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1.  Understanding the Burden of Adult Female Acne 
Objective: Typically regarded as an adolescent condition, acne among adult females is also prevalent. Limited data are available on the clinical characteristics and burden of adult female acne. The study objective was to describe clinical characteristics and psychosocial impact of acne in adult women. Design: Cross-sectional, web-based survey. Setting: Data were collected from a diverse sample of United States females. Participants: Women ages 25 to 45 years with facial acne (≥25 visible lesions). Measurements: Outcomes included sociodemographic and clinical characteristics, perceptions, coping behaviors, psychosocial impact of acne (health-related quality of life using acne-specific Quality of Life questionnaire and psychological status using Patient Health Questionnaire), and work/productivity. Results: A total of 208 women completed the survey (mean age 35±6 years), comprising White/Caucasian (51.4%), Black/African American (24.5%), Hispanic/Latino (11.1%), Asian (7.7%), and Other (5.3%). Facial acne presented most prominently on cheeks, chin, and forehead and was characterized by erythema, postinflammatory hyperpigmentation, and scarring. Average age of adult onset was 25±6 years, and one-third (33.7%) were diagnosed with acne as an adult. The majority (80.3%) had 25 to 49 visible facial lesions. Acne was perceived as troublesome and impacted self-confidence. Makeup was frequently used to conceal acne. Facial acne negatively affected health-related quality of life, was associated with mild/moderate symptoms of depression and/or anxiety, and impacted ability to concentrate on work or school. Conclusion: Results highlight the multifaceted impact of acne and provide evidence that adult female acne is under-recognized and burdensome.
PMCID: PMC3935648  PMID: 24578779
2.  Inflammatory Acne in the Asian Skin Type III Treated with a Square Pulse, Time Resolved Spectral Distribution IPL System: A Preliminary Study 
Laser Therapy  2012;21(2):105-111.
Background and aims: Acne remains a severe problem for both patients and clinicians. Various approaches using photosurgery and phototherapy have been reported with varying degrees of success and robustness of results. An improved intense pulsed light (IPL) system has become available with interesting beam characteristic which might improve IPL treatment of inflammatory acne in the Asian skin, Fitzpatrick type III/IV.
Subjects and Methods: The 18 study subjects comprised 15 females and 3 males with active mild to moderately severe inflammatory acne (mean age 25.3 ± 7.70 yr, range 17–47 yr, Burton scale 1-4, all Fitzpatrick type III Asian skin). They were treated once (8 subjects) or twice (10 subjects) with an IPL system offering both square pulse and time resolved spectral distribution technologies (420 nm cut-off filter, 30 ms pulse, 8 – 12 J/cm2, 2–3 passes). Clinical photography was taken at baseline and at 4 weeks after the final treatment. Percentage of acne clearance was assessed by an independent dermatological panel and graded from zero to 5, 5 being total clearance.
Results: All subjects completed the study. Post-treatment side effects were mild and transient, with virtually no downtime or postinflammatory hyperpigmentation (PIH) experienced by any subject. All subjects had some improvement and no exacerbation was seen in any subject. Clearance was evaluated by the panel as grade 4 in 5 subjects, grade 3 in 8, grade 2 in 4 and grade 1 in 1, so that 14 of 18 subjects (78%) had clearance of at least 60%. Patient evaluation was in general slightly better than that of the panel.
Conclusions: The special beam characteristics of the IPL system used in the present preliminary study achieved good to very good results in the treatment of acne in the Fitzpatrick type III Asian skin without PIH induction. The results suggested that acne treatment in the Asian skin using this system is both safe and effective, and merits larger population studies to further optimize parameters and standardize top-up treatments.
doi:10.5978/islsm.12-OR-06
PMCID: PMC3944487  PMID: 24610988
Acne vulgaris; endogenous PDT; square pulse; time resolved spectral distribution; Fitzpatrick Asian skin type III
3.  Acne vulgaris 
Clinical Evidence  2011;2011:1714.
Introduction
Acne vulgaris affects over 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women. Typical lesions of acne include comedones, inflammatory papules, and pustules. Nodules and cysts occur in more severe acne and can cause scarring and psychological distress.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of topical and oral treatments in people with acne vulgaris? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: topical treatments (adapalene, azelaic acid, benzoyl peroxide, clindamycin, erythromycin [alone or plus zinc]; isotretinoin, tetracycline, tretinoin); and oral treatments (doxycycline, isotretinoin, lymecycline, minocycline, oxytetracycline, tetracycline).
Key Points
Acne vulgaris affects over 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women. Typical lesions of acne include comedones, inflammatory papules, and pustules. Nodules and cysts occur in more severe acne, and can cause scarring and psychological distress.
Topical benzoyl peroxide should be considered as first-line treatment in mild acne. Topical benzoyl peroxide and topical azelaic acid reduce inflammatory and non-inflammatory lesions compared with placebo, but can cause itching, burning, stinging, and redness of the skin.
Topical antibiotics such as clindamycin and erythromycin (alone or with zinc) reduce inflammatory lesions compared with placebo, but have not been shown to reduce non-inflammatory lesions. Tetracycline may reduce overall acne severity. Antimicrobial resistance can develop with use of topical or oral antibiotics, and their efficacy may decrease over time.Tetracyclines may cause skin discoloration, and should be avoided in pregnant or breastfeeding women.Topical preparations of tretinoin, adapalene, and isotretinoin may reduce inflammatory and non-inflammatory lesions, but can also cause redness, burning, dryness, and soreness of the skin.
