Severe Cutaneous Reaction to Photodynamic Therapy With Blue Light

A 60-year-old male with a history of non-melanoma skin cancers and significant photodamage, without history of photosensitizing diseases, presented for a routine skin check. On exam, the patient was found to have diffuse erythematous scaling papules coalescing into plaques on his scalp and face. Photodynamic therapy (PDT) was decided upon, and 20% 5-aminolevulinic acid (ALA) was applied to these areas for four hours, after which he was placed in a U-shaped blue light (417 nm) at 10 J/cm2. The patient completed a total of 1000 seconds, tolerating the procedure well. He went immediately home and avoided bright light exposure for the rest of the day. That night, the patient reported having a fever of 101.1°F and elevated blood pressure. Two days after the procedure, he reported significant loss of skin and was evaluated at that time. He was found to have extensive facial crusting, oozing, loss of epithelium and pinpoint bleeding (Figure 1). He was placed on Ciprofloxacin 750 mg twice-daily for ten days and instructed on wet to dry dressings. After two weeks the patient was to found to have re-epithelialization with residual erythema (Figure 2). At three-month follow up, complete clearing of AKs was noted and at six months only two additional AKs were treated.

Photodynamic therapy takes advantage of the body's own heme biosynthetic pathway and specific absorption peaks of light. ALA is the precursor for protoporphyrin IX, an endogenous photosensitizer produced during the formation of heme for red blood cell synthesis. Topical ALA is a small, hydrophilic molecule that penetrates cellular membranes and localizes to interstial spaces. