Actinic Keratosis Clinical Presentation
- Author: James M Spencer, MD; Chief Editor: William D James, MD more...
Actinic keratoses are seen almost exclusively in whites, especially those with skin phototypes I and II. The incidence increases with each decade of life, and men have a slightly increased frequency of actinic keratosis.[21, 4] Actinic keratosis is correlated with long-term UV exposure, such as occurs in persons with outdoor occupations.
Patient who are immunosuppressed following organ transplantation are at markedly increased risk of developing actinic keratoses. The lesions still arise in areas of long-term exposure,[27, 6, 36] and they are thought to be actinically induced.
The typical patient with actinic keratoses is an elderly, fair-skinned, sun-sensitive person. The lesions arise in areas of long-term sun exposure, including the face, ears, bald scalp in men, and the dorsal forearms and hands.[5, 6] Actinic keratoses begin as small rough spots that are easier felt than seen, often described as being similar to rubbing sandpaper. With time, the lesions enlarge, usually becoming red and scaly; most are only 3-10 mm, but they may enlarge to several centimeters.[1, 2, 3] Note the images below.
Patients may develop multiple lesions within a single anatomic area, to the extent that the lesions collide and produce confluent actinic keratosis over a relatively large area. Variants may be brown (pigmented actinic keratosis), atrophic, bowenoid, lichen planus–like, or have exaggerated hyperkeratosis, producing a hornlike projection above the skin surface known as a cutaneous horn.
Actinic keratoses are induced by UV light. Both epidemiologic observations and molecular biologic characteristics of the tumor cells suggest UV light is sufficient by itself to induce actinic keratosis.[19, 25] Sensitivity to UV light is inherited; actinic keratoses occur more frequently in fair, redheaded, or blonde patients who burn frequently and tan poorly. Increased sun exposure and higher-intensity exposure increase the chance of actinic keratosis development. Immunosuppression following organ transplantation dramatically increases the risk of developing actinic keratoses ; however, actinic keratoses do not occur without sun exposure.
Additional studies have shown an association between cutaneous human papillomavirus and actinic keratosis.[37, 38, 39] The role of human papillomavirus in skin tumorigenesis was discovered the 1950s, and the group of known human papillomavirus types associated with skin tumorigenesis has been classified as beta-papillomavirus . Beta-papillomavirus DNA has been identified in healthy skin and in squamous cell carcinoma, basal cell carcinoma, and actinic keratosis. A 2007 study suggests that only a small association exists between beta-papillomavirus and actinic keratosis; however, when evaluated in combination with other risk factors including age, sun damage, and skin color, the risk for actinic keratosis increased as much as 13-fold. The exact mechanism by which this family of viruses contributes to tumor growth remains unknown.
Roewert-Huber J, Stockfleth E, Kerl H. Pathology and pathobiology of actinic (solar) keratosis - an update. Br J Dermatol. 2007 Dec. 157 Suppl 2:18-20. [Medline].
Schwartz RA. Premalignant keratinocytic neoplasms. J Am Acad Dermatol. 1996 Aug. 35(2 Pt 1):223-42. [Medline].
Schwartz RA, Bridges TM, Butani AK, Ehrlich A. Actinic keratosis: an occupational and environmental disorder. J Eur Acad Dermatol Venereol. 2008 May. 22(5):606-15. [Medline].
Frost CA, Green AC, Williams GM. The prevalence and determinants of solar keratoses at a subtropical latitude (Queensland, Australia). Br J Dermatol. 1998 Dec. 139(6):1033-9. [Medline].
Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000 Jan. 42(1 Pt 2):4-7. [Medline].
Franceschi S, Levi F, Randimbison L, La Vecchia C. Site distribution of different types of skin cancer: new aetiological clues. Int J Cancer. 1996 Jul 3. 67(1):24-8. [Medline].
James C, Crawford R, Martika M. Actinic Keratosis. James C, Crawford R, Martika M, Marks R, eds. WHO Pathology and Genetics, Skin Tumors. Lyon: IARC Press; 2006. 30-33.
Berhane T, Halliday GM, Cooke B, Barnetson RS. Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans. Br J Dermatol. 2002 May. 146(5):810-5. [Medline].
Marks VJ. Actinic keratosis. A premalignant skin lesion. Otolaryngol Clin North Am. 1993 Feb. 26(1):23-35. [Medline].
Sanmartin O, Guillen C. Images in clinical medicine. Fluorescence diagnosis of subclinical actinic keratoses. N Engl J Med. 2008 May 8. 358(19):e21. [Medline].
Spencer JM, Hazan C, Hsiung SH, Robins P. Therapeutic decision making in the therapy of actinic keratoses. J Drugs Dermatol. 2005 May-Jun. 4(3):296-301. [Medline].
Tutrone WD, Saini R, Caglar S, Weinberg JM, Crespo J. Topical therapy for actinic keratoses, I: 5-Fluorouracil and imiquimod. Cutis. 2003 May. 71(5):365-70. [Medline].
