Journal of the American Academy of Dermatology
Volume 63, Issue 2 , Pages 183-193 , August 2010

Photodynamic therapy for acne vulgaris: A critical review from basics to clinical practice: Part I. Acne vulgaris: When and why consider photodynamic therapy?

  • Fernanda H. Sakamoto, MD

      Affiliations

    • Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    • Department of Dermatology, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, Brazil
    • ,
  • José Daniel Lopes, MD, PhD

      Affiliations

    • Department of Immunology, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, Brazil
    • ,
  • R. Rox Anderson, MD

      Affiliations

    • Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    • Corresponding Author InformationReprint requests: Richard Rox Anderson, MD, Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit St, BHX 630, Boston, MA 02114.

References 

  1. Stern RS. The prevalence of acne on the basis of physical examination. J Am Acad Dermatol. 1992;26:931–935
  2. Stern RS. Dermatologists and office-based care of dermatologic disease in the 21st century. J Invest Dermatol Symp Proc. 2004;9:126–130
  3. Cunliffe WJ, Gould DJ. Prevalence of facial acne vulgaris in late adolescence and in adults. Br Med J. 1979;1:1109–1110
  4. Herane MI, Ando I. Acne in infancy and acne genetics. Dermatology. 2003;206:24–28
  5. Baldwin HE. The interaction between acne vulgaris and the psyche. Cutis. 2002;70:133–139
  6. Cunliffe WJ. Acne and unemployment. Br J Dermatol. 1986;115:386
  7. Wilkins JW, Voorhees JJ. Prevalence of nodulocystic acne in white and Negro males. Arch Dermatol. 1970;102:631–634
  8. Guy R, Green MR, Kealey T. Modeling acne in vitro. J Invest Dermatol. 1996;106:176–182
  9. Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty acids and acne. J Am Acad Dermatol. 1986;14(2 pt 1):221–225
  10. Kligman AM, Wheatley VR, Mills OH. Comedogenicity of human sebum. Arch Dermatol. 1970;102:267–275
  11. Voorhees JJ, Wilkins JW, Hayes E, Harrell ER. Nodulocystic acne as a phenotypic feature of the XYY genotype. Arch Dermatol. 1972;105:913–919
  12. Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol. 2003;121:20–27
  13. Thiboutot DM, Strauss JS. Diseases of the sebaceous gland, 6th ed. Vol I. New York: McGraw-Hill; 2003;p. 672-87
  14. Vowels BR, Yang S, Leyden JJ. Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne. Infect Immun. 1995;63:3158–3165
  15. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, et al. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. 2002;169:1535–1541
  16. Miyachi Y, Yoshioka A, Imamura S, Niwa Y. Effect of antibiotics on the generation of reactive oxygen species. J Invest Dermatol. 1986;86:449–453
  17. Cunliffe WJ, Meynadier J, Alirezai M, George SA, Coutts I, Roseeuw DI, et al. Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle. J Am Acad Dermatol. 2003;49(3 suppl):S218–S226
  18. Dubertret L, Alirezai M, Rostain G, Lahfa M, Forsea D, Niculae BD, et al. The use of lymecycline in the treatment of moderate to severe acne vulgaris: a comparison of the efficacy and safety of two dosing regimens. Eur J Dermatol. 2003;13:44–48
  19. Bossuyt L, Bosschaert J, Richert B, Cromphaut P, Mitchell T, Al Abadie M, et al. Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline. Eur J Dermatol. 2003;13:130–135
  20. Grosshans E, Belaich S, Meynadier J, Alirezai M, Thomas L. A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris. Eur J Dermatol. 1998;8:161–166
  21. Brown JM, Poston SM. Resistance of propionibacteria to antibiotics used in the treatment of acne. J Med Microbiol. 1983;16:271–280
  22. Eady EA, Gloor M, Leyden JJ. Propionibacterium acnes resistance: a worldwide problem. Dermatology. 2003;206:54–56
  23. Atzori L, Brundu MA, Orru A, Biggio P. Glycolic acid peeling in the treatment of acne. J Eur Acad Dermatol Venereol. 1999;12:119–122
  24. Lloyd JR. The use of microdermabrasion for acne: a pilot study. Dermatol Surg. 2001;27:329–331
  25. Kantor GR, Ratz JL, Wheeland RG. Treatment of acne keloidalis nuchae with carbon dioxide laser. J Am Acad Dermatol. 1986;14(2 pt 1):263–267
