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.     

New antibiotic therapies for acne and rosacea

Acne and rosacea compromise a substantial portion of the dermatology clinical practice. Over the past century, many treatment modalities have been introduced with antibiotics playing a major role. Today, both oral and topical antibiotics are used in the management of acne and rosacea, with several novel formulations and/or combination regimens recently introduced. The latest studies suggest anti-inflammatory actions to be the most likely mechanism of antibiotics in acne and rosacea, shifting the focus to subantimicrobial-dose oral antibiotics and/or topical antibiotic regimens as the preferred first-line agents. Here we will discuss the most recent oral and topical antibiotic therapies available for treatment of acne and rosacea, with special focus on efficacy data, indication, dosing, and mechanism of action.     

Bacteriological resistance in acne: A call to action

Acne is common in adolescence but is also increasingly seen in adulthood, with about 40% of adults being affected. Topical and systemic oral antibiotics have been used for more than 40 years in the treatment of acne lesions. In the 1970s, evidence of resistance to topical erythromycin and clindamycin was reported and, since then, antibiotic resistance in acne has been increasing worldwide. Antibiotic exposure can be significant in acne treatment because the patient population is large and there is a tendency for prolonged treatment regimens to be prescribed. The overuse of antibiotics is now considered a major public health problem. Action is therefore required to encourage judicial and appropriate use of antibiotics in acne management in line with available evidence-based guidelines. Alternatives to topical antibiotics for the treatment of acne should be considered. Topical antibiotics should no longer be used as monotherapy in acne treatment and use in combination regimens should be limited to a maximum of four weeks. Evidence from studies suggests that, as for topical antibiotics, oral antibiotics should not be used as monotherapy, but instead should be combined with a topical retinoid or benzoyl peroxide for a maximum of four months. Correct and appropriate use of antibiotics in the treatment of acne will help to preserve their utility in the face of increasing antibiotic resistance but greater awareness of the issues is required among prescribing physicians.     

Recent Advances in Acne Pathogenesis: Implications for Therapy

Acne pathogenesis is a multifactorial process that occurs at the level of the pilosebaceous unit. While acne was previously perceived as an infectious disease, recent data have clarified it as an inflammatory process in which Propionibacterium acnes and innate immunity play critical roles in propagating abnormal hyperkeratinization and inflammation. Alterations in sebum composition, and increased sensitivity to androgens, also play roles in the inflammatory process. A stepwise approach to acne management utilizes topical agents for mild to moderate acne (topical retinoid as mainstay ± topical antibiotics) and escalation to oral agents for more resistant cases (oral antibiotics or hormonal agents in conjunction with a topical retinoid or oral isotretinoin alone for severe acne). Concerns over antibiotic resistance and the safety issues associated with isotretinoin have prompted further research into alternative medications and devices for the treatment of acne. Radiofrequency, laser, and light treatments have demonstrated modest improvement for inflammatory acne (with blue-light photodynamic therapy being the only US FDA-approved treatment). However, limitations in study design and patient follow-up render these modalities as adjuncts rather than standalone options. This review will update readers on the latest advancements in our understanding of acne pathogenesis and treatment, with emphasis on emerging treatment options that can help improve patient outcomes.     

