Summary: many things may work, but the hormonal basis is absolutely essential to address first.
J Am Acad Dermatol. 2002 Aug;47(2):231-40.
Acne therapy: a methodologic review.
Lehmann HP, Robinson KA, Andrews JS, Holloway V, Goodman SN.
Department of Pediatrics, Johns Hopkins School of Medicine and Bloomberg School of Public Health, USA.
Acne is a very common problem with significant physical and psychological morbidity. The evidence basis for its treatment had not been systematically reviewed. Therefore, we performed an evidence review to provide researchers a basis for further studies, and to provide clinicians the background needed to interpret current and future clinical studies.
We summarize the methodologic state of the acne literature in patients with acne who do not have complicating co-morbidities.
This was an expert-advised literature synthesis. We used a structured literature search for English-language controlled trials in Cochrane CENTRAL, MEDLINE, OLDMEDLINE, HSTAT, CINAHL, and PsychInfo. Results underwent a structured data abstraction process, with review by at least 2 reviewers.
Out of 1588 unique articles, 250 articles (274 controlled trials) over the past 50 years were reviewed: 57 (21%) trials had at least one major weakness and no strengths; 125 (47%) trials had at least one major strength and at least one major weakness; 48 (18%) trials had at least one major strength, and no major weaknesses. The remaining 16 (6%) were of intermediate quality or did not provide enough information to make a determination. One fourth of studies did not report patient age; one fourth did not report on patient gender. Only 8% mentioned patient race; only 2% mentioned skin type; 0.4% mentioned diet; none scored sexual maturity or insurance status. There were 1237 outcomes. There were more than 25 methods of assessing acne severity and more than 19 methods for counting lesions. There were only two trials that formally assessed psychological outcomes. More than 140 treatments were tested in 251 comparisons.
Ranging over 50 years of research, the acne literature evidences great heterogeneity at all levels: patient characteristics, acne severity, outcome assessments, treatments, and comparisons. A list of methodologic recommendations is provided.
J Womens Health (Larchmt). 2012 Feb;21(2):223-30. Epub 2011 Dec 15.
Acne vulgaris in women: prevalence across the life span.
Perkins AC, Maglione J, Hillebrand GG, Miyamoto K, Kimball AB.
Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.
Acne vulgaris is a common skin disease with a large quality of life impact, characterized by comedones, inflammatory lesions, secondary dyspigmentation, and scarring. Although traditionally considered a disease of adolescence, reports suggest it is also a disease of adults, especially adult women. Our objectives were to determine acne prevalence in a large, diverse group of women and to examine acne by subtype and in relation to other skin findings, measurements, and lifestyle factors.
We recruited 2895 women aged 10-70 from the general population. Photographs were graded for acne lesions, scars, and dyspigmentation. Measurements were taken of sebum excretion and pore size, and survey data were collected.
Of the women studied, 55% had some form of acne: 28% had mild acne, and 27% had clinical acne, 14% of which was primarily inflammatory and 13% of which was primarily comedonal. Acne peaked in the teenage years, but 45% of women aged 21-30, 26% aged 31-40, and 12% aged 41-50 had clinical acne. Women with inflammatory acne were younger than those with comedonal acne (p≤0.001), and postmenopausal women had less acne than age-matched peers (p<0.0001). Acne was associated with facial hirsutism (p=0.001), large pores (p=0.001), and sebum excretion (p=0.002). Smokers had more, primarily comedonal, acne than nonsmokers.
The cross-sectional design precludes conclusions about progression of acne with age. Participation was restricted to women. The photographic nature of the study imposes general limitations. Techniques used in this study were not sufficiently sensitive to identify cases of subclinical acne. More than a quarter of women studied had acne, which peaked in the teens but continued to be prevalent through the fifth decade.
Pak J Biol Sci. 2011 Jun 1;14(11):658-63.
Therapeutic effects of biguanide vs. statin in polycystic ovary syndrome: a randomized clinical trial.
Navali N, Pourabolghasem S, Fouladi RF, Nikpour MA.
Department of Obstetrics and Gynecology, Women's Reproduction Health Research Center, Alzahra and Taleghani Hospitals, Tabriz University of Medical Sciences, Tabriz, Iran.
