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

Medium-Term Adverse Effects

The relative selectivity of PDT and the observation from large, multicentre studies that healing and cosmetic outcome are good mean that PDT is often selected as the treatment of choice to use for large areas and at difficult sites, such as lower legs, where healing may be problematic.[78,79,88,92,133–139] While changes of fibrosis can be seen histologically following PDT,[151] scarring is rarely reported;[88,137–139,152] indeed, PDT has been explored for its use in scar remodelling and potential to treat keloid scar,[153,154] although this requires further investigation. Rarely, milia cysts may occur following PDT if the basal membrane is disrupted; this may be difficult to distinguish from recurrent BCC,[155] but, in practice, this is an occasional adverse effect.

In early studies of the use of high-intensity PDT regimens for acne vulgaris, biopsy evidence of destruction of sebaceous glands was observed,[156] although current acne regimens are of lower intensity with regard to irradiation. As such, it is anticipated that the risk of permanent damage to sebaceous glands will be lowered, although further studies with histological evidence of this have not been undertaken. Sterile pustules are often reported following PDT for acne vulgaris, although true infection is rarely seen,[28,29] probably because of the anti-infective effects of PDT. Photo-onycholysis is well recognized with drug phototoxicity such as with psoralens,[157] and there are isolated reports of photo-onycholysis occurring following PDT when this has been undertaken at periungual sites, such as for viral warts and AK,[158,159] and even one case arising following blue-light ALA-PDT to AK on the face.[160]

Pigmentary Problems

Dyspigmentation may occur following PDT. In trials involving AK, extramammary Paget's disease, warts and acne, pigmentary changes have been observed, although are not usually prominent.[51,161–163] Hyperpigmentation may occur,[43] which seems particularly likely with darker skin phototypes, and has been seen in the context of using PDT for acne vulgaris.[156,164] However, in light-skinned populations, hyperpigmentation is rarely seen.[152] It is also not clear whether combining PDT with any pretreatment steps may increase the risk of pigmentation. In one study, while there was a trend to increased pigmentation with carbon dioxide laser-assisted PDT, this was not significantly different from PDT alone.[161]

If hyperpigmentation occurs, it is usually reversible over some weeks. In one study, biopsy of PDT-induced pigmentation showed histologically increased numbers of activated melanocytes.[165] Hypopigmentation may also occur, presumably as a postinflammatory insult, although this is rarely a problem clinically.[152]

Hair Problems

If PDT is undertaken at hair-bearing sites such as the scalp or beard area, there is potential for hair loss, and this has been observed following PDT treatment of large areas of SCC in situ and BCC.[166] However, this is not well reported in the literature but may be worth keeping in mind with regard to warning patients of this potential side-effect at the relevant treatment sites. Paradoxically, topical PDT may also increase hair growth, and one of the early studies of topical PDT was using haematoporphyrin derivative and ultraviolet A irradiation as an attempt to treat areas of alopecia areata.[167] Although that initial study was encouraging, subsequent studies have been disappointing, showing no convincing efficacy.[168,169] However, one report of a study in mice indicated that the presence of iron was required with ALA to stimulate hair growth, although this has not been investigated in humans.[170]