Tutrone WD, Saini R, Caglar S, Weinberg JM, Crespo J. Topical therapy for actinic keratoses, II: Diclofenac, colchicine, and retinoids. Cutis. 2003 May. 71(5):373-9. [Medline].
Fuchs J, Thiele J. The role of oxygen in cutaneous photodynamic therapy. Free Radic Biol Med. 1998 Mar 15. 24(5):835-47. [Medline].
Hantash BM, Stewart DB, Cooper ZA, Rehmus WE, Koch RJ, Swetter SM. Facial resurfacing for nonmelanoma skin cancer prophylaxis. Arch Dermatol. 2006 Aug. 142(8):976-82. [Medline].
Sherry SD, Miles BA, Finn RA. Long-term efficacy of carbon dioxide laser resurfacing for facial actinic keratosis. J Oral Maxillofac Surg. 2007 Jun. 65(6):1135-9. [Medline].
Winton GB, Salasche SJ. Dermabrasion of the scalp as a treatment for actinic damage. J Am Acad Dermatol. 1986 Apr. 14(4):661-8. [Medline].
Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan. 42(1 Pt 2):23-4. [Medline].
Leffell DJ. The scientific basis of skin cancer. J Am Acad Dermatol. 2000 Jan. 42(1 Pt 2):18-22. [Medline].
Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell. 1992 Aug 21. 70(4):523-6. [Medline].
Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994 Oct. 131(4):455-64. [Medline].
Feldman SR, Fleischer AB Jr, McConnell RC. Most common dermatologic problems identified by internists, 1990-1994. Arch Intern Med. 1998 Apr 13. 158(7):726-30. [Medline].
Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988 Apr 9. 1(8589):795-7. [Medline].
Backvall H, Asplund A, Gustafsson A, Sivertsson A, Lundeberg J, Ponten F. Genetic tumor archeology: microdissection and genetic heterogeneity in squamous and basal cell carcinoma. Mutat Res. 2005 Apr 1. 571(1-2):65-79. [Medline].
Nelson MA, Einspahr JG, Alberts DS, et al. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers. Cancer Lett. 1994 Sep 30. 85(1):23-9. [Medline].
Anwar J, Wrone DA, Kimyai-Asadi A, Alam M. The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classification schemes. Clin Dermatol. 2004 May-Jun. 22(3):189-96. [Medline].
Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007 Sep. 33(9):1099-101. [Medline].
Cockerell CJ. Histopathology of incipient intraepidermal squamous cell carcinoma ("actinic keratosis"). J Am Acad Dermatol. 2000 Jan. 42(1 Pt 2):11-7. [Medline].
Ackerman AB, Mones JM. Solar (actinic) keratosis is squamous cell carcinoma. Br J Dermatol. 2006 Jul. 155(1):9-22. [Medline].
Black HS, Herd JA, Goldberg LH, et al. Effect of a low-fat diet on the incidence of actinic keratosis. N Engl J Med. 1994 May 5. 330(18):1272-5. [Medline].
Drake LA, Ceilley RI, Cornelison RL, et al. Guidelines of care for actinic keratoses. Committee on Guidelines of Care. J Am Acad Dermatol. 1995 Jan. 32(1):95-8. [Medline].
Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006 Nov. 55(5):741-60; quiz 761-4. [Medline].
Cooper JZ, Brown MD. Special concern about squamous cell carcinoma of the scalp in organ transplant recipients. Arch Dermatol. 2006 Jun. 142(6):755-8. [Medline].
Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992 Jun. 26(6):976-90. [Medline].
Parrish JA. Immunosuppression, skin cancer, and ultraviolet A radiation. N Engl J Med. 2005 Dec 22. 353(25):2712-3. [Medline].
Green A, Battistutta D. Incidence and determinants of skin cancer in a high-risk Australian population. Int J Cancer. 1990 Sep 15. 46(3):356-61. [Medline].
Weissenborn SJ, Nindl I, Purdie K, et al. Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. J Invest Dermatol. 2005 Jul. 125(1):93-7. [Medline].
McBride P, Neale R, Pandeya N, Green A. Sun-related factors, betapapillomavirus, and actinic keratoses: a prospective study. Arch Dermatol. 2007 Jul. 143(7):862-8. [Medline].
Pfister H, Fuchs PG, Majewski S, Jablonska S, Pniewska I, Malejczyk M. High prevalence of epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population. Arch Dermatol Res. 2003 Dec. 295(7):273-9. [Medline].
Moy RL. Clinical presentation of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000 Jan. 42(1 Pt 2):8-10. [Medline].
Pock L, Drlik L, Hercogova J. Dermatoscopy of pigmented actinic keratosis--a striking similarity to lentigo maligna. Int J Dermatol. 2007 Apr. 46(4):414-6. [Medline].
