JJ Efficacy of percent chlorhexidine gluconate skin cleanser in the treatment of acne vulgaris Cutis 1987;39:551-3 12 Meier L, Stange R, Michalsen A, Uehleke B Clay jojoba oil facial mask for lesioned skin and mild acne— results of a prospective, observational pilot study Forsch Komplementmed 2012;19:75-9 13 Bettley FR The effect of a medicated wash on acne Br J Dermatol 1972;87:292-3 14 Shalita AR Comparison of a salicylic acid cleanser and a benzoyl peroxide wash in the treatment of acne vulgaris Clin Ther 1989;11:264-7 15 Raynaud JP, Cousse H, Martin PM Inhibition of type and type 5alpha-reductase activity by free fatty acids, active ingredients of Permixon J Steroid Biochem Mol Biol 2002;82:233-9 16 Mahmood T, Akhtar N, Khan BA, Khan HM, Saeed T Outcomes of 3% green tea emulsion on skin sebum production in male volunteers Bosn J Basic Med Sci 2010;10:260-4 17 Draelos ZD, Matsubara A, Smiles K The effect of 2% niacinamide on facial sebum production J Cosmet Laser Ther 2006;8:96-101 18 Poli F, Ribet V, Lauze C, Adhoute H, Morinet P Efficacy and safety of 0.1% retinaldehyde/ 6% glycolic acid (diacneal) for mild to moderate acne vulgaris A multicentre, double-blind, randomized, vehicle-controlled trial Dermatology 2005;210:14-21 19 Dobrev H Clinical and instrumental study of the efficacy of a new sebum control cream J Cosmet Dermatol 2007;6:113-8 20 Lassus A The effect of silicol gel compared with placebo on papulopustular acne and sebum production A double-blind study J Int Med Res 1996;24:340-4 21 Fernandez C, Adamson K, Dale M, Cunliffe WJ A randomized double-blind study to assess the effects of silicic acid compared to placebo in patients with mild to moderate acne J Dermatolog Treat 2005;16:287‑94 22 Burton JL, Shuster S Topical tetraynoic acid and sebum excretion Br J Dermatol 1970;82:626-7 23 Charakida A, Charakida M, Chu AC Double-blind, randomized, placebo-controlled study of a lotion containing triethyl citrate and ethyl linoleate in the treatment of acne vulgaris Br J Dermatol 2007;157:569-74 24 Capitanio B, Sinagra JL, Weller RB, Brown C, Berardesca E Randomized controlled study of a cosmetic treatment for mild acne Clin Exp Dermatol 2012;37:346-9 25 Prottey C, George D, Leech RW, Black JG, Howes D, Vickers CF The mode of action of ethyl lactate as a treatment for acne Br J Dermatol 1984;110:475-85 26 Pavicic T, Wollenweber U, Farwick M, Korting HC Anti-microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris Int J Cosmet Sci 2007;29:181-90 249 World Clinic Dermatology (Acne).indd 249 30-11-2013 17:05:06 Micali et al 27 Raman A, Weir U, Bloomfield SF Antimicrobial effects of tea-tree oil and its major components on Staphylo coccus aureus, Staph epidermidis and Propionibacterium acnes Lett Appl Microbiol 1995;21:242‑5 28 Enshaieh S, Jooya A, Siadat AH, Iraji F The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study Indian J Dermatol Venereol Leprol 2007;73:22-5 29 Lee TW, Kim JC, Hwang SJ Hydrogel patches containing triclosan for acne treatment Eur J Pharm Biopharm 2003;56:407-12 30 Domínguez-Delgado CL, Rodríguez-Cruz IM, Escobar-Chávez JJ, Calderón-Lojero IO, Quintanar-Guerrero D, Ganem A Preparation and characterization of triclosan nanoparticles intended to be used for the treatment of acne Eur J Pharm Biopharm 2011;79:102-7 31 Franz E, Weidner-Strahl S The effectiveness of topical antibacterials in acne: a double-blind clinical study J Int Med Res 1978;6:72-7 32 Mills OH, Kligman AM, Pochi P, Comite H Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris Int J Dermatol 1986;25:664-7 33 Elsaie ML, Abdelhamid MF, Elsaaiee LT, Emam HM The efficacy of topical 2% green tea lotion in mild-tomoderate