Topical Methyl Aminolevulinate Photodynamic Therapy for the Treatment of Actinic Keratosis



Actinic (or solar) keratosis (AK) is a common lesion in fair-skinned ­populations that develops as a result of solar damage to the skin. It is variously referred to as a precancerous lesion that may progress to squamous cell carcinoma (SCC) or as SCC (in situ type). Methyl aminolevulinate photodynamic therapy is still an evolving therapy for actinic keratosis that has good efficacy and provides excellent cosmetic outcomes. The objective of this chapter is to investigate the efficacy of topical methyl aminolevulinate photodynamic therapy (MAL-PDT), its cosmetic outcomes, and its side effects. Multiple electronic databases were searched for studies involving methyl aminolevulinate photodynamic therapy and actinic keratosis. Cochrane Central Register of Controlled Trials was also searched. Cited references of all trials were identified and key review articles were assessed for discussion of relevant outcomes investigated. A total of 11 studies that studied MAL-PDT to treat AK are included in this review. Four studies compared ­MAL-PDT and cryotherapy; three other studies compared MAL-PDT with placebo cream. Only one study compared MAL-PDT with both cryotherapy and placebo, while one report examined MAL-PDT in comparison with aminolevulic acid photodynamic therapy (ALA-PDT). The other two studies compared differences in treatment regimens, dose and treatment interval. MAL-PDT is effective as a treatment for AK lesions especially on the face and scalp. The cosmetic outcome is excellent and superior to cryotherapy in terms of minimum skin discoloration and scarring. The side effects, including skin “burning,” pain, and erythema, have been reported as tolerable.


Photodynamic Therapy Basal Cell Carcinoma Cosmetic Outcome Complete Response Rate Actinic Keratosis 


