New and emerging treatments in dermatology: acne

ABSTRACT:  Topical retinoids, benzoyl peroxide, azelaic acid, and topical and oral antibiotics remain the milestone of treatment for mild to moderate acne vulgaris. Oral isotretinoin is useful for the treatment of severe nodular acne, treatment-resistant acne, and acne with a risk of physical or psychological scarring. Hormonal treatment in female acne is useful in resistant or late-onset acne. With increasing concerns regarding teratogenicity of isotretinoin and increasing antibiotic resistance, there is a clear need for therapeutic alternatives to these long-used treatments. Research in the pathogenesis of acne has allowed for new therapies and future perspectives regarding acne to evolve. They include low-dose long-term isotretinoin regimens, insulin-sensitizing agents, 5α-reductase type 1 inhibitors, topical photodynamic therapy, new combination formulations, dietary interventions, and antiinflammatory agents such as lipoxygenase inhibitors.     

Medikamentöse Therapie der Akne

Acne is treated according to the clinical picture and the pathophysiologically relevant mechanisms, such as seborrhea, follicular hyperkeratosis, P. acnes colonisation,and inflammation. In mild forms of acne, topical therapy is most appropriate. Comedonal acne can be treated with topical retinoids; papulopustular acne with a combination of retinoids and topical antimicrobial substances (benzoyl peroxide, antibiotics, or azelaic acid). Moderate forms or those with extrafacial involvement can be treated with oral antibiotics combined with topical retinoids or benzoyl peroxide. Acne conglobata and other severe manifestations are treated with oral isotretinoin. Women are also treated with oral contraceptives containing anti-androgenic progestins. If inflammation is prominent, initial short term treatment with oral glucocorticoids is helpful. Second-line agents include oral zinc or dapsone. Following successful treatment, topical retinoids are suitable for maintenance therapy.     

Acne vulgaris

Acne vulgaris is worldwide the most common skin disease. Acne is an inflammatory disorder in whose emergence androgens, PPAR ligands, the IGF-1 signaling pathway, regulating neuropeptides and environmental factors are probably involved. These factors interrupt the natural cycling process in the sebaceous gland follicle and support the transition of microcomedones to comedones and inflammatory lesions. Proinflammatory lipids and cytokines are mediators for the development of acne lesions. Bacterial antigens can potentate the inflammatory phenomena. Acne is predominantly treated with combination therapy. Selecting a treatment regimen depends on the exact classification of acne type and severity. The development of scars is the main criterion for the choice of systemic therapy. Retinoids for mild comedonal acne and the combination of retinoids with antibiotics and/or benzoyl peroxide for mild to moderate papulopustular acne are the drugs of first choice for topical treatment. The use of topical antibiotics is not recommended any more because of the development of resistant bacterial strains. Systemic antibiotics, in combination with topical retinoids and/or benzoyl peroxide, for moderate papular/nodular acne and isotretinoin for severe nodular/conglobate acne are the columns of systemic acne treatment. Systemic anti-androgens are used in women against moderate papulopustular acne. Due to advances in the understanding of the underlying inflammatory mechanisms in recent years the development of new therapeutic agents with good efficacy and better side effect profile should be expected in the future.     

An expert view on the treatment of acne with systemic antibiotics and/or oral isotretinoin in the light of the new European recommendations

In 2003 the European Agency for the Evaluation of Medicinal Products amended the summary product characteristics for oral isotretinoin to standardise information provided from the different countries of the European Community. The Committee for Proprietary Medicinal Products recommended that among others, exclusively severe forms of acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to "adequate courses" of standard therapy with systemic antibacterials and local therapy should benefit from oral isotretinoin. However, no indication was provided on what were considered adequate courses or the possibility given to use oral isotretinoin as first line treatment. The aims of the present report were: 1) to provide a specialist view on when it is appropriate to introduce oral isotretinoin as a second line therapy for acne, taking into consideration optimum dosage and duration of systemic antibiotics prior to the start of the oral isotretinoin, and 2) to support the use of oral isotretinoin as first line therapy in specific cases for acne in clinical practice. The recommendations are based on an exhaustive literature review as well as on the personal experience of the members of an European panel of acne specialists. The EEP agreed with the decision made by the CPMP that oral isotretinoin should be administered as 2nd line therapy in those cases of severe acne, which were resistant to or which did not respond successfully to an initial combination regimen with systemic antibiotics and topical treatments (topical retinoids +/- benzoyl peroxide). However, the members emphasized that a number of prognostic factors, as well as psychosocial morbidity should be taken into account when choosing the regimen and that these factors may influence the use of oral isotretinoin as first line therapy.     

