Methods and Results Report - Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis -International League of Dermatological Societies in cooperation with the European Dermatology Forum

Journal of the European Academy of Dermatology and Venereology

Volumn 29, Issue 11, 2015, Pages e1-e66

  Werner, R N ^a   Jacobs, A ^a   Rosumeck, S ^a   Erdmann, R ^a   Sporbeck, B ^a   Nast, A ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOLEVULINIC ACID; AMINOLEVULINIC ACID METHYL ESTER; DICLOFENAC; FLUOROURACIL; HYALURONIC ACID; IMIQUIMOD; INGENOL MEBUTATE; PLACEBO; SALICYLIC ACID; 3-INGENYL ANGELATE; AMINOQUINOLINE DERIVATIVE; ANTINEOPLASTIC AGENT; DITERPENE; PROSTAGLANDIN SYNTHASE INHIBITOR;

ACTINIC KERATOSIS; CARBON DIOXIDE LASER; CONSENSUS; CRYOTHERAPY; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ERBIUM YAG LASER; ESTHETICS; HEALTH CARE PERSONNEL; HUMAN; IMMUNOCOMPROMISED PATIENT; PATIENT CODING; PHOTODYNAMIC THERAPY; PRACTICE GUIDELINE; PRIORITY JOURNAL; REVIEW; SQUAMOUS CELL CARCINOMA; CONSENSUS DEVELOPMENT; CURETTAGE; EVIDENCE BASED MEDICINE; GAS LASER; KERATOSIS, ACTINIC; LOW LEVEL LASER THERAPY; MULTIMODALITY CANCER THERAPY; PHOTOCHEMOTHERAPY; THERAPEUTIC USE;

AMINOQUINOLINES; ANTINEOPLASTIC AGENTS; COMBINED MODALITY THERAPY; CRYOTHERAPY; CURETTAGE; CYCLOOXYGENASE INHIBITORS; DICLOFENAC; DITERPENES; EVIDENCE-BASED MEDICINE; FLUOROURACIL; HUMANS; KERATOSIS, ACTINIC; LASER THERAPY; LASERS, GAS; PHOTOCHEMOTHERAPY;

EID: 84945458227     PISSN: 09269959     EISSN: 14683083     Source Type: Journal    
DOI: 10.1111/jdv.13179     Document Type: Review

References (164)

1. World Health Organization-Guidelines Review Committee. WHO handbook for guideline development. 2012. URL http://apps.who.int/iris/bitstream/10665/75146/1/9789241548441-eng.pdf (last accessed: 16 January 2014).
2. AGREE Next Steps Consortium. The AGREE II Instrument. 2009. URL: http://www.agreetrust.org (last accessed: 16 January 2014).
3. Higgins JPT, Green S,. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration; 2011 [updated March 2011; last accessed: 5 Jan 2014]; Available from: www.cochrane-handbook.org.
4. Atkins D, Best D, Briss PA, et al,. Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490.
5. Moher D, Liberati A, Tetzlaff J, Altman DG,. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.
6. Guyatt GH, Oxman AD, Kunz R, et al,. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 2011; 64: 395-400.
7. Scottish Intercollegiate Guidelines Network. SIGN Methodology Checklist 1: Systematic Reviews and Meta-analyses. 2013. URL http://www.sign.ac.uk/methodology/checklists/20121211-Checklist-for-systematic-reviews.doc (last accessed: 9 December 2013).
8. Gupta AK, Paquet M, Villanueva E, Brintnell W,. Interventions for actinic keratoses. Cochrane Database Syst Rev 2012; 12: CD004415.
9. Review Manager (RevMan) [Computer program]. Version 5.2. The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2012.
10. Brozek J, Oxman A, Schünemann H,. GRADEpro. [Computer program]. Version 3.2 for Windows. 2008. Available from gradepro.org, last accessed: January 21st, 2014.