Gold MH. Pharmacoeconomic analysis of the treatment of multiple actinic keratoses. J Drugs Dermatol. 2008 Jan. 7(1):23-5. [Medline].
Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med. 1993 Oct 14. 329(16):1147-51. [Medline].
Eaglstein WH, Weinstein GD, Frost P. Fluorouracil: mechanism of action in human skin and actinic keratoses. I. Effect on DNA synthesis in vivo. Arch Dermatol. 1970 Feb. 101(2):132-9. [Medline].
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 Oct. 9(5):209-14. [Medline].
Loven K, Stein L, Furst K, Levy S. Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. Clin Ther. 2002 Jun. 24(6):990-1000. [Medline].
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 Feb. 5(2):133-9. [Medline].
Stockfleth E, Sterry W, Carey-Yard M, Bichel J. Multicentre, open-label study using imiquimod 5% cream in one or two 4-week courses of treatment for multiple actinic keratoses on the head. Br J Dermatol. 2007 Dec. 157 Suppl 2:41-6. [Medline].
Hanke CW, Beer KR, Stockfleth E, Wu J, Rosen T, Levy S. 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 Apr. 62(4):573-81. [Medline].
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 Dec. 157 Suppl 2:25-31. [Medline].
Ulrich C, Busch JO, Meyer T, et al. Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six cases. Br J Dermatol. 2006 Aug. 155(2):451-4. [Medline].
Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012 Mar 15. 366(11):1010-9. [Medline].
Garbe C, Basset-Seguin N, Poulin Y, et al. Efficacy and safety of follow-up field treatment of actinic keratosis with ingenol mebutate 0·015% gel: a randomized, controlled 12-month study. Br J Dermatol. 2016 Mar. Vol 174(3):505-13. [Medline].
Augustin M, Tu JH, Knudsen KM, Erntoft S, Larsson T, Hanke CW. Ingenol mebutate gel for actinic keratosis: the link between quality of life, treatment satisfaction, and clinical outcomes. J Am Acad Dermatol. 2015 May. Vol 72(5):816-21. [Medline].
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. 2011 Nov 4. [Medline].
Boggs W. Ingenol Mebutate Gel Effective for Actinic Keratoses. Medscape. Mar 28 2013. Available at http://Available at: http://www.medscape.com/viewarticle/781629. Accessed: April 8, 2013.
Lebwohl M, Shumack S, Stein Gold L, Melgaard A, Larsson T, Tyring SK. Long-term follow-up study of ingenol mebutate gel for the treatment of actinic keratoses. JAMA Dermatol. 2013 Jun. 149(6):666-70. [Medline].
Jim On SC, Haddican M, Yaroshinsky A, Singer G, Lebwohl M. Reduced degree of irritation during a second cycle of ingenol mebutate gel 0.015% for the treatment of actinic keratosis. Cutis. 2015 Jan. 95(1):47-51. [Medline].
Berlin JM, Rigel DS. Diclofenac sodium 3% gel in the treatment of actinic keratoses postcryosurgery. J Drugs Dermatol. 2008 Jul. 7(7):669-73. [Medline].
Kurwa HA, Yong-Gee SA, Seed PT, Markey AC, Barlow RJ. A randomized paired comparison of photodynamic therapy and topical 5-fluorouracil in the treatment of actinic keratoses. J Am Acad Dermatol. 1999 Sep. 41(3 Pt 1):414-8. [Medline].
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 Dec. 150(12):1281-8. [Medline].
Braathen LR, Szeimies RM, Basset-Seguin N, et al. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. 2007 Jan. 56(1):125-43. [Medline].
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 May. 158(5):994-9. [Medline].
McLoone N, Donnelly RF, Walsh M, et al. Aminolaevulinic acid diffusion characteristics in 'in vitro' normal human skin and actinic keratosis: implications for topical photodynamic therapy. Photodermatol Photoimmunol Photomed. 2008 Aug. 24(4):183-90. [Medline].
Tarstedt M, Gillstedt M, Wennberg Larkö AM, Paoli J. Aminolevulinic acid and methyl aminolevulinate equally effective in topical photodynamic therapy for non-melanoma skin cancers. J Eur Acad Dermatol Venereol. 2016 Mar. Vol 30(3):420-23. [Medline].
Dirschka T, Radny P, Dominicus R, et al. Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo. Br J Dermatol. 2012 Jan. Vol 166(1):137-46. [Medline].
Dirschka T, Radny P, Dominicus R, et al. Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis. Br J Dermatol. 2013 Apr. Vol 168(4):825-36. [Medline].
Gholam P, Weberschock T, Denk K, Enk A. Treatment with 5-aminolaevulinic acid methylester is less painful than treatment with 5-aminolaevulinic acid nanoemulsion in topical photodynamic therapy for actinic keratosis. Dermatology. 2011. Vol 222(4):358-62. [Medline].
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 Sep. 43(9):687-92. [Medline].