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Treatment of actinic keratosis


Actinic keratoses (AKs or solar keratoses) are keratotic macules, papules, or plaques resulting from the intraepidermal proliferation of atypical keratinocytes in response to prolonged exposure to ultraviolet radiation. Although most AKs do not progress to squamous cell carcinoma (SCC), AKs are a concern because the majority of cutaneous SCCs arise from pre-existing AKs, and AKs that will progress to SCC cannot be distinguished from AKs that will spontaneously resolve or persist [1,2]. Because of these factors, most clinicians routinely treat AKs [3]. Improvement in associated symptoms and cosmetic appearance can be additional benefits of treatment.

The treatment of AKs will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of AKs are discussed separately. (See "Epidemiology, natural history, and diagnosis of actinic keratosis".)


Overview — Treatment options for actinic keratosis (AK) include destructive therapies (eg, surgery, cryotherapy, dermabrasion), topical medications (eg, 5-fluorouracil [5-FU], imiquimod, ingenol mebutate, diclofenac), chemical peels (eg, trichloroacetic acid), and photodynamic therapy (PDT). In general, lesion-directed treatments, such as cryotherapy and surgical procedures, are the primary approach for isolated lesions [3]. Field-directed therapies, such as topical 5-FU, imiquimod, ingenol mebutate, and diclofenac, are particularly useful for treating areas with multiple AKs. Evidence for efficacy of these therapies is derived from multiple randomized trials and systematic reviews [4-8].

One systematic review and meta-analysis of 83 randomized trials evaluating 24 treatments in over 10,000 patients found sufficient evidence to conclude that 3% diclofenac in 2.5% hyaluronic acid, 0.5% 5-FU, 5% imiquimod, and 0.025% to 0.05% ingenol mebutate are superior to placebo for complete clearance of lesions in the treated field in patients with AKs [4]. In addition, this systematic review and meta-analysis found that PDT performed with aminolevulinic acid (ALA-PDT) with red light or blue light or with methyl aminolevulinate (MAL-PDT) with red light was superior to placebo for the treatment of individual AK lesions [4]. The meta-analysis also found that treatment with imiquimod or PDT generally resulted in better cosmetic outcomes than 5-FU and cryotherapy [4].

A subsequent network meta-analysis of 26 individual or pooled randomized trials evaluated the relative efficacy in inducing complete lesion clearance for eight main interventions for AK [5]. This analysis suggests that topical 5-FU is the most effective treatment followed by: 5-aminolevulinic acid (ALA) PDT; topical imiquimod; ingenol mebutate; 5-methylaminolaevulinate (MAL) PDT; cryotherapy; topical diclofenac with hyaluronic acid; and placebo. However, the ranking of relative efficacies should be interpreted with caution because of the variability in the parameters used to describe the AK severity in the included studies.