11. Balshem H, Helfand M, Schunemann HJ, et al,. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011; 64: 401-406.
12. Guyatt GH, Oxman AD, Vist G, et al,. GRADE guidelines: 4. Rating the quality of evidence-study limitations (risk of bias). J Clin Epidemiol 2011; 64: 407-415.
13. Guyatt GH, Oxman AD, Kunz R, et al,. GRADE guidelines: 7. Rating the quality of evidence-inconsistency. J Clin Epidemiol 2011; 64: 1294-1302.
14. Guyatt GH, Oxman AD, Kunz R, et al,. GRADE guidelines: 8. Rating the quality of evidence-indirectness. J Clin Epidemiol 2011; 64: 1303-1310.
15. Guyatt GH, Oxman AD, Kunz R, et al,. GRADE guidelines 6. Rating the quality of evidence-imprecision. J Clin Epidemiol 2011; 64: 1283-1293.
16. Guyatt GH, Oxman AD, Montori V, et al,. GRADE guidelines: 5. Rating the quality of evidence-publication bias. J Clin Epidemiol 2011; 64: 1277-1282.
17. Guyatt GH, Oxman AD, Sultan S, et al,. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol 2011; 64: 1311-1316.
18. Guyatt G, Oxman AD, Akl EA, et al,. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383-394.
19. Guyatt GH, Oxman AD, Santesso N, et al,. GRADE guidelines: 12. Preparing Summary of Findings tables-binary outcomes. J Clin Epidemiol 2013; 66: 158-172.
20. Guyatt GH, Thorlund K, Oxman AD, et al,. GRADE guidelines: 13. Preparing Summary of Findings tables and evidence profiles-continuous outcomes. J Clin Epidemiol 2013; 66: 173-183.
21. Jones J, Hunter D,. Consensus methods for medical and health services research. BMJ 1995; 311: 376-380.
22. Andrews J, Guyatt G, Oxman AD, et al,. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol 2013; 66: 719-725.
23. Andrews JC, Schunemann HJ, Oxman AD, et al,. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength. J Clin Epidemiol 2013; 66: 726-735.
24. World Health Organization-Guidelines Review Committee. WHO handbook for guideline development. 2012. URL http://apps.who.int/iris/bitstream/10665/75146/1/9789241548441-eng.pdf (last accessed: 16 January 2014).
25. AGREE Next Steps Consortium. The AGREE II Instrument. 2009. URL http://www.agreetrust.org (last accessed: 16 January 2014).
26. Higgins JPT, Green S,. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration; 2011 [updated March 2011; last accessed: 5 Jan 2014]; Available from: www.cochrane-handbook.org.
27. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al,. Grading quality of evidence and strength of recommendations. BMJ 2004; 328 7454: 1490.
28. Moher D, Liberati A, Tetzlaff J, Altman DG,. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.
29. Gupta AK, Paquet M, Villanueva E, Brintnell W,. Interventions for actinic keratoses. Cochrane Database Syst Rev. 2012; 12: CD004415.
30. Scottish Intercollegiate Guidelines Network. SIGN Methodology Checklist 1: Systematic Reviews and Meta-analyses. 2013. URL http://www.sign.ac.uk/methodology/checklists/20121211-Checklist-for-systematic-reviews.doc (last accessed: 9 December 2013).
31. Hauschild A, Stockfleth E, Popp G, Borrosch F, Bruning H, Dominicus R, 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 5: 1066-74.
32. Lebwohl M, Melgaard A, Kobayashi K, Swanson N,. Local skin responses associated with ingenol mebutate gel for the treatment of actinic keratosis: two analyses of pooled data. J Am Acad Dermatol 2012; 1: AB153.
33. Scola N, Terras S, Georgas D, Othlinghaus N, Matip R, Pantelaki I, et al,. A randomized, half-side comparative study of aminolaevulinate photodynamic therapy vs. CO(2) laser ablation in immunocompetent patients with multiple actinic keratoses. British J Dermatol 2012; 167 6: 1366-73.
