Adverse Effects of Topical Photodynamic Therapy

A Consensus Review and Approach to Management

S.H. Ibbotson; T.H. Wong; C.A. Morton; N.J. Collier; A. Haylett; K.E. McKenna; R. Mallipeddi; H. Moseley; L.E. Rhodes; D.C. Seukeran; K.A. Ward; M.F. Mohd Mustapa; L.S. Exton


The British Journal of Dermatology. 2019;180(4):715-729. 

In This Article


While in vitro PDT may have cytotoxic and genotoxic effects,[182,183] the porphyrin-derived molecules used in topical PDT can also have both antioxidant and antimutagenic actions.[184] In hairless mouse models, both MAL-PDT and hexylaminolaevulinate (HAL)-PDT have separately been shown to delay the time to development of SCC, using repeated treatment regimens,[185–187] although caution is required in extrapolating these data to the human setting; indeed, only marginal effects on delayed tumour development were seen with daylight PDT when using HAL.[188] However, in a split-face study involving 25 renal transplant recipients, repeated topical PDT at 6-monthly intervals for 5 years delayed the development of AK when used as primary prevention, supporting an earlier randomized, within-patient study.[189] In this earlier study involving 81 patients with AK treated with either MAL-PDT or lesion-specific therapy such as cryotherapy, the former significantly reduced the development of new AK, although the effect was not maintained at longer-term follow-up over 2 years.[190] While PDT does not have the same mechanisms of action as ultraviolet radiation (e.g. it does not activate p53 but upregulates p21),[191] it is immunosuppressive.[192,193] The immunosuppressive effects of PDT appear to be reduced by lowering the irradiance of light delivery, and by nicotinamide.[194,195]

Unlike many cancer therapies, topical PDT is often repeated and there is no clear evidence of a cumulative toxic effect. However, there are observations of the development of eruptive keratoacanthomas after PDT,[196–198] which may be in association with the trauma inflicted on the skin by PDT aggravating or provoking the development of keratoacanthoma.[199] There are reports of the development of invasive and sometimes poorly differentiated SCC arising within a few months of PDT treatment.[200–202] There are also isolated reports of melanoma developing at the site of PDT,[203,204] and of a microcystic adnexal carcinoma developing at a site of SCC in situ treated by PDT several years earlier.[205] However, given that the majority of these patients had pre-existing, extensive field change, with precancerous and cancerous change, as well as a history of skin malignancies, association with PDT itself is very difficult to prove and these may well be coincidental cases. Likewise, the development of SCC arising after PDT for erythroplasia of Queyrat of the penis, as an isolated report,[206] may also have been coincidental. A recent retrospective study assessing cases of invasive SCC arising in areas previously treated by topical MAL-PDT identified 10 SCCs in 699 treated patients with no significant histological or immunohistochemical differences vs SCC lesions developing in non-PDT-treated areas. The patients who developed SCC all had multiple AK or SCC in situ and hence were predisposed to invasive SCC development, although an association with multiple (median of five treatments over 1 year) PDT sessions is highlighted.[207] However, vigilance is required, and reporting is to be encouraged. While longer-term follow-up of patients receiving PDT is ideal, it is often not practical as patients are often elderly and frail, and there are pressures on outpatient services.