  26. Garrett AB, Dufresne RG, Ratz JL, Berlin AJ. Carbon dioxide laser treatment of pitted acne scarring. J Dermatol Surg Oncol. 1990;16:737–740
  27. Paithankar DY, Ross EV, Saleh BA, Blair MA, Graham BS. Acne treatment with a 1,450 nm wavelength laser and cryogen spray cooling. Lasers Surg Med. 2002;31:106–114
  28. Quastler H. Radiotherapy of acne vulgaris; comparative tests of treatment technics. Radiology. 1950;54:247–256
  29. Pasieczny T, Grant P. Preliminary and short reports; a comparison in the treatment of acne vulgaris. J Invest Dermatol. 1951;16:71–74
  30. Strauss JS, Kligman AM. Effect of x-rays on sebaceous glands of the human face: radiation therapy of acne. J Invest Dermatol. 1959;33:347–356
  31. Bingham HG, Robinson DW. Radiation-induced malignancy in a patient with acne vulgaris. Report of four different histologic types. Am J Surg. 1967;114:472–476
  32. Epstein E. Thyroid cancer due to x-ray treatment of acne. JAMA. 1969;209:1529–1530
  33. Jones H, Blanc D, Cunliffe WJ. 13-cis retinoic acid and acne. Lancet. 1980;2:1048–1049
  34. Jones DH, Greenwood R, Cunliffe WJ. Dose-response relationship of sebum suppression by 13-cis-retinoic acid in severe acne. Br J Dermatol. 1983;109:366–367
  35. Strauss JS, Leyden JJ, Lucky AW, Lookingbill DP, Drake LA, Hanifin JM, et al. A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne. J Am Acad Dermatol. 2001;45:187–195
  36. Strauss JS, Rapini RP, Shalita AR, Konecky E, Pochi PE, Comite H, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol. 1984;10:490–496
  37. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. Isotretinoin for acne vulgaris—10 years later: a safe and successful treatment. Br J Dermatol. 1993;129:292–296
  38. Leyden JJ. Oral isotretinoin. How can we treat difficult acne patients?. Dermatology. 1997;195(suppl 1):29–33
  39. Ghaffarpour G, Mazloomi S, Soltani-Arabshahi R, Seyed KS. Oral isotretinoin for acne, adjusting treatment according to patient's response. J Drugs Dermatol. 2006;5:878–882
  40. Quereux G, Volteau C, N'Guyen JM, Dreno B. Prospective study of risk factors of relapse after treatment of acne with oral isotretinoin. Dermatology. 2006;212:168–176
  41. Zouboulis CC. The truth behind this undeniable efficacy—recurrence rates and relapse risk factors of acne treatment with oral isotretinoin. Dermatology. 2006;212:99–100
  42. Gollnick HP, Graupe K, Zaumseil RP. Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne. Eur J Dermatol. 2001;11:538–544
  43. DiGiovanna JJ, Langman CB, Tschen EH, Jones T, Menter A, Lowe NJ, et al. Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne. J Am Acad Dermatol. 2004;51:709–717
  44. Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol. 2001;45:515–519
  45. Robertson J, Polifka JE, Avner M, Chambers C, Delevan G, Koren G, et al. A survey of pregnant women using isotretinoin. Birth Defects Res A Clin Mol Teratol. 2005;73:881–887
  46. Abroms L, Maibach E, Lyon-Daniel K, Feldman SR. What is the best approach to reducing birth defects associated with isotretinoin?. PLoS Med. 2006;3:e483
  47. Berg M. Epidemiological studies of the influence of sunlight on the skin. Photodermatol. 1989;6:80–84
  48. Shteinberg MA, Tribulskaia ZF. Short-wave ultraviolet therapy of seborrhea and acne with the Kuf-3 lamp. [in Russian] Vestn Dermatol Venerol. 1963;37:70–71
  49. Mutzhas MF, Holzle E, Hofmann C, Plewig G. A new apparatus with high radiation energy between 320-460 nm: physical description and dermatological applications. J Invest Dermatol. 1981;76:42–47
  50. Sigurdsson V, Knulst AC, van Weelden H. Phototherapy of acne vulgaris with visible light. Dermatology. 1997;194:256–260
  51. van Weelden H, de Gruijl FR, van der Putte SC, Toonstra J, van der Leun JC. The carcinogenic risks of modern tanning equipment: is UV-A safer than UV-B?. Arch Dermatol Res. 1988;280:300–307
  52. Cornelius CE, Ludwig GD. Red fluorescence of comedones: production of porphyrins by Corynebacterium acnes. J Invest Dermatol. 1967;49:368–370
  53. Podymov VK, Gladkikh SP, Myskin VS, Muratov MA. Nature of fluorescence of secretions of the sebaceous glands in children depending on age and sex. [in Russian] Vestn Dermatol Venerol. 1980;4:7–8