34. Solaraze study 2. Solaraze gel: Diclofenac Sodium 3%-package insert.
35. 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. British J Dermatol 2011; 165 5: 1101-8.
36. Wiegell SR, Heydenreich J, Fabricius S, Wulf HC,. Continuous ultra-low-intensity artificial daylight is not as effective as red LED light in photodynamic therapy of multiple actinic keratoses. Photodermatol Photoimmunol Photomed 2011; 27 6: 280-5.
37. Krawtchenko N, Roewert-Huber J, Ulrich M, Mann I, Sterry W, Stockfleth E,. 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.
38. Foley P, Merlin K, Cumming S, Campbell J, Crouch R, Harrison S, et al,. A comparison of cryotherapy and imiquimod for treatment of actinic keratoses: lesion clearance, safety, and skin quality outcomes. J Drugs Dermatol 2011; 10 12: 1432-8.
39. 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 Dermatolog Treat 2003; 14 2: 99-9106.
40. 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.
41. Morton C, Campbell S, Gupta G, Keohane S, Lear J, Zaki I, et al,. Intra-individual, 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 5: 1029-36.
42. 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.
43. Hantash BM, Stewart DB, Cooper ZA, Rehmus WE, Koch RJ, Swetter SM,. Facial resurfacing for nonmelanoma skin cancer prophylaxis. Arch Dermatol 2006; 142 8: 976-82.
44. Gebauer K, Brown P, Varigos G,. Topical diclofenac in hyaluronan gel for the treatment of solar keratoses. Australas J Dermatol 2003; 44 1: 40-3.
45. Rivers JK, Arlette J, Shear N, Guenther L, Carey W, Poulin Y,. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 2002; 146 1: 94-9100.
46. Wolf JE, 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 11: 709-13.
47. Ulrich C, Johannsen A, Rowert-Huber J, Ulrich M, Sterry W, Stockfleth E,. Results of a randomized, placebo-controlled safety and efficacy study of topical diclofenac 3% gel in organ transplant patients with multiple actinic keratoses. Eur J Dermatol 2010; 20 4: 482-8.
48. Akarsu S, Aktan S, Atahan A, Koc P, Ozkan S,. Comparison of topical 3% diclofenac sodium gel and 5% imiquimod cream for the treatment of actinic keratoses. Clin Exp Dermatol 2011; 36 5: 479-84.
49. Kose O, Koc E, Erbil AH, Caliskan E, Kurumlu Z,. Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis. J Dermatolog Treat 2008; 19 3: 159-63.
50. Jorizzo J, Stewart D, Bucko A, Davis SA, Espy P, Hino P, et al,. Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis. Cutis 2002; 70 6: 335-9.
51. Weiss J, Menter A, Hevia O, Jones T, Ling M, Rist T, et al,. Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. Cutis 2002; 70 (2 Suppl.): 22-9.
52. Jorizzo J, Weiss J, Furst K, VandePol C, Levy SF,. 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 7: 813-6.
53. 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 6: 990-991000.
54. Smith S, Piacquadio D, Morhenn V, Atkin D, Fitzpatrick R,. Short incubation PDT versus 5-FU in treating actinic keratoses. J Drugs Dermatol 2003; 2 6: 629-35.
55. 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 2: 250-9.
56. 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 2: 144-7.
57. Swanson N, Abramovits W, Berman B, Kulp J, Rigel DS, 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 2-week cycles. J Am Acad Dermatol 2010; 62 4: 582-90.
58. 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 1: 133-41.
59. Gebauer K, Shumack S, Cowen PSJ,. Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial. Br J Dermatol 2009; 161 4: 897-903.
60. Jorizzo J, Dinehart S, Matheson R, Moore JK, Ling M, Fox TL, 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 2: 265-8.
61. Korman N, Moy R, Ling M, Matheson R, Smith S, McKane S, et al,. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol 2005; 141 4: 467-73.
62. Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, 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 5: 714-21.
