UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Photodynamic therapy

Authors
Edward V Maytin, MD, PhD
Christine B Warren, MD, MS
Section Editor
Craig A Elmets, MD
Deputy Editor
Rosamaria Corona, MD, DSc

INTRODUCTION

Photodynamic therapy (PDT) is a two-step treatment in which a drug that acts as a photosensitizer is administered to specifically target a diseased tissue of interest, followed by illumination with visible light to activate the drug and destroy the target tissue [1]. PDT was developed primarily for treatment of cancer and precancers. While PDT has been used to treat internal cancers in many parts of the body by administering a systemic photosensitizer and delivering light through an optical fiber, by far the most common application of PDT in clinical medicine is for treatment of cancer and precancer of the skin [2].

This topic will review the principles and practical applications of PDT for treating neoplastic and preneoplastic conditions of the skin. The use of PDT in oncology and internal medicine is discussed in specific topic reviews.

(See "Management of superficial esophageal cancer", section on 'ER plus PDT'.)

(See "Barrett's esophagus: Treatment with photodynamic therapy".)

(See "Endobronchial photodynamic therapy in the management of airway disease in adults".)

                          
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Jul 24, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Hasan T, Ortel B, Moor AC, Pogue BW. Photodynamic therapy of cancer. In: Cancer Medicine, 9th ed, Kufe D, Pollock RE, Weichselbaum RR, et al. (Eds), B.C. Decker, Inc., Hamilton 2017. p.537.
  2. MacCormack MA. Photodynamic therapy. Adv Dermatol 2006; 22:219.
  3. Juzeniene A, Peng Q, Moan J. Milestones in the development of photodynamic therapy and fluorescence diagnosis. Photochem Photobiol Sci 2007; 6:1234.
  4. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992; 14:275.
  5. Anand S, Ortel BJ, Pereira SP, et al. Biomodulatory approaches to photodynamic therapy for solid tumors. Cancer Lett 2012; 326:8.
  6. Anand S, Wilson C, Hasan T, Maytin EV. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy. Cancer Res 2011; 71:6040.
  7. Anand S, Rollakanti KR, Brankov N, et al. Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death. Mol Cancer Ther 2017; 16:1092.
  8. Rollakanti K, Anand S, Maytin EV. Topical calcitriol prior to photodynamic therapy enhances treatment efficacy in non-melanoma skin cancer mouse models. Proc SPIE Int Soc Opt Eng 2015; 9308:93080Q.
  9. Warren CB, Lohser S, Wene LC, et al. Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate. J Biomed Opt 2010; 15:051607.
  10. Rollakanti KR, Anand S, Davis SC, et al. Noninvasive Optical Imaging of UV-Induced Squamous Cell Carcinoma in Murine Skin: Studies of Early Tumor Development and Vitamin D Enhancement of Protoporphyrin IX Production. Photochem Photobiol 2015; 91:1469.
  11. Karrer S, Bosserhoff AK, Weiderer P, et al. Influence of 5-aminolevulinic acid and red light on collagen metabolism of human dermal fibroblasts. J Invest Dermatol 2003; 120:325.
  12. Karrer S, Bosserhoff AK, Weiderer P, et al. Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts. Br J Dermatol 2004; 151:776.
  13. 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.
  14. Reinhold U, Dirschka T, Ostendorf R, et al. A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz(®) ) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED(®) lamp. Br J Dermatol 2016; 175:696.
  15. www.euroderm.org/edf/index.php/edf-guidelines/category/5-guidelines-miscellaneous (Accessed on June 29, 2017).
  16. www.accessdata.fda.gov/drugsatfda_docs/label/2008/021415s003lbl.pdf (Accessed on June 27, 2017).
  17. Pariser DM, Houlihan A, Ferdon MB, et al. Randomized Vehicle-Controlled Study of Short Drug Incubation Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses of the Face or Scalp. Dermatol Surg 2016; 42:296.
  18. Touma D, Yaar M, Whitehead S, et al. A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodamage. Arch Dermatol 2004; 140:33.
  19. 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; 150:1281.
  20. Gupta AK, Paquet M, Villanueva E, Brintnell W. Interventions for actinic keratoses. Cochrane Database Syst Rev 2012; 12:CD004415.
  21. Fantini F, Greco A, Del Giovane C, et al. Photodynamic therapy for basal cell carcinoma: clinical and pathological determinants of response. J Eur Acad Dermatol Venereol 2011; 25:896.
  22. Arits AH, Mosterd K, Essers BA, et al. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial. Lancet Oncol 2013; 14:647.
  23. Cosgarea R, Susan M, Crisan M, Senila S. Photodynamic therapy using topical 5-aminolaevulinic acid vs. surgery for basal cell carcinoma. J Eur Acad Dermatol Venereol 2013; 27:980.
  24. Roozeboom MH, Arits AH, Nelemans PJ, Kelleners-Smeets NW. Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials. Br J Dermatol 2012; 167:733.
  25. Szeimies RM, Ibbotson S, Murrell DF, et al. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month follow-up. J Eur Acad Dermatol Venereol 2008; 22:1302.
  26. Basset-Seguin N, Ibbotson SH, Emtestam L, et al. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Eur J Dermatol 2008; 18:547.
  27. Rhodes LE, de Rie MA, Leifsdottir R, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol 2007; 143:1131.
  28. Mosterd K, Thissen MR, Nelemans P, et al. Fractionated 5-aminolaevulinic acid-photodynamic therapy vs. surgical excision in the treatment of nodular basal cell carcinoma: results of a randomized controlled trial. Br J Dermatol 2008; 159:864.
  29. Li Q, Gao T, Jiao B, et al. Tumor thickness predicts long-term complete response of facial basal cell carcinomas in Asian skin types iv/v treated with methyl aminolaevulinate photodynamic therapy. Photomed Laser Surg 2011; 29:501.
  30. Basset-Seguin N, Bissonnette R, Girard C, et al. Consensus recommendations for the treatment of basal cell carcinomas in Gorlin syndrome with topical methylaminolaevulinate-photodynamic therapy. J Eur Acad Dermatol Venereol 2014; 28:626.
  31. Pauwels C, Mazereeuw-Hautier J, Basset-Seguin N, et al. Topical methyl aminolevulinate photodynamic therapy for management of basal cell carcinomas in patients with basal cell nevus syndrome improves patient's satisfaction and reduces the need for surgical procedures. J Eur Acad Dermatol Venereol 2011; 25:861.
  32. Girard C, Debu A, Bessis D, et al. Treatment of Gorlin syndrome (nevoid basal cell carcinoma syndrome) with methylaminolevulinate photodynamic therapy in seven patients, including two children: interest of tumescent anesthesia for pain control in children. J Eur Acad Dermatol Venereol 2013; 27:e171.
  33. Loncaster J, Swindell R, Slevin F, et al. Efficacy of photodynamic therapy as a treatment for Gorlin syndrome-related basal cell carcinomas. Clin Oncol (R Coll Radiol) 2009; 21:502.
  34. Loncaster JA, Allan E. Photodynamic therapy in the management of a patient with Gorlin syndrome (naevoid basal cell carcinoma syndrome). Photodiagnosis Photodyn Ther 2006; 3:134.
  35. Mougel F, Debarbieux S, Ronger-Savlé S, et al. Methylaminolaevulinate photodynamic therapy in patients with multiple basal cell carcinomas in the setting of Gorlin-Goltz syndrome or after radiotherapy. Dermatology 2009; 219:138.
  36. Morton C, Horn M, Leman J, et al. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial. Arch Dermatol 2006; 142:729.
  37. Lehmann P. Methyl aminolaevulinate-photodynamic therapy: a review of clinical trials in the treatment of actinic keratoses and nonmelanoma skin cancer. Br J Dermatol 2007; 156:793.
  38. Calzavara-Pinton PG, Venturini M, Sala R, et al. Methylaminolaevulinate-based photodynamic therapy of Bowen's disease and squamous cell carcinoma. Br J Dermatol 2008; 159:137.
  39. Truchuelo M, Fernández-Guarino M, Fleta B, et al. Effectiveness of photodynamic therapy in Bowen's disease: an observational and descriptive study in 51 lesions. J Eur Acad Dermatol Venereol 2012; 26:868.
  40. Souza CS, Felicio LB, Ferreira J, et al. Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for non-melanoma skin cancer. Photodiagnosis Photodyn Ther 2009; 6:207.
  41. Gilaberte Y, Milla L, Salazar N, et al. Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy. J Invest Dermatol 2014; 134:2428.
  42. www.dusapharma.com/blu-u1.html (Accessed on June 12, 2017).
  43. Taylor M. Photodynamic therapy for acne: are we there yet? Br J Dermatol 2016; 174:712.
  44. Keyal U, Bhatta AK, Wang XL. Photodynamic therapy for the treatment of different severity of acne: A systematic review. Photodiagnosis Photodyn Ther 2016; 14:191.
  45. Ma Y, Chen Q, Liu Y, et al. Effects of 5-aminolevulinic acid photodynamic therapy on TLRs in acne lesions and keratinocytes co-cultured with P. acnes. Photodiagnosis Photodyn Ther 2016; 15:172.
  46. Hörfelt C, Funk J, Frohm-Nilsson M, et al. Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study. Br J Dermatol 2006; 155:608.
  47. Liu LH, Fan X, An YX, et al. Randomized trial of three phototherapy methods for the treatment of acne vulgaris in Chinese patients. Photodermatol Photoimmunol Photomed 2014; 30:246.
  48. Sakamoto FH, Torezan L, Anderson RR. Photodynamic therapy for acne vulgaris: a critical review from basics to clinical practice: part II. Understanding parameters for acne treatment with photodynamic therapy. J Am Acad Dermatol 2010; 63:195.
  49. Karrer S, Kohl E, Feise K, et al. Photodynamic therapy for skin rejuvenation: review and summary of the literature--results of a consensus conference of an expert group for aesthetic photodynamic therapy. J Dtsch Dermatol Ges 2013; 11:137.
  50. Ruiz-Rodriguez R, Sanz-Sánchez T, Córdoba S. Photodynamic photorejuvenation. Dermatol Surg 2002; 28:742.
  51. Dover JS, Bhatia AC, Stewart B, Arndt KA. Topical 5-aminolevulinic acid combined with intense pulsed light in the treatment of photoaging. Arch Dermatol 2005; 141:1247.
  52. Gold MH, Bradshaw VL, Boring MM, et al. Split-face comparison of photodynamic therapy with 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone for photodamage. Dermatol Surg 2006; 32:795.
  53. Levulan Kerastick [prescribing information]. Wilmington, MA: DUSA Pharmaceuticals, Inc.; 2010.
  54. Ameluz [prescribing information]. Wakefield, MA: Biofrontera Inc.; 2016.
  55. www.biofrontera.us.com/for-healthcare-professionals/bf-rhodoled/using-bf-rhodoled/ (Accessed on June 12, 2017).
  56. Metvixia [pacakge insert]. Fort Worth, TX: Galderma Laboratories, L.P.; 2017.
  57. Bencini PL, Galimberti MG, Pellacani G, Longo C. Application of photodynamic therapy combined with pre-illumination microneedling in the treatment of actinic keratosis in organ transplant recipients. Br J Dermatol 2012; 167:1193.
  58. Torezan L, Chaves Y, Niwa A, et al. A pilot split-face study comparing conventional methyl aminolevulinate-photodynamic therapy (PDT) with microneedling-assisted PDT on actinically damaged skin. Dermatol Surg 2013; 39:1197.
  59. Spencer JM, Freeman SA. Microneedling Prior to Levulan PDT for the Treatment of Actinic Keratoses: A Split-Face, Blinded Trial. J Drugs Dermatol 2016; 15:1072.
  60. Petukhova TA, Hassoun LA, Foolad N, et al. Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment of Actinic Keratoses: A Randomized Clinical Trial. JAMA Dermatol 2017; 153:637.
  61. Togsverd-Bo K, Haak CS, Thaysen-Petersen D, et al. Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial. Br J Dermatol 2012; 166:1262.
  62. Haak CS, Christiansen K, Erlendsson AM, et al. Ablative fractional laser enhances MAL-induced PpIX accumulation: Impact of laser channel density, incubation time and drug concentration. J Photochem Photobiol B 2016; 159:42.
  63. Bay C, Lerche CM, Ferrick B, et al. Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy: A Randomized Clinical Trial. JAMA Dermatol 2017; 153:270.
  64. 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; 11:1483.
  65. Bissonnette R, Bolduc C, Maari C, Nigen S. Short incubation photodynamic therapy with methylaminolevulinate and no occlusion for the treatment of actinic keratoses. J Am Acad Dermatol 2012; 67:1386.
  66. Ishida N, Watanabe D, Mizutani K, et al. Heating increases protoporphyrin IX production in normal skin after delivery of 5-aminolevulinic acid by iontophoresis. Photodermatol Photoimmunol Photomed 2009; 25:333.
  67. Willey A, Anderson RR, Sakamoto FH. Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A One-Year Follow-up Study. Dermatol Surg 2015; 41:1290.
  68. Uehlinger P, Ballini JP, van den Bergh H, Wagnières G. On the role of iron and one of its chelating agents in the production of protoporphyrin IX generated by 5-aminolevulinic acid and its hexyl ester derivative tested on an epidermal equivalent of human skin. Photochem Photobiol 2006; 82:1069.
  69. Campbell SM, Morton CA, Alyahya R, et al. Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma. Br J Dermatol 2008; 159:387.
