New Treatments for Acne

New Treatments for Acne

The treatment of acne continues to be a challenge to practicing clinicians and dermatologists. Among the available treatment oral isotretinoin remains the more effective acne medication and oral antibiotics the more prescribed treatments. Given the restrictions placed on the use of isotretinoin and the increase in antibiotic resistant strains of Propionibacterium acnes, there is a high clinical need for new treatment.

Acne pathogenesis is a complex mechanism in which different factors play a role. In the recent years the increased knowledge of the acne pathogenesis lead to the development of new and targeted drugs such as drugs blocking the activation of Toll-like receptor, PPAR antagonist, inhibitors of IL-1α and leukocyte chemotaxis, the antagonist of pro-inflammatory cytokines, the inhibitors of the production of reactive oxygen species and so on. A number of molecules named with abbreviations are studied and registered in the official sites.

Another problem is the tolerability of the currently available topical. In order to increase tolerability of these topical and of consequence to improve the patients’ compliance, new vehicles have been tested.

Finally, also a vaccination killed P. acnes may lead to an innovative approach of acne management.

This indicates that the research in the field of acne is very active and so it is probable that in the next years several new drugs will hit the market. This article reviews novel treatments in the management of acne.


Acne is a common chronic inflammatory dermatosis that affects more than 85% of adolescents and approximately 95% of the population [1].

The increased knowledge about the mechanisms of action regulating the development of acne lesions have stimulated further research in the hope of finding new active drugs [2].

A number of inducing factors, acting on a genetic predisposition, pave the way to the development of the following pathogenic events which lead to formation of acne lesions:

  1. hypercornification of the infrainfundibulum and sebaceous duct,
  2. hyperactivity of sebaceous glands and hyperseborrea,
  3. hyperactivity of P. acnes,
  4. inflammation and immunological host reaction.

Anatomically, the pilosebaceous unit is the cutaneous entity where the above mentioned events occur.

Hypercornification of the infrainfundibulum has been considered for a long time as the first of the sequence of events ending in the formation of inflammatory acne. More recent data have demonstrated the presence of inflammatory cells around the follicle before the appearance of the microcomedone [3]. As factors inducing hypercornification like androgens, growth factors, P. acnes and IL-1α may also directly induce inflammation, probably hypercornification and inflammation concur simultaneously at the start of the process leading to acne.

Clinically acne lesions are mainly localized on face, back and chest.

During active phase acne vulgaris is characterized by a mixture of different types of non inflammatory and inflammatory lesions which are concurrently present giving the dermatosis a polymorphic aspect. Non inflammatory lesions, also called comedones, include open comedones (blackheads) and closed comedones (whiteheads) depending on the presence or not of an evident opening to the surface of the skin. Inflammatory acne lesions may be superficial and relatively small like papules and pustules or deep and larger like nodules.

After the resolution of the acute inflammatory phase erythematous macules, postinflammatory hyperpigmentations and post-acne scars can persist. Post-acne scars occur in up to 90% of the acne patients and they are socially and estetically relevant in 22% of the sufferers [4].

On the basis of acne severity, current guidelines for acne treatment suggested to use a combination of topicals (retinoid plus antimicrobial agents) in patients affected with mild-tomoderate papulopustolar acne and a systemic antibiotic, usually tetracyclines, associated with topicals in patients with severe papulopustolar/moderate-to-severe nodular acne. Oral isotretinoin can be used in patients not responsive or relapsed after the use of previous systemic treatments [5].

Given that many current treatments have potential side effects as teratogenicity of oral isotretinoin and experience-reduced responsiveness as the increase of antibiotic resistance, there is a need to develop safer and effective options to treat this common disorder. Moreover some of the treatments commonly used are contraindicated in certain groups as pregnant women.

The Centers for Disease Control defined a chronic disease as a disease “that in general terms, has a prolonged course, that does not resolve spontaneously, and for which a complete cure is rarely achieved” [6]. As acne vulgaris is characterized by prolonged course, pattern of recurrences or relapse, manifestation as acute outbreaks or slow onset, psychological and social impact, according to the aforementioned definition, it can be considered a chronic disease.

Based on that, it is reasonable to use all the available “tools” to prevent the recurrences of acne. Maintenance therapy represents an adequate strategy to maintain the achieved therapeutical results and to minimize the risk of relapse [6]. The management of acne is a problem also in term of costs. In fact there is a tremendous number of visits made to both generalists and dermatologists for the treatment of acne. The direct cost of acne treatment is estimated to be more than $1 billion per year and approximately $100 millions are spent on over-the-counter acne medication [1]. To follow the authors propose a review of some emerging treatments is acne field.