Systemic antibiotic therapy of acne vulgaris

Background: Inflammatory, medium to severe acne vulgaris is treated with systemic antibiotics worldwide. The rationale is an effect on Propionibacterium acnes as well as the intrinsic anti‐inflammatory properties of these antibiotics. Although there are no correlations between the number of P. acnes and the severity of the disease, associations between the degree of humoral and cellular immune responses towards P. acnes and the severity of acne have been reported. Exact data on practical use of these compounds, such as differential efficacy or side effects are unavailable.A summary of currently available studies is presented. Methods: The data of studies of systemic antibiotic therapy of acne vulgaris up to 1975, the summary of literature in English up to 1999, a systematic review of minocycline from 2002 as well as the data of randomized controlled studies published and listed in Medline thereafter were reviewed. Results: Tetracyclines [tetracycline 1 000 mg daily, doxycycline 100 (?200) mg daily, minocycline 100 (?200) mg daily, lymecycline 300 (?600) mg] and erythromycin 1 000 mg daily are significantly more effective than placebo in the systemic treatment of inflammatory acne.The data for tetracycline are best founded. Clindamycin is similarly effective. Co‐trimoxazole and trimethoprim are likely to be effective. Clear differences between the tetracyclines or between tetracycline and erythromycin cannot be ascertained. The data for the combination with topical treatments [topical benzoyl peroxide (BPO) or retinoids] suggest synergistic effects.Therefore systemic antibiotics should not be used as monotherapy. In case of similar efficacy, other criteria, such as pharmacokinetics (doxycycline, minocycline, lymecycline have longer half‐lives than tetracyclines), the rate of side‐effects (tetracycline: side effect‐rate ～4 % mild side effects; erythromycin: frequent gastrointestinal complaints; minocycline: rare, but potentially severe hypersensitivity reactions; doxycycline: dose‐dependent phototoxic reactions), the resistance rate [percentage of resistant bacteria higher with erythromycin (～ 50 %) than with tetracycline‐therapy (～ 20 %)], and the costs of therapy have to be taken into account. Conclusions: The systemic antibiotic therapy of widespread papulo‐pustular acne not amenable to a topical therapy is effective and well‐tolerated. In general therapy can be carried out for 3 months and should be combined with BPO to prevent resistance.     

Acne therapy with topical benzoyl peroxide,antibiotics and azelaic acid

Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite the fact that only few randomized trials have been published, BPO is considered the standard in topical acne treatment. Anaerobic bacteria are reduced by oxidative mechanisms and the induction of resistant strains is reduced. Topical formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect is dose‐dependent, but the irritation increases with higher concentrations. Usually 5 % BPO is sufficient to control acne grade I‐II. Due to its strong oxidative potential, patients should be advised that BPO may bleach colored and dark clothing, bedding and even hair. BPO is safe for use in pregnant and lactating females because it is degraded to benzoic acid. It is a cost‐effective treatment for acne grade I–II. Patients with papulopustular acne grade I–II, particularly with marked inflammation, show satisfactory improvement with topical antibiotic treatment. The following compounds are available and effective: erythromycin, clindamycin and tetracycline (the latter being less frequently used). A review in 1990 suggested that topical tetracycline was ineffective in the treatment of acne. Along with eliminating Propionibacterium acnes, the main mechanism of topical antibiotics is their antiinflammatory effect. All three penetrate the epidermal barrier well and are similarly efficacious. Randomized trials have shown that in concentrations of 2–4 %, their effects are comparable to oral tetracycline and minocycline. Combination therapy with retinoids or benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and reduce comedones, while topical antibiotics primarily address inflammation. One side effect of topical antibacterial treatment is an increase in drug‐resistant resident skin flora with gram‐negative microorganisms prevailing, which can lead to gram‐negative folliculitis. All three antibiotics fluoresce under black light which may produce interesting effects in a discotheque. There are two reports of topical clindamycin causing pseudomembranous colitis after long‐term and widespread usage. Azelaic acid has a predominant antibacterial action, although it is not considered as an antibiotic in the classical sense. Furthermore, it possesses a modest comedolytic effect. Burning upon application is common. Since azelaic acid is naturally present, systemic side effects are not likely to occur, making it safe for acne treatment during pregnancy and lactation.     

Update on topical antibiotics in dermatology

Topical antibiotics are used for various purposes in dermatology. Some of the most common uses include treatment of acne, treatment and prevention of wound infection(s), impetigo or impetiginized dermatitis, and staphylococcal nasal carrier state. It is important for the dermatologist to be familiar with the spectrum of activity, the mechanism of action, and the variables that may interfere with the antibiotic of choice. The following discussion will review an update on topical antibiotic use in acne, wound care, impetigo, and in staphylococcal nasal carriers.     

