LEADING ARTICLE
`
`Am J Clin Dermatol 2012; 13 (6): 357-364
`1175-0561/12/0006-0357/$49.95/0
`Adis ª 2012 Springer International Publishing AG. All rights reserved.
`
`Newer Approaches to the Treatment of Acne Vulgaris
`
`Thierry Simonart
`
`Private Practice, Brussels, Belgium
`
`Abstract
`
`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.
`
`1. Introduction
`
`Acne vulgaris is one of the most common disorders en-
`countered in dermatology practice.[1,2] Epidemiologic studies
`in Western industrialized countries estimated the prevalence
`of acne in adolescents to be between 50% and 95%, depend-
`ing on the method of lesion counting.[3-5] Although acne is
`a disease primarily of adolescence, it may, to some degree,
`persist into adulthood in a significant proportion of in-
`dividuals, particularly women.[4,6] The disease burden of acne
`has the ability to elicit in some sufferers significant mental
`health concerns due to a heightened sense of shame relating to
`appearance.[7,8]
`Current understanding of acne pathogenesis continues to
`evolve. Acne is an androgen-dependent disorder of piloseb-
`aceous follicles. There are four primary pathogenic factors that
`interact to produce acne lesions: (i) increased and altered an-
`drogen-dependent sebum production; (ii) altered keratinization
`leading to comedones; (iii) Propionibacterium acnes follicular
`colonization; and (iv) release of inflammatory mediators into
`the skin.[1,2] Although family history and environment factors
`have an important role in the disease, the exact sequence of
`events and how they interact remains unclear. Management,
`therefore, is a multifactorial approach with several treatment
`options targeted toward the multiple factors contributing to
`acne pathogenesis. Treatment decisions for patients with acne
`
`are compounded by the profusion of available treatments and
`by the relative paucity of trials with active comparators. Con-
`cerns about antibiotic resistance and isotretinoin safety as well
`as the rise of novel adjunctive treatments bring new perspectives
`to the treatment of acne. Alternatives to refractory acne,
`aversion to prescription medications, adverse effects to con-
`ventional therapy, and poor adherence to conventional therapy
`drive interest in novel approaches. This review summarizes the
`latest developments in the treatment of acne and their rationale
`and likely place in treatment.
`
`1.1 Literature Search Parameters
`
`An extensive search was performed at the beginning of the
`project. A systematic electronic search strategy was used to
`retrieve all the recently published (January 2007–December
`2011) clinical trials investigating therapies for acne. This review
`focused on the therapy of acne and not on other forms of acne.
`We obtained data from MEDLINE (National Library of
`Medicine), PubMed, Current Contents, HomInform (Glasgow)
`[database of references to journal articles and books on home-
`opathy], reference lists, and textbooks. There was no restriction
`on language. The selected keywords were ‘acne,’ ‘comedones,’
`‘vulgaris,’ ‘treatment,’ ‘therapy,’ ‘retinoids,’ ‘isotretinoin,’ ‘ben-
`zoyl peroxide,’ ‘azelaic acid,’ ‘antibiotics,’ ‘dapsone,’ ‘laser,’
`‘light therapies,’ ‘vaccines,’ and ‘antimicrobial peptides.’
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`Simonart
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`2. Acne Therapy
`
`Table I. Conventional, emerging, and experimental anti-acne therapies for
`
`The large number of products and product combinations,
`and the scarcity of comparative studies, has led to disparate
`guidelines. Because of the paucity of evidence, these guidelines
`rely on the opinions of experts, many of whom declare significant
`potential conflicts of interest.[2,9-12] Conventional treatments
`include topical retinoids, benzoyl peroxide, azelaic acid, topical
`and systemic antibiotics, systemic isotretinoin, and combined
`oral contraceptives for women.[2,9-12] Novel approaches en-
`compass recent developments in conventional treatments as
`well as emerging therapies. These different therapies are sum-
`marized in table I.
`
`2.1 Retinoids
`
`2.1.1 Topical Retinoid Therapy
`Topical retinoids represent a mainstay of acne treatment
`because they expel mature comedones, reduce microcomedone
`formation, and exert anti-inflammatory effects through a
`number of pathways, including downregulating toll-like re-
`ceptors, cytokines, and nitric oxide.[13] Topical retinoids have a
`favorable safety profile distinct from the toxicity of their sys-
`temic counterparts. They are contraindicated in pregnancy, and
`women of childbearing age must use effective contraception.
`Local adverse effects, including erythema, dryness, itching, and
`stinging, occur frequently during the early treatment phase.
`Their impact varies with the vehicle formation, skin type, fre-
`quency and mode of application, use of moisturizers, and envi-
`ronment factors such as sun exposure or temperature.[13] They do
`not seem to cause temporary worsening of acne lesions.[14]
`The broad anti-acne activity and safety profile of topical
`retinoids justifies their use as first-line treatment in mild to
`moderate forms of acne, more particularly in comedonal forms
`of acne, as well as for maintenance therapy;[9-13] these agents
`can also minimize the potential for relapse, which is part of the
`natural history of acne.[15]
`inves-
`A meta-analysis of five multicenter, randomized,
`tigator-blind trials involving 900 patients showed adapalene
`0.1% gel to be as effective as, but less irritating than tretinoin
`0.025% gel,[16] so that adapalene should be selected in prefer-
`ence to tretinoin and isotretinoin.
`Fixed-combination products of topical retinoids and topical
`antibiotics (essentially clindamycin) or benzoyl peroxide are
`significantly more efficacious in reducing the number of inflam-
`matory and non-inflammatory lesions compared with retinoid
`monotherapy.[17-19] Furthermore, patients taking combination
`therapy show faster signs of improvement.[20] The quicker onset
`
`acne vulgaris
`
`Therapies
`
`Conventional
`
`Topical therapies
`
`Topical retinoids
`
`Fixed-combination products of topical
`retinoids and topical antibiotics or BPO
`
`BPO
`
`Azelaic acid
`
`Topical antibiotics
`
`Systemic therapies
`
`Isotretinoin
`
`Systemic antibiotics
`
`Oral contraceptives
`
`Emerging
`
`Topical dapsone
`
`Taurine bromamine
`
`Chemical peels
`
`Optical treatments
`
`Complementary and alternative
`medications
`
`Sodium sulfacetaminde
`
`Resveratrol
`
`Experimental
`
`Main concerns
`
`Local irritation
`
`Local irritation
`
`Local irritation
`
`Local irritation
`
`Antibiotic resistance
`
`Safety concerns
`
`Antibiotic resistance
`
`Lack of comparisons with
`other standard therapies
`
`Lack of comparisons with
`other standard therapies
`
`Lack of comparisons with
`other standard therapies
`
`Lack of comparisons with
`other standard therapies,
`local adverse effects
`
`Lack of comparisons with
`other standard therapies, local
`adverse effects, high cost
`
`Inconclusive results
`
`Clinical data limited to case
`series
`
`Clinical data limited to one
`open-label pilot study
`
`Vaccination, natural antimicrobial peptides Absence of published clinical
`data
`
`BPO = benzoyl peroxide.
`
`of action is believed to lead to greater patient adherence and to
`reduce the amount of antibiotic exposure and risk of P. acnes
`resistance.
`Lately, formulation technology has focused on providing
`more efficient penetration of the retinoids into the skin layers or
`greater stability to the retinoid molecules so that lower con-
`centrations of retinoids might afford better tolerability, but
`maintain good efficacy. These potential novel systems for agent
`delivery include microsponges, liposomes, nanoemulsions, and
`aerosol foams. A micronized formulation of tretinoin (0.05%)
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`gel has been developed that provides a more efficient delivery of
`tretinoin, because of its optimal particle size, no degradation by
`benzoyl peroxide, and better cutaneous tolerability than tretinoin
`microsphere (0.1%) gel without compromising efficacy.[21,22]
`Retinoic acid-loaded, solid, lipid nanoparticles represent an-
`other interesting alternative to reduce retinoic acid-induced
`skin irritation without reducing efficacy.[23] Retinol has a lower
`biologic activity but a better tolerability. Combination prod-
`ucts using retinol with substances with anti-inflammatory and
`antibacterial activity might increase this biologic activity.[24]
`
`2.1.2 Isotretinoin Therapy
`Oral isotretinoin was approved for use in acne in 1982.
`Targeting the four primary pathogenic factors of acne, it re-
`mains arguably the most effective acne medication available.
`Although comparative trials are missing, clinical experience
`confirms that the relapse rates after treatment with isotretinoin
`are the lowest among all the available therapies. Originally, it
`was reserved for severe, recalcitrant, nodular acne that was
`unresponsive to topical therapy. Although many authorities
`believe that isotretinoin should be reserved for severe acne not
`responding to appropriate antibiotics and topical therapy, the
`published data and opinion of some experts support systemic
`isotretinoin being considered as the first-line treatment for se-
`vere papulopustular, moderate nodular, and severe nodular/
`conglobate acne.[1,2,9-12,25,26] Reasons supporting oral
`iso-
`tretinoin as a first-line treatment for severe acne include clinical
`effectiveness, prevention of scarring, and quick improvement of
`a patient’s quality of life.
