Aetna considers photodynamic therapy (e.g., the ClearLight Acne PhotoClearing System, Omnilux Blue Photo Dynamic Therapy) experimental and investigational for the treatment of acne because of insufficient evidence of its effectiveness in comparison with established treatments for acne.
Aetna considers photodynamic therapy with topical aminolevulinic acid (Levulan Kerastick) experimental and investigational for the treatment of acne because of inadequate evidence of its effectiveness for this indication in comparison with established treatments for acne. See also CPB 0567 - Actinic Keratosis Treatments.
Aetna considers laser (e.g., the Candela Smooth Beam Laser System, fractional photothermolysis) experimental and investigational for the treatment of acne because its effectiveness for this indication has not been established.
Aetna considers intense pulsed light experimental and investigational for the treatment of acne because its effectiveness for this indication has not been established.
Aetna considers photopneumatic therapy experimental and investigational for the treatment of acne because its effectiveness for this indication has not been established.
The ClearLight Acne PhotoClearing (APC) System (Lumenis, Yokneam, Israel) is a light-based method of treating acne. According to the manufacturer, light in the violet-blue spectrum penetrates the skin and destroys surface and ductal Propionibacterium (P.) acnes bacteria. The manufacturer states that this spectrum of high-intensity light triggers the proliferation of endogenic porphyrins, which attack and destroy P. acnes bacteria within the skin. The manufacturer states that a typical treatment regimen consists of 8 treatments over 4 weeks.
The manufacturer's website cites the results of a multi-center clinical study to examine the effects of ClearLight treatments on more than 120 patients at 6 centers. The investigators used a high-intensity, 400 watt, enhanced (407 to 420 nm) metal halide lamp to deliver light to the acne-affected locations. The website reports that, after 8 bi-weekly treatments, 80 % of the patients with mild to moderate papulo-pustular acne showed significant improvement of non-inflammatory, inflammatory and total facial lesions. Inflammatory lesion count decreased by a mean of more than 60 %. Two weeks after the last treatment, the lesion count decreased by nearly 70 %. No side effects of the treatment were observed. However, this study has not been published in peer-reviewed medical literature.
The ClearLight was cleared by the U.S. Food and Drug Administration (FDA) based on a 510(k) application. Hence, the manufacturer was not required to provide the type of evidence of effectiveness that would be required to support a pre-market approval application (PMA). The manufacturer's website states that additional multi-center studies are underway to further support the efficacy of ClearLight technology in treating acne.
Based on the lack of peer reviewed published medical literature on the effectiveness of high intensity blue-spectrum (407 to 420 nm) light in acne treatment, the ClearLight System is considered investigational and experimental for this indication. Evidence-based guidelines from the Institute for Clinical Systems Improvement (2003) concluded that “[c]linical studies” of the ClearLight System “to date, are limited” and that “[o]utcome data are insufficient.”
Omnilux Blue Photo Dynamic Therapy (Photo Therapeutics Ltd., Cheshire, UK) is a method of photodynamic therapy similar to the ClearLight in that it involves the application of light in the blue spectrum. Omnilux Blue utilizes a panel of over 1,700 focused diodes to deliver 408 nm wavelength blue light that closely matches the peak absorption qualities of the targeted P. acne bacteria. The manufacturer states that this blue light creates a highly toxic environment for the superficial P. acne bacteria, which induces bacterial death and clears the skin from acne. Like the ClearLight, Omnilux Blue Photo Dynamic Therapy was cleared by the FDA based on a 510(k) pre-market notification. There is insufficient published scientific evidence evaluating the Omnilux Blue Photo Dynamic Therapy.
The Candela Smooth Beam Laser System differs from the ClearLight in that the former uses laser, which is light of a single wavelength. In contrast, the ClearLight uses light of a band of wavelengths in the ultraviolet-blue spectrum.
There have been a number of recently published studies of laser therapy of inflammatory acne. These studies, however, have been small and have not included comparisons with established treatments for acne vulgaris. In addition, given the small size and limited duration of published studies, there are unanswered questions about the generalization of the findings, about uncommon side effects, and the durability of results of laser treatments.
There are 2 published randomized controlled clinical studies of laser therapy of acne vulgaris. Neither study involved the Smooth Beam Laser System. These studies involved pulsed lasers using other wavelengths. Although one study (Seaton et al, 2003) (n = 41) reported positive results 12 weeks following a single treatment, another study (Orringer et al, 2004) (n = 40) reported no effect of laser treatments after 12 weeks. Thus, the effectiveness of laser for the treatment of acne has not been established.
Borelli and colleagues (2005) stated that the effectiveness of laser for the treatment of acne is still uncertain, photodynamic therapy shows promising results, but with marked adverse effects such as destruction of sebaceous glands. This is in agreement with the observations of Bhardwaj et al (2005) who noted that an evolving understanding of laser-tissue interactions involving P. acnes-produced porphyrins, and the development of infrared non-ablative lasers to target sebaceous glands, has lead to the development of an escalating number of laser, light and radiofrequency devices for acne. The authors stated that when used as monotherapy or in combination, these devices are showing promise as a method to clear acne in a convenient, non-invasive manner, though there remains a clear need for long-term data and randomized, blinded studies.
Jih et al (2006) assessed the dose response of a 1,450-nm diode laser for treatment of facial acne, sebum production, and acne scarring utilizing two laser fluences and ascertained long-term remission after laser treatment. A total of 20 patients (Fitzpatrick skin phototypes II to VI) received 3 treatments using the 1,450-nm diode laser (3 to 4 week intervals). Split face comparisons were performed by randomizing patients to 1 of 2 fluences (14 or 16 J/cm2) on the right or left side of the face. Clinical photographs, lesion counts, and sebum measurements were obtained at baseline and after each treatment. Investigators' and patients' subjective evaluations of response to treatment were assessed. Percentage reductions in mean acne lesion counts from baseline were 42.9 % (14 J/cm2) and 33.9 % (16 J/cm2) after 1 treatment and 75.1 % (14 J/cm2) and 70.6 % (16 J/cm2) after 3 treatments. There was persistent reduction of 76.1 % (14 J/cm2) and 70.5 % (16 J/cm2) at the 12-month follow-up (p < 0.01). Both objective as well as subjective improvements in acne scarring and sebum production were noted. Treatment-related pain was well-tolerated, and side effects were limited to transient erythema and edema at treatment sites. These investigators concluded that the 1,450-nm diode laser reduced inflammatory facial acne lesions even in Fitzpatrick skin phototypes IV to VI with minimal side effects. Significant improvement in acne lesion counts was noted after the first treatment and was maintained 12 months after the third treatment, indicating significant long-term clinical remission after laser treatment. The major drawbacks of this study were its small sample size, and comparison was limited to 2 laser fluences.
Orringer et al (2007) examined the effectiveness of an infrared laser in the treatment of acne. These investigators conducted a randomized, controlled, single-blind, split-face clinical trial of 46 patients with facial acne. Patients received a series of 3 non-ablative laser treatments using a novel neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to half of the face. Serial blinded lesion counts and global acne severity rating of standardized bilateral patient photographs were performed. Sebum production was measured, and patient self-assessment surveys were administered. A transient but statistically significant improvement in lesion counts of open comedones was demonstrated in treated skin as compared with untreated skin. There were no significant differences between treated and control sides of the face in terms of changes in mean papule or pustule counts. Grading of serial photographs revealed no significant differences between treated and untreated skin. Patient surveys indicated that the majority of patients found the treatments to be at least mildly effective for both acne and oiliness. The limitations of the current study only addressed the effectiveness of a single laser system employing a specific treatment regimen. The authors concluded that Infrared laser therapy may improve comedonal acne. They noted that additional work is needed to better define the degree and duration of the effect.
Hruza (2007a) commented that the 1,320-nm laser seems to be of minimal, if any, clinical use for treating acne. Many patients preferred the convenience of lasers to other therapies, but that percentage could drop precipitously when patients are faced with the cost of paying for laser treatment. The 1,450-nm wavelength that has been used most often for acne treatment is better absorbed by the sebaceous glands than the 1,320-nm wavelength, making the 1,320-nm laser less likely to be effective. Changing the treatment parameters and increasing the number of treatments could improve results. At this point, however, traditional, non-laser acne therapies remain the treatments of choice.
The Levulan Kerastick (DUSA Pharmaceuticals, Inc., Wilmington, MA) has been used for the treatment of acne. Levulan Kerastick includes topical aminolevulinic acid (ALA) activated using a blue light source and has been approved by the FDA for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp; therefore its use for acne vulgaris would be considered “off label”. The treatment entails topical application of ALA, which is absorbed and metabolized intracellularly to form the photosensitizing molecule protoporphyrin IX. According to the manufacturer, when this molecule is activated by light of an appropriate wavelength, oxygen radicals are released, which are thought to target and destroy the acne-associated bacterium, Proprionibacterium acnes as well as pilosebaceous units, resulting in a decrease in sebum production.
A number of authorities have concluded that there is insufficient evidence of the effectiveness of photodynamic therapy (PDT) with topical ALA in the treatment of acne. Gollnick and Krautheim (2003) observed that this treatment of acne has not yet been proven effective in controlled studies. Harper (2004) stated that controlled clinical trials on the use of phototherapy using ALA for management of acne are lacking at this time. Charakida et al (2004) concluded that further studies are needed to clarify the role of phototherapy with ALA as a monotherapy or an adjuvant treatment in the current management of acne vulgaris. Rotunda et al (2004) stated that research emphasizing long-term follow-up and comparative, randomized trials is necessary to determine whether emerging technologies such as light, laser, and radiofrequency energy will become a viable alternative to standard therapies such as antibiotics. Furthermore, Zakhary and Ellis (2005) stated that phototherapy using ALA is a promising new technique that is being studied extensively and used in a variety of cosmetic facial plastic arenas including off-label uses for photo-rejuvenation, and the treatment of acne vulgaris, sebaceous gland hyperplasia, rosacea, and hirsutism.
Recently, findings from several small studies (including controlled trials) have examined the effectiveness of PDT with ALA in acne vulgaris. In a randomized controlled study (n = 10), Pollock and colleagues (2004) examined the effectiveness of ALA-PDT in the treatment of acne. Patients with mild to moderate acne on their backs were recruited. Each patient's back was marked with 4 30-cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and non-inflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX) and surface P. acnes swabs performed. ALA cream (20 % in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 hours. Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm(-2), 15 J cm(-2)). Each patient was treated weekly for 3 weeks. At each visit, acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. There was a statistically significant reduction in inflammatory acne len counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites. However, there was no statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site.