Oxidative stress in acne

The results of a recent study suggest that also oxidative damage may play a role in the pathogenesis of acne. In fact the serum levels of malondialdehyde and xanthine oxidase activity in patients with acne vulgaris resulted significantly higher than those of the healthy controls. A significantly lower superoxide dismutase and catalase activity has been found in the acne group than in the control group. It shows that in acne patients is present an alterations in the antioxidant defence system [7].

Fullerene as  a new treatment for acne

Fullerene is a spherical carbon molecule with strong radical sponge activity that penetrates deep into the epidermis. Oxidative stress plays a role in acne formation, suggesting that oxygen radical scavengers are potential therapeutic agents. In a vitro study, fullerene significantly decreases sebum production by 27.4%, suggesting another possible pathway of fullerene’s effect on acne [8]. On the other hand, fullerene seems not to have antibacterial activity against P. acnes.

In an open trial including 11 patients with mild to moderate acne, fullerene 1% gel was given twice a day for 8 weeks [8]. At the end of the treatment comedos’ number decreased only in 3 patients and this reductions was not statistically significant. Inflammatory lesions decreased in a statistically significant way in 9 patients. Also pustules decreased to 87.6% indicating that fullerene strongly suppresses neutrophil infiltration, possibly through its potential antioxidant effect on skin cells.

No apparent side effects were experienced by all patients.

The authors concluded that fullerene has a mild effect on acne and it could be used as a skin care product for acne patients.

Recently, fullerenol, a novel polyhydroxylated fullerene, with many hydroxyl groups capable of potent radical-scavenging activity has been developed. Vitro results suggest that fullerenol could be a beneficial skin care reagent for controlling acne vulgaris by suppressing sebum in the inflammatory response and by reducing P. acnes lipase activity [9].

Taurine Bromamine

Taurine bromamine (TauBr) is a haloamine generated by eosinophil and neutrophils at the site of inflammation, that has anti-inflammatory and anti-oxidant properties [10]. In fact TauBr reacts and inactivates H2O2, induces the synthesis of heme oxygenase-1 (a stress inducible enzyme with anti-inflammatory and anti-oxidant capacity), suppresses the productions of cytokines and chemokines, and inhibits the activation of NF-kB. Moreover TauBr has strong microbicidal activity and, at non-cytotoxic concentrations, is able to kill P. acnes. In a double blind trials 3.5 mM TauBr cream was evaluated versus 1% clindamycin gel [11]. Both were applied twice-a-day for 6 weeks. Forty patients affected by mild to moderate inflammatory facial acne were enrolled. After 6 weeks of treatment, comparable reductions of acne lesions, 65% and 68%, were observed respectively in the TauBr and clindamycin groups. No adverse events were observed. The authors support the concept that TauBr can be used in the treatment of acne, especially in patients who are already developed antibiotic resistance.

Anti-microbial molecules

P. acnes, a gram-positive anaerobic bacterium, attaches to pilosebaceous gland wall and secretes an extracellular polysaccharide substance, the biofilm. This biofilm acts as a barrier between the cell populations underlying and the exterior environment. P. acnes is the major contributor of the inflammation as it releases chemotactic factors, pro-inflammatory cytochines and corticotrophin releasing hormone (CRH), increases the expression and activation of Toll-like receptors, produces lipases and Reactive Oxygen Substances (ROS), stimulates lipogenesis, lipid peroxidation and comedogenesis, drives to production of enzymes such as metalloproteases.

Moreover membrane fractions of P. acnes could act as superantigens, amplifying the inflammatory reaction [12-16].

Due to the important role of P. acnes in the pathogenesis of acne, antibiotics have frequently used in the treatment of acne.

Among topicals clindamycin and erythromycin are the most popular. Other types of topical antibiotics are available in different countries according to the local national licences, such as nadifloxacin, tetracyclines, clarithromycin and azithromycin. Among systemic antibiotics cyclines and macrolides are the most used. Recently a decrease in term of efficacy of these antibiotics, erythromycin in particular, have been detected due to the development of antibiotic-resistant propionibacteria [17].

The management of antibiotic-resistant, and of consequence how to used antibiotics in acne treatment, is a delight question. Anyway the presence of propionibacteria resistant to the common used antibiotics has led to the development of new molecules with antimicrobial properties.