`The evidence on the best dosage, including cumulative dos-
`age, is rare and partly conflicting. In most trials, higher dosages
`have lead to better response rates whilst having less favorable
`safety/tolerability profiles. However, there is cumulative evi-
`dence that low-dose isotretinoin might be a useful treatment
`option for moderate acne.[26-28] Attempts to determine the cu-
`mulative dose necessary to obtain an optimal treatment re-
`sponse and low relapse rate have not yet yielded sufficient
`evidence for a strong recommendation. Research is also needed
`to investigate whether isotretinoin could be beneficial if used
`sooner for moderate cases. Although effective against severe
`acne, isotretinoin is associated with significant adverse effects,
`including cheilitis, dry skin and mucous membranes, epistaxis,
`increased risk of cutaneous Staphylococcus aureus infections,
`temporary worsening of lesions, photosensitivity, increased
`serum lipids, myalgias, hyperlipidemia, pseudotumor cerebri,
`and teratogenicity.[2] Associations with inflammatory bowel
`disease are controversial.[29,30] There are plausible biologic
`mechanisms by which retinoids might induce psychopathol-
`
`ogy.[2] A systematic review of isotretinoin use and depression
`and suicidal behavior published in 2007 did not find any evi-
`dence to support the notion that depressive symptoms or
`diagnosis increased after treatment, and some in fact, demon-
`strated a trend toward fewer or less severe depressive symptoms
`after isotretinoin therapy.[31] The picture is a complex one as
`depression and suicidal ideation occur with severe acne in the
`absence of isotretinoin treatment.[32,33] The current recom-
`mendation is that patients with severe acne with a history of
`attempted suicide should not automatically be refused iso-
`tretinoin but should be monitored for suicidal behavior after
`treatment has ended.[34] Claims of injury have fueled hysteria
`among laypersons about the use of this drug. Overwhelmed
`with worries of its potential adverse effects, the public forgets
`that withholding isotretinoin therapy is not without its own
`risks. Isotretinoin therapy can prevent lifelong and permanent
`physical and psychological scarring that comes as a matter of
`course with severe acne.[2,25,26,35] Over 20 million people
`worldwide have taken the drug, with several studies demon-
`strating its safety and few long-term adverse effects.[35]
`
`2.2 Antibiotics
`
`2.2.1 Topical Antibiotics
`How topical antibiotics improve acne has not been clearly
`defined, but they seem to act directly on P. acnes colonization
`and its subsequent proinflammatory effects on comedogenesis.
`The most commonly used topical antibiotics are clindamycin
`and erythromycin. However, studies on P. acnes resistance have
`highlighted the need for treatment guidelines to restrict the use
`of antibiotics in order to limit the emergence of resistant strains.
`It has been argued that the most likely effect of resistance is to
`reduce the clinical efficacy of antibiotic-based treatment regi-
`mens to a level below that which would occur in patients with
`fully susceptible flora.[36] Some trials have suggested a clear
`association between P. acnes resistance to the appropriate an-
`tibiotic and poor therapeutic response.[36] 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.[37]
`Decreased clinical efficacy of antibiotics for dermatologic
`conditions other than acne or for non-dermatologic infectious
`diseases appears as another major threat. Monotherapy with
`topical antibiotics is thus no longer recommended.[2,9-12,36-38]
`
`2.2.2 Systemic Antibiotics
`Although antibiotics have shown effectiveness in terms of
`reducing the number of acne lesions, most antibiotic courses are
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`not curative. The use of antibiotics for acne has been questioned
`owing to resistance concerns, especially since they are re-
`peatedly used for long periods at low doses. Furthermore, there
`is a low evidence level that oral antibiotics are more effective
`than topical preparations for mild-to-moderate facial acne.[39]
`Tetracyclines are the first-line oral antibiotic therapy in acne.
