Phototherapy versus Adapalene 0.1% Gel in Treatment of Acne Vulgaris

Background: Phototherapy has been increasingly used for treatment of acne vulgaris. The targets of the action mechanism of each light treatment are generally thought to be P. acnes. Visible light has been proposed to work by decreasing P. acnes bacterial counts by activating endogenous porphyrins. Objective: To evaluate the effectiveness of phototherapy with Pulsed Light and Heat Energy (LHE) versus topical Adapalene 0.1% in the treatment of mild forms of acne. Method: During the period of 2 years were treated 99 patients with Acne vulgaris, 51 with mild form of Acne vulgaris were treated with Phototherapy and 48 patients with mild form were treated with topical Adapalene 0.1%.The effectiveness was based on the number of inflammatory and non-inflammatory elements in the beginning moment of therapy and in the intervals after two sessions, 4 sessions, 6 sessions, 8 sessions, one month after treatment with Phototherapy and after 2, 4, 6, 8, 10, 12 weeks treatment with Adapalene 0.1% Gel. Results: One month after the treatment with Phototherapy, the inflammatory and non-inflammatory elements cleaning reached 67.9 ± 6.2% in mild form and 68.4 ± 6.5% in moderate form of Acne vulgaris. Three months after the treatment with local treatment, the inflammatory and non-inflammatory elements cleaning reached 59.4 ± 5.8 in mild form and 71.4 ± 7.2 after treatment with local plus systemic in moderate form of Acne vulgaris. Conclusion: The treatment of Acne vulgaris with phototherapy LHE as mono-therapy is a medical alternative which gives good clinical results in a relatively short period of time (one month) and with minimal side effects.


Introduction
Acne vulgaris is the most common disease and is characterized by non-inflammatory, open or closed comedones and by inflammatory papules, pustule and nodules. Acne vulgaris affects the areas of skin with the densest population of sebaceous follicles. These areas include the face, the upper part of the chest and the back.

The pathophysiology of acne involves four key mechanisms of action
Abnormal proliferation and differentiation of keratinocytes, increased sebum production, hyper proliferation of Propionibacterium acnes, and an inflammatory response initiated by bacterial antigens and cytokines [1]. Acne vulgaris affects the areas of skin with the density of population of sebaceous follicles. These areas include the face, the upper part of the chest and the back P acnes are an anaerobic organism present in acnelessions [2]. The presence of P. acnes promotes inflammation through a variety of mechanisms. P. acnes stimulates inflammation by producing pro-inflammatory mediators that diffuse through the follicle wall [3][4][5][6][7][8].
Studies have shown that P. acnes activate the toll-like (TL) receptor 2 on monocytes and neutrophils. Activation of the TL receptor 2 then leads to the production of multiple pro inflammatory cytokines, including interleukins (IL) and IL8 and tumor necrosis factor (TNF). Hypersensitivity at P. acnes may also explain why some individuals develop inflammatory acne vulgaris while others do not [9].
Inflammation may be a primary phenomenon or a secondary phenomenon. Most of the evidence to date suggests a secondary inflammatory response to P. acnes [4,5]. However, IL-alpha expression has been identified in microcomedones and it may play a role in the development of acne [7]. Propionibacterium acnes are an obvious target for acne phototherapy since it is central to the inflammatory process [1]. P. acnes makes porphyrins, which are present in the follicle, in proportion to its population. Once the porphyrins are exposed to visible light, it becomes chemically active and transfers to an excited state, resulting in the formation of singlet oxygen, which combines with cell membranes to destroy the P. acnes.
This process is depended on the rate of production of excited porphyrin molecules, which is influenced by the concentration of porphyrins, the concentration of photons, the temperature, and the wavelength of photons [1].

Objective
The objective of this study is to compare the clinical efficacy of Phototherapy (LHE) versus Adapalene 0.1 Gel in the treatment of Acne Vulgaris.