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Literature review current through: Oct 2014. | This topic last updated: Oct 1, 2014.
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  1. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115:2523.
  2. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988; 1:795.
  3. Ceilley RI, Jorizzo JL. Current issues in the management of actinic keratosis. J Am Acad Dermatol 2013; 68:S28.
  4. Gupta AK, Paquet M, Villanueva E, Brintnell W. Interventions for actinic keratoses. Cochrane Database Syst Rev 2012; 12:CD004415.
  5. Gupta AK, Paquet M. Network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol 2013; 169:250.
  6. Nashan D, Meiss F, Müller M. Therapeutic strategies for actinic keratoses--a systematic review. Eur J Dermatol 2013; 23:14.
  7. Rahvar M, Lamel SA, Maibach HI. Randomized, vehicle-controlled trials of topical 5-fluorouracil therapy for actinic keratosis treatment: an overview. Immunotherapy 2012; 4:939.
  8. Askew DA, Mickan SM, Soyer HP, Wilkinson D. Effectiveness of 5-fluorouracil treatment for actinic keratosis--a systematic review of randomized controlled trials. Int J Dermatol 2009; 48:453.
  9. Lubritz RR, Smolewski SA. Cryosurgery cure rate of actinic keratoses. J Am Acad Dermatol 1982; 7:631.
  10. Thai KE, Fergin P, Freeman M, et al. A prospective study of the use of cryosurgery for the treatment of actinic keratoses. Int J Dermatol 2004; 43:687.
  11. Jeffes EW 3rd, Tang EH. Actinic keratosis. Current treatment options. Am J Clin Dermatol 2000; 1:167.
  12. Coleman WP 3rd, Yarborough JM, Mandy SH. Dermabrasion for prophylaxis and treatment of actinic keratoses. Dermatol Surg 1996; 22:17.
  13. Hauschild A, Popp G, Stockfleth E, et al. Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch. Exp Dermatol 2009; 18:116.
  14. Serra-Guillén C, Nagore E, Hueso L, et al. A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes. J Am Acad Dermatol 2012; 66:e131.
  15. Hadley J, Tristani-Firouzi P, Hull C, et al. Results of an investigator-initiated single-blind split-face comparison of photodynamic therapy and 5% imiquimod cream for the treatment of actinic keratoses. Dermatol Surg 2012; 38:722.
  16. Sotiriou E, Apalla Z, Maliamani F, et al. Intraindividual, right-left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities. J Eur Acad Dermatol Venereol 2009; 23:1061.
  17. Morton C, Campbell S, Gupta G, 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; 155:1029.
  18. Szeimies RM, Karrer S, Radakovic-Fijan S, et al. Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. J Am Acad Dermatol 2002; 47:258.
  19. Freeman M, Vinciullo C, Francis D, 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 Dermatolog Treat 2003; 14:99.
  20. Kaufmann R, Spelman L, Weightman W, 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; 158:994.
  21. Patel G, Armstrong AW, Eisen DB. Efficacy of Photodynamic Therapy vs Other Interventions in Randomized Clinical Trials for the Treatment of Actinic Keratoses: A Systematic Review and Meta-analysis. JAMA Dermatol 2014.
  22. Gupta AK, Davey V, Mcphail H. Evaluation of the effectiveness of imiquimod and 5-fluorouracil for the treatment of actinic keratosis: Critical review and meta-analysis of efficacy studies. J Cutan Med Surg 2005; 9:209.
  23. New treatments for actinic keratoses. Med Lett Drugs Ther 2002; 44:57.
  24. Levy S, Furst K, Chern W. A pharmacokinetic evaluation of 0.5% and 5% fluorouracil topical cream in patients with actinic keratosis. Clin Ther 2001; 23:908.
  25. Weiss J, Menter A, Hevia O, et al. Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. Cutis 2002; 70:22.
  26. Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: systematic review and meta-analysis. J Invest Dermatol 2006; 126:1251.
  27. (Accessed on May 09, 2007).
  28. Chen K, Yap LM, Marks R, Shumack S. Short-course therapy with imiquimod 5% cream for solar keratoses: a randomized controlled trial. Australas J Dermatol 2003; 44:250.
  29. Jorizzo J, Dinehart S, Matheson R, et al. Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head. J Am Acad Dermatol 2007; 57:265.
  30. Imiquimod (Aldara) for actinic keratoses. Med Lett Drugs Ther 2004; 46:42.
  31. Swanson N, Abramovits W, Berman B, et al. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles. J Am Acad Dermatol 2010; 62:582.
  32. Hanke CW, Beer KR, Stockfleth E, et al. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles. J Am Acad Dermatol 2010; 62:573.
  33. Lebwohl M, Dinehart S, Whiting D, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol 2004; 50:714.
  34. Anderson L, Schmieder GJ, Werschler WP, et al. Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol 2009; 60:934.
  35. Siller G, Gebauer K, Welburn P, et al. PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. Australas J Dermatol 2009; 50:16.
  36. Ogbourne SM, Hampson P, Lord JM, et al. Proceedings of the First International Conference on PEP005. Anticancer Drugs 2007; 18:357.