Picolinic Acid

Picolinic acid is an intermediate metabolite of the amino acid tryptophan that plays a role in zinc transport [18]. It chelates transition metal ions and is involved in the absorption and transport of transition metal ions. This molecule seems to work by perturbing zinc binding in zinc finger proteins and therefore leads to an alteration in chemokine expression. It has antibacterial properties and also modifies the immune response. In a open-label study picolinic acid 10% gel was applied twice daily on the face of 15 acne patients over a 12 week time [18]. A reduction of 58.2% (P < 0.001) in mean total lesion count, 55.5% (P < 0.001) in mean inflammatory lesion count and 59.7% (P < 0.005) in non-inflammatory lesion count was seen in this population. No serious adverse events or clinically significant changes in laboratory values were noted. The anti-inflammatory and antibacterial properties of lauric acid are already known, whereas recently also the anti-inflammatory and antibacterial properties of capric acid were investigated. Although to a lesser extent than lauric acid, also capric acid has bactericidal and anti-inflammatory activities against P. acnes probably through the inhibition of NF-κB activation and the phosphorylation of MAP kinases [19].


Calcipotriene is a vitamin D topical cream that seems to have antimicrobial properties and comedolytic activity. A study evaluating the effects of calcipotriene on the face and on the bacteria that cause acne is currently in phase of recruiting participants. In this study calcipotriene is compared with a placebo cream in a double blind way [20, 21].


Acne vaccine, obtained by inactivated P. acnes, targets a cell wall-anchored sialidase of P. acnes. Sialidases are thought to be used by P. acnes in order to catabolise sialoglycoconjugates to obtain sialic acids that ultimately act as substrates for energy production. It is also probable that sialidase may facilitate the adhesion of P. acnes to sebocytes [22].

Nakatsuji et al. demonstrated that intranasal immunization of mice with this vaccine generated in vivo protective immunity against P. acnes. The antibodies elicited attenuated IL- 8 production in human sebocytes but without effect on P. acnes growth. So, the authors suggested that these antibodies exhibit anti-inflammatory properties sufficient for clinical improvement but without an antimicrobial effect [23].

The question is whether the results obtained in mice can be translated to the human model and if these antibodies have the potential to cross-react with other human cells. Beside these killed pathogen-based vaccines various immunization-based approaches have been developed over the last decades, including monoclonal antibodies to the Christie, Atkins, Munch-Peterson factor of P. acnes and anti-Toll-like receptors vaccines.

The role of P. acnes in acne confers legitimacy on the possible benefits of immunizationbased approaches, which may represent a solution for limiting the development of antibioticresistant P. acnes [24].

Thiazolidinedione Derivatives

Propionibacterium acnes infections are difficult to treat due to the presence of biofilms at the infection site and the associated resistance towards conventional antimicrobials.

A recent study has clearly demonstrated the effect of two thiazolidinedione derivatives on Propionibacterium acnes biofilm formation in vitro. The compounds were shown to have a moderate to strong anti-biofilm activity when used in sub-inhibitory concentrations. These compounds do not affect P. acnes attachment but lead to increased dispersal of biofilm cells. This dispersal results in an increased killing of the P. acnes biofilm cells by conventional antimicrobials [25].

Antimicrobial Peptides

Natural antimicrobial peptides could be considered as a new type of antimicrobial reagents 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. Cathelicidines are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity [26].

Cathelicidin-BF has been purified from snake venoms of Bungarus fasciatus. It is synthesized by GL Biochem (Shanghai) Ltd. In vitro cathelicidin-BF exerts a rapid antimicrobial activity against P. acnes. Its MIC against two P. acnes strains is 4.7 μg/ml, which is comparable to the anti-P. acnes potential antibiotics of clindamycin (2.3 μg/ml).

Cathelicidin-BF was found to inhibit O2 - production induced by P. acnes. As a consequence it has anti-inflammatory properties because reduce the production of cytokines (such as IL-8, TNF-alpha, IL-1β and MCP-1) induced by O2 -. In vivo anti-inflammatory effect of cathelicidin-BF was confirmed by relieving P. acnes-induced ear swelling and granulomatous inflammation in mice [26].

A designed peptide named LZ1, with 15 amino acid residues, contains strong antimicrobial activity against Propionibacterium acnes. The minimal inhibitory concentration against three strains of P. acnes was only 0.6 μg/ml, which is 4 times lower than that of clindamycin. In experimental mice skin colonization model, LZ1 significantly reduced the number of P. acnes colonized on the ear, P. acnes-induced ear swelling, and inflammatory cell infiltration. It ameliorated inflammation induced by P. acnes by inhibiting the secretion of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. Combined with its potential bactericidal and anti-inflammatory properties, simple structure and high stability, LZ1 might be an ideal candidate for the treatment of acne [27].