In an uncontrolled pilot study (n = 18), Taub (2004) examined the effectiveness of PDT-ALA in the treatment of moderate to severe inflammatory acne. ALA remained in contact with skin for 15 to 30 minutes before exposure to blue light (ClearLight [Lumenis] or BLU-U [Dusa Pharmaceuticals, Inc.]) or the Aurora DSR (Syneron Medical Ltd.), which uses Electro-Optical Synergy (ELOS), a unique combination of optical and radiofrequency (RF) energy. Patients received 2 to 4 ALA-PDT treatments over 4 to 8 weeks or 2 cycles of ALA-PDT (weeks 2, 4) preceded by salicylic acid peel (weeks 1, 3) over 4 weeks. The average follow-up time was four months. The author found that patients with moderate to severe acne can achieve durable improvement with short-contact ALA-PDT.
A number of studies have reported on variations in PDT-ALA treatment regimen using different sources and intensities of light. Gold et al (2004) evaluated the effectiveness of ALA-PDT with activation by a SkinStation LHE (Radiancy, Inc., Orangeburg, NY), an intense pulsed light (IPL) and heat source in 20 patients with moderate to severe inflammatory acne vulgaris. Only 15 patients completed the trial and 12 responded to the treatment. Among respondents, reduction in active inflammatory acne lesions was, on average, 50.1 % at the end of the 4-week treatment period, 68.5 % 4 weeks after the final treatment, and 71.8 % 12 weeks after the final treatment.
In a self-controlled pilot study (n = 13), Santos et al (2005) reported the effect of PDT in acne vulgaris using topical ALA and IPL. Individuals with varying degrees of acne were treated after a 3-week washout period. Twenty percent ALA hydrochloride was applied to half of the face, and after 3 hours, the whole face was exposed to IPL using a 560 nm cut-off filter starting at a fluence of 26 J/cm. The procedure was done twice at 2-week intervals, and the patients were clinically evaluated on the 2nd, 4th, and 8th weeks. All patients had no apparent improvement on the 2nd week on both facial halves. In fact, some of the patients developed acute acneiform eruptions on the side treated with ALA. The investigators reported, however, by the 4th week, most of the patients had visible improvement of facial acne that was more significant on the ALA-treated side of the face. This persisted until the 8th week post-treatment. On the other hand, the facial half treated with IPL only showed a return to baseline of their facial acne. These authors concluded that the results of this study suggest that ALA-IPL is beneficial in the management of acne vulgaris. The investigators stated that this therapy may have potential use in combination with other forms of acne treatment or may be an alternative treatment for patients who do not want to take systemic retinoids.
In an uncontrolled study, Kimura and associates (2004) reported the use of PDT in combination with oral administration of delta-ALA and polychromatic visible light from a metal halide lamp in treating intractable acne on the body (n = 51). The investigators noted improvements in treatment, suggesting that orally administered ALA-PDT with a metal halide lamp may be effective for the treatment of acne on the body.
The available evidence for the use of PDT-ALA in the treatment of acne vulgaris is promising. However the evidence is largely limited to studies with small sample size and short-term follow-up. Furthermore, there are no studies directly comparing PDT-ALA with other established treatments for acne vulgaris. The clinical value of PDT-ALA in the treatment of acne vulgaris awaits findings from well-designed controlled studies with large sample size and long-term follow-up.
In a controlled, randomized, investigator-blinded study, Wiegell and Wulf (2006) compared the treatment effect and tolerability of PDT-ALA versus PDT-methyl aminolevulinate (PDT-MAL) in the treatment of patients with acne vulgaris. A total of 15 patients with at least 12 facial inflammatory acne lesions had one split-face PDT treatment with MAL and ALA. Twelve weeks after treatment there was a 59 % decrease in inflammatory lesions from baseline, with no significant differences in effectiveness between the two treatments. All patients experienced moderate to severe pain during illumination and developed erythema, pustular eruptions, and epithelial exfoliation after treatment, which were more severe and uniform in the PDT-ALA treated area. These investigators concluded that PDT appeared to be an effective treatment for inflammatory acne vulgaris with no significant differences in the response rate between PDT-ALA and PDT-MAL. Moreover, PDT-ALA resulted in more prolonged and severe adverse effects after treatment. The authors noted that although the study was paired and controlled, the results should be evaluated with consideration given for the number of participating patients.
The Institute for Clinical Systems Improvement's guidelines on acne management (2006) stated that there continue to be numerous studies about light treatment for acne, including blue light and photodynamic therapy with and without pre-treatment with topical medications. At this time, the evidence is inadequate to make a recommendation about the efficacy and safety of these treatments.
Guidelines from the British Association of Dermatology (2008) state that, although topical photodynamic therapy can improve inflammatory acne on the face and back, optimization of protocols, to sustain response while minimizing adverse effects, is awaited.
Horfelt et al (2006) examined the effectiveness and tolerability of methyl aminolevulinate (MAL)-PDT for treatment of moderate inflammatory facial acne. A total of 30 patients aged 15 to 28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 hours prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analog scale. Inflammatory and non-inflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (7 patients had severe acne on at least one side of the face) and each study visit using a 6-point rating scale. Data were analyzed on an intention-to-treat basis, including all 30 patients. There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54 % [95 % confidence interval (CI): 35 to 64 %] versus 20 % (95 % CI: 8 to 50 %), p = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. The authors concluded that MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Moreover, they noted that further studies are needed to optimize this promising procedure.