Various classes of medication are currently being used in Polycystic Ovary Syndrome (PCOS) patients including the biguanides and the statins. However, their efficacies are rarely compared. This study aimed to compare efficacy ofa biguanide and a statin in treating PCOS. In a randomized double-blind clinical trial, 400 women with PCOS were recruited within 15 months in Taleghani Hospital. They randomly received either a biguanide (metformin 500 mg three times daily) or a statin (simvastatin 20 mg daily) for three consecutive months. Changes of clinical and laboratory variables were compared. In the biguanide group the serum glucose status (abnormal fasting and non-fasting sugar and insulin levels and percentage of hyperinsulinemic cases) and menstrual abnormalities improved significantly after treatment (p < 0.05). In the statin group the lipid profile status (abnormal total cholesterol, high and low density lipoproteins), C-Reactive Protein (CRP), serum dehydroepiandrosterone sulfate, hyperinsulinemia, severity of acne and menstrual abnormalities improved significantly after treatment (p < 0.05). Comparing the two groups, the improvements in fasting blood sugar and serum insulin levels were significantly better in the biguanide group (p = 0.04 for both parameters); whereas the improvements in serum total cholesterol (p < 0.001), low density lipoprotein (p < 0.001), CRP (p < 0.001) and acne status (p = 0.04) were significantly superior in the statin receivers. Based on these results, each medication is only effective on some aspects of the disease. Overall, the simvastatin was superior to metformin with regard to the number of beneficial effects.
Cochrane Database Syst Rev. 2011 Oct 5;(10):CD008565.
Statins for women with polycystic ovary syndrome not actively trying to conceive.
Raval AD, Hunter T, Stuckey B, Hart RJ.
Shrimati Kaumudiniben Health Outcome Research Group (SKHORG), Near Depala's Chora, Dhrangadhra, Gujrat, India, 363310.
Statins, as lipid-lowering agents with pleiotropic actions, are likely not only to improve the dyslipidaemia associated with polycystic ovary syndrome but may also exert other beneficial metabolic and endocrine effects.
To assess the efficacy and safety of statin therapy for women with polycystic ovary syndrome (PCOS) who are not actively trying to conceive.
We searched the following databases (from inception to week 1, July 2011): the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL. We handsearched relevant conference proceedings and references of the identified articles for additional studies. We also contacted experts for further studies in progress.
Randomised controlled trials (RCTs) comparing a statin versus placebo or statin in combination with another drug versus another drug alone in women with PCOS.
DATA COLLECTION AND ANALYSIS:
Two review authors performed data collection and analysis independently.
Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies.
Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.
J Cosmet Dermatol. 2011 Dec;10(4):294-300. doi: 10.1111/j.1473-2165.2011.00587.x.
Fractional CO2 laser for the treatment of acne scars.
Omi T, Kawana S, Sato S, Bonan P, Naito Z.
Department of Dermatology, Queen's Square Medical Center, Yokohama, Japan. email@example.com
Numerous reports have been published on skin rejuvenation by the so-called fractional laser device that delivers a laser beam in a dot form over a grid pattern.
In this study, we characterized the effects of a fractional CO(2) laser on atrophic acne scars at the clinical and ultrastructural levels.
Seven healthy adult Japanese volunteers (aged 32-46 years, mean 37.6, five men and two women of Fitzpatrick skin type III) were recruited for this study. A fractional CO(2) laser device, SmartXide DOT (DEKA, Florence, Italy), was used with irradiation parameters set as follows: output power 10 W, pulse width 600 μs, dot spacing 800 μm, and stack 2 (irradiation output power 0.91 J/cm(2) ). A clinical examination and punch biopsy of each subject was performed before and just after the irradiation, and also at week 3 after three irradiation sessions. The biopsy specimens were stained with toluidine blue and were examined ultrastructurally.
Clinical improvement of the atrophic acne scars was observed at week 3 after the third irradiation session in all cases compared with the condition before treatment. Histologically, outgrowths of many degenerated elastic fibers were observed as irregular rod-shaped masses in the superficial dermis prior to the treatment in the region of the acne scars. At week 3 after the third irradiation, the degenerated elastic fibers were no longer observed, and the elastic fibers were elaunin-like.
The fractional CO(2) laser is considered to be very effective for treating atrophic acne scars.
© 2011 Wiley Periodicals, Inc.
J Cosmet Laser Ther. 2011 Dec;13(6):308-14.
Clinical efficacy of home-use blue-light therapy for mild-to moderate acne.
