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.     

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.     

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.     

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.     

Optimizing the use of topical retinoids in Asian acne patients

Acne vulgaris is a common disease among people in Asia. International guidelines and treatment recommendations emphasize the central role of topical retinoids in the management of acne. However, topical retinoids remain underutilized in clinical practise, which may be in part due to fear of retinoid‐associated dermatitis/lack of experience, particularly in Asian patients. There is a perception that Asian skin has a greater tendency toward sensitivity compared with Caucasian skin. In our clinical experience, topical retinoid therapy can be used with excellent effect to treat Asians with acne. This article discusses available published work regarding the use of topical retinoids in Asian populations, and presents tips for utilizing these important agents in daily practise. Optimizing use of topical retinoids may improve adherence and, in turn, therapeutic outcomes and patient satisfaction.     

Acne in ethnic skin: special considerations for therapy

Acne vulgaris occurs in people of all ethnicities and races. Although the pathophysiology and treatment options are similar in all skin phototypes, darker-skinned patients have higher incidence rates of two sequelae of acne: postinflammatory hyperpigmentation and keloidal scarring. Postinflammatory hyperpigmentation may also be triggered by skin irritation. In choosing therapies for patients of color, therefore, clinicians must find a balance between aggressive early intervention to target inflammatory acne lesions, and gentle treatments to increase tolerability and avoid skin irritation. For most patients, a combination of topical retinoids, and topical or oral antibiotics with hydroquinone (as needed) to control hyperpigmentation will be successful. For patients with sensitive skin, topical agents in lower concentrations and cream vehicles are preferred. If tolerated, the retinoid strength can be titrated upward after four to six weeks. Ethnic patients also need to be counseled on use of noncomedogenic and nonirritating skin and hair-care products. Individualized care and close monitoring is required.     

Topical treatment in acne: current status and future aspects

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2-5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO(2) laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.     

Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study

Background Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first‐line option in the treatment of moderate to severe acne vulgaris. Objectives To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%–BPO 2·5% (A/BPO) fixed‐dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. Methods A total of 378 subjects were randomized in a double‐blind, controlled trial to receive once‐daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects ‘clear’ or ‘almost clear’), skin tolerability, adverse events and patients’ satisfaction. Results The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (?74·1%) than in the lymecycline with vehicle group (?56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were ‘very satisfied’ was significantly greater (P = 0·031). Conclusion These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.     

Common Use of Prescription Off‐Label Acne Therapy in Children Younger Than 12 Years Old

Acne is occurring more frequently in younger age groups, but most available treatments are considered off‐label in young children. As the epidemiology of acne has changed to include younger children over the past 20 years, neither regulators, pharmaceutical companies, nor clinicians have understood the need or value of obtaining regulatory sanctions for problems physicians have managed using clinical judgment. The objective of this study was to analyze the frequency of off‐label acne treatment according to age and other demographic factors. We searched the National Ambulatory Medical Care Survey from 1993 to 2010 for visits in children younger than 12 years of age for the diagnosis of International Classification of Diseases, Ninth Revision, code 706.1. We tabulated leading acne treatments and assessed factors associated with off‐label prescribing. Off‐label but appropriate acne treatments were used in 29% of acne visits for children younger than 12 years of age. Dermatologists were more likely than pediatricians to prescribe off‐label treatment (p < 0.001). The most frequently used off‐label treatments were topical retinoids, followed by oral antibiotics. There was no significant trend in the rate of off‐label prescribing over time (p = 0.40). Off‐label treatment is well within the standard of care for young children with acne. More data on the use of topical retinoids in young children will improve our understanding of their use, which may help optimize treatment outcomes for children with acne.     

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.     

Systematic review on the rapidity of the onset of action of topical treatments in the therapy of mild‐to‐moderate acne vulgaris

The time until a patient achieves a relevant improvement during the treatment of a skin disease is important for selecting a therapy, but has been largely neglected in reviews and guidelines. The aim of this systematic review was to determine the time until the onset of action (TOA) of topical acne treatments. The primary outcome was the TOA defined as the time until a 25% reduction in the mean number of inflammatory lesions had been achieved. A systematic literature search in Medline and Embase was carried out. Clinical trials that evaluated head‐to‐head comparisons of treatments in patients suffering from mild‐to‐moderate papulopustular acne were included. Abstract and full‐text screening and data extraction were done independently by two investigators. With respect to inflammatory lesions, different concentrations of benzoyl peroxide (BPO) or adapalene did not seem to influence the TOA. BPO seemed to act more quickly than isotretinoin and tretinoin. Adapalene showed a shorter TOA than isotretinoin. Conflicting results were seen when comparing adapalene with tretinoin, with a tendency for adapalene to be faster. Clindamycin/BPO seemed to act more quickly than adapalene. Inconsistent results were seen for the comparison of clindamycin/BPO and BPO alone with a slight indication of a shorter TOA for clindamycin/BPO. Adapalene/BPO and clindamycin/BPO showed comparable TOA. When interpreting the data, the different study designs and the limited study quality need to be taken into account. Further research is needed to identify treatments that offer an early onset of action and possibly help to optimize patients' adherence. TOA should be considered as an additional outcome in acne trials.     