Yeung et al (2007) evaluated the effect on acne vulgaris of IPL alone and when IPL was combined with PDT using topical MAL in Asians. A total of 30 Chinese subjects with phototypes IV or V and moderate acne were enrolled for a randomized, half-facial treatment study with IPL alone, IPL with PDT, or as controls. Sixteen % MAL cream was applied to half of the face 30 minutes before treatment in the PDT group. The IPL was provided by the Ellipse Flex system (Danish Dermatologic Development, Denmark), which emitted wavelengths of 530 to 750 nm. Subjects were treated four times at 3-week intervals. Single passes of double pulses with a 10 milliseconds delay and a pulse duration of 2.5 milliseconds were used. The assessment of inflammatory and non-inflammatory acne lesions by two blinded investigators was based on standardized photographs that were taken before each treatment, and at 4 and 12 weeks after the final treatment. A total of 23 patients completed the study. The mean reduction of the inflammatory lesion count was 53 % in the PDT group, 22 % in the IPL group, and 72 % in the control group at 4 weeks, and 65 % in the PDT group, 23 % in the IPL group, and 88 % in control group at 12 weeks. The mean clearance of non-inflammatory lesions was 52 % in the PDT group, 15 % in the IPL group, and 14 % in the control group at 4 weeks, and 38 % in the PDT group and 44 % in the IPL group at 12 weeks, and an increase of 15 % was noted in the control group. Most patients experienced a reduction of inflammatory lesions that was not statistically significant on the PDT-treated side (p = 0.06) or the IPL-treated side (p = 0.82) at 12 weeks after treatment. Pre-treatment with MAL resulted in a better clearance of inflammatory acne than IPL alone. There were no statistically significant differences between the intervention groups and the control group in the mean reduction of inflammatory lesions. Significant reductions of non-inflammatory lesions were observed in the MAL-PDT group (38 %, p = 0.05) and IPL groups (43 %, p = 0.00) 12 weeks after treatment. Twenty-five % of the subjects in the PDT group withdrew because of intolerance to procedure-related discomfort. The authors concluded that MAL-PDT using IPL and MAL in Asians did not lead to significant improvement of moderate inflammatory acne compared with the control group. However, there was a delayed effect on non-inflammatory lesions, with significant reductions in both the PDT and IPL groups. A proportion of patients could not tolerate the discomfort that was related to PDT despite the short MAL incubation.
Hruza (2007b) commented that neither topical PDT nor IPL alone was effective for inflammatory acne in patients with Asian skin. The improvement in acne that did occur in these patients was probably caused by the nightly use of the topical retinoid during treatment, but the IPL-only treatment apparently reduced the retinoid’s benefits. The comedone reduction seen in recipients of the MAL-IPL combination resembles that produced by infrared lasers. Whether reducing comedones by these methods will, over time, lead to a reduction of inflammatory acne remains to be seen.
Haedersdal et al (2008) evaluated the effects of optical treatments for acne vulgaris. Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library. A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included PDT (5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and 1 trial described adequate allocation concealment. Most trials were intra-individual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, these researchers concluded that optical treatments possess the potential to improve inflammatory acne on a short-term basis with the most consistent outcomes for PDT (up to 68 % improvement, ALA, MAL and red light). IPL-assisted PDT seems to be superior to IPL alone. Only 2 trials compared optical versus conventional treatments, and further studies are needed. Side-effects from optical treatments included pain, erythema, edema, crusting, hyper-pigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL. The authors concluded that evidence from controlled clinical trials indicates a short-term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. They recommend that patients are pre-operatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments.
Hamilton et al (2009) performed a systematic review of RCTs of light and laser therapies for acne vulgaris. These investigators searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycInfo, LILACS, ISI Science Citation Index and Dissertation Abstracts International for relevant published trials. They identified 25 trials (694 patients), 13 of light therapy and 12 of light therapy plus light-activated topical cream (PDT). Overall, the results from trials of light alone were disappointing, but the trials of blue light, blue-red light and infrared radiation were more successful, particularly those using multiple treatments. Red-blue light was more effective than topical 5 % benzoyl peroxide cream in the short-term. 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 1 % adapalene gel, and the side-effects of therapy were unacceptable to many subjects. The authors concluded that some forms of light therapy were of short-term benefit. Patients may find it easier to comply with these treatments, despite the initial discomfort, because of their short duration. However, very few trials compared light therapy with conventional acne treatments, were conducted in patients with severe acne or examined long-term benefits of treatment.
Fractional photothermolysis (FP) has been recently introduced as a new concept in dermatological laser medicine. It employs an array of small laser beams to create many microscopic areas of thermal necrosis within the skin called microscopic treatment zones. In a pilot study, Yoo et al (2009) evaluated the safety and effectiveness of 1,540-nm FP for the treatment of acne scars in Asian skin. A total of 16 volunteers (Fitzpatrick skin types III to IV) with mild-to-moderate acne scars were enrolled. Acne scar lesions were treated with 1,540-nm FP (Starlux 1540). Three treatment sessions were carried out for each patient 4 weeks apart. Outcome assessments included the following 4 methods: (i) clinical evaluation of the photographs that were taken before and after the treatment; (ii) comparison of the quality of life (QOL) of the patients before and after the treatment; (iii) patients' satisfaction with the treatment; and (iv) comparison of the quantity of collagen and elastic fibers in the skin biopsies before and 12 weeks after the last treatment. A mild-to-moderate clinical improvement was observed in most of the patients. Moreover, the QOL of all the patients improved, and all of them were satisfied with the results of the treatment. Significant collagen and elastic-fiber increases were also observed after the treatment, and side effects were limited to transient erythema and edema, which occurred in 50 % of the patients. No severe side effect was observed. The authors concluded that 1,540-nm FP is a safe and effective method for improving acne scar, even in Asian skin.