Treatment of acne with topical antibiotics: lessons from clinical studies

BACKGROUND: Over the past 20 years, major concerns have been repeatedly expressed over antibiotic-resistant acne in Europe and in the U.S.A. However, the clinical significance of these resistance patterns is poorly defined so that topical antibiotics remain one of the cornerstones of acne management. OBJECTIVES: To determine whether we are facing decreased efficacy of topical formulations of erythromycin and clindamycin in clinical trials of therapeutic interventions for acne. METHODS: To review systematically the results of the clinical trials investigating topical formulations of erythromycin and clindamycin for the treatment of inflammatory acne and to establish whether or not there is a decrease in the efficacy of these topical antibiotic formulations since their widespread introduction in the mid 1970s. RESULTS: Of the 50 eligible controlled trials identified using a systematic electronic database search strategy, 45 (90%) incorporated a lesion count, making comparison across trials possible. Analysis of clinical studies investigating the effect of topical erythromycin in acne patients indicates a significant decrease in the effect of this antibiotic on inflammatory and noninflammatory lesion count over time (r = -2.140, P = 0.001 and r = -2.032, P = 0.001, respectively). Efficacy of topical clindamycin remained stable during the study period. CONCLUSIONS: There is a gradual decrease in the efficacy of topical erythromycin in clinical trials of therapeutic intervention for acne, which is probably related to the development of antibiotic-resistant propionibacteria.     

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.     

Efficacy and tolerability of a lotion containing triethyl citrate,ethyl linoleate,and GT peptide‐10 in the adjuvant treatment of hidradenitis suppurativa: Real‐life data

Hidradenitis suppurativa (HS) is a chronic disorder of terminal follicular epithelium in the apocrine gland‐bearing areas. The long term therapy is based mainly on topical and/or systemic antibiotic use that could result in antibiotic resistance. The aim of our study was to present the real‐life experience based on the efficacy and tolerability of a novel lotion containing triethyl‐citrate, ethyl‐linoleate, and g‐peptide‐10 in the treatment of mild to moderate HS that has already shown effectiveness in acne treatment. This was an open‐label study on 30 patients of both sexes affected by HS. Patients were divided into two groups: 15 with Hurley I and 15 with Hurley II–III. The subjects were treated with the topical lotion, three‐times‐daily for eight weeks, with control at 4 (T₁) and eight weeks (T₂). Any other concomitant treatment (both topical and/or systemic) was avoided during study period. Improvement was observed in both Sartorius score grading system and inflammatory and noninflammatory lesion counts. The novel lotion has proved to be effective and well‐tolerated topical agent alone or in association with other topical and/or systemic tratments in HS, without side effects     

A current review of topical benzoyl peroxide: new perspectives on formulation and utilization

Benzoyl peroxide (BPO) is the most widely used topical acne treatment, with significant antibacterial, antikeratolytic, and comedolytic activity. It has been shown to be extremely effective as monotherapy and in combination with antibiotics or retinoids for managing comedonal and inflammatory acne lesions. As numerous clinical studies have shown, the combination of BPO plus a topical antibiotic is not only more effective but also is often better tolerated than either agent alone. Unlike antibiotics, no bacterial resistance has been noted. Adding BPO to any long-term antibiotic regimen in acne is generally recommended to help reduce populations of drug-resistant variants. Although effective combinations of BPO and antibiotics or retinoids are used, BPO monotherapy can also be extremely effective in treating mild to moderate acne with no resistance issues.     

