A multicenter clinical evaluation of the treatment of mild to moderate inflammatory acne vulgaris of the face with visible blue light in comparison to topical 1% clindamycin antibiotic solution

Michael H. Gold

Abstract

Background: Blue light sources have been shown to be effective in the treatment of mild to moderate inflammatory acne vulgaris lesions.

Objective: We evaluated the safety and efficacy of a new blue light source in the treatment of mild to moderate inflammatory acne vulgaris in comparison to topical 1% clindamycin solution.

Results: Blue light therapy reduced inflammatory acne vulgaris lesions by an average of 34%, as compared to 14% for topical 1% clindamycin solution.

Conclusions: The blue light source presented in this report is a safe and effective treatment option available to our patients with mild to moderate inflammatory acne lesions.

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Introduction

The traditional treatment of acne vulgaris involves the use of a variety of topical and systemic medications. Recently, a new group of blue light sources has entered into the acne treatment therapeutic armamentarium to treat mild to moderate inflammatory acne vulgaris. These light sources are finding a useful niche for those seeking alternative/additional treatment options for this, at times, frustrating disease to treat. The purpose of this clinical trial was to evaluate the safety and efficacy of a new blue light source, the Blu-U[TM] Blue Light Photodynamic Therapy Illuminator Model 4170 (Dusa Pharmaceuticals, Wilmington, MA), Figure 1, in comparison to topical 1% clindamycin solution Cleocin T[TM] solution (UpJohn Pharmaceutical, Kalamazoo, MI) in the treatment of mild to moderate inflammatory acne vulgaris. Both the Blu-U and topical 1% clindamycin topical solution are approved/cleared for the treatment of acne vulgaris by the U.S. Food and Drug Administration (FDA). Topical 1% clindamycin solution is a successful and useful topical acne vulgaris therapy. Many studies have used this compound as a marker when evaluating new acne vulgaris therapies. (1) The Blu-U Blue Light Photodynamic Therapy Illuminator is an electrical Class I, Type B device which has FDA clearance for the treatment of moderate inflammatory acne vulgaris and in combination with Levulan[R] Kerastick[TM] (Dusa Pharmaceuticals, Wilmington, MA) (aminolevulinic acid HCl) for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp.

Materials and Methods

This clinical trial was a 2-center, randomized, investigator-blinded pilot study comparing the safety and efficacy of blue light alone compared to topical 1% clindamycin solution therapy in patients with mild to moderate inflammatory acne vulgaris of the face. The clinical trial was performed under the auspices of an institutional review board. The study design consisted of a 1-week washout phase followed by a 4-week treatment phase and concluded with a 4-week no treatment follow-up phase. During the 1-week washout phase, the patients refrained from using any medicated topical products to treat their facial acne vulgaris except for a standard facial cleanser, Cetaphil[R] cleanser (Galderma, Arlington, TX). Patients also had to be off systemic antibiotics for 4 weeks and systemic retinoids for 6 months prior to the study. Patients were excluded from participation if they had previously received light therapy of any kind in the past.

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During the 4-week treatment phase, patients were randomized to receive either a) two times per week therapy with the Blu-U or b) topical 1% clindamycin solution to be self-administered twice daily at home by the subject. For those receiving blue light therapy, each treatment consisted of 16 minutes and 40 seconds of light therapy (1000 seconds). In the follow-up phase, designed to evaluate the duration of effect for the therapies, patients again refrained from using any medications to treat their facial acne vulgaris while continuing to use the standard facial cleanser.

The status of each patient's facial acne vulgaris was evaluated periodically throughout the treatment and follow-up phases of this clinical trial. A blinded investigator evaluated the patient and performed acne vulgaris lesion counts, a global severity score analysis, and an overall improvement score. Adverse effects were to be noted and documented at all times during the time period of the clinical trial.

Results

Thirty-four patients signed an informed consent to participate in this clinical research investigation. Twenty-five completed the 4-week treatment phase (beginning with mild to moderate inflammatory acne vulgaris lesions) and 18 of these patients completed the 4-week follow-up phase (72%). Nine patients who signed an informed consent were not able to follow through with the 4-week treatment phase and were not included in the results of this study. The age range of the study participants was from 13 years of age to 55 years of age, with a mean age of 31.0 years. The study population of those finishing the 4-week treatment phase consisted of 22 females and 3 males. Sixteen of the patients were Caucasian, 7 were African-American, 1 was an American Indian, and 1 was of Chinese descent.

Thirteen of the patients evaluated were randomized to receive twice daily application of topical 1% clindamycin antibiotic solution; 12 of the patients were randomized to receive twice weekly blue light therapy. The number of non-inflammatory acne vulgaris lesions was evaluated at each visit and the number of inflammatory acne vulgaris lesions was evaluated at each study visit as well.