Cho et al (2009) assessed the safety and effectiveness of the FP with dynamic operating mode on acne scars and enlarged pores. A total of 12 patients with mild-to-moderate atrophic acne scars and enlarged pores were included in this study. Three sessions of FP were performed for acne scars and facial pores monthly. Two blinded dermatologists who compared before and after photos based on a quartile grading scale conducted objective clinical assessments of acne scar- and facial pore-treated areas. These investigators took a biopsy immediately after one treatment with the laser from one of the authors to assess the histological effects of the laser on facial pores. Follow-up results at 4 months after the last treatment revealed that, of the 12 patients, for acne scars, 5 demonstrated clinical improvements of 51 % to 75 % and 3 demonstrated improvements of 76 % to 100 %, and for facial pores, 5 demonstrated moderate clinical improvements of 26 % to 50 % and 3 demonstrated improvements of 76 % to 100 %. Side effects, including pain, post-treatment erythema, and edema, were resolved within 1 week. The authors concluded that the FP may provide a new treatment algorithm in some cases with acne scars and enlarged pores. They noted that considering the lack of placebo-controlled, split-face design of the study, optimized, prospective studies are needed to fully evaluate the effectiveness of FP with dynamic operating mode.
Tierney et al (2009) reviewed the Medline English literature and recent international conferences regarding FP technology, applications, and indications. Successful conditions treated with non-ablative FP reported in the literature include acne scarring; dyschromia and fine wrinkling of photoaging on the face, chest, neck, and hands; melasma; poikiloderma of Civatte; nevus of Ota; scars; minocycline hyper-pigmentation; telangiectatic matting; residual hemangioma; granuloma annulare; colloid milium; as well as disseminated superficial actinic porokeratosis. An advance in 2007 was the introduction of ablative FP (AFP), which results in significantly greater improvement in skin laxity and textural abnormalities. Most recently, AFP has demonstrated significantly greater improvement than non-ablative FP in reducing acne scarring and skin redundancy and laxity associated with photoaging. The authors concluded that through the induction of microthermal zones of injury, FP technology stimulates a robust and rapid wound healing response resulting in improvement in a diversity of aesthetic, inflammatory, and pre-neoplastic skin disorders. They stated that further investigation into the technology and diverse array of cutaneous conditions that can benefit from FP is highly needed.
Degitz (2009) noted that modern acne therapy uses anti-comedogenic, anti-microbial, anti-inflammatory, and anti-androgenic substances. As an additional approach in recent years, treatments have been developed based on the application of electromagnetic radiation. Visible light or infrared wave lengths are utilized by most techniques, including blue light lamps, intense pulsed light (IPL), PDT and lasers. The author assessed the various methods with regard to efficacy and their current role in the management of acne. Although ultraviolet radiation has been frequently used to treat acne, it is now regarded as obsolete due to the unfavorable risk-benefit ratio. Visible light, especially of blue wavelengths, appears to be suitable for the treatment of mild-to-moderate inflammatory acne. Photodynamic therapy is effective, but, due to considerable immediate side effects, it is best reserved for selected situations. Despite promising observations, IPL and lasers have to be evaluated in further studies, before they can be recommended.
Babilas et al (2010) stated that IPL devices use flashlamps and bandpass filters to emit polychromatic incoherent high-intensity pulsed light of determined wavelength spectrum, fluence, and pulse duration. Similar to lasers, the basic principle of IPL devices is a more or less selective thermal damage of the target. The combination of prescribed wavelengths, fluences, pulse durations, and pulse intervals facilitates the treatment of a wide spectrum of skin conditions. These investigators summarized the physics of IPL to provide guidance for the practical use of IPL devices, and to discuss the current literature on IPL in the treatment of unwanted hair growth, vascular lesions, pigmented lesions, acne vulgaris, and photo-damaged skin and as a light source for PDT and skin rejuvenation. A systematic search of several electronic databases, including Medline and PubMed and the authors experience on IPL was carried out. The authors concluded that most comparative trials attest IPLs similar effectiveness to lasers (level of evidence: 2b to 4, depending on the indication). However, they stated that large, controlled and blinded comparative trials with an extended follow-up period are necessary.
In an evidence-based update on the management of acne vulgaris, Ingram et al (2010) stated that PDT, phototherapy and laser therapy can not be recommended universally for acne until minimal post-inflammatory 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. They stated that future trials should use active comparators at optimum doses and avoid non-inferiority 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.
In a randomized split-face, investigator-blinded clinical study, Darne et al (2011) evaluated the effectiveness and long-term outcome of the 1,450-nm laser for inflammatory acne vulgaris. Participants over 16 years of age with moderate to severe acne vulgaris were recruited from a secondary care dermatology department. A split-face format was used: the side of the face to be treated was randomized with the other side serving as a within-patient control. Treatment was delivered with the Candela 1,450 nm Smoothbeam laser using a double-pass technique, 6-mm spot size, 210-ms pulse duration and fluence of 8 or 9 J cm(-2). Three treatments were performed monthly. The primary outcome was the change in inflammatory lesion count and grading (using the Leeds Revised Acne Grading Scale) between baseline and 4 weeks after the 3rd treatment on the treated side as compared with the change in the control side. Participants were followed-up every 3 months for 12 months after the last treatment. The single assessor was blinded as to the side treated. A total of 38 participants entered the study and 32 completed the study at the primary outcome measure. Within participants, on average, the lesion count reduced by the same amount on both sides of the face [median 0, 95 % CI: -4 to 2]. On average, acne grade reduced by the same amount on both sides (median 0, 95 % CI: -1 to 0). Twelve months after the last treatment (n = 23) the change in lesion count and grade between the treated and control sides of the face remained similar. Treatment was well- tolerated. The authors concluded that treatment with the 1,450-nm laser does not reduce inflammatory lesion count or acne grade when compared with a control side, using a split-face format in participants recruited from secondary care. Both sides of the face improved and a systemic effect of the laser is possible.