Analysis of common side effects of isotretinoin

Patients with severe recalcitrant nodular acne that is unresponsive to conventional therapy (including topical and systemic antibiotics) have few alternative effective treatment modalities other than the use of oral isotretinoin (Accutane). The cause of acne vulgaris is multifactorial, but the pathogenesis of this disorder of the pilosebaceous follicles arises mainly from endogenous factors. It is usually, but not always, associated with the onset of puberty. Severe acne, defined by the prevalence of facial and truncal inflammatory lesions, is a disfiguring disease that can often result in significant permanent scarring after the healing of deep inflammatory lesions and other disorders, such as systemic bacterial infections. Topical treatments are considered as the first line of therapy for less severe forms of acne, although systemic treatments such as antibiotics or antiandrogen agents are effective for either mild or moderate forms and sometimes effective for severe acne. However, in many patients with large numbers of nodules, longer treatment periods with these agents are required to reduce the count of inflammatory lesions. It has become increasingly evident that (because topical agents and antibiotic or antiandrogenic therapy have a slow onset of action) even mild or moderate acne that is treated in this way can result in scarring. In addition, the excessive use of systemic antibiotics has led to the detection of increasing numbers of antibiotic-resistant bacteria on the skin of patients with acne.(1) Therefore, because of its relatively rapid onset of action and its high efficacy with reducing more than 90% of the most severe inflammatory lesions, Accutane has a role as an effective treatment in patients with severe acne that is recalcitrant to other therapies.     

痤疮的抗生素治疗及耐药现状

痤疮丙酸杆菌在痤疮发生、发展过程中起着重要作用,外用或口服抗生素对痤疮炎性皮损有肯定疗效。然而随着抗生素的广泛使用,耐药问题日益严峻,研究表明超过50%的痤疮丙酸杆菌出现了耐药,尤其是对大环内酯类抗生素。本文对抗生素治疗痤疮的作用机理与使用现状、耐药机制与耐药现状进行综述。     

Topical 2% ketoconazole cream monotherapy significantly improves adult female acne: A double‐blind,randomized placebo‐controlled trial

The emergence of bacterial resistance is a global crisis. Prolonged use of antibiotics especially in acne is one issue of concern among dermatologists. Ketoconazole (KTZ) cream, a topical antifungal with anti‐inflammatory and antiandrogenic actions, can decrease lipase activity of Cutibacterium acnes in vitro. We evaluated the efficacy and safety of KTZ cream in mild adult female acne (AFA) by conducting a randomized, double‐blind, placebo‐controlled trial using KTZ 2% and placebo cream twice daily for 10 weeks. We assessed the improvement of clinical severity, measured by AFA score graded by investigators and participants, and the change of acne count. Forty‐one participants enrolled in our study. The proportion of participants with acne improvement from baseline (42.9% vs 9.5%, P = 0.015) and the success rate (45.0% vs 14.3%, P = 0.043) in the KTZ group were significantly higher than that of the placebo group. The most common adverse events were dryness and itching. The percentage change of acne count decreased significantly compared with baseline but did not differ statistically between the two groups (P = 0.268). We concluded that the KTZ monotherapy showed a plausible effect in improving AFA with excellent safety profile. It should be considered as a viable option for mild AFA treatment.     

Antibiotic resistance of microbial strains isolated from Korean acne patients

Over several decades, topical and systemic antibiotics have been the mainstay of treatment for acne vulgaris. The widespread and long‐term use of antibiotics in the treatment of acne has resulted in the spread of resistant bacterial strains and treatment failure. We aimed to examine the bacteriology of acne vulgaris and to evaluate its susceptibility to the antibiotics widely used for acne in Korea. We examined the species of bacteria aerobically and anaerobically isolated from 100 Korean acne patients. Among the bacteria isolated, Staphylococcus epidermidis (36 patients) was the most common, followed by Propionibacterium acnes (30 patients). Eleven strains of P. acnes (36.7%) and 25 strains of S. epidermidis (69.4%) were resistant to one or other of the antibiotics tested. A higher proportion of P. acnes isolates were resistant to clindamycin (30%) and erythromycin (26.7%), than to any other antibiotics tested (P = 0.0003). Some S. epidermidis isolates were resistant to tetracycline and doxycycline in addition to clindamycin and erythromycin. In the previous studies, few strains of P. acnes were found to be resistant to any of the antibiotics, but this study shows that antibiotic‐resistant strains have been increasing in Korea acne patients.     