South‐East Asia study alliance guidelines on the management of acne vulgaris in South‐East Asian patients

The management of acne in South‐East Asia is unique, as Asian skin and local variables require a clinical approach unlike that utilized in other parts of the world. There are different treatment guidelines per country in the region, and a group of leading dermatologists from these countries convened to review these guidelines, discuss current practices and recent advances, and formulate consensus guidelines to harmonize the management of acne vulgaris in the region. Emphasis has been placed on formulating recommendations to impede the development of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne Consensus Conference system for grading acne severity. The group recommends that patients may be treated with topical medications including retinoids, benzoyl peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a combination of retinoids and BPO with or without antibiotics for mild acne; topical retinoid with topical BPO and a oral antibiotic for moderate acne; and oral isotretinoin if the patient fails first‐line treatment (a 6‐ or 8‐week trial of combined oral antibiotics and topical retinoids with BPO) for severe acne. Maintenance acne treatment using topical retinoids with or without BPO is recommended. To prevent the development of antibiotic resistance, topical antibiotics should not be used as monotherapy or used simultaneously with oral antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection, is likewise recommended. Patient education and good communication is recommended to improve adherence, and advice should be given about the characteristics of the skin care products patients should use.     

Systemische Aknetherapie

The development of scarring in inflammatory acne may induce permanent disfigurement and considerable psychosocial impact on the lives of affected individuals. The early use of systemic acne therapy can help to prevent these unfortunate consequences. Antiinflammatory antibiotics such as tetracyclines are required in moderate to severe papulopustular acne. The recommended treatment duration is 3 months; combination with topical retinoids and benzoyl peroxide increases the speed and efficacy of lesion reduction and helps to prevent bacterial resistance. Oral isotretinoin is the treatment of choice in severe acne resistant to adequate conventional therapy. Hormonal treatment represents an alternative regimen for women with acne and is the first choice in late-onset acne and in those with clinical signs of hyperandrogenism.     

Antibiotic treatment for acne vulgaris

Although topical therapies alone can be very effective for milder acne, there are often cases for which oral antibiotics are needed to control disease. Through both antibacterial and antiinflammatory effects, oral antibiotics in combination with other drugs such as retinoids and benzoyl peroxide can be highly effective in the treatment of more severe disease. Patients and their parents often have many questions regarding the safety and efficacy of long-term antibiotic use. It is important for the physician to have a thorough understanding of the antibiotics at their disposal as well as their side effects. Through careful discussion, antibiotic compliance can be optimized and side effects minimized ultimately resulting in treatment success.     

Management of acne vulgaris: an evidence‐based update

This review summarizes clinically important findings from 3 systematic reviews, 1 updated guideline and a selection from the 62 randomized controlled trials (RCTs) published between February 2007 and January 2009 on the topic of acne vulgaris. Low glycaemic‐load diets might reduce acne severity but this remains unproven. Written patient information leaflets have not been surpassed by other communication methods. New combination topical treatments have not shown convincing advantages over current combination products such as clindamycin/benzoyl peroxide. Topical dapsone is superior to placebo but has yet to be compared with standard topical treatments. Long‐term topical tretinoin to prevent nonmelanoma skin cancer in elderly men was associated with higher all‐cause mortality, but there is currently no evidence of increased mortality for topical retinoid use when treating acne. All oral tetracyclines have similar efficacy, yet minocycline is the most costly. Oral isotretinoin monotherapy remains the gold‐standard treatment for severe acne. Flutamide plus the oral contraceptive pill is beneficial for acne associated with polycystic ovary syndrome. Photodynamic therapy, phototherapy and laser therapy cannot be recommended universally for acne until minimal postinflammatory pigmentation and longer‐term benefit can be shown, especially with current high costs. Development of non‐antibiotic therapies is preferable to minimize the risk of community antibiotic resistance. Future trials should use active comparators at optimum doses and avoid noninferiority comparisons unless appropriately powered. Trials need to shift from using multiple, unvalidated outcome measures to including patient‐reported and quality‐of‐life outcomes, and all trials should be registered on a public clinical‐trials database.     

Acne vulgaris treatment : the current scenario

Acne Vulgaris is one of the most common skin disorders which dermatologists have to treat. It mainly affect adolescent, though may present at any age. In recent years, due to better understanding of the pathogenesis of acne, new therapeutic modalities and various permutation and combinations have been designed. In topical agents; benzoyl peroxide, antibiotics, retinoids, etc are the mainstay of treatment; can be given in combinations. While systemic therapy includes oral antibiotics, hormonal therapy, and isotretinoin, depending upon the need of patients it has to be selected. Physical treatment in the form of lesion removal, photo-therapy is also helpful in few of them. Since various old and new topical and systemic agents are available to treat acne, it sometime confuse treating dermatologist. To overcome this, panel of physicians and researchers worked together as a global alliance and task force to improve outcomes in acne treatment. They have tried to give consensus recommendation for the treatment of acne. Successful management of acne needs careful selection of anti-acne agents according to clinical presentation and individual patient needs.     

