Topical Retinoids in Acne Vulgaris: A Systematic Review

Background

Topical retinoids are a first-line treatment for acne vulgaris.

Objective

This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris.

Methods

A PubMed and Embase search was conducted using the search terms ‘adapalene,’ ‘tretinoin,’ ‘tazarotene,’ and ‘acne vulgaris.’ Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12 years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria.

Results

Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator’s Static Global Assessment (24.1–28.8% and 13.3–17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1–34.9% vs 7–11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64–78.9% vs 41–56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012).

Conclusions

Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.

     

外用维A酸治疗寻常痤疮的疗效和安全性的系统评价

目的 评价外用维A酸治疗寻常痤疮的疗效和安全性,并与外用硫磺制剂、过氧苯甲酰、抗生素比较。方法 用Cochrane协作网系统评价方法,选择有随机对照的临床试验做系统评价。结果 截止2002年,纳入15个临床试验2439例患者。有4个临床试验示外用维A酸疗效明显优于安慰剂[RR(相对危险度)=1.87,95%CI(可信区间)为1.13~3.11],尤其对非炎性皮损(RR=12.70,95%CI为4.09~39.40)。有3个临床试验示维A酸疗效优于硫磺制剂(RR=1.75,95%CI为1.42~2.16)。与过氧苯甲酰对照的7个临床试验以及与抗生素对照的3个临床试验尚不能下结论。所有临床试验示外用维A酸制剂后,可出现红斑、脱屑等局部不良反应,虽无证据显示其系统不良反应,但对孕妇须非常谨慎。结论 外用维A酸治疗寻常痤疮有效,并优于硫磺制剂,但尚无证据表明优于过氧苯甲酰或外用抗生素。有局部不良反应。需进行更多质量高、大样本的随机对照试验,以证实外用维A酸治疗寻常痤疮的作用和地位。     

Topical Antimicrobial Treatment of Acne Vulgaris

Topical antimicrobial treatment is indicated for mild to moderate acne vulgaris. Our literature review includes searches of Ovid, MEDLINE, EMBASE, and the databases of the Cochrane Library. A detailed search strategy is included. All searches were limited to controlled trials and systematic reviews. No year limits were applied to the searches, but we focused on trials, guidelines, and reviews published since 2004, the year that the last review of topical antimicrobials was published in this journal. Several controlled trials demonstrate that benzoyl peroxide, topical antibiotics, and topical retinoids used in combination provide the greatest efficacy and safety profile for the treatment of mild to moderate acne, but there are few trials directly comparing different combinations of these topical therapies with one another. Additionally, robust studies comparing cost and efficacy of generic combinations of the above agents with proprietary fixed-dose combination therapies that may increase compliance are also lacking. Although they have not been extensively studied, alternative agents including dapsone, salicylic acid, azelaic acid, and zinc are safe and efficacious when combined with traditional therapies.     

Topical Zinc Therapy for Acne Vulgaris

Abstract: A double-blind study of 30 patients with mild to moderate acne vulgaris was conducted to evaluate the efficacy of a topically applied 2% zinc sulfate solution for acne therapy. Over a 12-week period, no difference was noted between placebo- and zinc-treated participants in regard to either the number or type of acne lesions. The irritancy due to topically applied zinc was significantly greater (p 0.05) than that due to the placebo. Zinc serum levels were not significantly elevated between the two regimens before, during, or after treatment. This study suggests that topical zinc therapy alone is not of significant benefit in the treatment of acne vulgaris.     

Topical Zinc Therapy for Acne Vulgaris

A double-blind study of 30 patients with mild to moderate acne vulgaris was conducted to evaluate the efficacy of a topically applied 2% zinc sulfate solution for acne therapy. Over a 12-week period, no difference was noted between placebo- and zinc-treated participants in regard to either the number or type of acne lesions. The irritancy due to topically applied zinc was significantly greater (p less than or equal to 0.05) than that due to the placebo. Zinc serum levels were not significantly elevated between the two regimens before, during, or after treatment. This study suggests that topical zinc therapy alone is not of significant benefit in the treatment of acne vulgaris.     