Gold MH, Sensing W, Biron JA.
Gold Skin Care Center, Department of Dermatology, School of Nursing, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN 37215, USA. firstname.lastname@example.org
Blue-light light-emitting diode (LED) therapy has become widely used for the treatment of inflammatory acne. In this study we evaluated the efficacy of a home use blue-light LED application in improving lesions and shortening their time to clearance.
This was an IRB approved randomized self-control study. For each patient (n = 30), 2 similar lesions, one of each side of the face were chosen for treatment with either a blue-light LED hand-held or sham device. Treatments (n = 4) were conducted twice daily in the clinic and lesions were followed-up till resolution. Reduction in blemishes size and erythema and the overall improvement were evaluated by both the physician and the patients. Time to lesion resolution was recorded.
There was a significant difference in the response of lesions to the blue-light LED application as opposed to the placebo in terms of reduction in lesion size and lesion erythema as well as the improvement in the overall skin condition (p < 0.025). Signs of improvement were observed as early as post 2 treatments. Time to resolution was significantly shorter for the blue-light LED therapy.
The results support the effectiveness of using blue-light LED therapy on a daily basis for better improvement and faster resolution of inflammatory acne lesions.
J Cosmet Laser Ther. 2006 Jun;8(2):71-5.
Combination blue (415 nm) and red (633 nm) LED phototherapy in the treatment of mild to severe acne vulgaris.
Goldberg DJ, Russell BA.
Skin Laser & Surgery Specialists of New York/New Jersey, and Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10022, USA. email@example.com
BACKGROUND AND OBJECTIVE:
Acne vulgaris represents both a challenge to the treating dermatologist and a major concern for the patient. Conventional treatments have proved inconsistent with often unacceptable side effects and high rates of recurrence. Non-thermal, non-laser, phototherapy for acne with a combination of blue and red light has recently attracted attention. The present study was designed to assess the efficacy of this combination phototherapy.
Twenty-four subjects, Fitzpatrick skin types II-V, with mild to severe symmetric facial acne vulgaris were recruited for the study. Subjects were well matched at baseline in terms of both age and duration of acne. Subjects were treated over eight sessions, two per week 3 days apart, alternating between 415 nm blue light (20 minutes/session, 48 J/cm2) and 633 nm red light (20 minutes/session, 96 J/cm2) from a light-emitting diode (LED)-based therapy system. Patients received a mild microdermabrasion before each session. Acne was assessed at baseline and at weeks 2, 4, 8 and 12.
Twenty-two patients completed the trial. A mean reduction in lesion count was observed at all follow-up points. At the 4-week follow-up, the mean lesion count reduction was significant at 46% (p=0.001). At the 12-week follow-up, the mean lesion count reduction was also significant at 81% (p=0.001). Patient and dermatologist assessments were similar. Severe acne showed a marginally better response than mild acne. Side effects were minimal and transitory. Comedones did not respond as well as inflammatory lesions.
Combination blue and red LED therapy appears to have excellent potential in the treatment of mild to severe acne. Treatment appears to be both pain- and side effect-free.
Hum Fertil (Camb). 2011 Dec;14(4):261-5. doi: 10.3109/14647273.2011.632058.
Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity.
Sivayoganathan D, Maruthini D, Glanville JM, Balen AH.
The Leeds Centre for Reproductive Medicine, Seacroft Hospital, Leeds, UK.
This study aimed to compare the spectrum of polycystic ovary syndrome (PCOS) symptoms in patients from four different specialist clinics.
A prospective cross-sectional observational study. Setting: The study was conducted at the infertility, gynaecology, endocrine and dermatology clinics at Leeds General Infirmary, U.K.
Seventy women presenting with features of PCOS: 20 from infertility, 17 from gynaecology, 17 from dermatology and 16 from endocrine clinics. Interventions: Participants were assessed for symptoms and signs of PCOS and underwent a full endocrine and metabolic profile and a pelvic ultrasound scan.
All subjects had experienced menstrual problems, 81% were overweight, 86% had polycystic ovaries on ultrasound, 56% had hirsutism, 53% had acne, 23% had acanthosis nigricans, 16% had alopecia and 38% had previously undiagnosed impaired glucose tolerance (IGT) or diabetes. A significant difference between the four clinic groups existed with regard to menstrual patterns (p = 0.0234), frequency distribution of presenting symptoms and the percentages of patients with PCOS who had already been diagnosed as having PCOS (p = 0.0088).