acne vulgaris J Drugs Dermatol 2009;8:358-64 34 Pasricha A, Bhalla P, Sharma KB Evaluation of lactic acid as an antibacterial agent Indian J Dermatol Venereol Leprol 1979;45:149-61 35 Garg T, Ramam M, Pasricha JS, Verma KK Long term topical application of lactic acid/lactate lotion as a preventive treatment for acne vulgaris Indian J Dermatol Venereol Leprol 2002;68:137-9 36 Fiorini-Puybaret C, Aries MF, Fabre B, Mamatas S, Luc J, Degouy A, et al Pharmacological properties of Myrtacine® and its potential value in acne treatment Planta Med 2011;77:1582-9 37 Veraldi S, Giovene GL, Guerriero C, Bettoli V Efficacy and tolerability of topical 0.2% Myrtacine® and 4% vitamin PP for prevention and treatment of retinoid dermatitis in patients with mild to moderate acne G Ital Dermatol Venereol 2012;147:491-7 38 Grange PA, Raingeaud J, Calvez V, Dupin N Nicotinamide inhibits Propionibacterium acnes-induced IL-8 production in keratinocytes through the NF-kappaB and MAPK pathways J Dermatol Sci 2009;56:106-12 39 Padula C, Ferretti C, Nicoli S, Santi P Combined patch containing salicylic acid and nicotinamide: role of drug interaction Curr Drug Deliv 2010;7:415-20 40 Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris Int J Dermatol 1995;34:434-7 41 Morganti P, Berardesca E, Guarneri B, Guarneri F, Fabrizi G, Palombo P, et al Topical clindamycin 1% vs linoleic acid-rich phosphatidylcholine and nicotinamide 4% in the treatment of acne: a multicentrerandomized trial Int J Cosmet Sci 2011;33:467-76 42 Emanuele E, Bertona M, Altabas K, Altabas V, Alessandrini G Anti-inflammatory effects of a topical preparation containing nicotinamide, retinol, and 7-dehydrocholesterol in patients with acne: a gene expression study Clin Cosmet Investig Dermatol 2012;5:33-7 43 Gao X, Deeb D, Media J, Divine G, Jiang H, Chapman RA, et al Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects Biochem Pharmacol 2003;66:2427-35 44 Fabbrocini G, Staibano S, De Rosa G, Battimiello V, Fardella N, Ilardi G, et al Resveratrol-containing gel for the treatment of acne vulgaris: a single-blind, vehicle-controlled, pilot study Am J Clin Dermatol 2011; 12:133‑41 45 Shalita AR Treatment of mild and moderate acne vulgaris with salicylic acid in an alcohol-detergent vehicle Cutis 1981;28:556-8, 561 46 Chen BT, Li WX, He RR, Li YF, Tsoi B, Zhai YJ, et al Anti-inflammatory effects of a polyphenols-rich extract from tea (Camellia sinensis) flowers in acute and chronic mice models Oxid Med Cell Longev 2012; 2012:537923 47 Sharquie KE, Al-Turfi IA, Al-Shimary WM Treatment of acne vulgaris with 2% topical tea lotion Saudi Med J 2006;27:83-5 250 World Clinic Dermatology (Acne).indd 250 30-11-2013 17:05:06 The Role of Dermocosmetics in Modern Acne Treatment 48 Sharquie KE, Noaimi AA, Al-Salih MM Topical therapy of acne vulgaris using 2% tea lotion in comparison with 5% zinc sulphate solution Saudi Med J 2008;29:1757-61 49 Khalil Z, Pearce AL, Satkunanathan N, Storer E, Finlay-Jones JJ, Hart PH Regulation of wheal and flare by tea tree oil: complementary human and rodent studies J Invest Dermatol 2004;123:683-90 50 Koh KJ, Pearce AL, Marshman G, Finlay-Jones JJ, Hart PH Tea tree oil reduces histamine-induced skin inflammation Br J Dermatol 2002;147:1212-7 51 Bassett IB, Pannowitz DL, Barnetson RS A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne Med J Aust 1990;153:455-8 52 Jarrousse V, Castex-Rizzi N, Khammari A, Charveron M, Dréno B Zinc salts inhibit in vitro toll-like receptor surface expression by keratinocytes Eur J Dermatol 2007;17:492-6 53 Cochran RJ, Tucker SB, Flannigan SA Topical zinc therapy for acne vulgaris Int J Dermatol 1985;24:188‑90 54 Montes LF, Wilborn