  1. 1.
    Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000;42:4–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2004;42:23–4.CrossRefGoogle Scholar
  3. 3.
    Leffell DJ. The scientific basis of skin cancer. J Am Acad Dermatol. 2000;42:18–22.PubMedCrossRefGoogle Scholar
  4. 4.
    Drake LA, Ceilley RI, Cornelison RL. Guidelines of care for actinic keratoses. J Am Acad Dermatol. 1995;32:95–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Squamous SG, Carcinoma C, Keratosis A, Keratosis S. Manual of skin disease. 5th ed. Philadelphia: JB Lippincott; 1985. 1985.Google Scholar
  6. 6.
    Marks R, Rennie G, Selwood T. The relationship of basal cell carcinomas and squamous cell carcinomas to solar keratoses. Arch Dermatol. 1998;124: 1039–42.CrossRefGoogle Scholar
  7. 7.
    Nelson MA, Einspahr JG, Alberts DS. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers. Cancer Lett. 1994;85(1):23–9.PubMedCrossRefGoogle Scholar
  8. 8.
    de Berker D, McGregor JM, Hughes BR. Guidelines for the management of actinic keratoses. Br J Dermatol. 2007;156:222–30.CrossRefGoogle Scholar
  9. 9.
    Parrish JA. Immunosuppression, skin cancer, and ultraviolet A radiation. N Eng J Med. 2005;353(25): 2712–3.CrossRefGoogle Scholar
  10. 10.
    Gold MH. Pharmacoeconomic analysis of the treatment of multiple actinic keratoses. J Drugs Dermatol. 2008;7(1):23–5.PubMedGoogle Scholar
  11. 11.
    Wolf JEJ, Talyor JR, Tschen E, Kang S. Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol. 2001;40:709–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Calzavara-Pinton PG, Venturini M, Sala R. Photodynamic therapy: update 2006 Part 2: clinical results. JEADV. 2007;21(4):439–51.PubMedGoogle Scholar
  13. 13.
    Angell-Petersen E, Sorensen R, Warloe T, Soler AM, Moan J, Peng Q, et al. Porphyrin formation in actinic keratosis and basal cell carcinoma after topical application of methyl 5-aminolevulinate. J Invest Dermatol. 2005;126(2):265–71.CrossRefGoogle Scholar
  14. 14.
    Peng Q, Soler A, Warloe T, Nesland J, Giercksky K. Selective distribution of porphyrins in skin thick basal cell carcinoma after topical application of methyl 5-aminolevulinate. J Photochem Photobiol B. 2001; 62(3):140–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Braathen LR, Szeimies R-M, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, et al. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. J Am Acad Dermatol. 2007;56(1):125–43.PubMedCrossRefGoogle Scholar
  16. 16.
    Faten G, Gilles V, Michele B, Richard B, Robert B. Photodynamic therapy with 5-aminolevulinic acid induces apoptosis and caspase activation in malignant T Cells. J Cutan Med Surg. 2001;5:8–13.Google Scholar
  17. 17.
    Noodt BB, Berg K, Stokke T, Peng Q, Nesland JM. Apoptosis and necrosis induced with light and 5-aminolaevulinic acid-derived protoporphyrin IX. Br J Cancer. 1996;74(1):22–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Szeimies RM, Karrer S, Radakovic-Fijan S, Tanew A, Calzavara-Pinton PG, Zane C, et al. Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. J Am Acad Dermatol. 2002;47(2):258–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Tarstedt M, Rosdahl I, Berne B, Svanberg K, Wennberg A-M. A randomized multicenter study to compare two treatment regimens of topical methyl aminolevulinate (Metvix)-PDT in actinic keratosis of the face and scalp. Acta Derm Venereol. 2005;85:1–5.CrossRefGoogle Scholar
  20. 20.
    Caekelbergh K, Annemans L, Lambert J, Roelandts R. Economic evaluation of methyl aminolaevulinate-based photodynamic therapy in the management of actinic keratosis and basal cell carcinoma. Br J Dermatol. 2006;155:784–90.PubMedCrossRefGoogle Scholar
  21. 21.
    Szeimies R-M, Matheson RT, Davis SA, Bhatia AC, Frambach Y, Klövekorn W, et al. Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study. Dermatol Surg. 2009;35: 586–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Pariser D, Loss R, Jarratt M, Abramovits W, Spencer J, Geronemus R, et al. Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: a ­randomized, double-blind placebo-controlled study. J Am Acad Dermatol. 2008;59(4):569–76.PubMedCrossRefGoogle Scholar
  23. 23.
    Freeman M, Vinciullo C, Francis D, Spelman L, Nguyen R, Fergin P, et al. A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study. J Dermatol Treat. 2003;14:99–106.CrossRefGoogle Scholar
  24. 24.
    Kaufmann R, Spelman L, Weightman W, Reifenberger J, Szeimies RM, Verhaeghe E, et al. Multicentre intraindividual randomized trial of topical methyl aminolaevulinate photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities. Br J Dermatol. 2008;158(5):994–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Moloney FJ, Collins P. Randomized, double-blind, prospective study to compare topical 5-aminolaevulinic acid methylester with topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratosis. Br J Dermatol. 2007;157:87–91.PubMedCrossRefGoogle Scholar
  26. 26.
    Morton C, Campbell S, Gupta G, Keohane S, Lear J, Zaki I, et al. Intraindividual, right–left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study. Br J Dermatol. 2006;5(155):1029–36.CrossRefGoogle Scholar
  27. 27.
    Pariser DM, Lowe NJ, Stewart DM, Jarratt MT, Lucky AW, Pariser RJ, et al. Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. J Am Acad Dermatol. 2003;48:227–32.PubMedCrossRefGoogle Scholar
  28. 28.
    Braathen LR, Paredes BE, Saksela O, Fritsch C, Gardlo K, Morken T, et al. Short incubation with methyl aminolevulinate for photodynamic therapy of actinic keratoses. J Eur Acad Dermatol Venereol. 2008;23:550–5.CrossRefGoogle Scholar
  29. 29.
    Kurwa HA, Yong Gee SA, Seed PT. A randomized paired comparison of photodynamic therapy and topical 5 fluorouracil in the treatment of actinic keratosis. J Am Acad Dermatol. 1999;41:414–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Rud E, Gederaas O, Hogset A. 5-aminolevulinic acid, but not 5-aminolevulinic esters, is transported into adenocarcinoma cells by BETA trabsporter. Photochem Photobiol. 2000;71:640–7.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Dermatology, Skin and Cancer FoundationThe University of MelbourneCarltonAustralia
  2. 2.Department of Medicine (Dermatology)St Vincent’s Hospital MelbourneFitzroyAustralia

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