This study emphasizes the importance of understanding the full spectrum of PCOS as presented to different specialty clinics. Not only is the syndrome under diagnosed but also are the significant associated morbidities such as IGT and type 2 diabetes. Different specialists need to appreciate the spectrum of health problems for women with PCOS that may extend beyond the specific symptoms that precipitated the initial referral.
Clin Endocrinol (Oxf). 1999 Dec;51(6):779-86.
Polycystic ovaries and associated clinical and biochemical features in young women.
Michelmore KF, Balen AH, Dunger DB, Vessey MP.
Division of Public Health and Primary Care, Institute of Health Sciences, Oxford, UK.
To determine the prevalence of polycystic ovaries as identified by ultrasound in a group of young, postmenarcheal women in the normal population, and to investigate how polycystic ovaries are related to the spectrum of clinical and biochemical symptoms associated with the polycystic ovary syndrome (PCOS).
Cross-sectional observational study.
SUBJECTS AND METHODS:
Volunteers were recruited from two universities and two general practice surgeries in Oxford. 230 women aged 18-25 years participated. Information collected and measurements performed included: a menstrual history, anthropometric measurements, clinical observation of acne and hirsutism, transabdominal pelvic ultrasound, and biochemical analysis of a fasting blood sample.
MAIN OUTCOME MEASURES:
Prevalence of polycystic ovaries and their association with symptoms of the polycystic ovary syndrome.
Polycystic ovarian morphology was identified in 74 (33%, 95% CI = 27-39%) of the 224 women who attended for an ultrasound scan. In the non-users of hormonal contraception, irregular menstrual cycles were 20% more common in women with polycystic ovaries than in women with normal ovaries (P = 0.07). There were no significant differences in acne, hirsutism, body mass index or body fat percentage between women with polycystic and normal ovaries. Analysis of biochemical data showed that women with polycystic ovaries had higher total serum testosterone concentrations (P = 0.03). The prevalence of PCOS in this age group was as low as 8% or as high as 26% depending on which criteria were applied to define the syndrome. Sub-group analyses of women according to ovarian morphology and features of PCOS revealed greater mean BMI in women with PCOS, and also indicated lower fasting insulin concentrations and greater insulin sensitivity in polycystic ovary and PCOS groups when compared to women with normal ovaries.
Polycystic ovaries are very common in this age group but are not necessarily associated with other symptomatology. The prevalence of polycystic ovary syndrome varies widely according to the definition applied. Sub-group analysis of women with polycystic ovaries according to the presence or absence of features of polycystic ovary syndrome does not reveal an increasing trend for progression of endocrine abnormalities usually associated with polycystic ovary syndrome.
Indian J Dermatol Venereol Leprol. 2011 Nov-Dec;77(6):688-94.
Oral isotretinoin in different dose regimens for acne vulgaris: a randomized comparative trial.
Agarwal US, Besarwal RK, Bhola K.
Department of Dermatology, SMS Medical College and Hospital, Jaipur, Rajasthan, India. firstname.lastname@example.org
Oral isotretinoin is recommended for severe nodulocystic acne in the doses of 1-2 mg/kg/day which is usually associated with higher incidence of adverse effects. To reduce the incidence of side-effects and to make it more cost-effective, the lower dose regimen of isotretinoin has been used.
To compare the efficacy and tolerability of oral isotretinoin in daily, alternate, pulse and low-dose regimens in acne of all types and also to assess whether it can be used for mild and moderate acne also.
One hundred and twenty patients with acne were randomized into four different treatment regimens each consisting of 30 patients. Group A was prescribed isotretinoin 1 mg/kg/day, Group B 1 mg/kg alternate day, Group C 1 mg/kg/day for one week/four weeks and Group D 20 mg every alternate day for 16 weeks. Patients were further followed for eight weeks to see any relapse. Side-effects were also recorded.
Though the daily high dose treatment Group A performed better initially at eight weeks, at the end of therapy at 16 weeks results were comparable in Group A , B and D. Patients with severe acne did better in Group A than in Group B, C and D. Patients with mild acne had almost similar results in all the groups while patients with moderate acne did better in Group A, B and D. Frequency and severity of treatment-related side-effects were significantly higher in treatment Group A as compared to Group B, C and D.