63. NCT00828568. A Therapeutic Equivalence Study of Two Imiquimod Cream 5% Treatments for Patients With Actinic Keratosis.
64. Ooi T, Barnetson RS, Zhuang L, McKane S, Lee JH, Slade HB, et al,. Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial. Br J Dermatol 2006; 154 1: 72-8.
65. Ortonne J-P, Gupta G, Ortonne N, Duteil L, Queille C, Mallefet P,. Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment. Exp Dermatol 2010; 19 7: 641-7.
66. Stockfleth E, Meyer T, Benninghoff B, Salasche S, Papadopoulos L, Ulrich C, et al,. A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses. Arch Dermatol 2002; 138 11: 1498-502.
67. Szeimies RM, Gerritsen MJ, Gupta G, Ortonne JP, Serresi S, Bichel J, et al,. Imiquimod 5% cream for the treatment of actinic keratosis: results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology. J Am Acad Dermatol 2004; 51 4: 547-55.
68. Ulrich C, Bichel J, Euvrard S, Guidi B, Proby CM, van de Kerkhof PC, 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): 25-31.
69. Sotiriou E, Apalla Z, Maliamani F, Zaparas N, Panagiotidou D, Ioannides D,. 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 9: 1061-5.
70. Serra-Guillen C, Nagore E, Hueso L, Llombart B, Requena C, Sanmartin O, et al,. A randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate. Brit J Dermatol 2011; 164 2: 429-33.
71. Serra-Guillen C, Nagore E, Hueso L, Traves V, Messeguer F, Sanmartin O, 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 4: e131-7.
72. Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B,. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012; 366 11: 1010-9.
73. Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, 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 6: 934-43.
74. Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, 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. Brit J Dermatol 2012; 166 1: 137-46.
75. Piacquadio DJ, Chen DM, Farber HF, Fowler JF Jr, Glazer SD, Goodman JJ, 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 1: 41-6.
76. Schmieder GJ, Huang EY, Jarratt M,. A multicenter, randomized, vehicle-controlled phase 2 study of blue light photodynamic therapy with aminolevulinic acid HCl 20% topical solution for the treatment of actinic keratoses on the upper extremities: the effect of occlusion during the drug incubation period. J Drugs Dermatol 2012; 11 12: 1483-9.
77. Szeimies RM, Radny P, Sebastian M, Borrosch F, Dirschka T, Krahn-Senftleben G, et al,. Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double-blind, placebo-controlled phase III study. Br J Dermatol 2010; 163 2: 386-94.
78. Taub AF, Garretson CB,. A randomized, blinded, bilateral intraindividual, vehicle-controlled trial of the use of photodynamic therapy with 5-aminolevulinic acid and blue light for the treatment of actinic keratoses of the upper extremities. J Drugs Dermatol 2011; 10 9: 1049-56.
79. 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 1: 87-91.
80. de Graaf YG, Kennedy C, Wolterbeek R, Collen AF, Willemze R, Bouwes Bavinck JN,. Photodynamic therapy does not prevent cutaneous squamous-cell carcinoma in organ-transplant recipients: results of a randomized-controlled trial. J Invest Dermatol 2006; 126 3: 569-74.
81. Willey A, Mehta S, Lee PK,. Reduction in the incidence of squamous cell carcinoma in solid organ transplant recipients treated with cyclic photodynamic therapy. Dermatol Surg 2010; 36 5: 652-8.
82. 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.
83. 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 2: 227-32.
84. Photocure-Australian. Metvixia cream, 16.8%. 2004.
85. Photocure-US. Metvixia cream, 16.8%. 2004.
86. Szeimies R-M, Matheson RT, Davis SA, Bhatia AC, Frambach Y, Klovekorn 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 4: 586-92.
87. Dragieva G, Prinz BM, Hafner J, Dummer R, Burg G, Binswanger U, et al,. A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant recipients. Br J Dermatol 2004; 151 1: 196-200.
