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Selective RAR agonists for acne vulgaris: A narrative review.
Kassir, M, Karagaiah, P, Sonthalia, S, Katsambas, A, Galadari, H, Gupta, M, Lotti, T, Wollina, U, Abdelmaksoud, A, Grabbe, S, et al
Journal of cosmetic dermatology. 2020;(6):1278-1283
Abstract
BACKGROUND Acne vulgaris is a chronic disfiguring inflammatory disease of adolescents and adults affecting up to 90% of the population around the world. The sequence of etiopathogenesis in acne is not completely understood but involves abnormalities in sebum production, follicular plugging, proliferation of propionibacterium acnes, and chronic inflammation. AIMS This review aims to summarize the features of the topical selective RAR agonists in treating acne vulgaris with a special emphasis on the 4th generation topical retinoid trifarotene. METHODS Studies were identified by searching electronic databases (MEDLINE and PubMed) till August 2019 and reference lists of respective articles. Only articles published in English language were included. RESULTS Topical retinoids have been first line of treatment for more than 30 years now in treating mild to moderate acne vulgaris. Third generation retinoids like adapalene and tazarotene are selective RAR and γ agonists, having an additional anti-inflammatory action along with their comedolytic effects and work well in combinations with topical antibiotics, due to the stability of chemical composition. CONCLUSION Trifarotene is a new 4th generation retinoid with selective action on RAR-γ receptor alone, which is specific for skin, and it is safe for long-term maintenance therapy with good efficacy and tolerability.
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FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial.
Poinas, A, Lemoigne, M, Le Naour, S, Nguyen, JM, Schirr-Bonnans, S, Riche, VP, Vrignaud, F, Machet, L, Claudel, JP, Leccia, MT, et al
Trials. 2020;(1):571
Abstract
BACKGROUND Acne vulgaris has increased in women over the past 10 years; it currently affects 20-30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone's efficacy in order to establish it as an alternative to cyclines. METHODS Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months. DISCUSSION The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage. TRIAL REGISTRATION ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.
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Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha-hydroxy acid) for acne.
Liu, H, Yu, H, Xia, J, Liu, L, Liu, GJ, Sang, H, Peinemann, F
The Cochrane database of systematic reviews. 2020;(5):CD011368
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Abstract
BACKGROUND Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. OBJECTIVES To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. SEARCH METHODS We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). AUTHORS' CONCLUSIONS Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.
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Acne related to dietary supplements.
Zamil, DH, Perez-Sanchez, A, Katta, R
Dermatology online journal. 2020;(8)
Abstract
Multiple prescription medications may cause or aggravate acne. A number of dietary supplements have also been linked to acne, including those containing vitamins B6/B12, iodine, and whey, as well as "muscle building supplements" that may be contaminated with anabolic-androgenic steroids (AAS). Acne linked to dietary supplements generally resolves following supplement discontinuation. Lesions associated with high-dose vitamin B6 and B12 supplements have been described as monomorphic and although pathogenesis is unknown, a number of hypotheses have been proposed. Iodine-related acne may be related to the use of kelp supplements and has been reported as monomorphic, inflammatory pustules on the face and upper trunk. Whey protein supplements, derived from milk and used for bodybuilding, are associated with papulonodular acne involving the trunk and sometimes the face. Finally, AAS-induced acne has been described as acne fulminans, acne conglobata, and acne papulopustulosa. With studies indicating that about half of US adults report using dietary supplements, it is important that dermatologists directly ask acne patients about their supplement use and educate them on the potential risks of even seemingly innocuous dietary supplements.
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Promising plant-derived secondary metabolites for treatment of acne vulgaris: a mechanistic review.
Soleymani, S, Farzaei, MH, Zargaran, A, Niknam, S, Rahimi, R
Archives of dermatological research. 2020;(1):5-23
Abstract
Acne vulgaris is the most common skin condition associated with inflammation of pilosebaceous unit. Since conventional therapies have not demonstrated desirable effectiveness and possess remarkable side effects, there is a growing interest in the use of herbal medicines for the management of acne vulgaris. In this study, plant-derived molecules investigated in acne vulgaris have been reviewed and their possible underlying mechanisms of action were discussed. For this purpose, different electronic databases including PubMed, Scopus, Cochrane library and Google Scholar were searched to obtain any in vitro, in vivo, or human studies evaluating the phytochemicals in the management of acne vulgaris. Data were collected from 1980 to 2018 (up to October). Most of the phytochemicals investigated in acne were from the category of polyphenols including resveratrol, myricitrin, schisandrin, terchebulin, alpha-mangotin, curcumin, ellagic acid and epigallocatechin 3-gallate. Moreover, alkaloids and terpenoids such as berberine, ursolic acid, lupeol were evaluated in acne vulgaris with less abundance. Various molecular mechanisms were involved in effects of phytochemicals including antioxidant (through down-regulation of H2O2, MDA, ROS and upregulation of SOD), anti-inflammatory (through reduction of proinflammatory cytokines, i.e., IL-1ß, IL-6, IL-8, TGF-β, TNF-α, NF-κB), immunomodulatory, antibacterial (against Propionibacterium acnes and Propionibacterium granulosum), antiandrogenic, reducing sebum production, and lipogenesis inhibitory activities. Therefore, phytochemicals seem to be a precious source for identifying new medicines for treatment of acne vulgaris; however, since most of studies are preclinical, further clinical studies are needed to achieve more conclusive and reliable results.