  37. Martin G, Swanson N. Clinical findings using ingenol mebutate gel to treat actinic keratoses. J Am Acad Dermatol 2013; 68:S39.
  38. Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesion-specific immune response. J Am Acad Dermatol 2012; 66:486.
  39. Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012; 366:1010.
  40. Lebwohl M, Shumack S, Stein Gold L, et al. Long-term follow-up study of ingenol mebutate gel for the treatment of actinic keratoses. JAMA Dermatol 2013; 149:666.
  41. Rivers JK, Arlette J, Shear N, et al. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 2002; 146:94.
  42. Wolf JE Jr, Taylor 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.
  43. Pirard D, Vereecken P, Mélot C, Heenen M. Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses: a meta-analysis of the recent studies. Arch Dermatol Res 2005; 297:185.
  44. Smith SR, Morhenn VB, Piacquadio DJ. Bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5-fluorouracil cream in the treatment of actinic keratoses of the face and scalp. J Drugs Dermatol 2006; 5:156.
  45. Kang S, Goldfarb MT, Weiss JS, et al. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. J Am Acad Dermatol 2003; 49:83.
  46. Weinstock MA, Bingham SF, VATTC Trial Group. High-dose topical tretinoin for reducing multiplicity of actinic keratoses (abstract). J Invest Dermatol 2010; 130 Suppl 1:S63.
  47. Carneiro RV, Sotto MN, Azevedo LS, et al. Acitretin and skin cancer in kidney transplanted patients. Clinical and histological evaluation and immunohistochemical analysis of lymphocytes, natural killer cells and Langerhans' cells in sun exposed and sun protected skin. Clin Transplant 2005; 19:115.
  48. Martin GM. Impact of interval and combination therapies on the management of actinic keratosis: review and clinical considerations. J Dermatolog Treat 2011; 22:288.
  49. Stockfleth E. The paradigm shift in treating actinic keratosis: a comprehensive strategy. J Drugs Dermatol 2012; 11:1462.
  50. Jorizzo J, Weiss J, Furst K, et al. Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial. Arch Dermatol 2004; 140:813.
  51. Jorizzo J, Weiss J, Vamvakias G. One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study. J Drugs Dermatol 2006; 5:133.
  52. Tan JK, Thomas DR, Poulin Y, et al. Efficacy of imiquimod as an adjunct to cryotherapy for actinic keratoses. J Cutan Med Surg 2007; 11:195.
  53. Monheit GD. Medium-depth chemical peels. Dermatol Clin 2001; 19:413.
  54. Lawrence N, Cox SE, Cockerell CJ, et al. A comparison of the efficacy and safety of Jessner's solution and 35% trichloroacetic acid vs 5% fluorouracil in the treatment of widespread facial actinic keratoses. Arch Dermatol 1995; 131:176.
  55. Hantash BM, Stewart DB, Cooper ZA, et al. Facial resurfacing for nonmelanoma skin cancer prophylaxis. Arch Dermatol 2006; 142:976.
  56. Ostertag JU, Quaedvlieg PJ, van der Geer S, et al. A clinical comparison and long-term follow-up of topical 5-fluorouracil versus laser resurfacing in the treatment of widespread actinic keratoses. Lasers Surg Med 2006; 38:731.
  57. Weiss ET, Brauer JA, Anolik R, et al. 1927-nm fractional resurfacing of facial actinic keratoses: a promising new therapeutic option. J Am Acad Dermatol 2013; 68:98.
  58. Katz TM, Goldberg LH, Marquez D, et al. Nonablative fractional photothermolysis for facial actinic keratoses: 6-month follow-up with histologic evaluation. J Am Acad Dermatol 2011; 65:349.
  59. Prens SP, de Vries K, Neumann HA, Prens EP. Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities. J Dermatolog Treat 2013; 24:227.
  60. Dréno B, Amici JM, Basset-Seguin N, et al. Management of actinic keratosis: a practical report and treatment algorithm from AKTeam™ expert clinicians. J Eur Acad Dermatol Venereol 2014; 28:1141.
  61. Ritchie SA, Patel MJ, Miller SJ. Therapeutic options to decrease actinic keratosis and squamous cell carcinoma incidence and progression in solid organ transplant recipients: a practical approach. Dermatol Surg 2012; 38:1604.
  62. Ingham AI, Weightman W. The efficacy and safety of topical 5% 5-fluorouracil in renal transplant recipients for the treatment of actinic keratoses. Australas J Dermatol 2014; 55:204.
  63. Ulrich C, Bichel J, Euvrard S, et al. Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients. Br J Dermatol 2007; 157 Suppl 2:25.
  64. Brown VL, Atkins CL, Ghali L, et al. Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in high-risk renal transplant recipients: randomized, double-blind, placebo-controlled trial. Arch Dermatol 2005; 141:985.
  65. Naylor MF, Boyd A, Smith DW, et al. High sun protection factor sunscreens in the suppression of actinic neoplasia. Arch Dermatol 1995; 131:170.
  66. Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993; 329:1147.
  67. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol 2003; 139:451.
  68. Ulrich C, Jürgensen JS, Degen A, et al. Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study. Br J Dermatol 2009; 161 Suppl 3:78.