Journal of the American Academy of Dermatology
Volume 63, Issue 2 , Pages 195-211 , August 2010

Photodynamic therapy for acne vulgaris: A critical review from basics to clinical practice: Part II. Understanding parameters for acne treatment with photodynamic therapy

  • Fernanda H. Sakamoto, MD

      Affiliations

    • Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    • Department of Dermatology at the Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, Brazil
  • ,
  • Luis Torezan, MD

      Affiliations

    • Department of Dermatology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), 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. Lange N. Pharmaceutical and biological considerations in 5-aminolevulinic acid in PDT. In:  Hamblin MR,  Mroz P editor. Advances in photodynamic therapy basic, translational, and clinical. 1st ed. Norwood, MA: Artech House; 2008;p. 59–91
  2. Uehlinger P, Zellweger M, Wagnieres G, Juillerat-Jeanneret L, van den Bergh H, Lange N. 5-Aminolevulinic acid and its derivatives: physical chemical properties and protoporphyrin IX formation in cultured cells. J Photochem Photobiol B. 2000;54:72–80
  3. Peng Q, Moan J, Warloe T, Iani V, Steen HB, Bjørseth A, et al. Build-up of esterified aminolevulinic-acid-derivative-induced porphyrin fluorescence in normal mouse skin. J Photochem Photobiol B. 1996;34:95–96
  4. Whitaker CJ, Battah SH, Forsyth MJ, Edwards C, Boyle RW, Matthews EK. Photosensitization of pancreatic tumour cells by delta-aminolaevulinic acid esters. Anticancer Drug Des. 2000;15:161–170
  5. Döring F, Walter J, Will J, Föcking M, Boll M, Amasheh S, et al. Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest. 1998;101:2761–2767
  6. Rud E, Gederaas O, Hogset A, Berg K. 5-aminolevulinic acid, but not 5-aminolevulinic acid esters, is transported into adenocarcinoma cells by system BETA transporters. Photochem Photobiol. 2000;71:640–647
  7. Rodriguez L, Batlle A, Di Venosa G, Battah S, Dobbin P, Macrobert AJ, et al. Mechanisms of 5-aminolevulinic acid ester uptake in mammalian cells. Br J Pharmacol. 2006;147:825–833
  8. Gaullier JM, Berg K, Peng Q, Anholt H, Selbo PK, Ma LW, et al. Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res. 1997;57:1481–1486
  9. Gederaas OA, Holroyd A, Brown SB, Vernon D, Moan J, Berg K. 5-Aminolaevulinic acid methyl ester transport on amino acid carriers in a human colon adenocarcinoma cell line. Photochem Photobiol. 2001;73:164–169
  10. Perotti C, Fukuda H, DiVenosa G, MacRobert AJ, Batlle A, Casas A. Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies. Br J Cancer. 2004;90:1660–1665
  11. Fritsch C, Homey B, Stahl W, Lehmann P, Ruzicka T, Sies H. Preferential relative porphyrin enrichment in solar keratoses upon topical application of delta-aminolevulinic acid methylester. Photochem Photobiol. 1998;68:218–221
  12. Wiegell SR, Wulf HC. Photodynamic therapy of acne vulgaris using methyl aminolaevulinate: a blinded, randomized, controlled trial. Br J Dermatol. 2006;154:969–976
  13. Wiegell SR, Wulf HC. Photodynamic therapy of acne vulgaris using 5-aminolevulinic acid versus methyl aminolevulinate. J Am Acad Dermatol. 2006;54:647–651
  14. Hörfelt C, Funk J, Frohm-Nilsson M, Wiegleb Edström D, Wennberg AM. Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study. Br J Dermatol. 2006;155:608–613
  15. Kimura M, Itoh Y, Tokuoka Y, Kawashima N. Delta-aminolevulinic acid-based photodynamic therapy for acne on the body. J Dermatol. 2004;31:956–960
  16. Bickers DR, Frank J. The porphyrias. In:  Wolff K,  Goldsmith LA,  Katz SI,  Gilchrest BA,  Paller A,  Leffell DJ editor. Fitzpatrick's dermatology in general medicine, 7th ed. Vol II:New York: McGraw-Hill; 2007;p. 1228–1256
  17. Webber J, Kessel D, Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res. 1997;68:31–37
  18. 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