  54. McGinley KJ, Webster GF, Leyden JJ. Facial follicular porphyrin fluorescence: correlation with age and density of Propionibacterium acnes. Br J Dermatol. 1980;102:437–441
  55. Matta M. Carriage of Corynebacterium acnes in school children in relation to age and race. Br J Dermatol. 1974;91:557–561
  56. Leyden JJ, McGinley KJ, Mills OH, Kligman AM. Propionibacterium levels in patients with and without acne vulgaris. J Invest Dermatol. 1975;65:382–384
  57. Meffert H, Scherf HP, Sonnichsen N. Treatment of acne vulgaris with visible light. [in German] Dermatol Monatsschr. 1987;173:678–679
  58. Lee WL, Shalita AR, Poh-Fitzpatrick MB. Comparative studies of porphyrin production in Propionibacterium acnes and Propionibacterium granulosum. J Bacteriol. 1978;133:811–815
  59. Kjeldstad B, Johnsson A. An action spectrum for blue and near ultraviolet inactivation of Propionibacterium acnes; with emphasis on a possible porphyrin photosensitization. Photochem Photobiol. 1986;43:67–70
  60. Papageorgiou P, Katsambas A, Chu A. Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris. Br J Dermatol. 2000;142:973–978
  61. Elman M, Lebzelter J. Light therapy in the treatment of acne vulgaris. Dermatol Surg. 2004;30(2 pt 1):139-4
  62. Lee SY, You CE, Park MY. Blue and red light combination LED phototherapy for acne vulgaris in patients with skin phototype IV. Lasers Surg Med. 2007;39:180–188
  63. Tzung TY, Wu KH, Huang ML. Blue light phototherapy in the treatment of acne. Photodermatol Photoimmunol Photomed. 2004;20:266–269
  64. Ammad S, Gonzales M, Edwards C, Finlay AY, Mills C. An assessment of the efficacy of blue light phototherapy in the treatment of acne vulgaris. J Cosmet Dermatol. 2008;7:180–188
  65. Omi T, Bjerring P, Sato S, Kawana S, Hankins RW, Honda M. 420 nm intense continuous light therapy for acne. J Cosmet Laser Ther. 2004;6:156–162
  66. Shnitkind E, Yaping E, Geen S, Shalita AR, Lee WL. Anti-inflammatory properties of narrow-band blue light. J Drugs Dermatol. 2006;5:605–610
  67. 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
  68. US Food and Drug Administration web site. ClearLight phototherapy device, model CL 420. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf/K013623.pdf. Accessed August 31, 2009.
  69. US Food and Drug Administration web site. BLU-U@ blue light photodynamic therapy illuminator, model 4170. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf3/k031805.pdf. Accessed August 31, 2009.
  70. Gavish M, Bachman I, Shoukrun R, Katz Y, Veenman L, Weisinger G, et al. Enigma of the peripheral benzodiazepine receptor. Pharmacol Rev. 1999;51:629–650
  71. Divaris DX, Kennedy JC, Pottier RH. Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized protoporphyrin IX fluorescence. Am J Pathol. 1990;136:891–897
  72. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B. 1990;6:143–148
  73. Svanberg K, Andersson T, Killander D, Wang I, Stenram U, Andersson-Engels S, et al. Photodynamic therapy of non-melanoma malignant tumours of the skin using topical delta-amino levulinic acid sensitization and laser irradiation. Br J Dermatol. 1994;130:743–751
  74. Jeffes EW, McCullough JL, Weinstein GD, Fergin PE, Nelson JS, Shull TF, et al. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study. Arch Dermatol. 1997;133:727–732
  75. Hongcharu W, Taylor CR, Chang Y, Aghassi D, Suthamjariya K, Anderson RR. Topical ALA-photodynamic therapy for the treatment of acne vulgaris. J Invest Dermatol. 2000;115:183–192
  76. Itoh Y, Ninomiya Y, Tajima S, Ishibashi A. Photodynamic therapy for acne vulgaris with topical 5-aminolevulinic acid. Arch Dermatol. 2000;136:1093–1095
  77. Itoh Y, Ninomiya Y, Tajima S, Ishibashi A. Photodynamic therapy of acne vulgaris with topical delta-aminolaevulinic acid and incoherent light in Japanese patients. Br J Dermatol. 2001;144:575–579
  78. Nowis D, Golab J. Photodynamic therapy and oxidative stress. In:  Hamblin MR,  Mroz P editor. Advances in photodynamic therapy basic, translational, and clinical. 1st ed. Norwood, MA: Artech House; 2008;p. 151–178