Oral antibiotics (doxycycline, erythromycin, lymecycline, minocycline, oxytetracycline, and tetracycline) are considered useful for people with more severe acne, although we don't know for sure whether they are effective. Oral antibiotics can cause adverse effects such as contraceptive failure.Minocycline has been associated with an increased risk of systemic lupus erythematosus and liver disorders.Oral isotretinoin has been associated with skin problems, change in liver function, teratogenesis, and psychiatric disorders.
PMCID: PMC3275168  PMID: 21477388
4.  Acne vulgaris 
BMJ Clinical Evidence  2008;2008:1714.
Introduction
Acne vulgaris affects over 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women. Typical lesions of acne include comedones, inflammatory papules, and pustules. Nodules and cysts occur in more severe acne and can cause scarring and psychological distress.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of topical and oral treatments in people with acne vulgaris? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 67 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: topical treatments (adapalene, azelaic acid, benzoyl peroxide, clindamycin, erythromycin (alone or plus zinc), isotretinoin, tetracycline, tretinoin), and oral treatments (doxycycline, isotretinoin, lymecycline, minocycline, oxytetracycline, tetracycline).
Key Points
Acne vulgaris affects over 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women. Typical lesions of acne include comedones, inflammatory papules, and pustules. Nodules and cysts occur in more severe acne, and can cause scarring and psychological distress.
Topical benzoyl peroxide should be considered as first-line treatment in mild acne. Topical benzoyl peroxide and topical azelaic acid reduce inflammatory and non-inflammatory lesions compared with placebo, but can cause itching, burning, stinging, and redness of the skin.
Topical antibiotics such as clindamycin and erythromycin (alone or with zinc) reduce inflammatory lesions compared with placebo, but have not been shown to reduce non-inflammatory lesions. Tetracycline may reduce overall acne severity. Antimicrobial resistance can develop with use of topical or oral antibiotics, and their efficacy may decrease over time.Tetracyclines may cause skin discoloration, and should be avoided in pregnant or breastfeeding women.Topical preparations of tretinoin, adapalene, and isotretinoin may reduce inflammatory and non-inflammatory lesions, but can also cause redness, burning, dryness, and soreness of the skin.
Oral antibiotics (doxycycline, erythromycin, lymecycline, minocycline, oxytetracycline, and tetracycline) are considered useful for people with more severe acne, although we don't know for sure whether they are effective. Oral antibiotics can cause adverse effects such as contraceptive failure.Minocycline has been associated with an increased risk of systemic lupus erythematosus, and of liver disorders.Oral isotretinoin has been associated with skin problems, change in liver function, teratogenesis, and psychiatric disorders.
PMCID: PMC2907987  PMID: 19450306
5.  Clindamycin 1.2% Tretinoin 0.025% Gel versus Clindamycin Gel Treatment in Acne Patients 
Background: Acne vulgaris affects individuals of all races and ethnicities. Understanding the safety and efficacy of topical agents benefits the practicing clinician when treating patients with skin of color. Purpose: To report observations in acne patients representing all six Fitzpatrick skin types based on a Phase 3 study that evaluated the efficacy and safety of a clindamycin phosphate 1.2% tretinoin 0.025% gel versus a clindamycin phosphate 1.2% gel alone. Methods: The two treatments were compared in a randomized, double-blind, multicenter, parallel, 12-week study employing a total of 2,010 patients with moderate-to-severe acne. Primary efficacy endpoints were 1) treatment success defined as percentage of patients who were clear or almost clear or achieved at least a 2-grade improvement in Evaluators Global Severity Scores at Week 12 and 2) percent change from baseline versus 12-week scores for noninflamed, inflamed, and total lesions. Results: The 12-week, 37.8-percent Evaluators Global Severity Scores treatment success for clindamycin phosphate 1.2% tretinoin 0.025% gel was greater than the 31.7 percent observed for clindamycin phosphate 1.2% gel alone (P = 0.002). Percent changes from baseline versus 12-week scores for noninflamed, inflamed, and total lesions obtained with clindamycin phosphate 1.2% tretinoin 0.025% gel (49.8, 60.9, and 54.5%, respectively) were significantly greater than those observed for clindamycin phosphate 1.2% gel alone (41.3, 54.8, and 46.9%, respectively); all comparisons P<0.001. Conclusion: Use of clindamycin phosphate 1.2% tretinoin 0.025% gel resulted in greater percent reductions of Evaluators Global Severity Scores treatment success scores and acne lesions in patients with all six Fitzpatrick skin types combined than clindamycin phosphate 1.2% gel alone. Both products were well tolerated, with no hypo- or hyperpigmentation noted. Side effects observed were similar to those previously reported for the individual ingredients.
PMCID: PMC3140902  PMID: 21779414
6.  The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris 
Dermato-endocrinology  2009;1(3):170-176.
Background:
Central or peripheral stress may induce the development of clinical inflammation in the pilosebaceous unit (PSU) leading to the development or to exacerbation of preexisting acne. The presence of a complete corticotropin-releasing hormone (CRH) system has been confirmed in human sebocytes in vitro. CRH is capable to induce lipid synthesis, steroidogenesis and interact with testosterone and growth hormone. α-Melanocyte-stimulating hormone (α-MSH) and its receptors can regulate melanogenesis as well as affect inflammation, apoptosis and sebogenesis.
Objectives:
The purpose of the study was to investigate by immunohistochemistry if changes of CRH/CRH-binding protein (CRHBP)/CRH receptors (CRHR) as well as melanocortin-1 receptor (MC-1R) expression are detectable in acne lesions vs. normal skin, especially in the sebaceous gland (SG).