Topical 1% Clindamycin Solution

The number of non-inflammatory acne vulgaris lesions at the first treatment visit varied from 9 to 95 lesions, with an average of 29 non-inflammatory lesions. At the 4-week treatment evaluation, lesion counts for non-inflammatory acne vulgaris lesions varied from 7 to 78, with an average of 20.3 lesions. The percent average improvement was calculated to be 30%. For the 9 patients in this group of patients who completed the 4-week follow-up phase, lesion counts for non-inflammatory acne vulgaris lesions varied from 4 to 38 lesions, with an average of 12.5 lesions. This sub-group of patients averaged a lesion count of 10.8 lesions at the end of the 4-week treatment phase (compared to the 20.3 lesions seen in this group as a whole). This shows a 14% change in the follow-up period for this sub-group of patients.

For inflammatory acne vulgaris lesions in the topical 1% clindamycin solution group of patients, the number of inflammatory acne vulgaris lesions present at the first treatment varied from 12 to 32 lesions, with an average of 17.4 lesions. At the 4-week treatment evaluation, lesion counts for inflammatory acne vulgaris lesions varied from 4 to 43 lesions, with an average of 15 lesions. The percent average improvement in this group was 14%. For the 9 patients in this group of patients who completed the 4-week follow-up phase, lesion counts for inflammatory acne vulgaris lesions varied from 4 to 19 lesions, with an average of 10.4 lesions. This sub-group of patients averaged a lesion count of 10.8 lesions at the end of the 4-week treatment phase (compared to 15 lesions seen in this group as a whole). The percentage change in this sub-group of individuals was not significant.

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Blue Light Group

Twelve patients completed the 4-week treatment phase and 9 of the patients finished their 4-week follow-up phase evaluations. Non-inflammatory acne vulgaris lesions present at the first treatment evaluation varied from 9 to 120 lesions, with an average of 29.4 non-inflammatory acne vulgaris lesions. At the 4-week treatment evaluation, lesion counts for non-inflammatory acne vulgaris lesions varied from 5 to 54 lesions, with an average of 23.3 lesions. The percent improvement was 21%. For the nine patients in this group who completed the 4-week follow-up phase, non-inflammatory acne vulgaris lesion counts varied from 8 to 40 lesions, with an average of 21.4 lesions. This subgroup of patients averaged a lesion count of 21.6 at the end of the 4-week treatment phase (as compared to 23.3 lesions seen in this group as a whole). The percentage change in this sub-group of individuals was not significant.

For inflammatory acne vulgaris lesions in the blue light group of patients, the number of lesions present at the first treatment evaluation varied from 16 to 34 lesions, with an average of 22.6 inflammatory acne vulgaris lesions. At the end of the 4-week treatment evaluation, lesion counts for inflammatory acne vulgaris lesions varied from 0 to 35, with an average of 14.5 lesions. The percent improvement in this group of individuals was 36%. For the nine patients in this group who completed their 4-week follow-up phase, lesion counts varied from 0 to 24 lesions, with an average of 11.1 lesions. This sub-group of patients averaged a lesion count of 11.1 inflammatory acne vulgaris lesions at the end of the 4-week treatment phase (compared to the 14.5 lesions seen in this group as a whole). The percentage change in this sub-group of individuals was not significant. Clinical examples of patients treated with the blue light source are shown in Figure 2 and Figure 3.

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Both groups of patients noted that the therapies were well tolerated with no significant adverse events reported in either group of patients. Improvement Scores and Global Improvement Scores were similar between both groups of patients.

Discussion

Acne vulgaris is one of the most common dermatologic conditions presenting to dermatologists for evaluation and treatment. It has been estimated that from 70% to 96% of our population will suffer from acne at some point in their lifetime. Reports have indicated that 40 million American adolescents and 25 million American adults are afflicted with acne vulgaris. (1) One third of these patients will likely present for evaluation and therapy, and acne vulgaris accounts for more than 30% of all dermatology visits each year. (2)

The etiology of acne vulgaris is multifactorial, with both genetic and hormonal influences known to play a significant role in the disease process. Family history can be found in the majority of cases of acne vulgaris. Hormonal influences for the development of acne vulgaris are known to commence at the time of puberty; however, hormonal influences can be involved in acne vulgaris at any point in one's lifetime.