  19. Anderson RR, Parrish JA. The optics of human skin. J Invest Dermatol. 1981;77:13–19
  20. Sakamoto FH, Wall T, Avram MM, Anderson RR. Lasers and flashlamps in dermatology. In:  Wolff K,  Goldsmith LA,  Katz SI,  Gilchrest BA,  Paller A,  Leffell DJ editor. Fitzpatrick's dermatology in general medicine, 7th ed. Vol II:New York: McGraw-Hill; 2007;p. 2263–2279
  21. Sakamoto FH, Tannous Z, Doukas AG, Farinelli WA, Smith NA, Zurakowski D, et al. Porphyrin distribution after topical aminolevulinic acid in a novel porcine model of sebaceous skin. Lasers Med Surg. 2009;41:154–160
  22. 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
  23. 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
  24. Karrer S, Baumler W, Abels C, Hohenleutner U, Landthaler M, Szeimies RM. Long-pulse dye laser for photodynamic therapy: investigations in vitro and in vivo. Lasers Surg Med. 1999;25:51–59
  25. Strasswimmer J, Grande DJ. Do pulsed lasers produce an effective photodynamic therapy response?. Lasers Surg Med. 2006;38:22–25
  26. Gold MH, Bradshaw VL, Boring MM, Bridges TM, Biron JA, Carter LN. The use of a novel intense pulsed light and heat source and ALA-PDT in the treatment of moderate to severe inflammatory acne vulgaris. J Drugs Dermatol. 2004;3(6 suppl):S15–S19
  27. Taub AF. Photodynamic therapy for the treatment of acne: a pilot study. J Drugs Dermatol. 2004;3(6 suppl):S10–S14
  28. Alexiades-Armenakas M. Long-pulsed dye laser-mediated photodynamic therapy combined with topical therapy for mild to severe comedonal, inflammatory, or cystic acne. J Drugs Dermatol. 2006;5:45–55
  29. Santos MA, Belo VG, Santos G. Effectiveness of photodynamic therapy with topical 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: comparative study. Dermatol Surg. 2005;31(8 pt 1):910–915
  30. Rojanamatin J, Choawawanich P. Treatment of inflammatory facial acne vulgaris with intense pulsed light and short contact of topical 5-aminolevulinic acid: a pilot study. Dermatol Surg. 2006;32:991–996
  31. Yeung CK, Shek SY, Bjerring P, Yu CS, Kono T, Chan HH. A comparative study of intense pulsed light alone and its combination with photodynamic therapy for the treatment of facial acne in Asian skin. Lasers Surg Med. 2007;39:1–6
  32. Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science. 1983;220:524–527
  33. Nelson JS. Selective photothermolysis and removal of cutaneous vasculopathies and tattoos by pulsed laser. Plast Reconstr Surg. 1991;88:723–731
  34. 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;2:393–396
  35. 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
  36. Oseroff AR, Shieh S, Frawley NP, Cheney R, Blumenson LE, Pivnick EK, et al. Treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic therapy. Arch Dermatol. 2005;141:60–67
  37. Cottrell WJ, Paquette AD, Keymel KR, Foster TH, Oseroff AR. Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid-photodynamic therapy of superficial basal cell carcinomas. Clin Cancer Res. 2008;14:4475–4483
  38. 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
  39. Itoh Y, Ninomiya Y, Tajima S, Ishibashi A. Photodynamic therapy for acne vulgaris with topical 5-aminolevulinic acid. Arch Dermatol. 2000;136:1093–1095
  40. 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
  41. Hong SB, Lee MH. Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris. Photodermatol Photoimmunol Photomed. 2005;21:322–325
  42. Akaraphanth R, Kanjanawanitchkul W, Gritiyarangsan P. Efficacy of ALA-PDT vs blue light in the treatment of acne. Photodermatol Photoimmunol Photomed. 2007;23:186–190
  43. Harris DR, Papa CM, Stanton R. Percutaneous absorption and the surface area of occluded skin. A scanning electron microscopic study. Br J Dermatol. 1974;91:27–32
