Pulsed dye laser treatment has been investigated as a potential therapy of acne vulgaris based on the observation that light of various wavelengths, including those in sunlight, may result in improvement in patients with acne vulgaris.  Photodynamic therapy (PDT) has also been investigated for the treatment of acne and involves topical application of aminolevulinic acid (ALA) that is absorbed and metabolized intracellularly. This policy addresses treatment of acne vulgaris using pulsed dye laser or photodynamic therapy.  

Note: Please see the following documents for related information:

• Cosmetic and Reconstructive Services: Skin Related (ANC.00007)
• Low Level Laser Therapy (MED.00043)
• Management of Rosacea (CG-MED-27)
• Photodynamic Therapy (MED.00017)
• Ultraviolet Light, Including Laser Therapy, for the Treatment of Skin Disorders (MED.00008).

Investigational/Not Medically Necessary:

The use of pulsed dye laser or photodynamic therapy is considered investigational/not medically necessary for the treatment of acne vulgaris.

Rationale

Pulsed dye laser
Pulsed dye laser has been used in the treatment of atrophic acne scarring; however it has more recently been investigated for the treatment of active inflammatory acne vulgaris.  Two randomized controlled trials have been published; however, these contain conflicting data.  In October of 2003, Seaton and colleagues reported in The Lancet a study involving 41 patients who were randomized to either a single low fluence pulsed dye laser treatment group or sham treatment control group and were followed for 12 weeks.  Eligible patients were aged between 18 and 45 years with mild to moderate facial inflammatory acne defined as the presence of at least 10 acne papules or pustules between the brow and jaw line, and an acne severity score of between 2 and 7 on the Leeds revised acne grading system.  (This is an accepted acne grading system that assigns a numerical score between 1 and 12, depending on severity.)  Both assessors and participants were blinded to the treatment allocations.  At 12 weeks, the mean acne grade had improved from baseline by 1.9 in the laser treated patients compared to 0.1 in the sham treatment control group.  Total lesion counts fell by 53% in the laser treatment group compared to 9% in the placebo treated patients, and inflammatory lesion counts fell by 49% and 10% respectively.  The authors conclude that: “laser treatment should be further explored as an adjuvant or alternative to daily conventional pharmacological treatments.”

In contrast, Orringer and colleagues reported in JAMA, June 2004, described a study of 40 patients enrolled in a randomized, single-blind, split-face clinical trial.  Patients were randomized to one of two treatment groups receiving either a single pulsed dye laser treatment to half of the face with the opposite non-treated side serving as control, or a pulsed dye laser treatment at baseline, and a repeat treatment two weeks later, with both treatments to the same half of the face and the opposite side again acting as control.  Inclusion criteria were age 13 years or older and the presence of acne with a severity rating of 2 or greater on the Leeds acne severity scale.  As with the Seaton study, significant acne therapies were withheld for a period prior to, and during the course of the trial, and patients were evaluated over a 12-week period.  In Orringer’s study, sebum production was also measured.  A panel of 3 dermatologists blinded to the treatment side evaluated standardized bilateral facial photographs at baseline, week 4 and week 12.  Close inter-rater reliability was demonstrated.  Of the 40 eligible patients, 19 were randomized to receive treatment to the left side of the face and 21 to the right side to account for any potentially uneven environmental effects (such as sunshine exposure driving with the window open).  At twelve weeks, changes in lesion counts (including pustules, comedones, macules, cysts, papules) for the treated side of the face compared with the untreated side showed no statistically significant difference from baseline.  In addition, no statistically significant difference in sebum production was found between the treated and untreated skin.

The authors of the split face study felt their protocol was important in terms of assessing changes in the patient’s acne compared to the natural course of the disorder, in that acne may undergo spontaneous improvement and flares which may not be accounted for in other study designs. (Note the Seaton study did not use a split face protocol.) The authors of this JAMA study conclude that: “…additional well designed studies are needed before the use of pulse dye laser becomes a part of acne therapy.”