`Overall, there is insufficient evidence to support one tetra-
`cycline over another in terms of efficacy.[40] There could be no
`justification in continuing to use minocycline as a first-line
`therapy in acne because of an uncertainty safety profile and a
`lack of advantages over other tetracyclines (i.e. first-generation
`cyclines, doxycycline and lymecycline).[40,41]
`In the range of dosages investigated in the clinical studies,
`the tetracycline dosage seems to have no impact on efficacy.[40]
`Although two trials of subantimicrobial dosing (i.e. the pre-
`scription of low doses that are anti-inflammatory but not
`antimicrobial) have shown a reduction in the number of in-
`flammatory and non-inflammatory lesions,[42,43] the studies are
`too small to make reliable estimates of bacterial resistance that
`could be promoted by the lower doses used.
`As a consequence of resistance concerns, the use of oral
`antibiotics should be limited (indication, duration) and topical
`antibiotic monotherapy should be avoided.[2,9-12,36-38] Other
`recommendations are that we should use stricter cross-infection
`control measures when assessing acne in the clinic and combine
`any topical/systemic antibiotic therapy with broad-spectrum
`antibacterial agents, such as benzoyl peroxide.[11,36,43]
`Although oral macrolides like erythromycin may represent
`an alternative in patients who are intolerant or allergic to tet-
`racyclines and may be used in pregnancy, there is little evidence
`to support the use of other oral antibiotics (i.e. clindamycin,
`cotrimoxazole, quinolones).
`
`2.3 Benzoyl Peroxide
`
`Benzoyl peroxide is a safe and effective over-the-counter
`preparation that reduces the number of P. acnes by suppress-
`ing growth without the risk of resistance selection. Low con-
`centration (2.5% or 5%) benzoyl peroxide is recommended,
`since it is less irritating and there is no clear evidence that
`stronger preparations are more effective.[44] Single-agent ben-
`zoyl peroxide works as well as oral antibiotics. It has greater
`activity than topical tretinoin against inflammatory lesions.[45]
`The anti-acne activity and safety profile of benzoyl peroxide
`justifies its use as first-line treatment in mild to moderate
`forms of acne, more particularly in papular/pustular forms
`of acne.[12,46] Several studies suggest that the efficacy of ben-
`zoyl peroxide can be enhanced when used in combination
`
`with topical retinoids, antibiotics (essentially clindamycin[19,46]
`and, more recently, nadifloxacin[47]), and tertiary amines,
`such as an allylamine. However, a recent systematic review
`showed that combination products containing benzoyl per-
`oxide were only incrementally better than benzoyl peroxide
`alone.[48]
`
`2.4 Azelaic Acid
`
`Azelaic acid has both antimicrobial and anticomedonal prop-
`erties. The data on azelaic acid (15% or 20%) show an inferior
`efficacy compared with benzoyl peroxide[49,50] in reducing non-
`inflammatory lesions but a similar efficacy in reducing inflam-
`matory lesions.[49,50] There are very little data comparing the
`efficacy of adapalene, topical isotretinoin, or topical antibiotics
`with azelaic acid. Azelaic acid shows a trend towards a better
`tolerability/safety profile compared with benzoyl peroxide
`(5%),[49] topical adapalene,[50] and tretinoin.[51]
`
`2.5 Topical Dapsone
`
`Topical dapsone 5% gel offers documented efficacy for the
`reduction of both inflammatory and non-inflammatory acne
`lesions. Topical dapsone is superior to placebo but has yet to be
`compared with standard topical treatments. It has been proven
`safe, presenting none of the hematologic risks associated with
`oral dapsone. With regard to safety, the studies demonstrated
`that the concentrations of dapsone and N-acetyl dapsone re-
`main low and do not accumulate over time once steady state is
`reached. Topical dapsone 5% gel also appears to be safe to use in
`patients with glucose-6-phosphate dehydrogenase deficiency.[52]
`Data suggest the vehicle formulation enhances healing and
`contributes to tolerability, making topical dapsone 5% gel a
`worthwhile anti-inflammatory treatment for patients with
`mild-to-moderate acne.[53,54]
`
`2.6 Taurine Bromamine
`
`Taurine bromamine, the product of taurine and hypobro-
`mous acid, exerts anti-inflammatory and antibacterial properties
`against P. acnes and Staphylococcus epidermidis. In a double-
`blind investigation, the efficacy and safety of 3.5 mM taurine
`bromamine cream versus clindamycin gel were comparable.[55]
`These data suggest that taurine bromamine can be used as a
`topical agent in the treatment of acne, especially in patients who
`have already developed antibiotic resistance, but needs to be
`confirmed by further studies.