Topical tazarotene therapy for psoriasis,acne vulgaris,and photoaging

Psoriasis, acne vulgaris and photoaging are common conditions. Tazarotene is a pro-drug of tazarotenic acid, a receptor-selective retinoid, which has shown efficacy in the treatment of these disorders. In the treatment of acne vulgaris, it has greater comedolytic activity than the currently available topical retinoids. In psoriasis, tazarotene normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation and has better anti-inflammatory effects than any of the currently available topical retinoids. It is most commonly used as combination therapy with a topical corticosteroid or phototherapy in psoriasis, or with an antibiotic in acne.     

The use of oral antibiotics in treating acne vulgaris: a new approach

Although acne is not an infectious disease, oral antibiotics have remained a mainstay of treatment over the last 40 years. The anti‐inflammatory properties of oral antibiotics, particularly the tetracyclines, are efficacious in treating inflammatory acne lesions. Common prescribing practices in Dermatology exert significant selection pressure on bacteria, contributing to the development of antibiotic resistance. Antibiotic use for acne not only promotes resistance in Propionibacterium acnes, but also affects other host bacteria with pathogenic potential. This review will summarize the commonly used treatments for acne vulgaris, and how they should be combined as rational treatment. The indications for using oral antibiotics in acne will be highlighted. Strategies described in the literature to conserve the utility of oral antibiotics will be summarized. These include limiting the duration of antibiotic therapy, concomitant use of a topical non‐antibiotic agent, use of subantimicrobial dose doxycycline, and the introduction of topical dapsone.     

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.     

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.

     

Prospective, open-label, comparative study of clindamycin 1%/benzoyl peroxide 5% gel with adapalene 0.1% gel in Asian acne patients: efficacy and tolerability

Background  Used as individual agents, topical antibiotics and benzoyl peroxide are known to be effective in treatment of acne. Clindamycin phosphate 1% with benzoyl peroxide 5% (CDP/BPO) is a new combination gel, made by rationale, in that combination drug is more effective than either ingredients used alone. Adapalene 0.1% (ADA) is the third-generation retinoid, shown to be as effective as other topical retinoid with well tolerability.
Objectives  To compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris.
Methods  Total of 69 patients, including 31 patients for CDP/BPO group and 38 for ADA group, with mild to moderate acne vulgaris were enrolled for a 12-week prospective, randomized, open-label comparative study of topical agents. Efficacy was assessed by lesion counts, acne grading system, and global improvement. Adverse events were also evaluated in scale of 0 (none) to 3 (severe).
Results  Both CDP/BPO and ADA were effective in reducing lesion counts and acne severity scale and showed significant global improvement. However, CDP/BPO offered greater efficacy against inflammatory lesions than ADA. Both drugs were well tolerated with minimal adverse drug reactions.
Conclusion  Combination formulation of CDP/BPO and ADA were shown to be both effective in decreasing total, inflammatory, and non-inflammatory lesion counts along with well tolerability in Asian patients with mild to moderate acne vulgaris.

Conflicts of interest

None declared     

What’s new in acne? An analysis of systematic reviews published in 2009–2010

This review highlights clinically important findings about acne treatment identified in nine systematic reviews published or indexed in the period March 2009 to February 2010. A systematic review of dietary influences on acne suggested that a possible role of dietary factors in acne cannot be dismissed, as the studies to date have not been sufficiently large or robust. Another review looked at benzoyl peroxide, which may be enjoying a comeback because of increasing bacterial resistance to antibiotics, and suggested that there was a lack of evidence that stronger preparations were more effective than weaker ones. The same team also carried out a systematic review addressing the question of whether topical retinoids cause an initial worsening of acne. They found no evidence to suggest initial worsening of acne severity, although there was evidence of skin irritation that typically settled by 8–12 weeks. A review of oral isotretinoin and psychiatric side‐effects reinforced a possible link between the two, although it pointed out that the better‐quality primary studies were still inconclusive. An updated Cochrane Review confirmed the efficacy of combined oral contraceptives (COCs) in reducing acne lesion counts. It also found that the evidence to support COCs containing cyproterone acetate over others was very limited. Another Cochrane Review failed to show any benefit of spironolactone for acne, based on limited studies. Three reviews examined laser and light therapies, and found some evidence of superiority only for blue or blue/red light treatment over placebo light, but a general absence of comparisons against other acne treatments. Photodynamic therapy had consistent benefits over placebo but was associated with significant side‐effects and was not shown to be better than topical adapalene.     

Newer Approaches to the Treatment of Acne Vulgaris

The multifactorial etiology of acne vulgaris makes it challenging to treat. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, azelaic acid, and systemic isotretinoin. Adjunctive and/or emerging approaches include topical dapsone, taurine bromamine, resveratrol, chemical peels, optical treatments, as well as complementary and alternative medications. The purpose of this paper is to discuss the therapies available for acne and their latest developments, including new treatment strategies (i.e. re-evaluation of the use of oral antibiotics and avoidance of topical antibiotic monotherapy, use of subantimicrobial antibiotic dosing, use of low-dose isotretinoin, optical treatments), new formulations (microsponges, liposomes, nanoemulsions, aerosol foams), new combinations (fixed-combination products of topical retinoids and topical antibiotics [essentially clindamycin] or benzoyl peroxide), new agents (topical dapsone, taurine bromamine, resveratrol) and their rationale and likely place in treatment. Acne vaccines, topical natural antimicrobial peptides, and lauric acid represent other promising therapies.     

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 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.