  79. Karrer S, Bosserhoff AK, Weiderer P, Landthaler M, Szeimies RM. Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts. Br J Dermatol. 2004;151:776–783
  80. Akamatsu H, Horio T. The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation. Dermatology. 1998;196:82–85
  81. Kick G, Messer G, Goetz A, Plewig G, Kind P. Photodynamic therapy induces expression of interleukin 6 by activation of AP-1 but not NF-kappa B DNA binding. Cancer Res. 1995;55:2373–2379
  82. Soukos NS, Ximenez-Fyvie LA, Hamblin MR, Socransky SS, Hasan T. Targeted antimicrobial photochemotherapy. Antimicrob Agents Chemother. 1998;42:2595–2601
  83. Hamblin MR, Hasan T. Photodynamic therapy: a new antimicrobial approach to infectious disease?. Photochem Photobiol Sci. 2004;3:436–450
  84. Horfelt C, Stenquist B, Larko O, Faergemann J, Wennberg AM. Photodynamic therapy for acne vulgaris: a pilot study of the dose-response and mechanism of action. Acta Derm Venereol. 2007;87:325–329
  85. Pollock B, Turner D, Stringer MR, Bojar RA, Goulden V, Stables GI, et al. Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action. Br J Dermatol. 2004;151:616–622
  86. Hong SB, Lee MH. Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris. Photodermatol Photoimmunol Photomed. 2005;21:322–325
  87. Bryld LE, Jemec GB. The bacterial flora of the skin surface following routine MAL-PDT. J Dermatolog Treat. 2006;17:222–223
  88. Yung A, Stables GI, Fernandez C, Williams J, Bojar RA, Goulden V. Microbiological effect of photodynamic therapy (PDT) in healthy volunteers: a comparative study using methyl aminolaevulinate and hexyl aminolaevulinate cream. Clin Exp Dermatol. 2007;32:716–721
  89. Orringer JS, Hammerberg C, Hamilton T, Johnson TM, Kang S, Sachs DL, et al. Molecular effects of photodynamic therapy for photoaging. Arch Dermatol. 2008;144:1296–1302
  90. Hayami J, Okamoto H, Sugihara A, Horio T. Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acid. J Dermatol. 2007;34:320–327
  91. Friedmann PS. Disappearance of epidermal Langerhans cells during PUVA therapy. Br J Dermatol. 1981;105:219–221
  92. Orenstein A, Haik J, Tamir J, Winkler E, Trau H, Malik Z, et al. Photodynamic therapy of cutaneous lymphoma using 5-aminolevulinic acid topical application. Dermatol Surg. 2000;26:765–769
  93. Zane C, Venturini M, Sala R, Calzavara-Pinton P. Photodynamic therapy with methylaminolevulinate as a valuable treatment option for unilesional cutaneous T-cell lymphoma. Photodermatol Photoimmunol Photomed. 2006;22:254–258
  94. Stott B, Korbelik M. Activation of complement C3, C5, and C9 genes in tumors treated by photodynamic therapy. Cancer Immunol Immunother. 2007;56:649–658
  95. Kang S, Cho S, Chung JH, Hammerberg C, Fisher GJ, Voorhees JJ. Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo. Am J Pathol. 2005;166:1691–1699
  96. Papakonstantinou E, Aletras AJ, Glass E, Tsogas P, Dionyssopoulos A, Adjaye J, et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol. 2005;125:673–684
  97. Karrer S, Bosserhoff AK, Weiderer P, Landthaler M, Szeimies RM. Influence of 5-aminolevulinic acid and red light on collagen metabolism of human dermal fibroblasts. J Invest Dermatol. 2003;120:325–331
  98. Ruiz-Rodriguez R, Sanz-Sanchez T, Cordoba S. Photodynamic photorejuvenation. Dermatol Surg. 2002;28:742–744
  99. Marmur ES, Phelps R, Goldberg DJ. Ultrastructural changes seen after ALA-IPL photorejuvenation: a pilot study. J Cosmet Laser Ther. 2005;7:21–24
  100. Anderson RR, Ortel B, Battle EF, Joe EK, inventors; Massachusetts General Hospital, assignee. Methods and devices for epithelial protection during photodynamic therapy. US patent 20040259855. December 23, 2004.
  101. Sitnik TM, Hampton JA, Henderson BW. Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate. Br J Cancer. 1998;77:1386–1394

 Funding sources: None.

 Conflicts of interest: The authors, editors, JAAD CME council members, and peer reviewers have no relevant financial relationships.

PII: S0190-9622(10)00019-8

doi: 10.1016/j.jaad.2009.09.056

Journal of the American Academy of Dermatology
Volume 63, Issue 2 , Pages 183-193 , August 2010

Article Tools

* Image Usage & Resolution