414 From the Dermatological Surgery & Laser Unit,St John’s Institute of Dermatology, St Thomas’ Hospital, a and the Department of Public Health Medicine,GKT School of Medicine,Kings College. b Accepted for publication April 21,1999. Reprint requests: Richard J. Barlow, MD, Dermatological Surgery & Laser Unit, St John’s Institute of Dermatology, St Thomas’ Hospital,London SE1 7EH,United Kingdom. Copyright © 1999 by the American Academy of Dermatology,Inc. 0190-9622/99/$8.00 + 0 16/1/99378 P hotodynamic therapy (PDT) using 5-aminole- vulinic acid (5-ALA) has been reported to be effective for actinic keratoses (AKs) and for selected skin tumors. 1-4 Topical 5-ALA accumulates preferentially in dysplastic cells and is a precursor to the photosensitizer protoporphyrin IX (Pp IX). 3 The absorption spectrum for Pp IX lies in the 400 to 730 nm wavelength range and its photoactivation results in generation of reactive oxygen intermediates including singlet oxygen. Topical 5-fluorouracil (5-FU) inhibits DNA synthe- sis through its action on thymidylate synthetase and is well established as a cheap, convenient, and selec- tive treatment of AKs. 5 It is most effective if applied twice a day for several weeks, and its main disadvan- tage is poor patient compliance because of pain and redness in affected areas. In this study we have compared the efficacy and tolerability of PDT with topical 5-FU in the treatment of AKs on the hands. PATIENTS AND METHODS Ethical approval was obtained from the Institutional Ethics Committee. Seventeen patients (8 men, 9 women), aged 53 to 79 years, were recruited into the study. All had a long history of AKs affecting the forearms and hands. Patients were randomized to apply 5-FU cream (5% wt/wt fluorouracil, Roche Products, Welwyn Garden City, UK) twice a day to one hand for 3 weeks and A randomized paired comparison of photodynamic therapy and topical 5-fluorouracil in the treatment of actinic keratoses Habib A. Kurwa, MRCP, a Simon A. Yong-Gee, MBBS, a Paul T. Seed, MSc, CStat, b Andrew C. Markey, MD, FRCP, a and Richard J. Barlow, MD, MRCP a London, United Kingdom Background: Photodynamic therapy (PDT) has not been compared with topical 5-fluorouracil (5-FU) in the treatment of epidermal dysplasia. Objective: The purpose of this study was to assess the efficacy and tolerability of these two treatment modalities in 17 patients with actinic keratoses on the backs of the hands. Methods: Each patient’s right and left hands were randomized to receive either a 3-week course of topical 5-FU applied twice per day or PDT using topical 5-aminolevulinic acid (5-ALA) and then, after 4 hours, irradiation with an incoherent light source consisting of a 1200 W metal halogen lamp emitting red light (580 to 740 nm). Each hand randomized for PDT received 150 J/cm 2 . The observed median fluence rate was 86 mW/cm 2 (interquartile range, 53 to 100 mW/cm 2 ). All patients were reviewed at 1, 4, and 24 weeks after starting treatment. Re su lts: Fourteen of 17 patients (82%) completed the study. The mean lesional area treated with topical 5- FU decreased from 1390 mm 2 (standard deviation [SD], 1130) to 297 mm 2 (SD, 209). This represents a mean reduction in lesional area of 70% (confidence interval [CI], 61%-80%). The mean lesional area treated with topical PDT decreased from 1322 mm 2 (SD, 1280) to 291 mm 2 (SD, 274), representing a mean reduction in lesional area of 73% (CI, 61%-84%). The reduction in lesional area elicited by the two treatment methods was similar (CI, –25% to 17%). There was no statistically significant difference between the treatment methods in overall symptom scores for pain and redness. Conclusion: One treatment with PDT using topical 5-ALA appears to be as effective and well tolerated as 3 weeks of twice-daily topical 5-FU, a cheap and widely available alternative. (J Am Acad Dermatol 1999; 41:414-8.)