Photopneumatic Technology Used in Combination with Profusion Therapy for the Treatment of Acne

Abstract

Background: 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 pubHshed studies on optical treatments, such as ultraviolet light, visible (blue) light, and intense pulsed Hght 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 deHver broadband pulsed Hght to the dermal targets, has demonstrated marked improvement in the appearance of acne lesions and side effects associated with acne. Objective: To demonstrate the safety and efficacy of using a combination treatment of the photopneumatic system and profusion therapy using three currently marketed topical agents for the treatment of mild-to-moderate acne on the face and/or body, including neck, chest, or back. Methods: A prospective, multicenter, dinical trial of 41 individuals with mild-to-moderate acne was performed. Patients received up to four treatments at 1- to 2-week intervals with the photopneumatic system and profusion therapy with three separate topical agents. Study investigators and subjects evaluated dinical efficacy at 1-month and 3-month follow-up visits. Results: At three months, a 69-percent reduction was noted in inflamed acne lesions and a 41-percent reduction in noninflamed acne lesions was noted by physician assessment. Additionally, at this same time point, subjects reported moderate-to-marked (26-75%) improvement in acne lesions. Eighty-one percent 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. Conclusion: The results, as well as the reported patient satisfaction and safety, suggest that the treatment of acne with the photopneumatic system in combination with profusion using currently available topical acne agents demonstrated significant treatment results.

Acne vulgaris is a common skin disease that affects more than 85 percent of adolescents and often continues into adulthood.1 Laser and Hght-based devices traditionally target the sebaceous glands, which are part of the pilosebaceous unit, the site of acne and commensal organisms, such as Propionibacterium acnes. P. acnes live on the fatty acids in the sebaceous glands and proHferate when the infundibulum of the pilosebaceous unit becomes blocked with sebum and sheds cells, immune reactions and inflammation occur, and, as a result, acne vulgaris develops.2 Ultraviolet Hght and visible (blue) Hght kill the bacterium and/or sebaceous cells through activated mechanisms of endogenous porphyrins and in turn cause a reduction in acne lesions.3,4

Intense pulsed light (IPL) systems have also been used for the treatment of acne on all skin types in the medical specialties of dermatology and plastic surgery. One of the more recent pulsed Hght combination treatments that has been cleared by the United States Food and Drug Administration (FDA) for the treatment of comedonal and pustular acne, in addition to inflammatory acne (including acne vulgaris), utilizes photopneumatic technology (Isolaz®, Solta Medical Inc., Hayward, California), which consists of a gentle pneumatic energy (vacuum) to draw the target tissue into the treatment tip and then deHvers broadband pulsed Hght (400–1200nm) to the dermal targets. The vacuum technique causes elevation of the sebaceous gland and other dermal structures toward the epidermal surface, where the pore is opened and the sebaceous contents are mechanically removed. The sebaceous gland is then treated with broadband light, followed by the release of the treatment area. This mechanism has been supported by histological evidence that this therapy mechanically removes comedo contents from the infundibulum, and ultrastructural evidence has shown that the P. acnes bacteria and the pilosebaceous unit are thermally injured after treatment.4,5 The profusion tip used in combination with this photopneumatic system is subsequently used on the treatment areas to assist in deHvery and profusion of therapeutic topicals to the cleansed sebaceous gland while the skin is again gently stretched via vacuum technology.5

The objective of this prospective, multi-center study was to evaluate the safety and efficacy of using the photopneumatic device followed by profusion using three different commercially available topical agents for the treatment of mild-to-moderate acne.

METHODS

Forty-one subjects (5 male, 36 female) aged 20 to 55 years with Fitzpatrick skin types I to VI were enrolled at three investigational centers. All subjects presented with mild-to-moderate acne (15 or more inflammatory or noninflammatory lesions). Subjects had not received microdermabrasion or immunosuppressive medication at least one month prior to enrollment. Subjects had not received laser or Hght treatment (at least 3 months prior to enrollment), dermabrasion, trichloroacetic acid (TCA) peel greater than 20 percent, botminum toxin type A, dermal fillers, photodynamic therapy (PDT), cosmetic surgery, or isotretinoin (at least 6 months prior to enrollment). Subjects had not used topical alpha hydroxy acids, retinoic acid, retinol, salicylic acid, or vitamins C and D or derivatives for 14 days prior to enrollment. Pregnancy, previous ablative laser treatment, excessive sun exposure during the course of the study, current or past cigarette smoking, and medications containing aminolevulinic acid were all exclusions from study participation.