We conclude that for severe acne either conventional high doses of isotretinoin may be used or we can give conventional high dose for initial eight weeks and later maintain on low doses. Use of isotretinoin should be considered in mild to moderate acne also, in low doses; 20 mg, alternate day seems to be an effective and safe treatment option in such cases.
Clin Drug Investig. 2011;31(8):599-604. doi: 10.2165/11539570-000000000-00000.
Combination of low-dose isotretinoin and pulsed oral azithromycin in the management of moderate to severe acne: a preliminary open-label, prospective, non-comparative, single-centre study.
De D, Kanwar AJ.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
The conventionally used dose of isotretinoin in acne causes significant dose-related adverse effects. Low-dose isotretinoin has been used successfully in mild to moderate papulopustular acne. Although isotretinoin acts against all mechanisms of acne formation, it has no significant direct antimicrobial effect.
To test whether the addition of an antibacterial enables use of isotretinoin in low doses even in moderate to severe acne.
This was a preliminary open-label, prospective, non-comparative, single-centre study carried out in a tertiary-care referral hospital. Seventy patients with grade 3 and 4 acne according to the US FDA global score were included in the study between October 2005 and December 2007. These patients were treated with a combination of low-dose isotretinoin (0.3 mg/kg/day) and pulsed oral azithromycin (500 mg/day over three consecutive days every 2 weeks). Response to treatment was assessed at monthly intervals and was recorded as a percentage decrease in overall severity of disease. Treatment was continued to complete clearance of lesions or to 16 weeks, whichever came later.
Sixty-two (93.9%) of 66 eligible patients had complete clearance of disease activity after a mean treatment duration of 21 weeks. The mean total cumulative dose of isotretinoin was 49.6 mg/kg. Seven (11.3%) patients had a relapse of disease during the post-treatment follow-up period. Fifty-three adverse effects were observed. Three patients had initial aggravation of disease that was managed with prednisolone and disappeared with continuation of treatment.
A combination of low-dose isotretinoin and oral azithromycin pulse is effective in severe acne and has a reasonably acceptable adverse-effect profile and low post-treatment relapse rates.
Arthritis Care Res (Hoboken). 2012 Mar;64(3):389-96. doi: 10.1002/acr.20692.
Independent association of serum retinol and β-carotene levels with hyperuricemia: A national population study.
Choi WJ, Ford ES, Curhan G, Rankin JI, Choi HK.
Arthritis Research Centre of Canada, Vancouver, British Columbia, Canada.
Uses of synthetic vitamin A derivatives (e.g., isotretinoin used for severe acne) and high doses of preformed vitamin A have been implicated in the pathogenesis of hyperuricemia and gout, whereas a trial reported that β-carotene may lower serum uric acid (UA) levels. We evaluated the potential population impact of these factors on serum UA in a nationally representative sample of US adults.
Using data from 14,349 participants ages ≥20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between serum retinol, β-carotene, and UA levels using weighted linear regression. Additionally, we examined the relationship with hyperuricemia using weighted logistic regression.
Serum UA levels increased linearly with increasing serum retinol levels, whereas serum UA levels decreased with increasing serum β-carotene levels. After adjusting for age, sex, dietary factors, and other potential confounders, the serum UA level differences from the bottom (referent) to the top quintiles of serum retinol levels were 0, 0.16, 0.32, 0.43, and 0.71 mg/dl (P for trend <0.001), and for β-carotene were 0, -0.15, -0.29, -0.27, and -0.40 mg/dl (P for trend <0.001), respectively. Similarly, the multivariate odds ratios of hyperuricemia from the bottom (referent) to top quintiles of serum retinol levels were 1.00, 1.30, 1.83, 2.09, and 3.22 (P for trend <0.001) and for β-carotene were 1.00, 0.85, 0.68, 0.73, and 0.54 (P for trend <0.001), respectively. The graded associations persisted across subgroups according to cross-classification by both serum retinol and β-carotene levels.
These nationally representative data raise concerns that vitamin A supplementation and food fortification may contribute to the high frequency of hyperuricemia in the US population, whereas β-carotene intake may be beneficial against hyperuricemia. The use of β-carotene as a novel preventive treatment for gout deserves further investigation.
Copyright © 2012 by the American College of Rheumatology.
Update and future of systemic acne treatment.
Zouboulis CC, Piquero-Martin J.
Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Berlin, Germany. email@example.com
Systemic treatment is required in patients with moderate-to-severe acne, especially when acne scars start to occur. Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline and limecycline) and macrolide antibiotics (erythromycin and azithromycin) are the agents of choice for papulopustular acne, even though the emerging resistant bacterial strains are minimizing their effect, especially regarding erythromycin. Systemic antibiotics should be administered during a period of 8-12 weeks. In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal treatment represents an alternative regimen in female acne, whereas it is mandatory in resistant, severe pubertal or post-adolescent forms of the disease. Compounds with anti-androgenic properties include estrogens combined with progestins, such as ethinyl estradiol with cyproterone acetate, chlormadinone acetate, desogestrel, drospirenone, levonogestrel, norethindrone acetate, norgestimate, and other anti-androgens directly blocking the androgen receptor (flutamide) or inhibiting androgen activity at various levels, corticosteroids, spironolactone, cimetidine, and ketoconazole. After 3 months of treatment control of seborrhea and acne can be obtained. Low-dose corticosteroids (prednisone, prednisolone, or dexamethasone) are indicated in patients with adrenal hyperandrogenism or acne fulminans. New developments and future trends represent low-dose long-term isotretinoin regimens, new isotretinoin formulations (micronized isotretinoin), isotretinoin metabolites, combination treatments to reduce toxicity, insulin-sensitizing agents, 5alpha-reductase type 1 inhibitors, antisense oligonucleotide molecules, and, especially, new anti-inflammatory agents, such as lipoxygenase inhibitors.
Copyright 2003 S. Karger AG, Basel
Health Technol Assess. 2005 Jan;9(1):iii-212.
Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.
Ozolins M, Eady EA, Avery A, Cunliffe WJ, O'Neill C, Simpson NB, Williams HC.
Department of Dermatology, University of Nottingham, UK.
To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains.
This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks.
Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England.
Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face.
Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group).
MAIN OUTCOME MEASURES:
The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots).
The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study.
The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability).
Br J Dermatol. 1996 Jan;134(1):107-13.
The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin-resistant propionibacteria.
Eady EA, Bojar RA, Jones CE, Cove JH, Holland KT, Cunliffe WJ.
Department of Microbiology, University of Leeds, U.K.
Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of erythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P < 0.001, Wilcoxon's matched pairs) and also significantly reduced the number of erythromycin-resistant propionibacteria (P < 0.05). In contrast, erythromycin alone reduced the total propionibacterial count by < 1.5 log10 c.f.u./cm2 after 6 weeks (P < 0.05) and did not affect the number of erythromycin-resistant strains. The combined formulation was significantly more effective at reducing total propionibacterial numbers at 6 (P < 0.01, Mann-Whitney) and 12 weeks (P < 0.05) than erythromycin alone, although, after 12 weeks, the anti-propionibacterial efficacy of both preparations was less marked. Five patients on combination therapy, and five treated with erythromycin alone, acquired erythromycin-resistant strains de novo at week 6 or week 12. In an open study in 21 acne patients, who each carried > 10(3) c.f.u. erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo anti-propionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant propionibacterial strains pretreatment.
Skin Therapy Lett. 2010 Mar;15(3):1-2, 5.
Does diet really affect acne?
Ferdowsian HR, Levin S.
Physicians Committee for Responsible Medicine, Washington, DC, USA.
Acne vulgaris has anecdotally been attributed to diet by individuals affected by this skin condition. In a 2009 systematic literature review of 21 observational studies and 6 clinical trials, the association between acne and diet was evaluated. Observational studies, including 2 large controlled prospective trials, reported that cow's milk intake increased acne prevalence and severity. Furthermore, prospective studies, including randomized controlled trials, demonstrated a positive association between a high-glycemic-load diet, hormonal mediators, and acne risk. Based on these findings, there exists convincing data supporting the role of dairy products and high-glycemic-index foods in influencing hormonal and inflammatory factors, which can increase acne prevalence and severity. Studies have been inconclusive regarding the association between acne and other foods.
Mol Nutr Food Res. 2008 Jun;52(6):718-26.
A pilot study to determine the short-term effects of a low glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled feeding trial.
Smith R, Mann N, Mäkeläinen H, Roper J, Braue A, Varigos G.