The pathogenesis of acne vulgaris is complex and involves microbial proliferation, inflammation, and abnormal desquamation of the follicular epithelium. Simplified, acne vulgaris is a disorder of the pilar unit and sebaceous glands where hormonal influence, primarily an increase in the production of androgens, causes dilation and obstruction of the pilo-sebaceous unit. These are evident as non-inflammatory acne vulgaris lesions, commonly known as open and closed comedones. As a result of the pilo-sebaceous unit obstruction, there is a proliferation of bacterial growth, predominantly growth of Propionobacterium acnes (P. acnes). Clinically, inflammatory acne lesions are produced, including papules, pustules, and cysts. (3)

The traditional treatment of mild to moderate acne vulgaris involves a myriad of topical and systemic medications. The medications include both topical and systemic antibiotics, topical benzoyl peroxides, topical salicylic acids, topical and systemic retinoids, and various combinations of the topical medicines. Hormonal therapy is also used, on occasion, in the treatment of acne vulgaris. All of these medications have shown effectiveness in therapy of acne vulgaris and the majority of dermatologists will utilize a combination approach when treating the patient afflicted with acne vulgaris. Each group of medications, however, has potential adverse effects, which could possibly limit their overall effectiveness in treating those with acne vulgaris. Some of the topical medications are irritating to the skin and many of these require extended use to show a positive effect in the therapy of acne vulgaris. The common systemic antibiotics, although effective in many cases of acne vulgaris, have, at times, significant adverse events and have recently shown a high percentage of drug resistance, up to 40% reported. (1,4) Recently, a report of increased exposure to systemic antibiotics and a potential association with breast cancer may have an effect on our prescribing habits with these agents. (5) Systemic retinoids, very useful for recalcitrant acne vulgaris cases, have teratogenic and psychological concerns, which have limited their overall use. (1)

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It has been known for many years that exposure to natural ultraviolet light is beneficial for many patients suffering from acne vulgaris. (6) It is not an uncommon occurrence to have patients comment on their lesional improvement following exposure to ultraviolet light, both natural and artificial. The exact mechanism for this improvement has not been fully elucidated, but presumably involves the natural destruction of the P. acnes bacteria in the sebaceous gland. This destruction of the P. acnes bacteria will lead to resolution of the acne lesion itself. The process by which this occurs is known as Photodynamic Therapy (PDT). This endogenous form of PDT does work for the treatment of acne vulgaris; however, the well documented harmful effects of ultraviolet light, including photoaging and the increased incidence of skin cancers, precludes its regular use in the treatment of acne vulgaris.

The photodynamic reaction, which is seen in the acne vulgaris lesions, involves the natural production of porphyrins by the P. acnes bacteria themselves during their proliferation in the sebaceous glands. The porphyrins, which are produced by the P. acnes, have a demonstrated absorption spectrum in the near-ultraviolet range of light. More specifically, it has been shown that the principal porphyrins produced by P. acnes is protoporphyrin IX and coproporphyrin III, which, as shown in Figure 4, has a peak absorption at 415 nanometers (nm). This falls in the blue light range of the photodynamic absorption spectrum. Therefore, phototherapy and PDT with blue light sources should be beneficial in the treatment of acne vulgaris.

The process by which this photodynamic effect occurs works through the photo-excitation of the P. acnes porphyrins after exposure of the appropriate wavelength of light. This will then lead to the production of singlet oxygen within the bacteria itself and ultimate destruction of the P. acnes bacteria. The reaction that takes place is very specific and acne clearance will occur. The surrounding tissues and structures are not affected in this PDT process. The reaction is very fast and has been demonstrated to be useful in vivo. Patient compliance to this therapy is high, with no pain or associated downtime with this procedure.

The medical literature has various reports with blue light sources being effective for the treatment of mild to moderate inflammatory acne vulgaris. Kawada et al (7) demonstrated an effect of low intensity blue light with wavelengths between 405 and 420 nm to be effective in clearing those affected with mild to moderate inflammatory acne vulgaris. Up to 64% of their patients responded favorably to the blue light source. Papageorgiou et al (8) reported on a combination blue light and red light source for those suffering from mild to moderate inflammatory acne vulgaris lesions. The blue light source was successful in reducing inflammatory lesions by 63% in this series. Still others (9,10) have evaluated other blue light sources for the treatment of acne vulgaris. These investigators showed a 60% to 70% improvement in mild to moderate inflammatory acne vulgaris lesions. However, up to 20% of these patients were considered non-responders and not included in the final analysis, which would have led to a lower percentage for lesional clearance.

Conclusion

The results from this clinical research trial support the concept of the blue light source as a safe and effective therapy for the treatment of mild to moderate inflammatory acne vulgaris. Throughout the past several decades, many acne vulgaris clinical trials have used topical 1% clindamycin solution as the benchmark in comparing or evaluating new acne vulgaris treatments or treatment strategies. This current research project also utilized topical 1% clindamycin solution in the attempt to show efficacy data versus, and in comparison with, the blue light source described.