ProOxy facial spray is a topical 15% Oxygen solution. A phase I open label pilot clinical trial evaluating the efficacy and safety of ProOxy spray in the treatment of moderate facial acne has been recently completed. In this study the spray were used twice daily for 3 months [28].


A mainstay in the pathogenesis of acne involves the overgrowth and proliferation of skin micro-organisms, primarily Proprionibacterium Acnes. Long term antibiotic therapy is usually prescribed for a period of 3 to 6 months or more. Povidone Iodine with its antiseptic property represents a promising avenue for the elimination of Proprionibacterium Acnes without the associated problems of long term antibiotic use, and the development of antibiotic-resistance. It is cosmetically acceptable, affordable, and easy to use. A phase II study with the aim to evaluate efficacy and safety of 3% Povidone-Iodine cream (Repigel- Mundipharma Pte Ltd.) versus placebo applied twice a day during 8 weeks has been registered in official site. Actually this study is not yet open for participant recruitment [28].

Anti-inflammatory treatments for acne


Zileuton (Zyflo™) directly inhibits lipogenesis in human sebocytes and blocks the activity of 5-lipoxygenase, an enzyme involved in the biosynthesis of the pro-inflammatory lipids leukotriene B4 (LTB4) and prostaglandin-E2 by arachidonic acid. LTB4 is considered to be a major player in the development of tissue inflammation, and it is also a natural ligand for PPAR-alpha [29].

In the first pilot clinical study with 10 patients with papulo-pustular acne Zileuton 4 x 600 mg/day per os for 3 months decreased the acne severity index in a time-dependent manner being 41% of the initial score at week 12 (P < 0.05). This was mostly due to a decrease of the number of inflammatory lesions, corresponding to 29% (P < 0.01). In addition total sebum lipids significantly decreased (35%, P < 0.05) [30].

These data were in agreement with a phase II multicentric clinical study including 101 patients with moderate-to-severe inflammatory facial acne, which showed an average reduction on the total number of lesions of 25.3% in the Zileuton group and 16.4% in the placebo group [28]. In all studies Zileuton was found to be safe and well tolerate.


Afamelanotide is a super potent α-melanocyte-stimulating hormone (α-MSH) analogue [31]. α-MSH is a melanocortin peptide that increases skin pigmentation during ultraviolet light-mediated tanning. However, many experimental in vitro and in vivo studies have demonstrated that α-MSH have also anti-inflammatory and antioxidative properties [32].

It is further reported as α-MSH have anti-bacterial effects against gram-positive bacteria, but it is unknown if it has antimicrobial effect also against P. acnes [33]. On the other hand, α-MSH increased lipid synthesis by human sebocytes in vitro [34]. In a phase II open-label pilot study, afamelanotide 16 mg was given subcutaneously to 3 patients with mild to moderate facial acne [31]. Two patients received 3 injections at 3-week intervals, one patient 2 injections at 4-week interval. The total lesion number, as well as the number of inflammatory acne lesions, declined in all patients 56 days after the first injection. Total lesions decreased from 68 to 30 and inflammatory lesions from 46 to 23.7. The number of non-inflammatory lesions declined dramatically in 2 patients, while in the third patient only a transient improvement was seen. No adverse events, except mild and short-term fatigue in one patient, were observed. Important abnormalities in laboratory data were not detected. A placebo-controlled trial on a much larger number of acne patients will be needed to confirm the preliminary data and to determinate the optimal dose of afamelanotide capable to suppressing skin inflammation.


Apremilast is an oral PDE4-inhibitor agent that has been shown to inhibit the production of TNF-α, IL-8 and neutrophil infiltration. It is usually use to treat different kind of arthritis. A phase II, open-label, single-arm pilot study evaluating the efficacy and safety of apremilast in the treatment of moderate to severe acne has been recently completed [28]. In this study 20 mg of apremilast was assumed twice a day for 12 weeks.


XOMA 052 (gevokizumab) is a recombinant humanised anti-interleukin 1β antibody that seem efficacy to treat different kind of disease such as diabetes, arthritis and Behcet’s disease. It is a sterile solution administered subcutaneously on day 0, 28 and 56. A phase II, randomized, double-blind, placebo controlled study to evaluate the efficacy and safety of gevokizumab in subjects with moderate to severe acne is registered and currently in phase of recruiting participants [28].