Subjects received up to four treatments with the photopneumatic system and profusion therapy at 1- to 2-week intervals (± 3 days). Treatments were performed on the face and/or off-face areas, including the neck, chest, or back, using settings of up to energy level 4 (corresponding to a fluence of up to 8J/cm²), up to vacuum level 3, and up to two passes per treatment session. All settings were dependent on patient tolerability and comfort. Immediately following completion of photopneumatic treatment, two additional passes of profusion therapy treatment were applied using one of three FDA-approved and commercially available topical acne agents: Proactiv® (Guthy-Renker LLC, Santa Monica, CaHfornia), ClenziDerm® M.D. (Obagi Medical, Long Beach, CaHfornia), and Murad® (Murad Inc.). Each study center chose one of the three topical acne agents for use during the entire course of the study. Subjects were provided with the same topical acne agent that was used during their treatment and instructed to use it at home daily over the course of the study. Subjects were scheduled for subsequent weekly treatments (four total), followed by study visits to assess clinical improvement at one month and three months after final treatment. The study was conducted according to Good Clinical Practice guideHnes and informed consent was obtained from all subjects prior to any study-related procedures.

Standardized digital photography of the treatment area was performed for each subject at baseline, before each treatment, and at the one-month and three-month follow-up visits. At baseline, study investigators evaluated the appearance of acne in the areas to be treated using the Burton Acne Scale (Table 1), Shamban Acne Scale (Table 2), lesion counts (inflamed and noninflamed), and assigned skin type (Fitzpatrick I-VI). Subjects also assessed appearance of acne using the Shamban Acne Scale at baseline.

TABLE 1.

Burton Acne Scale

GRADE 1	Sub-clinical acne	Few comedones visible only in close examination
GRADE 2	Comedonal acne	Comedones with slight inflammation
GRADE 3	Mild acne	Inflamed papules with erythema
GRADE 4	Moderate acne	Many inflamed papules and pustules
GRADE 5	Severe nodular acne	Inflamed papules and pustules with several deep nodular lesions
GRADE 6	Severe cystic acne	Many nodular cystic lesions with scarring

TABLE 2.

Shamban Acne Scale

ACNE (A)	SCARRING (S)	PIGMENTATION (P)
0 = None	0 = None	0 = None
1 = Mild	1 = Mild	1 = Mild
2 = Moderate	2 = Moderate	2 = Moderate
3 = Severe	3 = Severe	3 = Severe

The treatment area(s) were cleansed prior to each treatment. Protective eyewear was utilized during treatments to protect against potential exposure to broadband light. Subjects were asked to assess discomfort during photopneumatic treatment and profusion treatment, using a 1 to 5 discomfort scale (l=none, 2=slight, 3=moderate, 4=severe, 5=intolerable). Study investigators assessed the incidence of post-treatment responses, including erythema, edema, hyper-/hypo- pigmentation, Mistering, itchiness, dryness, and/or flaking, using a 0 to 3 scale (0=none, l=mild/minor, 2=moderate, 3=severe) at each treatment and follow-up visit, and recorded any additional side effects (such as bruising) during the course of the study.

Clinical appearance of the treatment areas was assessed by study investigators and study subjects at each treatment visit (after treatment 1) and at one and three months following final treatment. Follow-up evaluations were made for acne severity (Burton Acne Scale), lesion counts (inflamed and noninflamed), scarring and pigmentation (Shamban Acne Scale), and overall improvement in the appearance of acne (quartile improvement scale, 0-4). Subject satisfaction and treatment outcome experience was also assessed at the final follow-up visit.

RESULTS

Twenty-seven subjects (66%) completed the three-month follow-up visit. Twenty-five of these subjects completed four study treatments at one-week intervals. The remaining two subjects completed two and three treatments, respectively. Improvements in the appearance of acne were significant and occurred gradually over the course of the treatment series, with the highest reported improvement at the three-month follow-up visit, from both study investigators and subject self-assessments (Figure 1).

Figure 1.

Baseline and post-treatment photographs for three subjects. Baseline (A) and three months after four photopneumatic and profusion treatments using ProActiv® (B). Second row shows baseline (C) and three months after four photopneumatic and profusion treatments using ClenziDerm® MD (D). Third row shows baseline (E) and three months after four photopneumatic and profusion treatments using Murad® (F)

Investigator-assessed dinical improvement in mean acne severity (Burton Acne Scale) decreased from 3.95±0.6 (moderate acne) at baseline to 2.41±1.0 (comedonal to mild acne) at the final study visit three months after final treatment.

A 69-percent reduction in inflamed acne lesions and 41-percent reduction in noninflamed acne lesions were noted by physician assessment at the three-month follow up visit (Figure 2). Additionally, at this same time point, subjects reported moderate-to-marked (26-75%) improvement in acne lesions.

Figure 2.

Study investigators assessed average number of lesions, including inflamed and noninflamed, at each study visit for all three investigational sites. Data points include 95% confidence intervals. Number of subjects at each time point is 41, 37, 33, 32, 26, and 27, respectively.

Study investigators observed gradual improvement in the severity of acne, scarring, and pigmentation associated with acne over the course of the study using the Shamban Acne Scale (Figure 3).

Figure 3.

Study investigator assessed severity of acne, scarring, and pigmentation at each study visit using the Shamban Acne Scale. Each category: acne (A), scarring (S), and pigmentation (P) is scored using a 0-3 severity scale (0=none, 1=mild, 2=moderate, 3=severe). Data includes subjects from all three investigational sites. Data points include 95% confidence intervals. Number of subjects at each time point is 41, 37, 33, 32, 26, and 27, respectively.

Subject-rated satisfaction with clinical results was reported to be “very satisfied – satisfied” at the final study visit. No statistically significant differences in dinical observations were noted between the study sites or between topical agents used for profusion treatment and at-home daily use.

Photopneumatic treatment discomfort was reported by subjects to be 1.9/5±0.1 (corresponding to “slight” discomfort) and 0.91/5±0.1 for the profusion treatment (corresponding to “no” discomfort). Post-treatment skin responses after treatment one included mild erythema for nearly all subjects and mild edema in approximately five percent of subjects. Erythema and edema decreased in severity and percentage of subjects as the treatment series progressed. Mid edema was observed in 9 of 26 subjects one month post treatment and in 5 of 27 subjects at the final visit three months following treatment. There were no instances of edema reported at the one- or three-month follow-up visits. Other side effects and post-treatment skin responses observed during the one- and three-month follow-ups included mild hypo/hyperpigmentation (15% at 1 month and 11% at 3 months), mild dryness (11% at 1 month and 7% at 3 months), and mild flaking (11% at 1 month and 3 months). One subject had mild bruising on the forehead after treatment one due to a high vacuum level used on the forehead, which was resolved by the third treatment visit (within 14 days). There were no additional side effects or serious adverse events.

DISCUSSION

This is the largest prospective pubHshed study using photopneumatic treatment to date. The data demonstrated a gradual and significant improvement in the appearance of acne over the course of the treatment series, with results progressing into the follow-up visits. Inflamed and noninflamed lesion counts were significantly reduced over time, with even a considerable reduction (a combined average 34% reduction) after a single photopneumatic treatment with profusion. Treatment discomfort was negligible to minimal for all subjects with minimal severity in post-treatment skin responses. Post-treatment skin responses were consistent with those observed for photopneumatic treatment alone (i.e., without profusion therapy).

The effectiveness of photopneumatic devices for the treatment of mild-to-moderate acne vulgaris has been shown in several previous studies.6-8 In a retrospective study by Shamban and Narurkar,6 average physician-rated clearance of acne was visually estimated at 90 percent and average subject rated clearance was estimated at 78 percent after 2 to 4 treatments with the photopneumatic device performed at 3- to 5-week intervals for 56 subjects presenting with mild-to-severe acne.6 Independent physician assessment of pretreatment and post-treatment photographs for 11 of these subjects showed a decrease in inflammatory acne lesion counts from 5.5±3.25 to 1.5±1.0, respectively. Gold et al7 demonstrated significant reductions in lesion counts for both inflammatory (p=0.0137) and noninflammatory (p=0.0383) acne lesions in 11 subjects after a series of four photopneumatic treatments done at three-week intervals.7 Finally, in a prospective study of 18 subjects with mild-to-severe acne, Wanitphakdeedecha et al8 noted mild-to-moderate improvement in acne lesion counts and overall skin appearance after four photopneumatic treatments performed at two-week intervals. No adverse events were reported in any of these studies.

Omi et al9 demonstrated that the addition of the profusion tip to the photopneumatic system resulted in eariier dermal remodeHng of normal skin. The authors’ study specifically examined the combination treatment of the photopneumatic system and profusion therapy using three different FDA-approved and currently marketed topical acne agents. Regardless of the topical acne agent used, results showed continual improvement in the appearance of acne after the series of four treatments, which may suggest that the topical agents used maintained dinical results and may provide patients with a convenient way to continue targeting the P. acnes bacteria on the treated areas.

This present study followed subjects for three months after the treatment series. Further long-term data may be warranted to determine the lasting effects of photopneumatic treatment with profusion therapy when used in conjunction with topical acne products. The authors’ study had the shortest interval between treatments to date (1 week) with no deleterious side effects. Future studies are needed to determine the optimum treatment regimen in combination with current treatment modalities.

CONCLUSION

While photopneumatic treatments alone have shown to destroy P. acnes bacteria and clinically improve the appearance of acne and overall appearance of the skin, the series of combination treatments using photopneumatic technology with topical profusion therapy has also demonstrated significant treatment results, which continue to show lasting effects for at least three months after treatment. Since acne is a fluid disease with many components of active and dormant disease present simultaneously, the combination of energy-based devices in conjunction with topical medications should produce the best outcomes.