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Clinical assessment of topical erythromycin gel with and without zinc acetate for treating mild-to-moderate acne vulgaris.
Sayyafan, MS, Ramzi, M, Salmanpour, R
The Journal of dermatological treatment. 2020;(7):730-733
Abstract
Purpose: Erythromycin is an effective topical antibiotic for treating mild-to-moderate inflammatory acne vulgaris, especially papules acne during puberty as well as papules - pustular acne in adult women. Erythromycin is a macrolide antibiotic that has long been used as a topical dosage form to treat acne. It has favorable effects in resolving inflammatory acne lesions not only by reducing Propioni bacterium acnes density, but also by directly inhibiting neutrophil chemotactic factors and reactive oxygen species (ROS) production. Zinc, a metallic element has bacteriostatic activity against Propioni bacterium acnes. Combining zinc with antibiotic (erythromycin) can reduce antibiotic resistance and increase antibiotic absorption in-to the skin.Material and methods: In the present study, erythromycin (2% w/v) with zinc acetate (1.2% w/v) as 'topical gel' and erythromycin (2% w/v) gel alone were evaluated for treating mild to moderate inflammatory acne vulgaris. This double-blind study was carried out on 102 patients 13-25 years of age, divided into two groups. The group A received erythromycin and group B received erythromycin with zinc acetate topical gels during 3 weeks. Acne grading and lesion counts for comedones, papules and pustules were performed during each visit zero, first, second and third weeks.Results: Erythromycin treatment (with zinc acetate) gel showed to be more effective than erythromycin (alone) gel with respect to reducing the number of acne lesions and severity grade of acne.Number of lesions and severity of acne were significantly reduced at the end of 3rd week in both groups (p < .001). Conclusions: In conclusion, it can be stated that erythromycin with and without zinc acetate was clinically effective, and both formulations produced a significant reductions in acne grading as well as inflamed and noninflamed lesion counts (p < .000). Statistically, there was no significant difference between formulation A and B.
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Observation for clinical effect of acupuncture combined with conventional therapy in the treatment of acne vulgaris.
Kou, L, Yu, N, Ren, J, Yang, B, Tao, Y
Medicine. 2020;(18):e19764
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INTRODUCTION Acne vulgaris is a chronic inflammatory disease of the sebaceous glands that occurs in adolescent men and women. In recent years, the incidence of acne has increased year by year, so it is of great significance to find a precise and effective treatment and further explore its possible mechanism of action. The purpose of this study will be to explore a treatment method that has both traditional Chinese medicine characteristics and significant effects, and provides a higher level of evidence for acupuncture for acne vulgaris. It also provides patients with more treatment options. METHODS/DESIGN The study will be a randomized controlled trial divided into 2 parallel groups. This pragmatic randomized controlled trial will recruit 66 patients who are diagnosed with acne vulgaris. 30-minutes acupuncture sessions will be provided to patients assigned to the intervention group. All participants will continue to receive conventional treatment. The selection of outcomes will be evaluated by the skin lesions score scale. DISCUSSION This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with acne vulgaris. TRIAL REGISTRATION NUMBER CTR2000030427.
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Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review.