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.     

Benzoyl peroxide: enhancing antibiotic efficacy in acne management

Benzoyl peroxide is one of the most widely used topical agents for acne. It has potent antibacterial and mild anti-inflammatory and comedolytic effects. To treat mild to moderate acne, it can be used alone or in combination with topical antibiotics and topical retinoids. The combination of benzoyl peroxide with either erythromycin or clindamycin is synergistic and well-tolerated. In more severe acne, when oral antibiotics are required, benzoyl peroxide can contribute to suppressing the emergence of resistant strains of Propionibacterium acnes.     

Current state of acne treatment: highlighting lasers, photodynamic therapy, and chemical peels

Acne vulgaris continues to be a challenge to dermatologists and primary care physicians alike. The available treatments reflect the complex and multifactorial contributors to acne pathogenesis, with topical retinoids as first-line therapy for mild acne, topical retinoids in combination with anti-microbials for moderate acne, and isotretinoin for severe nodular acne. Unfortunately, these conventional therapies may not be effective against refractory acne, can lead to antibiotic resistance, and is associated with adverse effects. With the rise of new technologies and in-office procedures, light and laser therapy, photodynamic therapy, chemical peels, and comedo extraction are growing in popularity as adjunctive treatments and may offer alternatives to those who desire better efficacy, quicker onset of action, improved safety profile, reduced risk of antibiotic resistance, and non-systemic administration. Whereas adjunctive therapies are generally well-tolerated, the number of randomized controlled trials are few and limited by small sample sizes. Furthermore, results demonstrating efficacy of certain light therapies are mixed and studies involving photodynamic therapy and chemical peels have yet to standardize and optimize application, formulation, and exposure times. Nevertheless, adjunctive therapies, particularly blue light and photodynamic therapy, show promise as these treatments also target factors of acne pathogenesis and may potentially complement current conventional therapy.     

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。     

A practical approach for the use of oral isotretinoin for infantile acne

Infantile acne is a rare occurrence. It is more common in boys and predominately occurs on the cheeks in infants between the ages of 1 and 16 months. Clinically, the lesions range from comedones to inflammatory papulopustules to cysts. Successful therapies include topical tretinoin, benzoyl peroxide and topical and oral erythromycin. For more serious cases, oral isotretinoin (Accutane) has been reported to successfully treat recalcitrant infantile cystic acne. We describe two additional patients with infantile cystic acne treated successfully with oral isotretinoin. The dose of isotretinoin used ranged from 0.2 mg/kg/day to 1.5 mg/kg/day. The treatment duration varied from 5 to 14 months. Careful monthly monitoring is recommended because of the many side effects reported with isotretinoin. Practical tips for the administration of oral isotretinoin in infants are reviewed.     

Strategy of acne therapy with long-term antibiotics

A study of the outcome of conventional antibiotic treatment in 543 patients with acne was performed. All were treated initially with erythromycin 1 g/day and topical 5% benzoyl peroxide. The median improvement at 6 months was 78%, with an interquartile range of 67-90%. Four-hundred and eight of the 492 who completed 6 months' treatment showed over 50% improvement and 247 of the 279 patients treated for a subsequent 6 months with benzoyl peroxide alone, continued to do well. Another subgroup of 174 patients, was continued for 6 months with systemic antibiotic and 5% benozyl peroxide. No significant benefit was gained, however, by maintaining successfully treated patients on a further 6 months of systemic antibiotics. Of the 84 patients who did less well, 18 were given alternative treatment (Diane, isotretinoin). The other 60, subsequently referred to as slow responders, were continued on antibiotics (erythromycin, 31; minocin, 29; cotrimoxazole, 4; trimethoprim, 2) and benzoyl peroxide. Those prescribed minocycline for the second 6 months appeared to have greater benefit (64%) than those receiving erythromycin (57%). This level of improvement was still lower than that seen in those who responded well within 6 months (78%). Of the risk factors analysed, the poorest response occurred in males with truncal acne. Age at presentation, duration and severity did not adversely affect therapeutic outcome. Side-effects were minimal.     