It should be noted that both studies contained small numbers of patients, especially given the high prevalence of acne in the target populations, and the different protocols utilized, together with the conflicting results obtained, do not allow conclusions to be drawn as to the effectiveness of pulsed dye laser treatment of active and/or inflammatory acne vulgaris.  Harper(2004) wrote in the Journal of the American Academy of Dermatology in an article entitled “An update on the pathogenesis and management of acne vulgaris” suggests that while lasers are being used in individuals with acne vulgaris, controlled clinical studies are still needed.

Although the Food and Drug Administration has approved the Candela Smoothbeam Laser System, there has been no documented studies determining efficacy and safety of this device.

Photodynamic therapy
There are only a few published reports regarding the use of photodynamic therapy in the treatment of acne.  Most of these studies involve small numbers of patients, utilize differing light sources, and are case series trials. Only a few controlled trials are available that report on the use of photodynamic therapy for the treatment of cane vulgaris.  One pilot study, published in August 2000, used an aggressive ALA-photodynamic therapy treatment dose to test the possibility of effects on acne vulgaris (Hongcharu, 200).  They noted that each treatment was painful or pruritic, caused acute erythema and edema, occasionally caused blistering and purpura, or caused an acute acneiform eruption lasting up to three weeks, and usually led to hypopigmentation that faded gradually over weeks or months.  Consequently they state: “To most people, these side-effects would be tolerable in practice only if PDT were able to permanently improve acne, which remains a distinct possibility.” (Note the study follow up period was 20 weeks, however.)  The authors go on to say: “Dose-response characteristics for ALA-PDT treatment of acne are unknown.  We plan future studies exploring the precise dosimetry.”  In separate recent reviews (2003, 2004) of acne management, Gollnick and colleagues stated that: “Photodynamic therapy has not yet been proven efficacious in controlled studies,” while Harper (2004) states that: “Controlled clinical trials are lacking at this time.”

A controlled trail by Weigell and colleagues of 21 patients receiving photodynamic therapy with methyl aminolaevulinate and 15 controls reported significant improvements in the treatment group compared to the controls (2006).  After twelve weeks of treatment there was a 68% reduction in inflammatory lesions vs. no change in the control group.  However, as previously discussed, all patients experienced moderate to severe pain during treatment and developed erythema, pustular eruptions and epithelial exfoliation.  Seven treatment patients (33.3%) dropped out of the study due to adverse effects.

A 2005 Hayes report on photodynamic therapy for acne vulgaris stated that the evidence is insufficient to recommend photodynamic therapy as a treatment for acne vulgaris at this time.  Also that preliminary evidence suggests that photodynamic therapy and ALA may significantly improve acne symptoms, but the sample size and the number of studies were too small to determine efficacy and safety. The reproducibility and extent of the beneficial outcome, as well as safety, need to be confirmed in additional studies.

Background/Overview

Pulsed dye laser
Pulsed dye laser treatment has been investigated as a potential therapy based on the observation that light of various wavelengths, including those in sunlight, may result in improvement in patients with acne vulgaris.  Pulsed dye lasers generally emit light wavelengths that are strongly absorbed by oxygenated hemoglobin, and high irradiation energy densities (fluences) are used to treat vascular lesions such as port wine stains.  These high fluences ablate small blood vessels and cause subcutaneous bleeding (purpura).  Lower non-ablative fluences are non-purpuric however, and treatment can result in increased collagen production with improvement in the appearance of wrinkles and atrophic acne scarring.  The development of inflammatory acne lesions is closely associated with the presence of propionibacterium acnes, a protoporphyrin-containing organism that is killed by exposure to light of specific wavelengths.  This process is one of the proposed mechanisms explaining the potential benefit of low fluence pulsed dye laser in the treatment of active acne lesions.

In January 2004, the U.S. Food and Drug Administration (FDA) approved the marketing of at least one pulsed dye laser (NLite System-ICN Photonics Ltd.) for the treatment of inflammatory acne vulgaris.

Photodynamic therapy
This technique, which is also being investigated for the treatment of acne, involves topical application of aminolevulinic acid (ALA) that is absorbed and metabolized intracellularly to form the photosensitizing molecule protoporphyrin IX.  When this 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 photodynamic therapy system, Levulan® Kerastick™ includes topical 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.”  {It should be noted however, that certain phototherapy devices (as opposed to photodynamicsystems) e.g., ClearLight and ClearTouch™ light sources, have received FDA approval for acne treatment.}

Definitions

Acne Vulgaris: a chronic, inflammatory disease characterized by the formation of open and closed comedones (whiteheads and blackheads), erythematous papules and pustules, pseudocysts and nodules. It is generally a condition of adolescence involving the face, neck, upper trunk and upper arms

Photodynamic Therapy (PDT): involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases

Coding

The following codes for treatments and procedures applicable to this policy are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational/Not Medically Necessary:

CPT

HCPCS

ICD-9 Diagnosis

References

Peer Reviewed Publications:

1. Elman E, Lebzelter J. Light Therapy in the Treatment of Acne Vulgaris. Dermatol. Surg. 2004; 30(2 Pt 1):139-46.
2. Goldman MP, Boyce SM. A single-center study of aminolevulinic acid and 417 NM photodynamic therapy in the treatment of moderate to severe acne vulgaris. J Drugs Dermatol. 2003;2(4):393-6.
3. Gollnick HP, Krautheim A. Topical treatment in acne: current status and future aspects. Dermatology. 2003; 206(1):29-36.
4. Harper J.C. An update on the pathogenesis and management of acne vulgaris. Journal of the American Academy of Dermatology. 2004; 51(1 suppl):S36-8.
5. Hongcharu WJ, Taylor CR, Chang Y, et al. Topical ALA-photodynamic therapy for the treatment of acne vulgaris. Invest. Dermatol. 2000; 115(2):183-192.
6. Glaich AS, Friedman PM, Jih MH, Goldberg LH. Treatment of inflammatory facial acne vulgaris with combination 595-nm pulsed-dye laser with dynamic-cooling-device and 1,450-nm diode laser. Lasers Surg Med. 2006; 38(3):177-180. 
7. Itoh Y, Ninomiya Y, Tajima S, Ishibashi A. et al. Photodynamic therapy of acne vulgaris with topical delta-aminolevulinic acid and incoherent light in Japanese patients. Br. J Dermatol. 2001; 144(3):575-579.
8. Orringer JS,  Orringer JS, Kang S, Hamilton T, et al.   Treatment of acne vulgaris with a pulsed dye laser, a randomized controlled trial. JAMA. 2004; 291(23): 2834-2839. 
9. Seaton E.D.,Seaton ED, Charakida A, Mouser PE, et al. Pulsed-dye laser treatment for inflammatory acne vulgaris: randomized controlled trial. Lancet, 2003; 362:1347-1352. 
10. Wiegell SR, Wulf HC Photodynamic therapy of acne vulgaris using 5-aminolevulinic acid versus methyl aminolevulinate. J Am Acad Dermatol. 2006; 54(4):647-651.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Academy of Dermatology. Guidelines for care for Acne Vulgaris management. Available at: http://www.aad.org/NR/rdonlyres/FAD10239-F59B-486 C-8082-28545B54F59A/0/Acne_Guideline.pdf. Accessed on February 9, 2007.
2. Centers for Medicare and Medicaid Services. National Coverage Determination for Laser Procedures. NCD #140.5.  Effective May 1, 1997.  Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd.  Accessed on February 9, 2007.
3. Food and Drug Administration (FDA). Candela Smoothbeam Laser System. Available at: http://www.fda.gov/cdrh/pdf3/k030834.pdf.  Accessed on April 3, 2006.
4. Hayes Inc. Hayes Medical Technology Directory. Phototherapy for Acne Vulgaris. Lansdale, PA: Hayes, Inc. December 1, 2005. Search updated December 31, 2006.
   

Web Sites for Additional Information

1. National Library of Medicine (NIH); Acne.  Available at:  http://www.nlm.nih.gov/medlineplus/ency/article/000873.htm.  Accessed on February 9, 2007.

Index

Policy History

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by an means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

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