Method
During the period of 2 years were treated 99 patients with Acne vulgaris, 51 with mild form of Acne vulgaris were treated with Phototherapy and 48 patients with mild form were treated with topical Adapalene 0.1% Gel.
For acne classification we used a recent proposal by the US FDA for a five-category global system. In this scale, the five categories ranged from • Clear, indicating no inflammatory or non-inflammatory lesions.
• Almost clear, rare non-inflammatory lesions with no more than one papules/pustule. • Mild, some non-inflammatory lesions, no more than a few papules or pustules but no nodules. • Moderate, up to many non-inflammatory lesions, may have some inflammatory lesions, but no more than one small nodule. • Severe, up to many non-inflammatory and inflammatory lesions, but no more than a few nodules.
The continuous variables were presented through mean value and standard deviation and the categorical variables were presented in absolute and in percentage value. Continuous variables were compared through the Student's t-test and one-way ANOVA, which is used when more than two groups are compared. The Chi-square test was used for analysing the differences between the categorical variables. A p value less than <0.05 is considered significant.
In the first group, the study included the total of 51 patients treated with phototherapy at average age 18.06 ± 3.33 years, 62.7% of whom were female and 37.3% were male. The average age of the subjects in the study was 18.06 years old with a minimum age of 14 years and maximum 27 years (

The Inclusion Criteria Applied for Phototherapy
Age over 14 years old, general good health, the ability of complying with the study protocol and an acne severity grade of mild to moderate form.

Exclusion criteria hormonal/endocrinal disorders
Exclusion criteria hormonal/endocrinal disorders, pregnant or lactating, having a history with herpes simplex, suffer of collagenases, have been treated with retinoid within the past 6 months, treated with sulphonamides, tetracycline, thiazides, antidepressant tricyclic, anti inflamatore non-steroidal, suffer from epilepsy, have a history of skin cancer, have tanned by sun within the last 30 days.

Treatment's Parameters of Phototherapy
Before the treatment, depending on the skin's phototype, the energy level setting was done by which of the patients would be treated (  The full treatment of patients was conducted in eight sessions. Treatments were administered twice a week for a four week period. Each session consisted of two consecutive applications that last 10-15 min. In the second application the energy level was raised by 5-10 units. Adjustable pulse durations 35 ms and an optical fluence of 3.5 J/cm 2 per pulse.
Pulses per face treatment was about 40, the device used for treatment was skin station, production of Radiancy Company. The device emits light energy with wavelengths 430-1100 nm.

Clinic Evaluation Parameters
The main clinical indicators studied where the noninflammatory elements were included

Results of Clinical Parameters
One month after the treatment with Phototherapy, the inflammatory and non-inflammatory elements cleaning, reached 67.9 ± 6.2% in mild form and 68.4 ± 6.5% in moderate form of Acne vulgaris. After 8 sessions of treatment with phototherapy, inflammatory elements show greater improvements as compared to non-inflammatory ones (p=0.001). The results of the one month long treatment (eight sessions) are converted in percentage as follows: Percentage presentation of the decrease of inflammatory, noninflammatory and total elements before treatments, after 2 sessions, four sessions, six sessions, eight sessions and one month after treatment.
All patients completed the treatment according to the treatment protocols of photo therapy (LHE), with minimum side effects. A positive response was seen in all patients during treatment with photo therapy (LHE). By continuously monitoring the patients, it was found that the effect of treatment was almost undetectable after the first two sessions, and became noticeable after four sessions. The effect increased further as the treatment progressed. At the end of the treatment (after eight sessions), it was seen that important statistical differences existed between inflammatory and non-inflammatory elements as compared to the pre-treatment average baseline.