Results:
Very strong expression of CRH was observed in acne-involved skin in SG cells comparing with weaker expression in non-involved and normal skin SG. The strongest reaction for CRHBP in acne-involved SG was in differentiating sebocytes. CRHR-1 and -2 exhibited the strongest expression in sweat glands and SG, respectively. Sebocytes and cells of the ductus seboglandularis (DSG) of acne-involved and non-involved skin showed very intense MC-1R expression in contrast to less intense scattered immunoreactivity in normal skin samples.
Methods:
33 patients with acne vulgaris and 8 age-matched volunteers without acne participated in the study. Skin biopsies were taken from acne-involved face, the non-involved thigh skin of the same patients and from normal human skin.
Conclusions:
These data suggest that NP, such as the complete CRH system and MC-1R, are involved in the pathogenesis of acne.
PMCID: PMC2835910  PMID: 20436885
neuropeptides; corticotropin releasing hormone; melanocortin receptor; sebaceous gland; acne
7.  Acne Vulgaris and Quality of Life Among Young Adults in South India 
Indian Journal of Dermatology  2015;60(1):33-40.
Acne vulgaris is a chronic condition affecting more than 85% of adolescents and young adults. It is one of the most common diseases affecting humanity and its impact on quality of life (QoL) is important. The impact of acne on QoL in Indian patients remains undocumented. The study was undertaken to detect the impact of acne vulgaris and related factors that may influence the QoL.
Materials and Methods:
This was a hospital-based, prospective, cross-sectional, prestructured, questionnaire-based study done on 140 consenting individuals, who attended the Dermatology outpatient department. Acne vulgaris was graded using simple grading system. QoL was measured using a combination of skin disease-specific (Dermatological Life Quality Index (DLQI)) and acne-specific (Cardiff Acne Disability Index (CADI)) questionnaires.
Results:
Majority of our study population were students (103, 73.6%). Face (139, 99.3%) was the commonest site of acne and comedones 133, 95% were the commonest type of lesion. Most of the individuals 66, 47.1% were observed to have grade 1 acne. The mean DLQI score was 6.91 and the mean CADI score was 5.2. Association between the scores was statistically significant. Age, occupation, marital status, family, and treatment history played a role in affecting the QoL. Diet, smoking, and alcohol did not influence the QoL.
Conclusion:
Though acne had impact on patient's QoL, it was less severe in our study. It is important for health professionals to incorporate QoL measurements when managing acne patients to provide better and appropriate care.
doi:10.4103/0019-5154.147784
PMCID: PMC4318060  PMID: 25657394
Acne; influencing factors; quality of life; young adults
8.  Cutaneous induction of corticotropin releasing hormone by Propionibacterium acnes extracts 
Dermato-endocrinology  2009;1(2):96-99.
The skin commensal bacillus Propionibacterium acnes is known to play a major role in the development of acne vulgaris and it is established that this bacteria is involved both in the induction and maintenance of the inflammatory phase of acne. The corticotropin releasing hormone (CRH), a neuropeptide originally isolated from the hypothalamus, is also produced by the skin. CRH has been reported to play a role in the inflammation, the production of sebum and finally the differentiation of keratinocytes. At the therapeutic level, zinc is known to act specifically on inflammatory lesions with still partially known mechanisms and thus could play an important role in the development of inflammatory acne lesions. Our objective was to study the modulation of CRH expression by keratinocytes induced by P. acnes extracts. CRH expression was examined using immunohistochemistry technique on deep-frozen sections of normal human skin explants incubated with two different extracts of P. acnes and with or without zinc salts. We observed that the membrane fraction (FM) of P. acnes increased the CRH expression in the epidermis. This result indicates that P. acnes, by stimulating the production of CRH, can both modulate the differentiation of keratinocytes and increase the local inflammation, arguing that this bacterium plays a role not only in the development of inflammatory acne lesions but also in the formation of the microcomedo in the early stages of acne.
PMCID: PMC2835898  PMID: 20224691
acne; Propionibacterium acnes; stress; corticotropin releasing hormone; zinc
9.  Multilocus Sequence Typing (MLST) Analysis of Propionibacterium acnes Isolates From Radical Prostatectomy Specimens 
The Prostate  2012;73(7):770-777.
BACKGROUND
Inflammation is commonly observed in radical prostatectomy specimens, and evidence suggests that inflammation may contribute to prostate carcinogenesis. Multiple microorganisms have been implicated in serving as a stimulus for prostatic inflammation. The pro-inflammatory anaerobe, Propionibacterium acnes, is ubiquitously found on human skin and is associated with the skin disease acne vulgaris. Recent studies have shown that P. acnes can be detected in prostatectomy specimens by bacterial culture or by culture-independent molecular techniques.
METHODS
Radical prostatectomy tissue samples were obtained from 30 prostate cancer patients and subject to both aerobic and anaerobic culture. Cultured species were identified by 16S rDNA gene sequencing. Propionibacterium acnes isolates were typed using multilocus sequence typing (MLST).
RESULTS
Our study confirmed that P. acnes can be readily cultured from prostatectomy tissues (7 of 30 cases, 23%). In some cases, multiple isolates of P. acnes were cultured as well as other Propionibacterium species, such as P. granulosum and P. avidum. Overall, 9 of 30 cases (30%) were positive for Propionibacterium spp. MLST analyses identified eight different sequence types (STs) among prostate-derived P. acnes isolates. These STs belong to two clonal complexes, namely CC36 (type I-2) and CC53/60 (type II), or are CC53/60-related singletons.