Benzoyl Peroxide-Based Combination Therapies for Acne Vulgaris

Benzoyl peroxide, with its broad-spectrum antimicrobial activity, is among the most widely used topical agents in the treatment of inflammatory acne vulgaris. Benzoyl peroxide is marketed either alone or in combination with other topical antibiotics; namely, erythromycin and clindamycin. The combination products confer specific advantages over benzoyl peroxide alone, particularly in decreasing the in vivo follicular counts of Propionibacterium acnes, the anaerobic bacterium implicated in the pathogenesis of acne. In addition, the topical treatment of inflammatory acne has been complicated by the development of P acnes resistance to topical erythromycin and clindamycin. Combination products containing benzoyl peroxide and the topical antibiotics have been shown to both: (i) prevent the development of antibiotic resistance in acne patients; and (ii) confer significant clinical improvement to patients who have already developed antibiotic resistance.     

What’s new in acne? An analysis of systematic reviews and clinically significant trials published in 2010–11

This review summarizes important clinical developments in acne treatment identified in five systematic reviews and two significant primary research studies, published between March 2010 and February 2011. Although evidence showing a direct link between development of bacterial resistance and oral antibiotic therapy for acne is not convincing, prescribers can still tailor their practice to minimize future risks by stopping treatment when appropriate, using benzoyl peroxide, and avoiding combining topical and systemic antimicrobials. A systematic review evaluating combination products containing benzoyl peroxide did not show convincing evidence that such products are superior to monotherapies. A systematic review of combined oral contraceptives confirmed their efficacy for acne in women. However, another systematic review of botanical products for acne failed to provide any good-quality evidence of benefit. A large, well-reported retrospective cohort study attempted to clarify the potential link between isotretinoin and depression/suicide. Although suicide risk peaked 6 months after isotretinoin treatment, an increased risk was present before initiation of isotretinoin, making it difficult to attribute the increased risk to isotretinoin alone. However, those with a history of suicide attempts before treatment made fewer new attempts than those whose behaviour started during treatment. This suggests that patients with severe acne with a history of attempted suicide should not automatically be refused isotretinoin. Another randomized controlled trial of 60 patients from Korea suggested that low-dose isotretinoin dose than might provide a better long-term outcome with minimal side-effects for people with moderate acne.     

Lack of irritative potential of nadifloxacin 1% when combined with other topical anti-acne agents

Background. Diverse options are available for the treatment of acne. Topical therapy is standard, especially in cases of mild to moderate acne, while the current treatments for acne vulgaris are topical keratolytics and topical antibiotics. Tolerability is a critical factor in patient compliance with topical acne therapies. The simultaneous use of more than one topical preparation with different active ingredients may cause increased irritation. However, the multifactorial aetiologies of acne, and the need to prevent development of bacterial resistance, require new acne‐treatment combinations. Combining agents that target the different aetiological factors of acne can help increase efficacy and reduce response time. Aim. To compare the dermal irritation produced by an anti‐acne cream containing 1% nadifloxacin with that produced by additional treatment with four different topical anti‐acne products in a 21‐day open application test in 40 healthy volunteers. Methods. This was a randomized, double‐blind (observer‐blind), single‐centre, phase I clinical study with an intraindividual comparison. The topic anti‐acne products (nadifloxacin, adapalene, benzoyl peroxide, azelaic acid and isotretinoin) were applied without occlusion, either alone or in combination with nadifloxacin, to the skin test areas. One test area was left untreated. Results. Most of the mean irritation scores were 0, and all were < 1. Conclusions. Combined application of nadifloxacin with any of the other four topical anti‐acne products did not lead to substantial intolerance reactions compared with the effects after application of the products alone.     

A clinical and therapeutic study of 29 patients with infantile acne

BACKGROUND: Infantile acne is a relatively uncommon condition; there are few data in the literature on the optimum treatment for this disorder. OBJECTIVES: To review treatment results in infantile acne. METHODS: We performed a retrospective review of 29 patients (24 boys and five girls) treated over a 25-year period. RESULTS: The age at onset was 6-16 months (median 9). The acne was mild in 24%, moderate in 62% and severe in 14%. The type of acne was predominantly inflammatory (59%), but was comedonal in 17%, showed a mixed pattern in 17% and was nodular in 7%. No infants had any clinically obvious endocrinopathy. Patients with mild acne responded well to topical treatment (benzoyl peroxide, erythromycin and retinoids). All but two infants with moderate acne responded well to oral (paediatric) erythromycin 125 mg twice daily and topical therapy. Patients with erythromycin-resistant Propionibacterium acnes required trimethoprim 100 mg twice daily. Most patients were able to stop oral antibiotics within 18 months. In 38% of children, long-term oral antibiotics (> 24 months) were required. The time for clearance of the acne was 6-40 months (median 18). One patient required oral isotretinoin that cleared the acne in 4 months. Five patients (17%) were left with scarring. CONCLUSIONS: This study confirms the male predominance of infantile acne. Treatment is similar to that of adult acne, with the exclusion of the use of tetracyclines. When necessary, oral isotretinoin can be used.