88. Werner RN, Jacobs A, Rosumeck S, Nast A,. Online consensus conferences for clinical guidelines development-A survey among participants from the International Guidelines for the Treatment of Actinic Keratosis. J Eval Clin Pract 2014; 20 6: 853-6.
89. Morsy H, Kamp S, Jemec GB,. Outcomes in randomized controlled trials in psoriasis: what has changed over the last 20 years? J Dermatolog Treat 2007; 18 5: 261-7.
90. 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 2: 277-83.
91. Fariba I, Ali A, Hossein SA, Atefeh S,. Atarzadeh Behbahan SA. Efficacy of 3% diclofenac gel for the treatment of actinic keratoses: a randomized, double-blind, placebo controlled study. Indian J Dermatol Venereol Leprol 2006; 72 5: 346-9.
92. Haddad A, Santos ID, Gragnani A, Ferreira LM,. The effect of increasing fluence on the treatment of actinic keratosis and photodamage by photodynamic therapy with 5-aminolevulinic acid and intense pulsed light. Photomed Laser Surg 2011; 29 6: 427-32.
93. Persaud AN, Shamuelova E, Sherer D, Lou W, Singer G, Cervera C, et al,. Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis. J Am Acad Dermatol 2002; 47 4: 553-6.
94. Siller G, Gebauer K, Welburn P, Katsamas J, Ogbourne SM,. 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 1: 16-22.
95. Weinstock MA, Bingham SF, Digiovanna JJ, Rizzo AE, Marcolivio K, Hall R, et al,. Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affair randomized chemoprevention trial. J Investigat Dermatol 2012; 132 6: 1583-90.
96. Wiegell SR, Fabricius S, Gniadecka M, Stender IM, Berne B, Kroon S, et al,. Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study. Brit J Dermatol 2012; 166 6: 1327-32.
97. 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 4: 250-5.
98. 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; 62 4: 573-81.
99. McEwan LE, Smith JG,. Topical diclofenac/hyaluronic acid gel in the treatment of solar keratoses. Australas J Dermatol 1997; 38 4: 187-9.
100. Ostertag JU, Quaedvlieg PJ, van der Geer S, Nelemans P, Christianen ME, Neumann MH, 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 8: 731-9.
101. Zeichner JA, Stern DWK, Uliasz A, Itenberg S, Lebwohl M,. Placebo-controlled, double-blind, randomized pilot study of imiquimod 5% cream applied once per week for 6 months for the treatment of actinic keratoses. J Am Acad Dermatol 2009; 60 1: 59-62.
102. Akar A, Bulent Tastan H, Erbil H, Arca E, Kurumlu Z, Gur AR,. Efficacy and safety assessment of 0.5% and 1% colchicine cream in the treatment of actinic keratoses. J Dermatolog Treat 2001; 12 4: 199-203.
103. Alberts DS, Dorr RT, Einspahr JG, Aickin M, Saboda K, Xu MJ, et al,. Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine. Cancer Epidemiol Biomarkers Prev 2000; 9 12: 1281-6.
104. Alirezai M, Dupuy P, Amblard P, Kalis B, Souteyrand P, Frappaz A, et al,. Clinical evaluation of topical isotretinoin in the treatment of actinic keratoses. J Am Acad Dermatol 1994; 30 3: 447-51.
105. Apalla Z, Sotiriou E, Panagiotidou D, Lefaki I, Goussi C, Ioannides D,. The impact of different fluence rates on pain and clinical outcome in patients with actinic keratoses treated with photodynamic therapy. Photodermatol Photoimmunol Photomed 2011; 27 4: 181-5.
106. Azimi H,. Comparison of the efficacy of cryotherapy and 0.1% Acnalen gel vs. cryotherapy and placebo in the treatment of actinic keratoses. Pak J Med Sci 2012; 28 1: 4.
107. Bercovitch L,. Topical chemotherapy of actinic keratoses of the upper extremity with tretinoin and 5-fluorouracil: a double-blind controlled study. Br J Dermatol 1987; 116 4: 549-52.
108. Chen AC, Martin AJ, Halliday GM, Surjana D, Damian D,. Nicotinamide for skin cancer chemoprevention. Asia-Pacific J Clin Oncol 2012; 8: 308.
109. Deonizio JM, Mulinari-Brenner FA,. Cryopeeling for treatment of photodamage and actinic keratosis: liquid nitrogen versus portable system. An Bras Dermatol 2011; 86 3: 440-4.
110. Foote JA, Ranger-Moore JR, Einspahr JG, Saboda K, Kenyon J, Warneke J, et al,. Chemoprevention of human actinic keratoses by topical DL-alpha-tocopherol. Cancer Prev Res (Phila) 2009; 2 4: 394-400.
111. Galitzer BI,. Effect of retinoid pretreatment on outcomes of patients treated by photodynamic therapy for actinic keratosis of the hand and forearm. J Drugs Dermatol 2011; 10 10: 1124-32.
112. Hauschild A, Popp G, Stockfleth E, Meyer K-G, Imberger D, Mohr P, 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 2: 116-21.
113. Hirata Y, Koga S, Fukui N, Yu A, Koshida S, Kosaka Y, et al,. 5-Aminolevulinic acid-mediated photodynamic therapy to superficial malignant skin tumors using Super Lizer. J Dermatol 2011; 38 8: 748-54.
114. Huyke C, Reuter J, Rodig M, Kersten A, Laszczyk M, Scheffler A, et al,. Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study. J Dtsch Dermatol Ges 2009; 7 2: 128-33.
115. 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 2: 133-9.
116. Jorizzo JL, Markowitz O, Lebwohl MG, Bourcier M, Kulp J, Meng TC, 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 9: 1101-8.
117. Kang S, Goldfarb MT, Weiss JS, Metz RD, Hamilton TA, Voorhees JJ, et al,. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. J Am Acad Dermatol 2003; 49 1: 83-90.
118. Kulp-Shorten C, Konnikov N, Callen J,. Comparative Evaluation of the efficacy and Safety of Masoprocol and 5-Fluorouracil Cream for the Treatment of Multiple Actinic Keratoses of the Head and Neck. Journal of Geriatric Dermatology 1993; 1: 161-8.
119. Misiewicz J, Sendagorta E, Golebiowska A, Lorenc B, Czarnetzki BM, Jablonska S,. Topical treatment of multiple actinic keratoses of the face with arotinoid methyl sulfone (Ro 14-9706) cream versus tretinoin cream: a double-blind, comparative study. J Am Acad Dermatol 1991; 24 3: 448-51.
120. Moloney F, Vestergaard M, Radojkovic B, Damian D,. Randomized, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses. Br J Dermatol 2010; 162 5: 1138-9.
121. Moriarty M, Dunn J, Darragh A, Lambe R, Brick I,. Etretinate in treatment of actinic keratosis. A double-blind crossover study. Lancet 1982; 1 8268: 364-5.
122. NCT00774787. Topical imiquimod cream in combination with cryotherapy for the treatment of actinic keratoses.
123. Olsen EA, Abernethy ML, Kulp-Shorten C, Callen JP, Glazer SD, Huntley A, 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.
124. Pflugfelder A, Welter AK, Leiter U, Weide B, Held L, Eigentler TK, et al,. Open label randomized study comparing 3 months vs. 6 months treatment of actinic keratoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of the German Dermatologic Cooperative Oncology Group. J Euro Acad Dermatol Venereol 2012; 26 1: 48-53.
125. Seckin D, Cerman AA, Yildiz A, Ergun T,. Can topical calcipotriol be a treatment alternative in actinic keratoses? A preliminary report J Drugs Dermatol 2009; 8 5: 451-4.
126. Shaffelburg M,. Treatment of actinic keratoses with sequential use of photodynamic therapy; and imiquimod 5% cream. J Drugs Dermatol 2009; 8 1: 35-9.
127. Sotiriou E, Apalla Z, Chovarda E, Goussi C, Trigoni A, Ioannides D,. Single vs. fractionated photodynamic therapy for face and scalp actinic keratoses: a randomized, intraindividual comparison trial with 12-month follow-up. J Euro Acad Dermatol Venereol 2012; 26 1: 36-40.
128. Surjana D, Halliday GM, Damian DL,. Nicotinamide for skin cancer prevention. Aust J Dermatol 2012; 53: 5.
129. Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL,. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Investig Dermatol 2012; 132 5: 1497-500.
130. Szeimies RM, Bichel J, Ortonne JP, Stockfleth E, Lee J, Meng TC,. A phase II dose-ranging study of topical resiquimod to treat actinic keratosis. Br J Dermatol 2008; 159 1: 205-10.
131. Tan JKL, Thomas DR, Poulin Y, Maddin F, Tang J,. Efficacy of imiquimod as an adjunct to cryotherapy for actinic keratoses. J Cutan Med Surg 2007; 11 6: 195-201.
132. Tarstedt M, Rosdahl I, Berne B, Svanberg K, Wennberg AM,. 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 5: 424-8.
133. Thompson SC, Jolley D, Marks R,. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993; 329 16: 1147-51.
134. 2 laser: a randomized clinical trial. Brit J Dermatol 2012; 166 6: 1262-9.
135. Tong DW, Barnetson RS,. Beta-1,3-D-glucan gel in the treatment of solar keratoses. Aust J Dermatol 1996; 37 3: 137-8.
136. von Felbert V, Hoffmann G, Hoff-Lesch S, Abuzahra F, Renn CN, Braathen LR, et al,. Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodes. Br J Dermatol 2010; 163 3: 607-15.
137. Wiegell SR, Fabricius S, Stender IM, Berne B, Kroon S, Andersen BL, et al,. A randomized, multicentre study of directed daylight exposure times of 1(1/2) vs. 2(1/2) h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp. Br J Dermatol 2011; 164 5: 1083-90.
138. Wiegell SR, Haedersdal M, Eriksen P, Wulf HC,. Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial. Br J Dermatol 2009; 160 6: 1308-14.
139. Wiegell SR, Haedersdal M, Philipsen PA, Eriksen P, Enk CD, Wulf HC,. Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study. Br J Dermatol 2008; 158 4: 740-6.
140. Willey A,. Temperature-modulated photodynamic therapy for the treatment of actinic keratoses on the extremities. J Am Acad Dermatol. 2012; 66: 4 (Suppl. 1): AB177.
141. Hadley J, Tristani-Firouzi P, Hull C, Florell S, Cotter M, Hadley M,. 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 5: 722-7.
142. Jeffes EW, McCullough JL, Weinstein GD, Kaplan R, Glazer SD, Taylor JR,. Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. J Am Acad Dermatol 2001; 45 1: 96-104.
143. Damian D, Surjana D, Martin A, Halliday G,. Oral nicotinamide for skin cancer prevention. 41st Annual Meeting of the European Society for Dermatological Research, ESDR 2011 Barcelona Spain. J Invest Dermatol 2011; 131 (Suppl. 2): S99.
144. Szeimies RM, Stockfleth E, Moor ACE, Stocker M, Ortland C, Hauschild A,. A new 5-ALA-patch for the photodynamic therapy of actinic keratoses. Phot Photodynam Therapy 2011; 8 2: 200.
145. Van der Geer S, Krekels GA,. Treatment of actinic keratoses on the dorsum of the hands: ALA-PDT versus diclofenac 3% gel followed by ALA-PDT. A placebo-controlled, double-blind, pilot study. J Dermatolog Treat 2009; 20 5: 259-65.
