1,464
Views
62
CrossRef citations to date
0
Altmetric
Surgery & Cancer

Real-world approach to actinic keratosis management: practical treatment algorithm for office-based dermatology

, , , , , , , , , , , , & show all
Pages 431-442 | Received 03 Aug 2016, Accepted 23 Oct 2016, Published online: 13 Nov 2016

References

  • Goldberg LH, Mamelak AJ. Review ofactinic keratosis. Part I: etiology, epidemiology and clinical presentation. J Drugs Dermatol. 2010;9:1125–32.
  • Fenske NA, Spencer J, Adam F. Actinic keratoses: past, present and future. J Drugs Dermatol. 2010;9:S45–9.
  • Feldman SR, Fleischer AB. Jr,. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87:201–7.
  • Stockfleth E, Ortonne JP, Alomar A. Actinic keratosis and field cancerisation. Eur J Dermatol. 2011;21(Suppl 1):3–12.
  • Ulrich M, Krueger-Corcoran D, Roewert-Huber J, et al. Reflectance confocal microscopy for noninvasive monitoring of therapy and detection of subclinical actinic keratoses. Dermatology. 2010;220:15–24.
  • Fernandez-Figueras MT, Carrato C, Saenz X, et al. Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol. 2015;29:991–7.
  • Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000;42:23–4.
  • Green A, Battistutta D. Incidence and determinants of skin cancer in a high-risk Australian population. Int J Cancer. 1990;46:356–61.
  • Werner RN, Stockfleth E, Connolly SM, et al. Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis – International League of Dermatological Societies in cooperation with the European Dermatology Forum – short version. J Eur Acad Dermatol Venereol. 2015;29:2069–79.
  • Chetty P, Choi F, Mitchell T. Primary care review of actinic keratosis and its therapeutic options: a global perspective. Dermatol Ther (Heidelb). 2015;5:19–35.
  • Rosen T, Lebwohl MG. Prevalence and awareness of actinic keratosis: barriers and opportunities. J Am Acad Dermatol 2013;68(1 Suppl 1):S2–9.
  • Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000;142:1154–9.
  • Frost C, Williams G, Green A. High incidence and regression rates of solar keratoses in a queensland community. J Invest Dermatol. 2000;115:273–7.
  • Schwartz RA, Bridges TM, Butani AK, Ehrlich A. Actinic keratosis: an occupational and environmental disorder. J Eur Acad Dermatol Venereol 2008;22:606–15.
  • Flohil SC, van der Leest RJ, Dowlatshahi EA, et al. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol 2013;133:1971–8.
  • Traianou A, Ulrich M, Apalla Z, et al. Risk factors for actinic keratosis in eight European centres: a case-control study. Br J Dermatol. 2012;167(Suppl 2):36–42.
  • Stockfleth E, Ulrich C, Meyer T, Christophers E. Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment. Recent Results Cancer Res. 2002;160:251–8.
  • Uhlenhake EE. Optimal treatment of actinic keratoses. Clin Interv Aging. 2013;8:29–35.
  • MacKie RM. Awareness, knowledge and attitudes to basal cell carcinoma and actinic keratoses among the general public within Europe. J Eur Acad Dermatol Venereol. 2004;18:552–5.
  • Olsen EA, Abernethy ML, Kulp-Shorten C, et al. A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol. 1991;24(5 Pt 1):738–43.
  • Schmitz L, Kahl P, Majores M, et al. Actinic keratosis: correlation between clinical and histological classification systems. J Eur Acad Dermatol Venereol. 2016;30:1303–7.
  • Röwert-Huber J, Patel MJ, Forschner T, et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol. 2007;156(Suppl 3):8–12.
  • Huerta-Brogeras M, Olmos O, Borbujo J, et al. Validation of dermoscopy as a real-time noninvasive diagnostic imaging technique for actinic keratosis. Arch Dermatol. 2012;148:1159–64.
  • Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Dtsch Dermatol Ges. 2007;5:970–6.
  • Zalaudek I, Giacomel J, Schmid K, et al. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model. J Am Acad Dermatol. 2012;66:589–97.