The blue light source described in this report, Blu-U, is an affordable blue light source that does have a positive effect in patients suffering from mild to moderate inflammatory acne vulgaris. The current clinical evaluation showed that both inflammatory and non-inflammatory acne vulgaris lesions will respond in a positive fashion to the twice-weekly blue light therapy for the recommended 4 weeks of therapy. The results from this clinical trial show that blue light therapy may be superior to topical 1% clindamycin solution especially for inflammatory acne vulgaris; this was demonstrated in the treatment phase of this research project and in the post-treatment phase as well. The resolution of 36% of active acne lesions for blue light therapy compared to 14% for the clindamycin group shows the effectiveness of the blue light source in the treatment of mild to moderate inflammatory acne vulgaris.

Patients tolerated the treatments well and there were no significant adverse effects noted during the course of this research project. Blue light therapy has a place in the treatment of acne vulgaris and should be considered in our treatment paradigm when confronted with our patients' suffering from acne vulgaris. Clinicians need to determine how to incorporate this new therapy into their everyday clinical practice of dermatology. Combination therapies with topical antibiotics and topical retinoids, along with the blue light source, may offer an ideal treatment program for many of our patients with mild to moderate inflammatory acne vulgaris.

This was a small clinical trial and more patients should be evaluated in the future to see if the percent changes demonstrated in this clinical trial hold up to further evaluations. Responders and non-responders were included in our evaluations, which lower the overall percentage as compared to other reports previously described with a blue light source. Various combination therapy clinical trials should be undertaken to determine the optimum way to utilize the blue light source. These would include increasing the treatment times for blue light therapy and increasing the number of blue light treatments, all in an attempt to demonstrate increased patient efficacy. Also, adding topical 20% 5-aminolevulinic acid is known to enhance light sources and should be studied in patients with mild to moderate acne vulgaris.

Our patients are interested in our new technologies and we have blue light sources, which are efficacious in treating inflammatory acne vulgaris. Young patients are surrounded by technology on a daily basis--blue light fits this bill. Older patients yearn for new therapies for acne vulgaris and by utilizing new technologies, such as the blue light sources for inflammatory acne vulgaris, they too will be excited to incorporate this into their acne treatment routine.

References

1. Leyden JJ. Therapy for acne vulgaris. N Engl J Med. 1997; 336:1156-1162.

2. Del Rossa JQ. Acne in the adolescent patient: inter-relationship of psychological impact and therapeutic options. Today Ther Trends. 2001; 19:473-484.

3. Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol. 2003; 49:S200-S10.

4. Gollnick H, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003; 49(1Suppl):S1-S37.

5. Velice, CM, et al. Antibiotic use in relation to the risk of breast cancer. JAMA. 2004; 291:827-835.

6. Sigurdsson V, et al. Phototherapy of acne vulgaris with visible light. Dermatology. 1997; 194:256-260.

7. Kawada A, et al. Acne phototherapy with a high-intensity, enhanced narrow-band, blue light source: an open study and in vitro investigation. J Dermatol Sci. 2002; 30:129-135.

8. Papageorgiou P, et al. Phototherapy with blue (415nm) and red (660nm) light in the treatment of acne vulgaris. Br J Dermatol. 2000; 142:973-978.

9. Med Lett Drug Ther. 2003; 45(1159):50-51.

10. Elman M, Slatkine M, Harth Y. The effective treatment of acne vulgaris by a high-intensity, narrow band 405-420 nm light source. J Cosmet Laser Ther. 2003; 5:111-117.

Michael H. Gold MD, (a) Jaggi Rao MD, (d) Mitchel P. Goldman MD, (b) Tancy M. Bridges NP, (c) Virginia L. Bradshaw NP, (c) Molly M. Boring NP, (c) April N. Guider RN (c)

a. Medical Director, Gold Skin Care Center, Tennessee Clinical Research Center Nashville, TN

b. Medical Director, Dermatology/Cosmetic Laser Associates of LaJolla and LaJolla Spa MMD, La Jolla, CA

c. Gold Skin Care Center, Tennessee Clinical Research Center, Nashville, TN

d. Dermatology/Cosmetic Laser Associates of LaJolla and LaJolla Spa MD, La Jolla, CA

ADDRESS FOR CORRESPONDENCE

Michael H. Gold, MD

Gold Skin Care Center

2000 Richard Jones Road

Suite 220

Nashville, TN 37215.

Phone: 615-383-2400.

e-mail: drgold@goldskincare.com

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