In a review on acne vulgaris, Williams et al (2012) stated that although several forms of light therapies (e.g., broad-spectrum light sources, infrared lasers, IPL, and PDT) can improve acne initially, longer-term outcomes and comparisons with conventional acne therapies are needed.
Pierard-Franchimont et al (2011) re-visited adjunctive physical treatments of acne, including light/laser treatments and PDT. These researchers summarized findings about such treatment modalities with particular emphasis on safety and effectiveness. A number of laser/light-based modalities have been developed to meet the increasing demand for new acne treatments. The current devices correspond, on the one hand, to light-emitting diode therapy and, on the other hand, to the 532-nm potassium titanyl phosphate (KTP) laser, the 585- and 595-nm PDL, the 1,450-nm diode laser, the 1,320-nm Nd:YAG laser and IPL. Photodynamic therapy is also available. It is claimed that light/laser treatments might induce a faster response compared with the 1 to 3 months needed for response to traditional oral and topical treatments. The authors concluded that PDL showed effectiveness in some patients with mild-to-moderate acne. The relative effectiveness compared with other treatments is unconfirmed; from the published information, evidence-based effectiveness assessment of light/laser therapies in acne remains almost impossible.
Smith et al (2011) highlighted clinically important findings about acne treatment identified in 9 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 to 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 effectiveness 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; PDT had consistent benefits over placebo but was associated with significant side-effects and was not shown to be better than topical adapalene.
Faghihi et al (2012) evaluated the effectiveness of IPL as a tool for diminishing erythematous reactions in the tissues) for the treatment of residual erythematous macules following facial acne. A total of 35 patients were registered in the study. Patient recruitment occurred between January 2010 and June 2011, and the study was completed in October 2011. Every patient received 3 IPL sessions, with a 2-week interval, on the right side of his/her face. Also, these researchers recommended the patients to apply topical erythromycin solution 2 % twice-daily on their entire face from start to end of the study (i.e., until 3 months after the 3rd IPL session). An independent physician counted the number of erythematous macules before every IPL session and 1 and 3 months after the last session. A total of 33 patients completed the study and were enrolled in analysis. Results of the study show that IPL therapy decreases the number of erythematous macules along the time. The authors concluded that IPL can accelerate the improvement rate of persistent erythematous macules remained after inflammatory acne subsides. However, they stated that more studies are needed to explain the exact role of it.
Simonart (2012) stated that the multi-factorial 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 (light-based treatments), as well as complementary and alternative medications. These investigators discussed 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, light-based 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 anti-microbial peptides, and lauric acid represent other promising therapies.
Ferris et al (2012) stated that acne vulgaris is both a dermatologic and psychosocial challenge for many patients, and while topical therapy and cleansers continue to be the gold standard of treatment, the use of lasers and light will continue to play a role that will likely expand in management of acne. Modalities that have been explored include PDT with and without photosensitizers, KTP laser, PDL, infrared and fractional lasers. The authors concluded that the future application of these devices in acne therapy will likely include combination therapy and exploration of more precisely targeted chromophores.
Erceg et al (2013) noted that the position of the PDL in the treatment of inflammatory skin diseases is still unclear. Evidence-based recommendations are lacking. These investigators sought to systematically review all available literature concerning PDL treatment for inflammatory skin diseases and proposed a recommendation. They searched for publications dated between January 1992 and August 2011 in the database PubMed. All studies reporting on PDL treatment for an inflammatory skin disease were obtained and a level of evidence was determined. Literature search revealed 52 articles that could be included in this study. The inflammatory skin diseases treated with PDL consisted of: psoriasis, acne vulgaris, lupus erythematodes, granuloma faciale, sarcoidosis, eczematous lesions, papulopustular rosacea, lichen sclerosis, granuloma annulare, Jessner lymphocytic infiltration of the skin, and reticular erythematous mucinosis. The effectiveness of PDL laser treatment for these inflammatory skin diseases was described and evaluated. The authors concluded that PDL treatment can be recommended as an effective and safe treatment for localized plaque psoriasis and acne vulgaris (recommendation grade B). For all other described inflammatory skin diseases, PDL seems to be promising, although the level of recommendation did not exceed level C. The main drawback of this study was that most conclusions formulated are not based on RCTs.
The European guidelines on “Topical photodynamic therapy part 2: Emerging indications -- field cancerization, photorejuvenation and inflammatory/infective dermatoses” (Morton et al, 2013) stated that PDT has been studied for the treatment, and possible prevention, of superficial skin cancers in immunosuppressed patients. As a topical photosensitizer can be applied over large areas, PDT is also increasingly used for field cancerization in photo-damaged skin, with evidence of potential to delay the development of actinic keratoses and basal cell carcinoma, although direct evidence of prevention of invasive squamous cell carcinoma remains limited. Photodynamic therapy has been studied in patch/plaque-stage cutaneous T-cell lymphoma, with efficacy more likely in unilesional disease. Accumulating evidence supports the use of PDT in acne and several other inflammatory/infective dermatoses including cutaneous leishmaniasis, although protocols are still to be refined. The authors concluded that PDT is a therapeutic option for photo-rejuvenation, with improvement in fine wrinkles, mottled hyper-pigmentation, roughness and sallowness reported. They did not mention PDT as a therapeutic option for acne.