Shiunko and Chuoko,topical Kampo medicines,inhibit the expression of gehA encoding the extracellular lipase in Cutibacterium acnes

Antimicrobial agents have been used for eradication of Cutibacterium (formerly Propionibacterium) acnes that is an exacerbation factor of the skin disease acne vulgaris. However, the use of antibiotics is associated with an increased risk of promoting the emergence of resistant bacteria and leading to skin dysbiosis. Traditional Japanese Kampo medicines, such as Keigairengyoto, are used to treat acne. However, there is incomplete understanding regarding their functional mechanism in treatment of acne. In this study, we examined the antimicrobial and anti‐lipase activity of the Kampo medicines used empirically for acne treatment. Three oral medicines, Keigairengyoto, Seijoboufuto and Jumihaidokuto, were found to inhibit the growth of C. acnes and decrease the lipase activity. Especially, Keigairengyoto caused remarkable decrease of bacterial lipase activity. Furthermore, topical medicines such as Shiunko and Chuoko significantly decreased the lipase activity in a dose‐dependent manner, without inhibiting C. acnes growth. The topical medicines were found to inhibit the expression of gehA, which codes for extracellular lipase. Our results indicate that Shiunko and Chuoko have potential as effective acne therapeutic agents, especially because they do not promote the emergence of antimicrobial‐resistant bacteria and skin dysbiosis.     

The effective treatment of acne vulgaris by a high‐intensity,narrow band 405–420 nm light source

BACKGROUND: Available topical treatments are slow and frequently irritating. Oral therapies may be associated with increased bacterial resistance (antibiotics) or possible severe side effects (oral isotretinoin). In vitro and in vivo exposure of acne bacteria to 405–420?nm ultraviolet (UV) free blue light results in the photo‐destruction of these bacteria through the effects on the porphyrins produced naturally by Propionibacterium acnes. A novel, high‐intensity, narrow band 420?nm UV free blue light has been shown to decrease inflammatory acne lesions after eight bi‐weekly treatments.

OBJECTIVES: To examine the effects of high‐intensity, narrow band 420?nm UV free blue light (ClearLight^?) on inflammatory acne lesions.

METHODS: Three studies were carried out to examine the clinical effects of high‐intensity, narrow band blue light on papulo‐pustular acne: the split‐face dose–response study, the full‐face open trial and the split‐face, double‐blind controlled study. The studies enrolled 10, 13 and 23 patients respectively.

RESULTS: The data show more than an 80% response to 420?nm acne phototherapy with a significant reduction of 59–67% of inflammatory acne lesions after only eight treatments of 8–15 minutes. The reduction in lesions was steady in the follow‐ups at 2, 4 and 8 weeks after the end of therapy. Prolonged remission was evident in the 8 weeks after the end of therapy. No adverse effects or patient discomfort were noted in any of the patients.

CONCLUSIONS: Acne phototherapy by high intensity, narrow band 405–420?nm light is proven to be an attractive, fast, effective, non‐invasive alternative to current topical and parenteral anti‐acne remedies.     

Topical retinoids in acne – an evidence‐based overview

Topical retinoids are important tools in the management of acne because they act against comedones and microcomedones and have direct anti‐inflammatory effects. The substances approved for acne treatment comprise tretinoin (all‐trans‐retinoic acid),isotretinoin (13‐cis retinoic acid) as well as the synthetic third‐generation polyaromatic retinoids adapalene and tazarotene,the latter being approved for acne treatment in the US only.Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild to moderate acne but differ in efficacy and tolerability. Tazarotene 0.1% is more effective than tretinoin 0.025% or 0.1% microsphere gel or adapalene 0.1% gel or cream (EBM‐level 2c). Adapalene 0.1% is equally effective to tretinoin 0.025% or tretinoin microsphere 0.1% gel or tretinoin 0.05% cream or isotretinoin 0.05% gel (EBM‐level 2c). Adapalene 0.1% gel is significantly better tolerated than tazarotene 0.1% gel, tretinoin 0.025% and tretinoin 0.05% gel, tretinoin 0.05% cream,tretinoin microsphere 0.1% gel or isotretinoin 0.05% gel (EBM‐level 2c).The safety profile of topical retinoids differs from their systemic counterparts and is related mainly to local adverse effects, such as erythema, dry‐ness,itching and stinging.The currently available evidence justifies the use of topical retinoids in most types of acne and during maintenance treatment.     

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.