Average ± SD
The difference in the number of elements (total) between the start and end of therapy  Table 3: Comparison of phototherapy on acne vulgaris. Table 3, appear averages and standard deviation in the difference in the occurrence of clinical signs of acne vulgaris before and after treatment and% of improving the clinical signs (total elements, inflammatory and non-inflammatory elements). When analyzed in percentage, the improvement is better significantly in inflammatory elements while percentage improvement in total elements and elements non-inflammatory don't have significant changes.  In Table 4, the improvement of clinical signs presented in % reduction in the number of inflammatory and non-inflammatory telements is under treatment and gender. When analysing the t test is not made in response to significant changes in the two ranks phototherapy of acne vulgaris by gender. No changes in total treatment effect according to sex in the case of acne vulgaris mild and moderate grade.  In Table 5, no changes in total treatment effect according to photo type in the case of acne vulgaris mild.
Compare the photo type setting no significant change in percentage of improving the clinical signs of acne vulgaris in patients with mild form. Photo type is not to assess the effectiveness of treatment with phototherapy acne vulgaris. One month after the treatment stated in percentage, this effect was 70.4 ± 6.9% inflammatory elements and 63.3 ± 12.4% for non-inflammatory elements in mild form (Figures 1 to 4).   In the second group study included the total of 47 patients with mild form of acne vulgaris they were treated locally with Adapalene 0.1% Gel. The average age of the subjects in the study was 18.7 years old with a minimum age of 13 years and maximum 27 years.

Exclusion Criteria
Exclusion criteria prohibited enrolment of subjects with acne requiring isotretinoin therapy or other dermatologic conditions requiring interfering treatment. Women were excluded if they were under hormonal/endocrinal disorders, pregnant, nursing or planning a pregnancy as were men with facial hair that would interfere with the assessments (Table 6).

Variables
No. of patient standard treatment (%)

Results
The results of 12 weeks treatment are converted in percentage as follows Percentage presentation of the decrease of inflammatory, noninflammatory and total elements before treatments, after 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks and 12 weeks. At the end of the treatment (after eight sessions) it was seen that important statistical differences existed between inflammatory and non-inflammatory elements as compared to the pre-treatment average baseline. After three months treatment with local treatment, the inflammatory and non-inflammatory elements cleaning, reached 59.4 ± 5.8% (Table 7 and Figures 5 and 6).

Mild grade Average ± SD
The difference in the number of elements (total) between the start and end of therapy 15.9 ± 2.8 The The percentage of improvement of clinical signs no inflammatory elements 58.9 ± 6.8 Table 7: Comparison of local treatment on acne vulgaris.

Discussion
The results show that phototherapy, pulsating light heat energy (LHE) emitted by the Skin Station apparatus, is an effective and rapid treatment compared to any other alternative treatment. The continuous monitoring of the patients before, during and one month after the treatment showed satisfactory results in clearing out the inflammatory and non-inflammatory elements of acne vulgaris ( Figure  7 and Table 8).  Table 8: The progress of the total numbers of elements in the treatment with phototherapy vs. local therapy. Figure 7: The progress of total number of elements in the treatment with phototherapy vs. local therapy.
Phototherapy appears to be effective and with satisfactory results in clearing out the inflammatory and non-inflammatory elements at the end of the treatment, as well as one month after the treatment. The results are better for the inflammatory elements. The results are statistically equal for both genders, independent of age. The results are statistically equal for both the photo types II, III, IV. Phototherapy LHE has obliterating and anti-inflammatory effects P acnes. Propionibacterium acnes are an obvious target for acne phototherapy since it is central to the inflammatory process11. P.acnes makes porphyrins, which are present in the follicle, in proportion to its population. Once the porphyrin is exposed to visible light, it becomes chemically active and transfers to an excited state, resulting in the formation of singlet oxygen, which combines with cell membranes to destroy the P. acnes [1,2,10]. This process is depended on the rate of production of excited porphyrin molecules, which is influenced by the concentration of porphyrins, the concentration of photons, the temperature and the wavelength of photons [8]. Phototherapy has an obvious advantage in the treatment of mild grade of Acne vulgaris compared with local treatment

Conclusion
Although topical and oral therapies are considered the first line of treatment, significant adverse side effects or bacterial resistance may exist. Thus, there is an unmet need for well-tolerated therapy that provides effective acne clearance without the risk of side effects.
Recently, a significant advancement in photobiology and laser/lightbased technology created new possibilities to treat acne. Based on successful in vitro and in vivo studies and human clinical trials conducted in the last 5 years, it is evident that the amelioration of acne with light-based therapy is comparable to the effects of oral antibiotics, and improvement is maintained for several months. Furthermore, it appears that these systems offer faster resolution and fewer side effects and lead to patient satisfaction. Based on this study it is concluded that