Topical Antibacterial Treatments for Acne Vulgaris

Topical antibacterial agents are an essential part of the armamentarium for treating acne vulgaris. They are indicated for mild-to-moderate acne, and are a useful alternative for patients who cannot take systemic antibacterials. Topical antibacterials such as clindamycin, erythromycin, and tetracycline are bacteriostatic for Propionibacterium acnes, and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P. acnes, as well as inhibition of leukocyte chemotaxis. Benzoyl peroxide is a non-antibiotic antibacterial agent that is bactericidal against P. acnes and has the distinct advantage that thus far, no resistance has been detected against it. Combined agents such as erythromycin/zinc, erythromycin/tretinoin, erythromycin/isotretinoin, erythromycin/benzoyl peroxide, and clindamycin/benzoyl peroxide are increasingly being used and have been proven to be effective. They generally demonstrate good overall tolerability and are useful in reducing the development of antibacterial resistance in P. acnes. The selection of a topical antibacterial agent should be tailored for specific patients by choosing an agent that matches the patient's skin characteristics and acne type. Topical antibacterial agents should generally not be used for extended periods beyond 3 months, and topical antibacterials should ideally not be combined with systemic antibacterial therapy for acne; in particular, the use of topical and systemic antibacterials is to be avoided as far as possible.     

Current Options for the Topical Treatment of Acne Vulgaris

Abstract: The etiopathogenesis of acne vulgaris, a common disorder of youth and adolescence, includes four primary processes: hyperkeratinization (plugging) of the pilosebacous follicles, increased testosterone levels, bacterial colonization with Proplonibacterium acnes, and inflammation. No single agent has yet been developed that addresses all of these factors. Combination regimens, therefore, which usually include an antibiotic and an agent to reduce follicular plugging, have become the mainstay of treatment. Despite a relative dearth of new treatments for almost a decade, recent research has produced a number of new significant oral and topical agents. Azelaic acid, a naturally occurring dicarboxylic acid analogue, has shown promise, and a group of retinoids that include adapalene, tazarotene, and reformulations of tretinoin represent new and forthcoming agents for topical treatment of acne vulgaris. Some studies indicate that several of these agents are associated with less skin irritation than previous formulations while they retain potent comedoiytic activity. Adapalene also possesses significant anti-inflammatory activity.     

Treatment of Acne Vulgaris with Topical Clindamycin Phosphate: A Double-Blind Study

In a double-blind study, 1% clindamycin phosphate in aqueous-alcohol vehicle was compared with the vehicle alone on the opposite side. Of 29 patients evaluated, the clindamycin-treated side was found to be better in 11, the placebo side was better in four, and both sides were improved in five. No benefit was found in the remaining nine patients. These results were not considered statistically significant. Following discontinuance of treatment a prominent flare was noted in 14 of 19 patients who had previously improved on one side or the other, and this was considered significant (p less than .05). One percent clindamycin phosphate in equal parts of alcohol and water is apparently beneficial for some, but not for all patients with inflammatory acne.     

女性寻常痤疮患者月经期前应用阿达帕林凝胶治疗的临床观察

目的评价女性寻常痤疮患者月经期前10天应用阿达帕林凝胶治疗的疗效及安全性。方法57例女性寻常痤疮患者,皮损据Pillsbury改良分级法分为Ⅱ、Ⅲ级,随机分为治疗及对照两组,治疗均为外用阿达帕林凝胶,用药方法为治疗组月经前10天开始用药,来月经时停止;对照组为连续用药,疗程均为8周。结果 两组疗效相当(P>0.05),治疗组不良反应发生率低于对照组(P<0.05)。结论对Ⅱ、Ⅲ级女性寻常痤疮患者可应用月经前10天外用阿达帕林凝胶的方法治疗,疗效与连续用药相当,但用药时间短,不良反应发生率低,安全性好。     

Minocycline in Acne Vulgaris

Minocycline is a semi-synthetic, second-generation tetracycline. It was introduced in 1972 and has both antibacterial and anti-inflammatory properties. Minocycline is used for a variety of infectious diseases and in acne. Even today, new indications beyond the antibacterial indications are being investigated such as its use in neurologic diseases. Formerly, minocycline was thought to have a superior efficacy in the treatment of inflammatory acne, especially with respect to antibacterial-resistant Propionibacterium acnes. A thorough review of the literature, however, shows that minocycline is not more effective in acne than other tetracyclines. Compared with first-generation tetracyclines, minocycline has a better pharmacokinetic profile, and compared with doxycycline it is not phototoxic. However, minocycline has an increased risk of severe adverse effects compared with other tetracyclines. It may induce hypersensitivity reactions affecting the liver, lung, kidneys, or multiple organs (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] syndrome) in the first weeks of treatment and, with long-term treatment, may cause autoimmune reactions (systemic lupus erythematosus, autoimmune hepatitis). In addition, CNS symptoms, such as dizziness, are more frequent compared with other tetracyclines. Long-term treatment may induce hyperpigmentation of the skin or other organs. Resistance of P. acnes to minocycline also occurs, dependent on the prescribing behavior. Considering the aspects of efficacy, its adverse effect profile, resistance, price, and alternatives, minocycline is no longer considered the first-line antibacterial in the treatment of acne.     