  • Malvehy J. A new vision of actinic keratosis beyond visible clinical lesions. J Eur Acad Dermatol Venereol. 2015;29(Suppl 1):3–8.
  • Ulrich M, Themstrup L, de Carvalho N, et al. Dynamic optical coherence tomography in dermatology. Dermatology. 2016;232:298–311.
  • Pellacani G, Neri L, Longo C. Comment to: ‘Evidence and consensus based (S3) Guidelines for the Treatment of Actinic Keratosis’. J Eur Acad Dermatol Venereol. 2016;30:e114.
  • 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;26:976–90.
  • Brantsch KD, Meisner C, Schonfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. 2008;9:713–20.
  • Perez-Reyes N, Farhi DC. Squamous cell carcinoma of head and neck in patients with well-differentiated lymphocytic lymphoma. Cancer. 1987;59:540–4.
  • Esmann S, Jemec GB. Management of actinic keratosis patients: a qualitative study. J Dermatolog Treat. 2007;18:53–8.
  • Esmann S, Vinding GR, Christensen KB, Jemec GB. Assessing the influence of actinic keratosis on patients' quality of life: the AKQoL questionnaire. Br J Dermatol. 2013;168:277–83.
  • Esmann S, Jemec GB. Patients' perceptions of topical treatments of actinic keratosis. J Dermatolog Treat. 2014;25:375–9.
  • Shergill B, Zokaie S, Carr AJ. Non-adherence to topical treatments for actinic keratosis. Patient Prefer Adher. 2013;8:35–41.
  • Stockfleth E, Peris K, Guillen C, et al. A consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis. Int J Dermatol. 2015;54:509–15.
  • Stockfleth E, Peris K, Guillen C, et al. Physician perceptions and experience of current treatment in actinic keratosis. J Eur Acad Dermatol Venereol. 2015;29:298–306.
  • Peris K, Neri L, Fargnoli MC, Pellacani G. Physicians' concerns towards prescription adherence and treatment effectiveness in the clinical management of actinic keratosis. G Ital Dermatol Venereol. 2014;149:193–8.
  • Krawtchenko N, Roewert-Huber J, Ulrich M, et al. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007;157(Suppl 2):34–40.
  • 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;43:687–92.
  • Simon JC, Dominicus R, Karl L, et al. A prospective randomized exploratory study comparing the efficacy of once-daily topical 0.5% 5-fluorouracil in combination with 10.0% salicylic acid (5-FU/SA) vs. cryosurgery for the treatment of hyperkeratotic actinic keratosis. J Eur Acad Dermatol Venereol. 2015;29:881–9.
  • Stockfleth E, Ferrandiz C, Grob JJ, et al. Development of a treatment algorithm for actinic keratoses: a European consensus. Eur J Dermatol. 2008;18:651–9.
  • Actikerall. Summary of product characteristics. Available from: https://www.medicines.org.uk/emc/medicine/24614. 2014. Accessed July 2016.
  • Stockfleth E, Kerl H, Zwingers T, Willers C. Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results. Br J Dermatol. 2011;165:1101–8.
  • Szeimies RM, Dirschka T, Prechtl A, Melzer A. Efficacy of low-dose 5-fluorouracil/salicylic acid in actinic keratoses in relation to treatment duration. J Dtsch Dermatol Ges. 2015;13:430–8.
  • Gaspari AA. Mechanism of action and other potential roles of an immune response modifier. Cutis. 2007;79(4 Suppl):36–45.
  • Sauder DN. Immunomodulatory and pharmacologic properties of imiquimod. J Am Acad Dermatol. 2000;43(1 Pt 2):S6–S11.
  • Schon M, Bong AB, Drewniok C, et al. Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J Natl Cancer Inst. 2003;95:1138–49.
  • Alomar A, Bichel J, McRae S. Vehicle-controlled, randomized, double-blind study to assess safety and efficacy of imiquimod 5% cream applied once daily 3 days per week in one or two courses of treatment of actinic keratoses on the head. Br J Dermatol. 2007;157:133–41.
  • 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;57:265–8.