Ectopeptidase Inhibitors

Inhibitiors of dipeptidylpeptidase IV and APN stimulate the expression of IL-1 receptor antagonist, thus they could be expected to reduce primarily comedogenesis and, secondarily, inflammation [35]. In vitro these inhibitors suppressed proliferation, enhanced terminal differentiation and slightly decreased total neutral lipid production, and suppressed proliferation and IL-2 production of P. acnes-stimulated T cells. Moreover the level of IL-1 receptor antagonist results significantly up-regulated.

Other new therapies for acne


Talarozole (R115866-Rambazole™) is an inhibitor of cytochrome P450-mediated catabolism of endogenous all-trans retinoic acid in the skin. So it enhances intracellularly the endogenous levels of all-trans-retinoic acid. By virtue of this property, and the proven positive effects of retinoids in the treatment of acne, talarozole could potentially be an useful drug for acne [28].

It was developed by Barrier Therapeutics Inc initially under license from Johnson and Johnson and after acquired by Stiefel Laboratories Inc (GlaxoSmithKline) [36]. A phase II clinical trial of an oral formulation of talarozole in patients with psoriasis and acne, and a phase I clinical trial of a topical formulation have been completed [37].

Oral talarozole 1 mg once daily for 12 weeks was assumed by 17 males affected by moderate to severe acne in a phase II trial. At the end of the treatment a mean reduction in inflammatory lesion count of 77.4% (P < 0.001), in non-inflammatory lesion count of 58.3% (P < 0.001) and in total lesion count of 76.0% (P < 0.001) was observed. Nine patients complained of side effects, mainly eczema and stomach discomfort, but they were mild in most of the cases. The authors concluded that talarozole is efficacious in acne treatment and well tolerate [38].

As far as topical formulation is concerned, gels containing talarozole (0.35% and 0.07%) were applied once daily for 9 days on the buttock of 16 healthy patients in a phase I, doubleblind vehicle-controlled study [39].

Talarozole treatment increased the mRNA expression of cellular retinoic acid binding protein 2 (CRABP29), cytokeratins (KRT4), CYP26A1 and CYP26B1 dose dependently, and decreased the expression of KRT2 and IL-1alpha compared with vehicle-treated skin. Both the two examined dosages showed a low irritancy [39].

An European placebo-controlled Phase II trial evaluating a topical containing talarozole 0.35% administered once-daily for 12 weeks in 80 acne patients has been conducted. Twenty-five% of patients in talarozole group and 8% in placebo group resulted to be clear or almost clear [28].

Cortexolone 17α-Propionate

Cortexolone 17α-propionate (cortodoxone) is a new and the first topical anti-androgen that competes at the human androgen-receptor level. It seems to have also mild antiinflammatory properties.

A randomized, double-blind, parallel-group, comparative trial, with placebo and tretinoin 0.05% cream, has been performed to evaluate the safety and efficacy of 8 weeks treatment with cortexolone 17α-propionate 1% cream applied once a day in acne patients [40].

Seventy-seven patients with mild to moderate facial acne were enrolled in the study. Cortexolone 17α-propionate 1% cream decreased the total lesion count and inflammatory lesion count; the improvement was significantly better than placebo. In comparison with tretinoin, cortexolone 17α-propionate 1% cream was always clinically more effective without reaching a statistically significant level.

The time to reach 50% improvement showed significant differences among the groups with a median time of 42.5 days for cortexolone 17α-propionate 1%, 44.0 days for tretinoin and 57.0 days for placebo.

A total of 8 subjects (11%) experienced 14 adverse events which were distributed as follows: 5 in placebo group, 6 in tretinoin group and 3 in cortexolone 17α-propionate group. None was judged serious to required treatment discontinuation.

A double-blind, placebo-controlled, dose-escalating Phase II trial in 360 patients with mild-to-moderate facial acne is ongoing to evaluating the safety and efficacy of cortexolone 17α-propionate for 12 weeks [28].


Epigallocatechin-3-Gallate (EGCG) is the major polyphenolic constituent of green tea know as a potent anti-carcinogenic, anti-inflammatory, anti-proliferative and anti-microbial activities. Also anti-androgenic properties have been reported.

In SEB-1 sebocytes EGCG reduces sebum production by modulating AMPK-SREBP-1 signalling pathway and reduces inflammation by suppressing the NK-kB and AP-1 pathway. Moreover EGCG decreases the viability of P. acnes, thus targeting almost all the pathogenic feature of acne.

In a 8-week randomized, split-face, clinical trial EGCG improved acne and it is well tolerated [41].

Tea tree oil gel is also under study in the treatment of mild to moderate facial acne. In a phase II open label study the gel is applied twice daily for 12 weeks. Oligonucleotides Inhibition of the expression of androgen receptor by antisense oligonucleotides reduces in vitro the enhanced proliferation of sebocytes challenged by testosterone and DHT [42]. They could be consider a novel strategy for the blockage of the androgen receptor and could be represent a specific therapeutic approach in androgen-associated acne.

Natural products - Homeopathic medicine

A long list of natural product have been tested in the treatment of acne and in general in the treatment of cutaneous disease, including green tea, essential oil, various plant extracts, etc.

Studies on cell lines revealed that flavonoid, alkaloid, essential oil, phenol and phenolic compound, tannin, xanthone and xanthone derivative, and the bisnaphthquione derivative are effective in treatment of acne. Animal studies showed that diterpene acid, phenylpropanoid glycosides, acteoside and flavonoids have anti-inflammatory activity. Eleven human studies revealed that Camellia sinensis has 5α-reductase inhibitory and anti-inflammatory activities. Also anti-bacterial effect has been shown by oleoresin of Commiphora mukul [43].

Below we have listed only some of these studies just to underline how the research of new anti-acne molecules derived from nature is active.


Resveratrol is a natural phytoalexin produced by some spermatophytes, such as grapes and other plants. It exhibits activity against P. acnes as well as anti-inflammatory properties [44]. In a pilot single-blind study including 20 patients with facial acne resveratrol incorporated in a carboxymethylcellulose-based gel was applied daily on the right side of the face for 60 days.

As a control the hydrogel vehicle was applied to the left side [44]. Clinical evaluation showed a reduction in the acne score of 53.47% on the resveratrol-treated sides and of 6.10% on the vehicle-treated sides. No adverse events were registered. The authors concluded that resveratrol could be a valid alternative in acne treatment. This effectiveness should be tested at different concentration and formulation, and in a larger group of patients.


Curcumin in the vehicles significantly inhibited the growth of P. acnes in the skin when evaluated by the bioluminescence assay [45].

Ethanolic Rosemary Extract

Ethanolic rosemary extract (ERE) has been showed to significantly suppress the secretion and mRNA expression of pro-inflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes-stimulated monocyte THP-1 cells. In vivo mouse model intradermal injection of ERE attenuated the P. acnes-induced ear swelling and granulomatous inflammation. Further studies are needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes-induced inflammation [46].

Essential Oil and Aromatherapy

A randomized controlled trial involving 192 participants divided in 3 groups (treatment with essential oil-aromatherapy-wait list control) has been provided high-quality evidence of the effectiveness of essential oil and aromatherapy in the treatment of acne [47].

Marine-Derived Ingredients

Potential benefits may be offered also by natural, marine-derived ingredients such as those derived from brown seaweed (Laminaria digitata) and a novel seaweed oligosaccharidezinc complex (SOZC) [48].

Homoeopatic Medicine

The efficacy of some lesser known homoeopatic medicines in acne treatment has been recent assessed in open label phase I studies. Zingiber officinalis are pills to assumed 4 times a day for 7 days. The same is for azadurachta indica and lappa arctium [28].

Instrumental treatments

Headheld Heat Device

A phase 4 open label study comparing a popular handheld heat devised and a topical treatment with BPO 4% in the treatment of individual acne lesions is currently registered under the sponsoritation of the University of British Columbia [28].

Acleara Needle Insert

A open-label study assessing the efficacy of Acleare Needle Insert in acne vulgaris has been completed. Fifteen subjects were enrolled. Each subject could have up to 5 lesions treated with this system and received up to 3 follow up visits [28].

Clear Device

Clear device is a light based devise. A clinical research, involving 50 patients, assessed the efficacy of this device to treat mild to moderate inflammatory acne and determined if the patients are able to use the device properly. Two sessions a week for 4 weeks, for a total of 8 sessions, and 2 follow-up visits were performed. The patients treated themselves with the clear device. The average improvement of acne lesions was 56.7% after one month and 57.7% after three months [28].

KLOX Biophotonic System

An opel label split face phase III study evaluating KLOX Biophotonic System versus no treatment in moderate to severe acne is ongoing. This system provides the application of KLOX KLGA0105-01 photo-convert gel and after the use of KLOX THERA lamp. This procedure is performed twice a week for 6 weeks followed by a 6 week follow up period [28].