Serum Zinc in Acne Vulgaris

Serum zinc levels in acne patients and in matched healthy controls of both sexes and within the same age group (16-20 years age) were estimated. Women, whether diseased or healthy, have shown a significantly lower mean serum zinc level than the corresponding men. In advanced grades of acne, both men and women have a significantly lower level than the corresponding control groups. Within the same sex group, those with advanced grades have revealed a significantly lower level than those with slight grades.     

Anti-Androgens in Treatment of Acne Vulgaris

Abstract: ABSTRAGT: Seventy-five women suffering from acne vulgaris classified into three groups according to the grade of the disease. Anti-androgenic tablets cyproterone acetate (CPA), were given in three cycles. The total numher of patients whose condition improved was 52% after the first cycle, 55% after the second cycle, and 81.3% after the third cycle. No serious side effects were encountered. CPA is a suitable therapeutic modility for AV in women who use contraceptives.     

Anti-Androgens in Treatment of Acne Vulgaris

Seventy-five women suffering from acne vulgaris classified into three groups according to the grade of the disease. Anti-androgenic tablets cyproterone acetate (CPA), were given in three cycles. The total number of patients whose condition improved was 52% after the first cycle, 55% after the second cycle, and 81.3% after the third cycle. No serious side effects were encountered. CPA is a suitable therapeutic modility for AV in women who use contraceptives.     

Spotlight on Adapalene in Acne Vulgaris

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favorable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.     

Studies on the Mechanism of Action of Topical Benzoyl Peroxide and Vitamin A Acid in Acne Vulgaris

Although systemic telracycline remains the most frequent treatment for acne vulgaris, this report indicates that more effective antibacterial therapy can be achieved topically. The effective agent, benzoyl peroxide, produced a mild desquamation: while concommitantly reducing the fatty acids in sebum more dramatically than systemic tetracycline. Bacterial cultures demonstrated the potential of this peroxide to inhibit the growth of C. acnes recovered from sebaceous follicles. Since the mechanism of benzoyl peroxide is different than topical vitamin A acid, combination therapy has been evaluated in over 1,000 acne patients. The clearing of acne lesions is now routine in the majority of these cases within the initial three months of therapy.     

Phototherapy in the Treatment of Acne Vulgaris

Acne vulgaris is a common dermatosis affecting 80% of the population. To date, different treatments have been used to manage this condition. Antibacterials and retinoids are currently the mainstay of treatment for acne, but their success rate varies. Phototherapy is emerging as an alternative option to treat acne vulgaris. Studies examining the role of different wavelengths and methods of light treatment have shown that phototherapy with visible light, specifically blue light, has a marked effect on inflammatory acne lesions and seems sufficient for the treatment of acne. In addition, the combination of blue-red light radiation seems to be superior to blue light alone, with minimal adverse effects. Photodynamic therapy has also been used, even in nodular and cystic acne, and had excellent therapeutic outcomes, although with significant adverse effects. Recently, low energy pulsed dye laser therapy has been used, and seems to be a promising alternative that would allow the simultaneous treatment of active acne and acne scarring. Further studies are needed to clarify the role of phototherapy as a monotherapy or an adjuvant treatment in the current management of acne vulgaris.     

The Management of Acne Vulgaris in Pregnancy

Acne vulgaris is a common condition in adolescence and also for many women of childbearing age. The management of acne in pregnancy is complicated by the lack of clinical studies and pharmacokinetic data in this patient population and safety concerns regarding retinoid use in pregnancy. Of primary concern to both patients and clinicians is the safety profile of medications used during pregnancy. This review seeks to clarify what management options are available to treat acne during pregnancy and what data are available to guide decision making. Topical treatments are considered the safest option during pregnancy. They have the best safety profile and minimize the levels of systemic absorption, and therefore the least risk of fetal exposure. If these are applied properly with a strong emphasis on adherence, excellent results can be achieved.     

光疗法治疗寻常痤疮新进展

光疗法是治疗寻常痤疮的一种安全有效的新疗法。文章分别介绍了蓝光、红光、激光以及光疗联合5-氨基酮戊酸治疗寻常痤疮的作用机制、治疗方法、技术发展和可能的不良反应。