CONCLUSIONS
MLST typing results indicated that prostate-derived P. acnes isolates do not fall within the typical skin/acne STs, but rather are characteristic of STs associated with opportunistic infections and/or urethral flora. The MLST typing results argue against the likelihood that prostatectomy-derived P. acnes isolates represent contamination from skin flora.
doi:10.1002/pros.22621
PMCID: PMC4124636  PMID: 23184509
prostate cancer; inflammation; Propionibacterium acnes; MLST; infection
10.  Racial Differences in Clinical Characteristics, Perceptions and Behaviors, and Psychosocial Impact of Adult Female Acne 
Objective: Limited data are available on racial differences in clinical characteristics and burden in adult female acne. The objective was to describe racial differences in clinical characteristics, psychosocial impact, perceptions, behaviors, and treatment satisfaction in facial adult female acne. Design: Cross-sectional, web-based survey. Setting: Diverse sample of United States women. Participants: Women between the ages of 25 and 45 years with facial acne (≥25 visible lesions). Measurements: Outcomes included sociodemographic characteristics, psychosocial impacts, perceptions, behaviors, and treatment satisfaction. Racial differences were evaluated using descriptive statistics and t-test/chi-square analyses. Results: 208 females participated (mean age 35±6 years); 51.4 percent were White/Caucasian and 48.6 percent were non-White/Caucasian women [Black/African American (n=51); Hispanic/Latina (n=23); Asian (n=16); Other (n=ll)]. Age of acne onset (mean 14.8±5 vs. 17.0±8 years, p<0.05) and acne concern occurred earlier (16.6±7 vs. 19.3±9 years, p<0.05) in White/Caucasian than non-White/Caucasian subjects. Facial acne primarily presented on chin (28.0%) and cheeks (30.8%) for White/Caucasian women versus cheeks (58.4%) for non-White/Caucasian women. Non-White/Caucasian women experienced more postinflammatory hyperpigmentation than White/Caucasian women (p<0.0001). Facial acne negatively affected quality of life (QoL) in both groups, and most participants (>70%) reported some depression/anxiety symptoms. More White/Caucasian than non-White/Caucasian women were troubled by facial acne (88.8% vs. 76.2%, p<0.05). Lesion clearance was most important to White/Caucasian women (57.9 vs. non-White/Caucasian 31.7%, p<0.001); non-White/Caucasian females focused on postinflammatory hyperpigmentation clearance (41.6% vs. Caucasian 8.4%, p<0.0001). Conclusion: Results highlight racial differences in participant-reported clinical characteristics, attitudes, behaviors, and treatment satisfaction. These findings may inform clinicians about racial differences in facial adult female acne and guide treatment recommendations toward improving care.
PMCID: PMC4106354  PMID: 25053980
11.  Zileuton, a new efficient and safe systemic anti-acne drug 
Dermato-endocrinology  2009;1(3):188-192.
Tissue inflammation is a major component of the acne process. Leukotriene B4 (LTB4) is considered to be a major player in the development of tissue inflammation. Synthesis of LTB4 is controlled by the enzyme 5-lipoxygenase. Since Zileuton blocks the activity of 5-lipoxygenase, experimental and clinical studies have been conducted to test mode of function, as well as efficacy and safety of this compound in the treatment of acne vulgaris. Human SZ95 sebocytes and inflammatory cells in vitro express the enzymes of the leukotriene pathway at mRNA and protein levels and enzymes involved in the biosynthesis of LTB4 are activated in sebaceous glands of acne lesions. Pre-treatment of SZ95 sebocytes with Zileuton partially prevented short-term arachidonic acid-induced effects, such as induction of LTB4, increase of neutral lipid content and stimulation of interlekin-6 release. Long-term treatment with Zileuton directly reduced the content of neutral lipids and interleukin-6 release from SZ95 seb ocytes. PPAR mRNA levels were not regulated by Zileuton. In a first pilot clinical study with 10 patients with papulopustular acne Zileuton 4 × 600 mg/d p.o. for 3 months decreased the acne severity index in a time-dependent manner being 41% of the initial score at week 12 (p < 0.05). This was mostly due to a decrease of the number of inflammatory lesions of 29% (p < 0.01). In addition, total sebum lipids significantly decreased (35%, p < 0.05) and the pro-inflammatory free fatty acids (22%) and lipoperoxides (26%) were markedly diminished in patients’ sebum under treatment. The magnitude of clinical improvement strongly correlated with the reduction of total sebum lipids (p = 0.0009, r2 = 0.81) and free fatty acids (p = 0.0003, r2 = 0.82). In a further study, a 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea, responded with normalization of the casual skin surface lipids and similar reduction of facial sebum synthesis under treatment with Zileuton over 2weeks and—after a wash-out phase—low-dose isotretinoin (10 mg/2nd d) over 5 weeks. These data are in agreement with a phase II multicenter, clinical study in 101 patients with mild to moderate inflammatory facial acne conducted in the US, which showed a significant efficacy of Zileuton in a subset of patients with moderate acne, whereas those patients treated with Zileuton showed a significant mean decrease in inflammatory lesions compared to the placebo group. In all clinical studies, Zileuton was found to be safe and well tolerated.
PMCID: PMC2835912  PMID: 20436887
zileuton; acne; seborrhea; sebaceous gland; sebocytes; skin
12.  Comparative Study of Oral Isotretinoin Versus Oral Isotretinoin + 20% Salicylic Acid Peel in the Treatment of Active Acne 
Background:
Acne is a self limiting condition that often results in scarring and disfigurement disproportionate to its clinical severity. Isotretinoin is considered the gold standard in the medical management of severe form of acne vulgaris. Salicyclic acid (SA) peels, a β- hydroxy acid peel has got sebosuppressive effect and helps in faster resolution of acne with minimal scarring. It also decreases the post inflammatory hyperpigmentation. Combining both the modalities is usually not advocated because of expected excessive dryness and irritation
Aims:
To compare the efficacy of oral isotretinoin and oral isotretinoin with 20% SA peels in patients with moderate to severe acne.