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`2.7 Chemical Peels
`
`The most common chemicals used include a-hydroxy acids
`such as glycolic acid and b-hydroxy acids such as salicylic
`acids.[1,56] In vitro data demonstrate that glycolic acid has mod-
`erate growth inhibitory and bactericidal effects on P. acnes.[57]
`Search of the literature revealed very few clinical trials of peels
`in acne;[56] a majority of these trials included small numbers of
`patients, were not controlled, and were open label. The evi-
`dence that is available does support the use of chemical peels in
`acne as all trials had generally favorable results despite differ-
`ences in assessments, treatment regimens, and patient pop-
`ulations. Notably, no studies of chemical peels have used an
`acne medication as a comparator.[56]
`
`2.8 Other Topical Therapies
`
`Salicylic acid is an exfoliant and is a component of many
`over-the-counter preparations. No studies support routine use
`of salicylic acid in preference to other topical therapies. Some
`data suggest that the addition of salicylic acid to other topical
`therapies (i.e. clindamycin plus benzoyl peroxide) may improve
`the clinical outcome.[58]
`An over-the-counter emollient foam, containing sodium
`sulfacetaminde 10% and sulfur 5% exhibiting moisturization
`properties as well as antibacterial activities against P. acnes
`in vitro has been shown to be effective in a limited series of
`patients with acne.[59] Further studies are obviously required to
`assess its usefulness.
`Recently, a single-blind, vehicle-controlled, pilot study
`showed positive results for resveratrol on acneic skin. Resver-
`atrol
`is a natural phytoalexin exhibiting activity against
`P. acnes as well as anti-inflammatory properties and is produced
`by some spermatophytes, such as grapes and other plants.[60]
`
`2.9 Oral Contraceptives
`
`All types of combined oral contraceptives seem to be effec-
`tive in reducing inflammatory and non-inflammatory acne le-
`sions, but there is no clear evidence that those containing ad-
`ditional cyproterone offered any further benefit.[61] Although
`there are few studies comparing combined oral contraceptives
`with other acne treatments, hormonal therapy is regarded as an
`excellent choice for women who need oral contraception.[9,61,62]
`However, dermatologists have historically been reluctant to
`prescribe oral contraceptives for acne because of long-standing
`recommendations requiring a preliminary pelvic examination
`and Papanicolaou smear before initiation of therapy. In recent
`
`guideline shifts, expert panels and major health organizations
`have reached a consensus that oral contraceptive provision no
`longer necessitates the performance of a pelvic examination and
`Papanicolaou smear.[63] Another Cochrane review failed to
`show any benefit of spironolactone for acne, based on limited
`studies.[64]
`
`2.10 Optical Treatments (Laser Therapy, Light Sources, and
`Photodynamic Therapy)
`
`Optical therapies that have been used to treat acne include
`broad-spectrum continuous-wave visible light (blue and red),
`intense pulsed light, pulsed dye lasers, potassium titanyl phos-
`phate lasers, photodynamic therapy (PDT), and pulsed diode
`laser.
`Light therapy is based on the observation that P. acnes is
`capable of synthesizing chromophores such as porphyrins.[65]
`Whereas blue light has been shown to photoinactivate P. acnes,
`it does not penetrate skin very far. On the other hand, red light,
`which is less effective at porphyrin activation, can reach deeper
`sebaceous glands.[66] Compared with light therapy, lasers have
`the ability to concentrate coherent light on a smaller area of
`tissue. Although there are some studies of the treatment of non-
`inflammatory lesions with laser and light sources, the published
`evidence is still very scarce. There is conflicting evidence regard-
`ing the efficacy of red light against inflammatory lesions com-
`pared with placebo. Blue light has superior efficacy against
`inflammatory lesions/total lesions compared with placebo.[67,68]
`The combination of blue-red light therapy may act synergistically
`and be more effective at reducing the number of inflammatory
`lesions.[67] There is insufficient evidence regarding the efficacy of
`all other light and laser interventions compared with placebo.[69]
`PDT refers to the use of aminolevulinic acid, methyl-
`aminolevulinic acid, or other photosensitizing agents to en-
`hance the effect of subsequent light or laser therapy. Topical
`application of these molecules results in significant build-up of
`porphyrins in sebaceous glands and the efficacy of PDT in acne
`is believed to be related in part to a decrease in sebaceous gland
`activity following light activation of the photosensitizer. Most
`trials of PDT showed some benefit, which was greater with
`multiple treatments, and better for non-inflammatory acne
`lesions. However, the improvements in inflammatory acne
`lesions were not better than with topical adapalene 1% gel.[70]
`There are also some studies showing that treatment with the
`infrared 1450 nm diode laser reduces inflammatory acne lesions
`and may provide a long-term remission in acne. The presumed
`mechanism of acne improvement is through heating of the se-
`baceous gland and reduced sebaceous gland activity.[71]
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`A photopneumatic platform (IsolazÔ; Aesthera Corpo-
`ration, Pleasanton, CA, USA) combining vacuum pressure
`with a broadband light source device has also been shown to
`improve mild to moderate inflammatory and comedonal
`acne.[72,73] The vacuum suction raises target structures in the
`dermis closer to the surface of the skin prior to exposure, al-
`lowing for more efficient energy transmission.[72,73]
`The clinical development of optical therapies is also limited
`by adverse effects, including pain, erythema, edema, crusting,
`hyperpigmentation, and pustular eruptions.[69,70]
`Thus, although optical therapy may improve acne initially, a
`standardized treatment protocol, longer term outcomes, com-
`parisons with conventional acne therapies, and widespread
`clinical experience are still lacking. Accordingly, optical treat-
`ments are not included among first-line treatments,[69,70] espe-
`cially with current high costs.