146. Celecoxib may be effective in preventing non-melanoma skin cancers. Int J Cancer Res 2011; 7: 65.
147. Ingenol mebutate (Picato) for actinic keratoses. Med Letter Drugs Therap 2012; 54: 35-6.
148. Anderson L, Melgaard A, Schmeider G, Xu Z,. Two-day topical treatment with ingenol mebutate gel, 0.05% for actinic keratoses on the trunk and extremities: analysis of data pooled from two trials. J Am Acad Dermatol 2012; 66: 4 (Suppl. 1): AB159.
149. Berman B, Melgaard A, Marmur E, Larsson T,. Three-day topical treatment with ingenol mebutate gel, 0.015% for actinic keratoses on the face and scalp: analysis of data pooled from two trials. J Am Acad Dermatol. 2012; 1: AB3.
150. Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, et al,. Efficacy and safety comparison of photodynamic therapy with BF-200 ALA versus Metvix for the treatment of actinic keratosis: a prospective, randomized, placebo-controlled multinational, phase III study. J German Soc Dermatol 2011; 9: 196-7.
151. Hauschild A,. Photodynamic therapy for actinic keratoses: procedure matters? Brit J Dermatol 2012; 166 1: 3-5.
152. Hollestein LM, Koomen ER, Nijsten T,. Chemoprevention for keratinocytic (pre)cancers: balancing the risks and benefits. Arch Dermatol 2012; 148 5: 638-40.
153. Keating GM,. Ingenol mebutate gel 0.015% and 0.05%: in actinic keratosis. Drugs 2012; 72 18: 2397-405.
154. Lee J, Jorizzo J, Lebwohl M, Markowitz O, Levy S,. Cryosurgery followed by imiquimod 3.75% to treat actinic keratosis. J Am Acad Dermatol 2011; 66: 2 (Suppl. 1): AB2.
155. Prado R, Francis SO, Mason MN, Wing G, Gamble RG, Dellavalle R,. Nonmelanoma skin cancer chemoprevention. Dermatol Surg 2011; 37 11: 1566-78.
156. Stockfleth E, Ulrich M, Kerl H, Willers C,. Long-term sustained efficacy of low dose 5-fluorouracil combined with 10% salicylic acid as a lesion directed treatment for actinic keratoses. Melanoma Res 2011; 21: e53.
157. 2 laser: A randomized clinical trial (British Journal of Dermatology (2012) 166 (1262-9)). Brit J Dermatol 2012; 167 2: 461.
158. Willey A, Sakamoto F,. Temperature modulated photodynamic therapy for the treatment of actinic keratoses on the extremities. Lasers Surg Med 2011; 43: 957-8.
159. Willey A, Sakamoto F,. Temperature modulated photodynamic therapy for the treatment of actinic keratoses on the extremities. Lasers Surg Med 2012; 44: 8.
160. Almagro BM, Herrera-Acosta E, Herrera-Ceballos E, Mendiola-Fernandez MV, Lopez-Navarro N, Bosch-Garciea R, et al,. Efficacy of photodynamic therapy associated to pretreatment with AHA peel in facial diffuse photodamage. J Am Acad Dermatol 2012; 66: 4 (Suppl. 1): AB175.
161. Palm MD, Goldman MP,. Safety and efficacy comparison of blue versus red light sources for photodynamic therapy using methyl aminolevulinate in photodamaged skin. J Drugs Dermatol 2011; 10 1: 53-60.
162. Stockfleth E, Zwingers T, Willers C,. Recurrence rates and patient assessed outcomes of 0.5% 5-fluorouracil in combination with salicylic acid treating actinic keratoses. Euro J Dermatol 2012; 22 3: 370-4.
163. Perrett CM, McGregor JM, Warwick J, Karran P, Leigh IM, Proby CM, et al,. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Br J Dermatol 2007; 156 2: 320-8.
164. Swanson N,. Multicenter, randomized, parallel-group, double-blind, vehicle-controlled study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.05% in patients with actinic keratoses on nonhead locations. J Am Acad Dermatol 2010; 62 (3 Suppl. 1): AB2.