Materials and Methods:
60 consecutive patients with moderate to severe facial acne attending the skin department were randomized in to 2 groups. 1st group received 20mg oral isotretinoin once daily for 16 weeks and 2nd group received 20mg oral isotretinoin once daily along with 20% SA peels every two weeks for 16 weeks. Baseline grading of acne was done with Michelsons Acne severity index (MASI).Right and left sides of the face were scored separately and total score was taken. Severity score was assessed monthly .Clinical photographs were obtained for evaluation every month. Patients were asked to follow up once every 2 weeks or earlier in case of any adverse events.
Results:
Patients in both the groups revealed a reduction in the number of lesions. The 1st group showed a reduction of approximately 73.4% after receiving 20mg oral isotretinoin for 16 weeks. The 2nd group showed a reduction of approximately 92.5 % after receiving 20mg oral isotretinoin along with 20% SA peel once every 2 weeks for 16 weeks.
Conclusion:
Both oral isotretinoin and combination of oral isotretinoin with 20% SA peels once every 2 weeks are effective in treating moderate to severe acne but the combination showed significantly better clearance of acne than monotherapy with isotretinoin.
doi:10.4103/0974-2077.123403
PMCID: PMC3884884  PMID: 24470716
Acne; isotretinoin; salicylic acid peel
13.  Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis 
Background
Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne.
Objective
The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin.
Methods
In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of treatment.
Results
Based on evidence from the published literature, patients treated with A-BPO/D would be expected to have an initial 72% reduction in inflammatory lesions, and patients treated with oral isotretinoin would have an 80% to 90% reduction of these lesions. The median weekly cost for the basic treatment model was $44 for A-BPO/D and $62 for oral isotretinoin. The weekly median costs for the long-term model were $44 for patients initially receiving a regimen of A-BPO/D followed by a maintenance regimen of A-BPO monotherapy and $50 for patients receiving an initial regimen of A-BPO/D who required a subsequent regimen of oral isotretinoin. The weekly cost for oral isotretinoin in the long-term model was $62.
Conclusions
The comparison of these 2 treatments demonstrated that they are both effective in treating severe acne, and that A-BPO/D was less expensive weekly than oral isotretinoin. These models show that A-BPO/D is safer than and is a more cost-effective alternative to oral isotretinoin for treating patients with severe acne vulgaris.
PMCID: PMC4031741  PMID: 24991389
14.  Efficacy and Safety of Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel for the Treatment of Acne and Acne-induced Post-inflammatory Hyperpigmentation in Patients with Skin of Color 
Objective: To assess the efficacy and safety of a topical gel containing clindamycin 1.2% and tretinoin 0.025% for the treatment of acne and acne-induced postinflammatory hyperpigmentation (PIH) in darker skinned patients. Design: Randomized, double-blind, placebo-controlled study. Setting: Two United States clinical sites. Participants: Thirty-three patients 12 years of age or older with skin types IV to VI, mild-to-moderate facial acne, and PIH were enrolled. Measurements: Patients applied clindamycin phosphate/tretinoin gel or a nonmedicated vehicle each evening and a sun protection factor 30 sunscreen daily. Changes in skin erythema and hyperpigmentation were measured using a chromameter and photographic images. Efficacy was assessed using the Evaluators Global Acne Severity Scale, lesion counts, Post-inflammatory Hyperpigmentation Severity Scales and Patient’s Global Assessment Scale. Safety and tolerability were assessed by adverse event reports and a Safety Assessment Scale. Results: The mean (SD) baseline inflammatory lesion count was 11.9 (11.1) in clindamycin/tretinoin-treated patients, decreasing by 5.5 (6.56) after 12 weeks while the mean baseline inflammatory lesion count was 13.6 (11.15) in placebo-treated patients, decreasing by 4.1 (11.36) (p=0.05 for change from baseline, clindamycin/tretinoin vs. placebo). Clindamycin/tretinoin-treated patients generally demonstrated superior efficacy versus placebo treatment. The clindamycin/tretinoin topical gel was well tolerated, causing little or no irritation, although one patient withdrew due to periorbital edema of moderate severity possibly related to clindamycin/tretinoin gel. Conclusion: Although limited by small sample size, the results of this pilot study suggest clindamycin phosphate 1.2% and tretinoin 0.025% topical gel is a safe and effective option for treating mild-to-moderate acne in patients with skin of color.
PMCID: PMC3396458  PMID: 22798973
15.  Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: Implications of probiotics in acne vulgaris 
Increasing evidence demonstrates that commensal microorganisms in the human skin microbiome help fight pathogens and maintain homeostasis of the microbiome. However, it is unclear how these microorganisms maintain biological balance when one of them overgrows. The overgrowth of Propionibacterium acnes (P. acnes), a commensal skin bacterium, has been associated with the progression of acne vulgaris. Our results demonstrate that skin microorganisms can mediate fermentation of glycerol, which is naturally produced in skin, to enhance their inhibitory effects on P. acnes growth. The skin microorganisms, most of which have been identified as Staphylococcus epidermidis (S. epidermidis), in the microbiome of human fingerprints can ferment glycerol and create inhibition zones to repel a colony of overgrown P. acnes. Succinic acid, one of four short-chain fatty acids (SCFAs) detected in fermented media by nuclear magnetic resonance (NMR) analysis, effectively inhibits the growth of P. acnes in vitro and in vivo. Both intralesional injection and topical application of succinic acid to P. acnes-induced lesions markedly suppress the P. acnes-induced inflammation in mice. We demonstrate for the first time that bacterial members in the skin microbiome can undergo fermentation to rein in the overgrowth of P. acnes. The concept of bacterial interference between P. acnes and S. epidermidis via fermentation can be applied to develop probiotics against acne vulgaris and other skin diseases. In addition, it will open up an entirely new area of study for the biological function of the skin microbiome in promoting human health.
doi:10.1007/s00253-013-5394-8
PMCID: PMC3888247  PMID: 24265031
Acne; Fermentation; P. acnes; Probiotic; S. epidermidis; Skin Microbiome
16.  Safety and Effectiveness of a New Blue Light Device for the Self-treatment of Mild-to-moderate Acne 
Objective: To assess the safety and effectiveness of treating acne for eight weeks using a new blue light device at a dose of ˜2J/cm2/day (representing typical full-face treatment) or ˜29J/cm2/day (representing the typical dose after localized spot treatment of acne). Design: Prospective, single-center, open-label study evaluating two levels of blue light in each subject. Setting: Subjects were recruited from the local community for self-treatment at home. Participants: Thirty-two subjects with mild or moderate facial acne vulgaris. Measurements: Inflammatory lesion count; number, severity, and redness of flares; improvement in skin characteristics (overall appearance, clarity, radiance, tone, texture, and smoothness); tolerability; subject satisfaction. Results: The blue light treatment was associated with significant reductions from baseline in inflammatory lesion count as early as Week 1 with ˜29J/cm2/day and Week 3 with ˜2J/cm2/day (P≤ 0.01). It was also associated with significant reductions in the number, severity, and redness of flares and with improvements in the skin’s appearance, clarity, radiance, tone, texture, and smoothness. Overall, 53 percent of subjects considered the treatment much gentler than traditional acne treatments and 61 percent were satisfied. Three adverse events were probably related to treatment—minimal transient skin dryness (2) and minimal transient hyperpigmentation (1). Conclusion: The blue light treatment is effective and well tolerated, offering rapid, gentle, and convenient treatment of inflammatory acne. The blue light device offers a valuable alternative to antibiotics and potentially irritating topical treatments and can also be used adjunctively to complement other therapies.
PMCID: PMC3366451  PMID: 22808306
17.  Taurine bromamine (TauBr) - its role in immunity and new perspectives for clinical use 
Journal of Biomedical Science  2010;17(Suppl 1):S3.
This review is an attempt to summarize our knowledge about taurine bromamine (TauBr) properties, its role in innate immunity and its therapeutic potential.
TauBr and taurine chloramine (TauCl) are major haloamines generated by eosinophils and neutrophils at a site of inflammation. Both haloamines share anti-inflammatory and anti-oxidant properties. TauBr, similarly to TauCl, decreases the production of proinflammatory mediators. Their anti-inflammatory and anti-oxidant activities are enhanced by their ability to induce the expression of heme oxygenase-1 (HO-1). TauCl is more stable than TauBr. On the other hand, only TauBr was found to be highly membrane-permeable showing stronger microbicidal activity than TauCl.
In the light of the anti-inflammatory and antimicrobial properties of TauBr we discuss its therapeutic potential in local treatment of inflammation, especially acne vulgaris, the most common inflammatory skin disorder. TauBr, at non-cytotoxic concentrations, is able to kill Propionibacterium acnes, the skin bacteria involved in pathogenesis of acne vulgaris.
As topical antibiotics used in the therapy of acne are associated with the emergence of resistant bacteria, topical TauBr seems to be a good candidate for an alternative therapy.
Recently, in a double blind trial, the efficacy of TauBr was compared with the efficacy of clindamycin, one of the most common topical antibiotics used in acne therapy. Comparable reduction of acne lesions was observed in the TauBr and clindamycin groups of patients with mild and moderate inflammatory facial acne vulgaris. We conclude that this pilot study supports our concept that TauBr can be used as a topical agent in the treatment of acne vulgaris, especially in patients who have already developed antibiotic resistance. Further studies are necessary to substantiate the more extended use of TauBr as an anti-inflammatory and anti-oxidant agent in human medicine.
doi:10.1186/1423-0127-17-S1-S3
PMCID: PMC2994406  PMID: 20804605
18.  Acne: a review of immunologic and microbiologic factors 
Postgraduate Medical Journal  1999;75(884):328-331.
Acne vulgaris is a self-limiting skin disorder seen primarily in adolescents, whose aetiology appears to be multifactorial. The four main aetiological factors are hypercornification of the pilosebaceous duct, increased sebum production, colonization with Propionibacterium acnes, and subsequently the production of inflammation. Considerable investigation has addressed the immunologic reaction to extracellular products produced by the acne-causing organism, P acnes. The immunologic response involves both humoral and cell-mediated pathways. Further research should clarify the role of complement, cytotoxins, and neutrophils in this acne-forming response.