School of Applied Sciences, RMIT University, Melbourne, Australia. firstname.lastname@example.org
Observational evidence suggests that dietary glycemic load may be one environmental factor contributing to the variation in acne prevalence worldwide. To investigate the effect of a low glycemic load (LGL) diet on endocrine aspects of acne vulgaris, 12 male acne sufferers (17.0 +/- 0.4 years) completed a parallel, controlled feeding trial involving a 7-day admission to a housing facility. Subjects consumed either an LGL diet (n = 7; 25% energy from protein and 45% from carbohydrates) or a high glycemic load (HGL) diet (n = 5; 15% energy from protein, 55% energy from carbohydrate). Study outcomes included changes in the homeostasis model assessment of insulin resistance (HOMA-IR), sex hormone binding globulin (SHBG), free androgen index (FAI), insulin-like growth factor-I (IGF-I), and its binding proteins (IGFBP-I and IGFBP-3). Changes in HOMA-IR were significantly different between groups at day 7 (-0.57 for LGL vs. 0.14 for HGL, p = 0.03). SHBG levels decreased significantly from baseline in the HGL group (p = 0.03), while IGFBP-I and IGFBP-3 significantly increased (p = 0.03 and 0.03, respectively) in the LGL group. These results suggest that increases in dietary glycemic load may augment the biological activity of sex hormones and IGF-I, suggesting that these diets may aggravate potential factors involved in acne development.
Am J Clin Nutr. 2007 Jul;86(1):107-15.
A low-glycemic-load diet improves symptoms in acne vulgaris patients: a randomized controlled trial.
Smith RN, Mann NJ, Braue A, Mäkeläinen H, Varigos GA.
School of Applied Sciences, RMIT University, Melbourne, Australia. email@example.com
Although the pathogenesis of acne is currently unknown, recent epidemiologic studies of non-Westernized populations suggest that dietary factors, including the glycemic load, may be involved.
The objective was to determine whether a low-glycemic-load diet improves acne lesion counts in young males.
Forty-three male acne patients aged 15-25 y were recruited for a 12-wk, parallel design, dietary intervention incorporating investigator-blinded dermatology assessments. The experimental treatment was a low-glycemic-load diet composed of 25% energy from protein and 45% from low-glycemic-index carbohydrates. In contrast, the control situation emphasized carbohydrate-dense foods without reference to the glycemic index. Acne lesion counts and severity were assessed during monthly visits, and insulin sensitivity (using the homeostasis model assessment) was measured at baseline and 12 wk.
At 12 wk, mean (+/-SEM) total lesion counts had decreased more (P=0.03) in the low-glycemic-load group (-23.5 +/- 3.9) than in the control group (-12.0 +/- 3.5). The experimental diet also resulted in a greater reduction in weight (-2.9 +/- 0.8 compared with 0.5 +/- 0.3 kg; P<0.001) and body mass index (in kg/m(2); -0.92 +/- 0.25 compared with 0.01 +/- 0.11; P=0.001) and a greater improvement in insulin sensitivity (-0.22 +/- 0.12 compared with 0.47 +/- 0.31; P=0.026) than did the control diet.
The improvement in acne and insulin sensitivity after a low-glycemic-load diet suggests that nutrition-related lifestyle factors may play a role in the pathogenesis of acne. However, further studies are needed to isolate the independent effects of weight loss and dietary intervention and to further elucidate the underlying pathophysiologic mechanisms.
Bosn J Basic Med Sci. 2010 Aug;10(3):260-4.
Outcomes of 3% green tea emulsion on skin sebum production in male volunteers.
Mahmood T, Akhtar N, Khan BA, Khan HM, Saeed T.
Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
This study was aimed to depict potential effects of stable formulation (water in oil emulsion), containing 3% green tea (Camellia sinensis L) extract on skin sebum production in healthy human volunteers. For this purpose formulation was designed using 3% ethanolic green tea extract and Abil®EM90 was used as an emulsifier. Formulation was applied to the cheeks of healthy human volunteers (n=10) for a period of 8 weeks. Measurements for skin sebum production were considered using Sebumeter MPA 5. Results were compiled and any effect produced by the formulation was justified statistically. It was observable that statistically significant (p < 0.5%) results were found for skin sebum production after long term application of the formulation. 3% formulation of green tea extract was ideal in all aspects and can be experienced in skin disorders like acne to further investigate its effects in unhealthy volunteers.