`
`2.11 Complementary and Alternative Medications
`
`The use of complementary and alternative medications
`(CAMs) in acne is widespread and there is a growing public
`demand for the application of CAMs to acne.[74,75] A systematic
`review of CAMs for the treatment of acne in 2006 identified
`15 randomized controlled trials covering various approaches
`such as Aloe vera, pyridoxine, fruit-derived acids, kampo
`(Japanese herbal medicine), and ayurvedic herbal
`treat-
`ments.[76] Although mechanisms of potential benefit for some
`of the CAMs were biologically plausible, the included studies
`were generally of poor methodologic quality and inconclusive.
`Analogously, a systematic review of botanical products for
`acne failed to provide any good-quality evidence of bene-
`fit.[74,77] There is no controlled trial evaluating the efficacy of
`homeopathic remedies in acne.[75]
`
`2.12 Nutrition
`
`quired to determine if dietary modification will reduce long-
`term acne burden.
`
`2.13 Promising Therapies
`
`In the more distant future, vaccination with killed P. acnes
`and sialidase-based vaccines may lead to novel avenues of im-
`munologic intervention.[2,83]
`Over the past years, natural antimicrobial peptides have
`attracted considerable interest as a new type of antimicrobial
`agent for several reasons, including their relative selectivity
`towards targets (microbial membranes), their rapid mechanism
`of action and, above all, the low frequency in selecting resistant
`strains. Several antimicrobial peptides including epinecidin-
`and granulysin-derived peptides, omiganan pentahydrochloride,
`and frog skin peptides have been found to exert activity against
`P. acnes.[84,85] The anti-inflammatory effects combined with
`potent antimicrobial activities and O2-production-inhibition
`activities of cathelicidin indicate its potential as a novel ther-
`apeutic option for acne.[85]
`The strong activity of lauric acid (C12 : 0) against P. acnes,
`a middle chain, free fatty acid commonly found in natural
`products, also highlights its potential as an alternative treat-
`ment option to the antibiotic therapy of acne.[86]
`
`3. Conclusions
`
`Acne continues to remain a challenge to practicing clinicians
`and dermatologists. As the pathogenesis of acne lesions is
`complex, so is the myriad of available treatments. Despite sig-
`nificant developments, oral isotretinoin remains so far the most
`effective acne medication available. Given the restrictions
`placed on the use of isotretinoin and the increase in antibiotic-
`resistant strains of P. acnes, there is a high clinical need for new
`treatments.
`
`Some level of evidence supports the association of acne and
`high glycemic loads, certain dairy products (especially milk),
`ingestion.[78,79] The apparent
`and refined sugar product
`absence of acne in native non-Westernized populations, the
`Kitavan Islanders of Papua New Guinea and the Ache´ hunter-
`gatherers of Paraguay,[80] has led to the proposal that high
`glycemic loads in a Western diet could have a role in acne,
`perhaps through hyperinsulinemia leading to increased an-
`drogens, increased insulin-like growth-factor-1, and altered
`retinoid signaling.[80-82] A randomized controlled trial showing
`that a low glycemic load diet might improve acne provides
`preliminary support for this theory.[81] Future studies are re-
`
`Acknowledgments
`
`No sources of funding were used to prepare this article. The author has
`no conflicts of interest that are directly relevant to the content of this
`article.
`
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