  • Lee PK, Harwell WB, Loven KH, et al. Long-term clinical outcomes following treatment of actinic keratosis with imiquimod 5% cream. Dermatol Surg. 2005;31:659–64.
  • Stockfleth E, Christophers E, Benninghoff B, Sterry W. Low incidence of new actinic keratoses after topical 5% imiquimod cream treatment: a long-term follow-up study. Arch Dermatol. 2004;140:1542
  • Peris K, Micantonio T, Fargnoli MC, et al. Imiquimod 5% cream in the treatment of Bowen's disease and invasive squamous cell carcinoma. J Am Acad Dermatol. 2006;55:324–7.
  • Schulze HJ, Cribier B, Requena L, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol. 2005;152:939–47.
  • Gollnick H, Barona CG, Frank RG, et al. Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe. Eur J Dermatol. 2008;18:677–82.
  • Quirk C, Gebauer K, De'Ambrosis B, et al. Sustained clearance of superficial basal cell carcinomas treated with imiquimod cream 5%: results of a prospective 5-year study. Cutis. 2010;85:318–24.
  • Lacarrubba F, Potenza MC, Gurgone S, Micali G. Successful treatment and management of large superficial basal cell carcinomas with topical imiquimod 5% cream: a case series and review. J Dermatolog Treat. 2011;22:353–8.
  • Micali G, Lacarrubba F, Nasca MR, De Pasquale R. The use of imiquimod 5% cream for the treatment of basal cell carcinoma as observed in Gorlin's syndrome. Clin Exp Dermatol. 2003;28(Suppl 1):19–23.
  • Micali G, Lacarrubba F, Nasca MR, et al. Topical pharmacotherapy for skin cancer: part II. Clinical applications. J Am Acad Dermatol. 2014;70:979–12.
  • Micali G, Lacarrubba F, Nasca MR, Schwartz RA. Topical pharmacotherapy for skin cancer: part I. Pharmacology. J Am Acad Dermatol. 2014;70:965–12.
  • Alchin DR. Ingenol mebutate: a succinct review of a succinct therapy. Dermatol Ther (Heidelb). 2014;4:157–64.
  • Zarchi K, Jemec GB. Ingenol mebutate: from common weed to cancer cure. Curr Probl Dermatol. 2015;46:136–42.
  • Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012;366:1010–9.
  • Ricci F, Tambone S, Neri L, et al. Real-life efficacy and safety of ingenol mebutate for the treatment of actinic keratosis of the face and scalp: a single arm retrospective study. J Dermatolog Treat. 2016. [Epub ahead of print]. doi: 10.3109/09546634.2016.1161162.
  • 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;62:582–90.
  • Stockfleth E, Gupta G, Peris K, et al. Reduction in lesions from Lmax: a new concept for assessing efficacy of field-directed therapy for actinic keratosis. Results with imiquimod 3.75%. Eur J Dermatol. 2014;24:23–7.
  • Kopera D, Kerl H. Visualization and treatment of subclinical actinic keratoses with topical imiquimod 5% cream: an observational study. Biomed Res Int. 2014;2014:135916
  • Hanke CW, Swanson N, Bruce S, et al. Complete clearance is sustained for at least 12 months after treatment of actinic keratoses of the face or balding scalp via daily dosing with imiquimod 3.75% or 2.5% cream. J Drugs Dermatol. 2011;10:165–70.
  • Gupta G, Stockfleth E, Peris K, et al. Long-term sustained lesion clearance from Lmax with imiquimod 3.75%, a new field-directed treatment for actinic keratosis. J Eur Acad Dermatol Venereol. 2015;29:1840–2.
  • Tambone S, Fargnoli MC, Capizzi R, Peris K. Clinical experience of imiquimod 3.75% for actinic keratosis: results from a case series. G Ital Dermatol Venereol. 2015; [Epub ahead of print].
  • Dirschka T, Peris K, Gupta G, et al. Imiquimod 3.75% in actinic keratosis: efficacy in patients with and without rest periods during treatment. J Eur Acad Dermatol Venereol. 2016;30:1416–7.