Liu, H, Yu, H, Xia, J, Liu, L, Liu, G, Sang, H, Peinemann, F
Journal of evidence-based medicine. 2020;(4):275-283
Abstract
OBJECTIVE The effects of topical azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid (alpha-hydroxy acid) for acne are unclear. We aimed to assess the effects of these topical treatments by collecting randomized controlled trials. METHODS We searched The Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS up to May 2019. We also searched five trials registers. Two review authors independently extracted data and assessed risk of bias. Meta analyses were performed by using Review Manager 5 software. RESULTS We included a total of 49 trials involving 3880 participants. In terms of treatment response (measured using participants' global self-assessment of acne improvement, PGA), azelaic acid was probably less effective than benzoyl peroxide (RR = 0.82, 95% CI 0.72-0.95). However, there was probably little or no difference in PGA when comparing azelaic acid to tretinoin (RR = 0.94, 95% CI 0.78-1.14). There may be little or no difference when comparing salicylic acid to tretinoin (RR = 1.00, 95% CI 0.92-1.09). There were no studies measured PGA when evaluating nicotinamide. With respect to alpha-hydroxy acid, there may be no difference in PGA when comparing glycolic acid to salicylic-mandelic acid (RR = 1.06, 95% CI 0.88-1.26). We were uncertain about the effects of sulfur and zinc. Adverse events associated with these topical treatments were always mild and transient. CONCLUSIONS Moderate-quality evidence was available for azelaic acid and low- to very-low-quality evidence for other topical treatments. Risk of bias and imprecision limit our confidence in the evidence.
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An Advanced, Physician-Strength Retinol Peel Improves Signs of Aging and Acne Across a Range of Skin Types Including Melasma and Skin of Color.
Sadick, N, Edison, BL, John, G, Bohnert, KL, Green, B
Journal of drugs in dermatology : JDD. 2019;(9):918-923
Abstract
Background: Facial chemical peels are highly sought after by patients with photodamage, acne, and melasma. An advanced, physician-strength superficial peel, containing 3% retinol with other firming and volumizing ingredients was developed to exfoliate, improve the appearance of fine lines and wrinkles, and plump and firm skin, while promoting a bright, even complexion. Objective: A clinical study was conducted to evaluate the tolerability, safety, and efficacy of the 3% retinol peel with a supportive homecare regimen across a range of peel candidates, females aged 18-65 years, with photodamage, acne, hyperpigmentation or melasma, and skin of color, over a series of 2-4 peels. Method: The 3% retinol peel formulation was administered under physician direction in 6-week intervals. Subjects with photodamaged skin, acne, hyperpigmentation/melasma, or skin of color (Fitzpatrick skin types IV-VI) received 2-4 peels along with a supportive homecare regimen. Dermatologist grading, self-assessment, and digital photography documented tolerability and efficacy parameters. Results: 24 subjects participated in the study with a total of 78 peels administered (Photodamage group, n=14 [with an Acne subgroup, n=5]; Melasma group, n=5; Skin of Color, n=5). The 3% retinol peel along with the homecare regimen was well tolerated under physician direction in all skin types and conditions assessed. Obvious peeling was noticeable in many subjects 3 days post-peel and resolved by day 7. In the photodamaged group, dermatologist clinical grading of fine lines, wrinkles, pore size, laxity, mottled pigmentation, lack of clarity/radiance, and overall photodamage was significantly improved (P<0.05). Benefits were observed in all groups and supported by self-assessment. Digital photography demonstrated tolerability in the days immediately post-peel, along with benefits to photodamage. Conclusion: The 3% retinol superficial peel was well tolerated and an efficacious cosmetic treatment under physician supervision in subjects of all skin types to firm skin, improve fine lines and wrinkles, and promote a bright, even complexion. J Drugs Dermatol. 2019;18(9):918-923.
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Topical probiotics: the unknowns behind their rising popularity.
Lee, GR, Maarouf, M, Hendricks, AJ, Lee, DE, Shi, VY
Dermatology online journal. 2019;(5)
Abstract
OBJECTIVE Topical probiotics have been used for skin care and treatment since the early 20th century. Over the past decade, there has been a dramatic surge of commercially-available topical probiotic products. We conducted a systematic search of clinical data relating to the use of topical probiotics and identified relevant clinical and regulatory gaps. METHODS PubMed and Google Scholar searches were conducted for trials and reviews of probiotics. FDA definitions of cosmetics, drugs, and regulation of topical probiotics were reviewed. RESULTS Topical probiotics have shown efficacy in a number of limited trials, particularly those involving the treatment of acne, atopic dermatitis, and rosacea. However, there is a paucity of literature on the safety profiles, mechanistic action, and therapeutic potential of topical probiotic products. Several regulatory gaps exist, including approval and classification of topical probiotic products by the FDA; currently there are no topical probiotic products the FDA has approved as drugs. CONCLUSION With increasing popularity among the general public, but insufficient clinical data to demonstrate large-scale effectiveness and a thorough understanding of side effects, there is a need for further mechanistic and clinical investigation, as well as improved regulation and standardization of topical probiotic products.