WH, Montes CM Topical acne treatment with acetylcysteine: clinical and experimental effects Skinmed 2012;10:348-51 55 Xhauflaire-Uhoda E, Piérard-Franchimont C, Piérard GE Effects of various concentrations of glycolic acid at the corneoxenometry and collaxenometry bioassays J Cosmet Dermatol 2008;7:194-8 56 Abels C, Kaszuba A, Michalak I, Werdier D, Knie U, Kaszuba A A 10% glycolic acid containing oil-in-water emulsion improves mild acne: a randomized double-blind placebo-controlled trial J Cosmet Dermatol 2011;10:202-9 57 Hunt MJ, Barnetson RS A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne Australas J Dermatol 1992;33:131-4 58 Scherdin U, Presto S, Rippke F, Nielsen J, Strassner M, Imadojemun A, et al In vivo assessment of the efficacy of an innovative face care system in subjects with mild acne vulgaris Int J Cosmet Sci 2004;26:221-9 59 Baldo A, Bezzola P, Curatolo S, Florio T, Lo Guzzo G, Lo Presti M, et al Efficacy of an alpha-hydroxy acid (AHA)-based cream, even in monotherapy, in patients with mild-moderate acne G Ital Dermatol Venereol 2010;145:319-22 60 Tran C, Kasraee B, Grand D, Carraux P, Didierjean L, Sorg O, et al Pharmacology of RALGA, a mixture of retinaldehyde and glycolic acid Dermatology 2005;210:6-13 61 Bordat P, Chesnoy S Mixing glycolic acid with retinaldehyde: RALGA, a technical achievement Dermatology 2005;210:2-5 62 Dréno B, Nocera T, Verrière F, Vienne MP, Ségard C, Vitse S, et al Topical retinaldehyde with glycolic acid: study of tolerance and acceptability in association with anti-acne treatments in 1,709 patients Dermatology 2005;210:22-9 63 Dréno B, Castell A, Tsankov N, Lipozencic J, Serdaroglu S, Gutierrez V, et al Interest of the association retinaldehyde/glycolic acid in adult acne J Eur Acad Dermatol Venereol 2009;23:529-32 64 Roberts NC Corrective cosmetics-need, evaluation and use Cutis 1988;41:439-41 65 Shear NH, Graff L Camouflage cosmetics in dermatologic therapy Can Fam Physician 1987;33:2343-6 66 Hayashi N, Imori M, Yanagisawa M, Seto Y, Nagata O, Kawashima M Make-up improves the quality of life of acne patients without aggravating acne eruptions during treatments Eur J Dermatol 2005;15:284-7 67 Holme SA, Beattie PE, Fleming CJ Cosmetic camouflage advice improves quality of life Br J Dermatol 2002;147:946-9 68 Tedeschi A, Dall’Oglio F, Micali G, Schwartz RA, Janniger CK Corrective camouflage in pediatric dermatology Cutis 2007;79:110-2 69 Leyden JJ, Wortzman M, Baldwin EK Antibiotic-resistant Propionibacterium acnes suppressed by a benzoyl peroxide cleanser 6% Cutis 2008;82:417-21 70 Dréno B, Katsambas A, Pelfini C, Plantier D, Jancovici E, Ribet V, et al Combined 0.1% retinaldehyde/6% glycolic acid cream in prophylaxis and treatment of acne scarring Dermatology 2007;214:260-7 71 Kharfi M, Tekaya N, Zeglaoui F, Ezzine N, Mokhtar I, Kamoun F, et al [Comparative study of the efficacy and tolerance of 12% glycolic acid cream and 0.05% retinoic acid cream for polymorphic acne] Tunis Med 2001;79:374-7 251 World Clinic Dermatology (Acne).indd 251 30-11-2013 17:05:06 ... a twin study of acne in women J Invest Dermatol 20 02; 119:1317 -22 29 Herance MI, Ando I Acne in infancy and acne genetics Dermatology 20 03 ;20 6 :24 -8 30 Coates P, Vyakrnam S, Eady EA, Jones CE,... onset acne patients does not differ Br J Dermatol 20 00;1 42: 885- 92 32 Zouboulis CC, Piquero-Martin J Update and future of systemic acne treatment Dermatology 20 03; 20 6:37‑53 1 42 World Clinic Dermatology. .. examined >25 years: 54% females, 40% males Collier et al.15 1,013 >20 Males and females US, 20 06 Survey Females vs males: • 20 29 years: 50.9% vs 42. 5% • 30–39 years: 35 .2% vs 20 .1% • 40–49 years: 26 .3%