  • Quist SR, Gollnick HP. Imiquimod 3.75% cream (Zyclara) for the treatment of actinic keratoses. Expert Opin Pharmacother. 2011;12:451–61.
  • 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;131:176–81.
  • Gupta AK. The management of actinic keratoses in the United States with topical fluorouracil: a pharmacoeconomic evaluation. Cutis. 2002;70:30–6.
  • Pomerantz H, Hogan D, Eilers D, et al. Long-term efficacy of topical fluorouracil cream, 5%, for treating actinic keratosis: a randomized clinical trial. JAMA Dermatol. 2015;151:952–60.
  • 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;24:990–1000.
  • Segatto MM, Dornelles SI, Silveira VB, Frantz GO. Comparative study of actinic keratosis treatment with 3% diclofenac sodium and 5% 5-fluorouracil. An Bras Dermatol. 2013;88:732–8.
  • 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;5:156–9.
  • Tanghetti E, Werschler P. Comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp. J Drugs Dermatol. 2007;6:144–7.
  • Smith S, Piacquadio D, Morhenn V, et al. Short incubation PDT versus 5-FU in treating actinic keratoses. J Drugs Dermatol. 2003;2:629–35.
  • Epstein E. Does intermittent “pulse” topical 5-fluorouracil therapy allow destruction of actinic keratoses without significant inflammation? J Am Acad Dermatol. 1998;38:77–80.
  • Efudix. Summary of product characteristics. Available from: http://www.medicines.org.uk/emc/medicine/6219/SPC/Efudix+Cream. 2014. Accessed July 2016.
  • Diclofenac sodium 3%. Summary of product characteristics. Available from: http://www.medicines.org.uk/emc/medicine/21229/SPC. 2012. Accessed July 2016.
  • Gebauer K, Brown P, Varigos G. Topical diclofenac in hyaluronan gel for the treatment of solar keratoses. Australas J Dermatol. 2003;44:40–3.
  • 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;146:94–100.
  • 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;40:709–13.
  • Nelson CG. Diclofenac gel in the treatment of actinic keratoses. Ther Clin Risk Manag. 2011;7:207–11.
  • Marmur ES, Schmults CD, Goldberg DJ. A review of laser and photodynamic therapy for the treatment of nonmelanoma skin cancer. Dermatol Surg. 2004;30(2 Pt 2):264–71.
  • Lacour JP, Ulrich C, Gilaberte Y, et al. Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III study throughout Europe. J Eur Acad Dermatol Venereol. 2015;29:2342–8.
  • Rubel DM, Spelman L, Murrell DF, et al. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol. 2014;171:1164–71.
  • Pariser DM, Lowe NJ, Stewart DM, 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.
  • 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;14:99–106.
  • Pariser D, Loss R, Jarratt M, 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;59:569–76.
  • Piacquadio DJ, Chen DM, Farber HF, et al. Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials. Arch Dermatol. 2004;140:41–6.
  • Hauschild A, Stockfleth E, Popp G, et al. Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies. Br J Dermatol. 2009;160:1066–74.
  • 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;168:825–36.
  • Stockfleth E. The paradigm shift in treating actinic keratosis: a comprehensive strategy. J Drugs Dermatol. 2012;11:1462–7.
  • Jorizzo JL, Markowitz O, Lebwohl MG, et al. A randomized, double-blinded, placebo-controlled, multicenter, efficacy and safety study of 3.75% imiquimod cream following cryosurgery for the treatment of actinic keratoses. J Drugs Dermatol. 2010;9:1101–8.
  • Hoover WD, III, Jorizzo JL, Clark AR, et al. Efficacy of cryosurgery and 5-fluorouracil cream 0.5% combination therapy for the treatment of actinic keratosis. Cutis. 2014;94:255–9.
  • Shaffelburg M. Treatment of actinic keratoses with sequential use of photodynamic therapy; and imiquimod 5% cream. J Drugs Dermatol. 2009;8:35–9.
  • Tavin E, Persky M. Metastatic cutaneous squamous cell carcinoma of the head and neck region. Laryngoscope. 1996;106(2 Pt 1):156–8.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.