Calzavara-Pinton et al (2013) noted that experimental investigations have demonstrated that PDT-MAL may be a useful treatment in several inflammatory skin disorders and aesthetic indications. These investigators assessed the effectiveness, tolerability and safety of off-label MAL-PDT in daily clinical practice in 20 Italian hospital centers; a retrospective observational study of medical records of patients treated for off-label inflammatory and aesthetic indications was carried out. In all patients standard treatment options had been ineffective, unacceptably toxic, or medically contraindicated. Clinical data regarding 221 patients affected by 22 different diseases were collected. The most common off-label indication was acne vulgaris, with greater than 75 % improvement in 72.8 % of patients. Other disorders of the sebaceous gland, i.e., acne rosacea, hidradenitis suppurativa and sebaceous hyperplasia, were less responsive. Alopecia areata did not show any improvement. Granuloma annulare and necrobiosis lipoidica showed marked or moderate response in the majority of treated patients. The rate of patients with complete remission was lower for inflammatory skin disorders with hyperkeratosis, i.e., psoriasis (6/17) and porokeratosis (3/16). The efficacy for lichenoid dermatoses was dependent on the clinical variant (erosive and scleroatrophic were more responsive than hypertrophic). Only 1 of 6 patients with Zoon balanitis had a marked improvement. MAL-PDT of venous leg ulcers, photo-aging and hypertrophic scars led to a marked remission in 3/5, 3/6 and 5/8 patients, respectively. Treatment in 24 subjects had to be interrupted because of strong pain and burning. Long-term adverse events were not registered. Most patients with marked improvement had lasting remission with overall excellent cosmetic outcomes. The present findings demonstrated a high interest in off-label uses of MAL-PDT for inflammatory skin disorders. According to the observed clinical responses, safety, and favorable cosmetic results, MAL-PDT seems to have a potential therapeutic role for the treatment of granulomatous dermal disorders and follicular inflammatory diseases whereas results in other conditions are less encouraging.
An UpToDate review on “Light-based, adjunctive, and other therapies for acne vulgaris” (Dover and Batra, 2013) states that “The role of laser and other light-based therapies in the treatment of acne is not clearly defined. We suggest that light-based therapies should not be used as first-line treatment for acne vulgaris (Grade 2B). These therapies may be utilized as an adjunct to medical acne therapy or as an option for patients who decline medical therapy although further studies are necessary to clarify their role”.
Omi and colleagues (2008) stated that photopneumatic therapy is a novel technology that combines pneumatic energy with a broad-band light source to manipulate the optical characteristics of the skin. A vacuum suction raises target structures in the dermis closer to the surface of the skin prior to exposure, allowing for more efficient energy transmission. These researchers tested the hypothesis that a combination of pulsed light and suction would affect sebaceous plugging within diseased pilo-sebaceous apparati at a histological level, resulting in the rapid clearance of acne lesions. A total of 8 individuals were treated with photopneumatic therapy once-weekly for a total of 5 treatments. Punch biopsies of the treated areas were obtained just after the 1st exposure, just before the 3rd exposure and immediately after the 5th exposure. Those specimens were examined by conventional and by electron microscopy for any alterations following treatment. Immediately following the 1st treatment, the mechanical extrusion of comedo contents from the infundibulum was observed histologically. One week after the 2nd treatment, thermally injured bacteria as well as direct thermal injury to pilo-sebaceous apparati were observed ultra-structurally. The authors concluded that these results correlated with clinical reports on decreased sebaceous gland activity after photopneumatic therapy and may mechanistically give rise to the rapid regression of acne lesions.
Omi (2012) noted that recent reports indicated that a variety of light-based devices have been used for acne treatment and skin rejuvenation. A new technology combining intense pulsed light with negative pressure, photopneumatic technology, has recently attracted interest. This study assessed acne treatment and skin rejuvenation with this novel approach. For the treatment of acne trial, a total of 5 Japanese volunteers (1 male, 4 females; mean age of 28.6 years; skin type III) with mild-to-moderate/moderate active acne participated. The face was treated in 2 sessions, 2 weeks apart. Biopsies were obtained immediately after the 1st session and 1 week after the 2nd session, and routinely processed for transmission electron microscopy (TEM). For the skin rejuvenation trial, a total of 5 Japanese volunteers (3 males, 2 females; mean age of37.6 years, skin type III), the volar aspect of both forearms was treated with the 530-nm head at P6 (around 12 J/cm(2)). The left arm was then treated with a pre-infused profusion tip and vacuum only; a total of 4sessions were given, 14-day intervals. Biopsies were taken from both arms 2 weeks after the 2nd session and 3 weeks after the 4th session; 50 % of each biopsy was assessed with histo- and immune-histochemistry, and the other with TEM. For the acne trial, a combination of physical extraction of comedones, mild photo-thermal damage of the follicle and damage to identified bacilli was noted post-treatment, with macroscopic improvement of the skin. For the skin rejuvenation trial, significant morphological and immuno-histochemical differences were seen between the control and profusion-treated arms at the 1st assessment. These differences became less significant at the 2nd assessment. The author concluded that macroscopically and histologically, photopneumatic technology improved acne lesions, suggesting a synergistic effect between the components of the technology. In skin rejuvenation, the profusion therapy accelerated the regenerative process, and could have excellent additional potential as a non-invasive trans-epidermal drug delivery system.