  44. Guillaume JC, De Rigal J, Leveque JL, Galle P, Touraine R, Dubertret L. Study of the correlation between transepidermal water loss and percutaneous penetration of steroid. [author's transl] Dermatologica. 1981;162:380–390
  45. Rhodes LE, Tsoukas MM, Anderson RR, Kollias N. Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin. J Invest Dermatol. 1997;108:87–91
  46. Joe EK, Anderson RR, Ortel BH. Spatial confinement of 5-aminolevulinic acid-based photodynamic therapy by thermal and chemical inhibition. Presented at the Fourth International Investigative Dermatology Meeting, April 30-May 4, 2003, Miami Beach, FL.
  47. Sakamoto FH, Doukas A, Farinelli WA, Tannous Z, Anderson RR. Skin temperature can control ALA-Photodynamic therapy. Presented at the 27th Annual Meeting of the American Society for Laser Medicine and Surgery, April 11-15, 2007, Grapevine, TX.
  48. Langan SM, Collins P. Randomized, double-blind, placebo-controlled prospective study of the efficacy of topical anaesthesia with a eutetic mixture of lignocaine 2.5% and prilocaine 2.5% for topical 5-aminolaevulinic acid-photodynamic therapy for extensive scalp actinic keratoses. Br J Dermatol. 2006;154:146–149
  49. Auletta M, Gange RW, Tan OT, Matzinger E. Effect of cutaneous hypoxia upon erythema and pigment responses to UVA, UVB, and PUVA (8-MOP + UVA) in human skin. J Invest Dermatol. 1986;86:649–652
  50. Youn JI, Gange RW, Maytum D, Parrish JA. Effect of hypoxia on sunburn cell formation and inflammation induced by ultraviolet radiation. Photodermatol. 1988;5:252–256
  51. Webber J, Luo Y, Crilly R, Fromm D, Kessel D. An apoptotic response to photodynamic therapy with endogenous protoporphyrin in vivo. J Photochem Photobiol B. 1996;35:209–211
  52. Bissonnette R, Nigen S, Bolduc C, Mery S, Nocera T. Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid. Dermatol Surg. 2008;34:1469–1476
  53. Wulf HC, Philipsen P. Allergic contact dermatitis to 5-aminolaevulinic acid methylester but not to 5-aminolaevulinic acid after photodynamic therapy. Br J Dermatol. 2004;150:143–145
  54. Hohwy T, Andersen KE, Solvsten H, Sommerlund M. Allergic contact dermatitis to methyl aminolevulinate after photodynamic therapy in 9 patients. Contact Dermatitis. 2007;57:321–323
  55. Harries MJ, Street G, Gilmour E, Rhodes LE, Beck MH. Allergic contact dermatitis to methyl aminolevulinate (Metvix) cream used in photodynamic therapy. Photodermatol Photoimmunol Photomed. 2007;23:35–36
  56. Jungersted JM, Dam TN, Bryld LE, Agner T. Allergic reactions to Metvix (ALA-ME). Contact Dermatitis. 2008;58:184–186
  57. Kaae J, Philipsen PA, Haedersdal M, Wulf HC. Immediate whealing urticaria in red light exposed areas during photodynamic therapy. Acta Derm Venereol. 2008;88:480–483
  58. Gniazdowska B, Rueff F, Hillemanns P, Przybilla B. Allergic contact dermatitis from delta-aminolevulinic acid used for photodynamic therapy. Contact Dermatitis. 1998;38:348–349
  59. Yokoyama S, Nakano H, Nishizawa A, Kaneko T, Harada K, Hanada K. A case of photocontact urticaria induced by photodynamic therapy with topical 5-aminolaevulinic acid. J Dermatol. 2005;32:843–847
  60. Kerr AC, Ferguson J, Ibbotson SH. Acute phototoxicity with urticarial features during topical 5-aminolaevulinic acid photodynamic therapy. Clin Exp Dermatol. 2007;32:201–202
  61. Ruiz-Rodriguez R, Sanz-Sanchez T, Cordoba S. Photodynamic photorejuvenation. Dermatol Surg. 2002;28:742–744
  62. Pagnoni A, Kligman AM, el Gammal S, Stoudemayer T. Determination of density of follicles on various regions of the face by cyanoacrylate biopsy: correlation with sebum output. Br J Dermatol. 1994;131:862–865
  63. Pierard GE. Rate and topography of follicular sebum excretion. Dermatologica. 1987;175:280–283

 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)00020-4

doi: 10.1016/j.jaad.2009.09.057

Journal of the American Academy of Dermatology
Volume 63, Issue 2 , Pages 195-211 , August 2010