Keywords: acne vulgaris; Propionibacterium acnes
PMCID: PMC1741272  PMID: 10435165
19.  A Meta-analysis to Investigate the Relation Between Fitzpatrick Skin Types and Tolerability of Adapalene-Benzoyl Peroxide Topical Gel in Subjects with Mild or Moderate Acne 
The overall goal of acne management for all patients is to select treatments that effectively address as many pathogenic factors as possible while minimizing side effects. Acne therapy in darker skin patients presents unique challenges due to differences in the risk of postinflammatory hyperpigmentation, which may develop in response to acne itself or to irritation secondary to treatment. One combination treatment currently available is a gel formulation containing a retinoid (adapalene 0.1%) in fixed combination with an antimicrobial (benzoyl peroxide 2.5%). Results from three randomized, double-blind, vehicle-controlled, clinical trials of adapalene-benzoyl peroxide were combined in a retrospective meta-analysis that included 909 patients treated for 12 weeks and assessed at each visit for erythema, scaling, dryness, and stinging/burning. Only Week 1 results were included in the meta-analysis because the worst severity of cutaneous irritation was found to occur at this timepoint in all three trials. For each study, and for the meta-analysis, comparisons were made using the Cochran-Mantel-Haenszel test. There were no statistically significant differences in dryness, scaling, and stinging/burning with adapalene-benzoyl peroxide treatment when subjects with Fitzpatrick skin types I to III were compared to subjects with Fitzpatrick skin types IV to VI (P=NS). Erythema assessments were statistically different based on skin types, as subjects with Fitzpatrick skin types IV to VI were rated as having “none” more often than those with Fitzpatrick skin types I to III (P<0.001). This could be due to the difficulty in visualizing erythema in patients with darker skin types, mainly Fitzpatrick skin types VI. Acne patients with Fitzpatrick skin types IV to VI were not found to be more susceptible to cutaneous irritation from treatment with the adapalene-benzoyl peroxide gel than patients with Fitzpatrick skin types I to III.
PMCID: PMC2945860  PMID: 20877537
20.  Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin 
PLoS Pathogens  2009;5(7):e1000527.
Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. Propionibacterium acnes (P. acnes), a gram-positive anareobic bacterium, plays a critical role in the development of these inflammatory lesions. This study aimed at determining whether reactive oxygen species (ROS) are produced by keratinocytes upon P. acnes infection, dissecting the mechanism of this production, and investigating how this phenomenon integrates in the general inflammatory response induced by P. acnes. In our hands, ROS, and especially superoxide anions (O2•−), were rapidly produced by keratinocytes upon stimulation by P. acnes surface proteins. In P. acnes-stimulated keratinocytes, O2•− was produced by NAD(P)H oxidase through activation of the scavenger receptor CD36. O2•− was dismuted by superoxide dismutase to form hydrogen peroxide which was further detoxified into water by the GSH/GPx system. In addition, P. acnes-induced O2•− abrogated P. acnes growth and was involved in keratinocyte lysis through the combination of O2•− with nitric oxide to form peroxynitrites. Finally, retinoic acid derivates, the most efficient anti-acneic drugs, prevent O2•− production, IL-8 release and keratinocyte apoptosis, suggesting the relevance of this pathway in humans.
Author Summary
Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. It is the most common skin disease, affecting up to 80% of individuals at some point between the ages of 11 and 30 years. Propionibacterium acnes (P. acnes) plays a role in the development of inflammatory acne lesions, but whether it causes inflammation by itself or through indirect mechanisms is not clear yet. Therefore, by exposing epidermal cells to P. acnes in vitro, we tested whether reactive oxygen species (ROS) production (oxidative burst) was involved in the inflammatory process. We found that one particular ROS, superoxide anion, was generated by epidermal cells following P. acnes stimulation. This phenomenon is associated with the production of a soluble pro inflammatory molecule, IL-8, and epidermal cell death. The abrogation of P. acnes-induced oxidative burst by the most commonly used and most efficient treatments of acne suggests that superoxide anions produced by epidermal cells are critical in the development of acne inflammatory lesions.
doi:10.1371/journal.ppat.1000527
PMCID: PMC2709429  PMID: 19629174
21.  The efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: A randomized double-blind study 
Background:
Acne vulgaris, a common human skin condition, is an inflammatory disease characterized by comedones, papules, nodules and possibly scarring.
This study aimed to evaluate the efficacy of a combination of 5% dapsone gel plus oral isotretinoin in the treatment of acne vulgaris.
Materials and Methods:
A randomized, placebo-controlled, study was carried out on patients with moderate to severe acne. The patients were randomly divided in two groups: (dapsone gel and vehicle gel). All Patients were administered oral isotretinoin 20 mg daily and topical gel twice a day for 8 weeks. The Global Acne Assessment Score (GAAS), the number lesions and side-effects were documented at base line and weeks 4, 8 and 12.
Results:
A total of 58 patients (age range: 18-25 years) were included in our study. The number of lesions was significantly lower in the dapsone-treated group at all follow-up visits (P < 0.001). The mean GAAS score in the dapsone-treated group and in the Placebo-treated group decreased, but there was no statistical difference in two groups (P < 0.001). The side-effects on the dapsone-treated group were a mild burning sensation in 7 patients (24.13%), mild erythema of the skin and mild dryness in 4 (13.79%) and 3 (10.34%) cases respectively (P < 0.001). In our study, adverse effects were common but they were minor and tolerable. No clinically significant changes in laboratory parameters were observed (P < 0.001).
Conclusions:
Dapsone gel was an effective medication for patients who received isotretinoin for acne vulgaris treatment resulting in a significant reduction of the number of lesions.
doi:10.4103/2277-9175.139413
PMCID: PMC4166047  PMID: 25250291
Acne vulgaris; isotretinoin; 5% dapsone gel
22.  The impact of acne vulgaris on quality of life and psychic health in young adolescents in Greece. Results of a population survey* 
Anais brasileiros de dermatologia  2012;87(6):862-869.
BACKGROUND
Acne vulgaris can severely affect social and psychological functioning.
OBJECTIVE
The aim of this study was to investigate the impact of acne vulgaris and its severity on Quality of Life of young adolescents in Greece.