Lee and colleagues (2012) stated that acne vulgaris is the most common skin disease worldwide, with many available treatment modalities, including oral and topical medications and laser therapy. Recently, a novel device, Isolaz (Pleasanton, CA) that combines vacuum pressure and a broad-band light source (400 nm to 1,200 nm) was developed for the treatment of acne. In an open-label, split-face trial, these researchers determined the safety and effectiveness of photopneumatic therapy for the treatment of acne vulgaris of the face. A total of 20 adults with mild-to-moderate facial acne vulgaris received 4 successive treatments on one side of the face with a combined photopneumatic device (IPL: fluence = 5.8 J/cm(2); negative pressure = iMP mode) at 2-week intervals. Acne lesions on the opposite side of the face were not treated. Lesion counts were performed at baseline, prior to each treatment session, and at 3 months after the final treatment session. Significant lesion improvements and reduced numbers of acne lesions were observed on the treated side of the faces. Most patients experienced global clinical improvement. No severe side effects occurred during the study, with only a few patients experiencing transient erythema, purpura and/or exacerbation of pre-existing acne. The authors concluded that photopneumatic therapy is a safe and effective treatment for mild-to-moderate acne vulgaris. The findings of this small (n = 20), open-label study need to be validated by well-designed studies.
Narurkar et al (2013) stated that topical and oral medications, such as retinoids, benzoyl peroxide, antibiotics, and isotretinoin, have been the standard of care for the treatment of mild-to-moderate acne for the last several decades. More recently, a number of published studies on optical treatments, such as ultraviolet light, visible (blue) light, and IPL systems, have also shown clinical improvement in the appearance of acne. Specifically, photopneumatic technology, which utilizes gentle pneumatic energy (vacuum) to draw the target tissue into the treatment tip and then deliver broad-band pulsed light to the dermal targets, has demonstrated marked improvement in the appearance of acne lesions and side effects associated with acne. In a prospective, multi-center, clinical trial, these researchers examined the safety and effectiveness of using a combination treatment of the photopneumatic system and profusion therapy using 3 currently marketed topical agents for the treatment of mild-to-moderate acne on the face and/or body, including neck, chest, or back. A total of 41 individuals with mild-to-moderate acne were included in this study. Patients received up to 4 treatments at 1- to 2-week intervals with the photopneumatic system and profusion therapy with 3 separate topical agents. Study investigators and subjects evaluated clinical effectiveness at 1-month and 3-month follow-up visits. At 3 months, a 69 % reduction was noted in inflamed acne lesions and a 41 % reduction in non-inflamed acne lesions was noted by physician assessment. Additionally, at this same time-point, subjects reported moderate-to-marked (26 % to 75%) improvement in acne lesions; 81 % of subjects (22/27) were either satisfied or very satisfied with treatment outcome. There were no adverse events caused by malfunction of the device, and no serious adverse events or deaths. The authors concluded that these findings, as well as the reported patient satisfaction and safety, suggested that the treatment of acne with the photopneumatic system in combination with profusion using currently available topical acne agents demonstrated significant treatment results.
An UpToDate review on “Light-based, adjunctive, and other therapies for acne vulgaris” (Dover and Batra, 2014) states that “Light/Laser Therapies -- Clinician-administered light sources are used for the treatment of acne, though well designed clinical trials supporting the benefit of these treatments are limited …. Photopneumatic technology is a newer therapeutic modality. It has been less extensively studied for the treatment of acne than other light treatments. Photopneumatic devices combine gentle negative pressure with broadband pulsed light (400 to 1,200 nm). The suction pressure helps to open follicular ostia through the evacuation of sebum and brings pilosebaceous units closer to the treatment tip. The broadband light exerts antibacterial and antiinflammatory effects …. The role of laser and other light-based therapies in the treatment of acne is not clearly defined. We suggest that light-based therapies should not be used as first-line treatment for acne vulgaris (Grade 2B). These therapies may be utilized as an adjunct to medical acne therapy or as an option for patients who decline medical therapy although further studies are necessary to clarify their role”.
|CPT Codes / HCPCS Codes / ICD-9 Codes|
|CPT codes not covered for indications listed in the CPB:|
|17110||Destruction (eg, laser surgery, electrosurgery, cryosurgery, chemosurgery, surgical curettement), of benign lesions other than skin tags or cutaneous vascular proliferative lesions; up to 14 lesions|
|17111||15 or more lesions|
|96567||Photodynamic therapy by external application of light to destroy pre-malignant and/or malignant lesions of the skin and adjacent mucosa (e.g., lip) by activation of photosensitive drug(s) each phototherapy exposure session|
|+ 96570||Photodynamic therapy by endoscopic application of light to ablate abnormal tissue via activation of photosensitive drug(s); first 30 minutes (List separately in addition to code for endoscopy or bronchoscopy procedures of lung and esophagus)|
|+ 96571||each additional 15 minutes (List separately in addition to code for endoscopy or bronchoscopy procedures of lung and esophagus)|
|96920 - 96922||Laser treatment for inflammatory skin disease (psoriasis)|
|Other CPT codes related to the CPB:|
|HCPCS codes covered if selection criteria are met:|
|J7309||Methyl aminolevulinate (MAL) for topical administration, 16.8%, 1 gram|
|HCPCS codes not covered for indications listed in the CPB:|
|J7308||Aminolevulinic acid HCL for topical administration, 20%, single unit dosage form (354 mg)|
|ICD-9 codes not covered for indications listed in the CPB:|
|706.0 - 706.1||Acne|
Photodynamic Therapy (ClearLight Acne PhotoClearing System; Omnilux Blue Photo Dynamic Therapy):
Laser Treatment for Acne:
Photodynamic Therapy with Aminolevulinic Acid (ALA) for Acne:
Fractional Photothermolysis for Acne:
Intense Pulsed Light for Acne: