Adverse effects of topical photodynamic therapy: a consensus review and approach to management

1. Adverse effects of topical photodynamic therapy: a consensus review and approach to management S.H. Ibbotson,1 T.H. Wong,2 C.A. Morton,2 N.J. Collier,3 A. Haylett,3 K.E. McKenna,4 R. Mallipeddi,5 H. Moseley,1 L.E. Rhodes,3 D.C. Seukeran,6 K.A. Ward,7 M.F. Mohd Mustapa8 and L.S. Exton8 1Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee, U.K. 2Stirling Community Hospital, Stirling, U.K. 3Photobiology Unit, Dermatology Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, U.K. 4Department of Dermatology, Belfast City Hospital, Belfast, U.K. 5St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London, U.K. 6The James Cook University Hospital, Middleborough, U.K. 7Cannock Chase Hospital, Cannock, U.K. 8British Association of Dermatologists, London, U.K. British Journal of Dermatology. DOI: 10.111/bjd.17131

2. Lead author: Professor Sally Ibbotson

3. Introduction What’s already known? • Photodynamic therapy (PDT) is widely used in dermatology • Pain is the most well documented adverse effect • Methods of effective pain relief are limited

4. Objective • To review and summarise the published evidence relating to the adverse effects of PDT and to interpret this in the context of patient risk and approaches to management

5. Methods • A detailed literature search was undertaken to identify adverse effects of topical photodynamic therapy and approaches to management of these adverse effects • This was undertaken within the larger process of reviewing and updating the BAD Guideline for use of PDT using the GRADE methodology (Br J Dermatol 2018; doi: 10.1111/bjd.16838)

6. Results • Pain and discomfort during PDT were the only significant acute adverse effects of PDT • Phototoxic inflammation is to be expected • Management approaches of modification of the PDT regimen by reducing the irradiance of light delivery (<50mWcm-2) minimises this adverse effect • This approach usually ensured that treatment could be effectively delivered, and is at least as effective as conventional higher irradiance regimens

7. Results • Contact allergy to the pro-drug preparations used in topical PDT was encountered rarely (1-2% risk of sensitization) • This should be considered when patients have a more severe or atypical reaction to PDT, with a low threshold for patch testing • Patients receiving multiple treatments to large areas were most at risk • No other significant or commonly encountered longer term adverse effects were documented • Notably, there was no significant evidence of cumulative toxicity or photocarcinogenesis • A preventative role of topical PDT may be considered

8. Discussion • Based on the current evidence, topical PDT is generally a well tolerated treatment • Phototoxic inflammation is an expected effect of PDT • Pain and discomfort can be minimised by adjusting the treatment regimen and using low irradiance light delivery • Other methods of pain relief are of limited benefit • Erythema and oedema usually resolve within a few days • Other adverse effects such as scarring, pigmentary changes and hair loss are uncommon and generally not treatment limiting

9. ConclusionsWhat does this study add? • This review scrutinised the literature relating to the adverse effects of topical PDT and management approaches • PDT-induced pain can usually be effectively prevented and managed through adjustments to PDT regimens, such as using lower irradiance light delivery • Phototoxic reactions are to be expected • Other adverse effects are uncommon and not limiting

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