METHODS
We conducted a questionnaire based survey among 1560 adolescent between the ages of 11 and 19 years old and 1531 of these were completed. Adolescents with acne filled all the questions including the Children Dermatology Life Quality Index. Adolescents without acne filled the questions about age, family history of acne, stress and smoking. Data were analyzed with Pearson Chi Square test.
RESULTS
Acne prevalence was 51.2% affecting both sexes equally. Self reported mild acne was present in 71.2% and moderate-severe acne in 28.8% of the study population. The mean age of the study population was 15.77y. The median score of Children Dermatology Life Quality Index was 4.02. The impact of acne on quality of life is associated with the severity of the acne (p<0.0001). Patients with moderate/severe acne experience greater psychosocial and emotional impairment (p<0.0001). Body image is modified proportionally to the severity of acne (p<0.0001). Symptoms and treatment of acne are factors that also influence their quality of life. Girls and boys are equally affected. Stress and heredity are correlated with acne and its severity (p<0.0001). We didn't find any correlation between smoking and acne.
CONCLUSION
Acne affects Quality of Life of young adolescents in Greece. The impact is proportional to the severity of acne. More severe acne is associated with greater effect on quality of life with implications for self esteem, body image and relationships with others.
doi:10.1590/S0365-05962012000600007
PMCID: PMC3699905  PMID: 23197205
Acne vulgaris; Adolescent; Health of institutionalized adolescents; Quality of life
23.  Propionibacterium acnes induces an interleukin-17 response in acne vulgaris that is regulated by vitamin A and vitamin D 
Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes plays a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of Th17 and Th1, but not Th2 responses in human PBMCs. P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA and IL-17RC, and triggered IL-17 secretion from CD4+, but not CD8+ T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naïve CD4+CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6 and TGF-β neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and vitamin D could be effective tools to modulate Th17-mediated diseases such as acne.
doi:10.1038/jid.2013.334
PMCID: PMC4084940  PMID: 23924903
24.  Polymorphisms in the promoters of MMP-2 and TIMP-2 genes in patients with acne vulgaris 
Acne, a chronic inflammatory skin disease, can be seen at any age but it most often occurs in adolescents and young people. Several factors, including increased sebum production, abnormal cornification of the pilosebaceous units, proliferation of Propionibacterium acne, and extracellular matrix (ECM) remodeling, are thought to be associated with the pathogenesis of the acne. The remodeling of the ECM is regulated by a balance between matrix metalloproteinases (MMPs) and their inhibitors called tissue inhibitors of metalloproteinases (TIMPs). The current study investigated the potential association between MMP-2 (-1306 C/T) and TIMP-2 (-418 G/C) polymorphisms and the risk for acne in a Turkish population. The study was conducted with 85 subjects who presented to the Dermatology Department of Duzce University Hospital. DNA was isolated from 2 ml of peripheral blood taken from each subject, and their genotypes were analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CC, CT, and TT genotypes for MMP-2 (-1306 C/T) polymorphism were similar between the patient and control group (24 [55.8%], 17 [39.5%], and 2 [4.7%], respectively, vs. 21 [50%], 18 [42.9%], and 3 [7.1%], respectively). However, the distribution of the GG, GC, and CC genotypes for TIMP-2 (-418 G/C) polymorphism were different between the patient and control group (30 [69.8%], 9 [14.8%] and 4 [9.3%], respectively, vs. 26 [61.9%], 14 [33.3%], and 2 [4.8%], respectively). The results demonstrated that the TIMP-2 (-418 CC) genotype was nearly two times more common in the patient group compared to the control group (p=0.686, OR=1.45). It may be possible that the TIMP-2 (-418 CC) genotype increases the tendency to develop acne vulgaris by disrupting the balance between MMPs and TIMPs. Further investigations are needed to clarify more precisely the relationship between acne and MMP-TIMP genes.
PMCID: PMC3832336  PMID: 24260605
Acne vulgaris; MMPs; TIMPs; polymorphism
25.  An Assessment of the Efficacy and Safety of CROSS Technique with 100% TCA in the Management of Ice Pick Acne Scars 
Background:
Chemical reconstruction of skin scars (CROSS) is a technique using high concentrations of trichloroacetic acid (TCA) focally on atrophic acne scars to induce inflammation followed by collagenisation. This can lead to reduction in the appearance of scars and cosmetic improvement.
Aims:
The aim of this pilot study is to investigate the safety of the CROSS technique, using 100% TCA, for atrophic ice pick acne scars.
Settings and Design:
Open prospective study.
Material and Methods:
Twelve patients with predominant atrophic ice pick post acne scars were treated with the CROSS technique, using 100% TCA, applied with a wooden toothpick, at two weekly intervals for four sittings. Efficacy was assessed on the basis of the physician’s clinical assessment, photographic evaluation at each sitting and patient’s feedback after the fourth treatment, and at the three-month and six-month follow-up period, after the last treatment.
Results:
More than 70% improvement was seen in eight out of ten patients evaluated and good results (50 – 70% improvement) were observed in the remaining two patients. No significant side effects were noted. Transient hypopigmentation and hyperpigmentation was observed in one patient each. Physician’s findings were in conformity with the patient’s assessment. Three months after the last treatment, one patient noted a decrease in improvement with no further improvement even at the six-month follow-up period.
Conclusion:
The CROSS technique with 100% TCA is a safe, efficacious, cost-effective and minimally invasive technique for the management of ice pick acne scars that are otherwise generally difficult to treat. In few patients the improvement may not be sustained, probably due to inadequate or delayed collagenisation.
doi:10.4103/0974-2077.69020
PMCID: PMC2956965  PMID: 21031068
Chemical reconstruction of skin scars; ice pick acne scars; trichloroacetic acid 100%

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