  70. Anand S, Honari G, Hasan T, et al. Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo. Clin Cancer Res 2009; 15:3333.
  71. Martin GM. In-office Painless Aminolevulinic Acid Photodynamic Therapy: A Proof of Concept Study and Clinical Experience in More Than 100 Patients. J Clin Aesthet Dermatol 2016; 9:19.
  72. Gandy J, Labadie B, Bierman D, Zachary C. Photodynamic Therapy Effectively Treats Actinic Keratoses Without Pre-Illumination Incubation Time. J Drugs Dermatol 2017; 16:275.
  73. Wiegell SR, Haedersdal M, Philipsen PA, et al. 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; 158:740.
  74. Wiegell SR, Wulf HC, Szeimies RM, et al. Daylight photodynamic therapy for actinic keratosis: an international consensus: International Society for Photodynamic Therapy in Dermatology. J Eur Acad Dermatol Venereol 2012; 26:673.
  75. Lane KL, Hovenic W, Ball K, Zachary CB. Daylight photodynamic therapy: the Southern California experience. Lasers Surg Med 2015; 47:168.
  76. Glazer-Hockstein C, Dunaief JL. Could blue light-blocking lenses decrease the risk of age-related macular degeneration? Retina 2006; 26:1.
  77. Barkana Y, Belkin M. Laser eye injuries. Surv Ophthalmol 2000; 44:459.
  78. Hunter JJ, Morgan JI, Merigan WH, et al. The susceptibility of the retina to photochemical damage from visible light. Prog Retin Eye Res 2012; 31:28.
  79. Vassileva SG, Mateev G, Parish LC. Antimicrobial photosensitive reactions. Arch Intern Med 1998; 158:1993.
  80. Babilas P, Schreml S, Landthaler M, Szeimies RM. Photodynamic therapy in dermatology: state-of-the-art. Photodermatol Photoimmunol Photomed 2010; 26:118.
  81. Wolfe CM, Hatfield K, Cognetta AB Jr. Cellulitis as a postprocedural complication of topical 5-aminolevulinic acid photodynamic therapy in the treatment of actinic keratosis. J Drugs Dermatol 2007; 6:544.
  82. Ribeiro CF, Souza FH, Jordão JM, et al. Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients. An Bras Dermatol 2012; 87:418.
  83. Steinbauer J, Schreml S, Karrer S, et al. Phototoxic reactions in healthy volunteers following photodynamic therapy with methylaminolevulinate cream or with cream containing 5-aminolevulinic acid: a phase II, randomized study. Photodermatol Photoimmunol Photomed 2009; 25:270.
  84. Warren CB, Karai LJ, Vidimos A, Maytin EV. Pain associated with aminolevulinic acid-photodynamic therapy of skin disease. J Am Acad Dermatol 2009; 61:1033.
  85. Babes A, Sauer SK, Moparthi L, et al. Photosensitization in Porphyrias and Photodynamic Therapy Involves TRPA1 and TRPV1. J Neurosci 2016; 36:5264.
  86. Grapengiesser S, Ericson M, Gudmundsson F, et al. Pain caused by photodynamic therapy of skin cancer. Clin Exp Dermatol 2002; 27:493.
  87. Halldin CB, Gillstedt M, Paoli J, et al. Predictors of pain associated with photodynamic therapy: a retrospective study of 658 treatments. Acta Derm Venereol 2011; 91:545.
  88. Fritsch C, Stege H, Saalmann G, et al. Green light is effective and less painful than red light in photodynamic therapy of facial solar keratoses. Photodermatol Photoimmunol Photomed 1997; 13:181.
  89. Morton CA, Whitehurst C, Moore JV, MacKie RM. Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy. Br J Dermatol 2000; 143:767.
  90. Kasche A, Luderschmidt S, Ring J, Hein R. Photodynamic therapy induces less pain in patients treated with methyl aminolevulinate compared to aminolevulinic acid. J Drugs Dermatol 2006; 5:353.
  91. 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; 157:87.
  92. Wiegell SR, Stender IM, Na R, Wulf HC. Pain associated with photodynamic therapy using 5-aminolevulinic acid or 5-aminolevulinic acid methylester on tape-stripped normal skin. Arch Dermatol 2003; 139:1173.
  93. Wiegell SR, Wulf HC. Photodynamic therapy of acne vulgaris using 5-aminolevulinic acid versus methyl aminolevulinate. J Am Acad Dermatol 2006; 54:647.
  94. Pagliaro J, Elliott T, Bulsara M, et al. Cold air analgesia in photodynamic therapy of basal cell carcinomas and Bowen's disease: an effective addition to treatment: a pilot study. Dermatol Surg 2004; 30:63.
  95. Stangeland KZ, Kroon S. Cold air analgesia as pain reduction during photodynamic therapy of actinic keratoses. J Eur Acad Dermatol Venereol 2012; 26:849.
  96. Tyrrell J, Campbell SM, Curnow A. The effect of air cooling pain relief on protoporphyrin IX photobleaching and clinical efficacy during dermatological photodynamic therapy. J Photochem Photobiol B 2011; 103:1.
  97. Langan SM, Collins P. Randomized, double-blind, placebo-controlled prospective study of the efficacy of topical anaesthesia with a eutetic mixture of lignocaine 2.5% and prilocaine 2.5% for topical 5-aminolaevulinic acid-photodynamic therapy for extensive scalp actinic keratoses. Br J Dermatol 2006; 154:146.
  98. Holmes MV, Dawe RS, Ferguson J, Ibbotson SH. A randomized, double-blind, placebo-controlled study of the efficacy of tetracaine gel (Ametop) for pain relief during topical photodynamic therapy. Br J Dermatol 2004; 150:337.
  99. Skiveren J, Haedersdal M, Philipsen PA, et al. Morphine gel 0.3% does not relieve pain during topical photodynamic therapy: a randomized, double-blind, placebo-controlled study. Acta Derm Venereol 2006; 86:409.
  100. Berking C, Herzinger T, Flaig MJ, et al. The efficacy of photodynamic therapy in actinic cheilitis of the lower lip: a prospective study of 15 patients. Dermatol Surg 2007; 33:825.
  101. Wennberg AM. Pain, pain relief and other practical issues in photodynamic therapy. Australas J Dermatol 2005; 46 Suppl 3:S3.
  102. Mikolajewska P, Juzeniene A, Moan J. The effect of lidocaine on PpIX photobleaching and outcome of ALA-PDT in vitro. Photodiagnosis Photodyn Ther 2007; 4:249.
  103. Paoli J, Halldin C, Ericson MB, Wennberg AM. Nerve blocks provide effective pain relief during topical photodynamic therapy for extensive facial actinic keratoses. Clin Exp Dermatol 2008; 33:559.
  104. Klein A, Karrer S, Horner C, et al. Comparing cold-air analgesia, systemically administered analgesia and scalp nerve blocks for pain management during photodynamic therapy for actinic keratosis of the scalp presenting as field cancerization: a randomized controlled trial. Br J Dermatol 2015; 173:192.
  105. Halldin CB, Paoli J, Sandberg C, et al. Nerve blocks enable adequate pain relief during topical photodynamic therapy of field cancerization on the forehead and scalp. Br J Dermatol 2009; 160:795.
  106. Serra-Guillen C, Hueso L, Nagore E, et al. Comparative study between cold air analgesia and supraorbital and supratrochlear nerve block for the management of pain during photodynamic therapy for actinic keratoses of the frontotemporal zone. Br J Dermatol 2009; 161:353.
  107. Fink C, Uhlmann L, Enk A, Gholam P. Pain management in photodynamic therapy using a nitrous oxide/oxygen mixture: a prospective, within-patient, controlled clinical trial. J Eur Acad Dermatol Venereol 2017; 31:70.
  108. Wiegell SR, Haedersdal M, Wulf HC. Cold water and pauses in illumination reduces pain during photodynamic therapy: a randomized clinical study. Acta Derm Venereol 2009; 89:145.
  109. Cottrell WJ, Paquette AD, Keymel KR, et al. Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid-photodynamic therapy of superficial basal cell carcinomas. Clin Cancer Res 2008; 14:4475.
  110. Zeitouni NC, Paquette AD, Housel JP, et al. A retrospective review of pain control by a two-step irradiance schedule during topical ALA-photodynamic therapy of non-melanoma skin cancer. Lasers Surg Med 2013; 45:89.
  111. Wiegell SR, Petersen B, Wulf HC. Topical corticosteroid reduces inflammation without compromising the efficacy of photodynamic therapy for actinic keratoses: a randomized clinical trial. Br J Dermatol 2014; 171:1487.
  112. Vanaman Wilson MJ, Jones IT, Wu DC, Goldman MP. A randomized, double-blind, placebo-controlled clinical trial evaluating the role of systemic antihistamine therapy for the reduction of adverse effects associated with topical 5-aminolevulinic acid photodynamic therapy. Lasers Surg Med 2017; 49:738.
  113. Kumar N, Warren CB. Photodynamic therapy for dermatologic conditions in the pediatric population: a literature review. Photodermatol Photoimmunol Photomed 2017; 33:125.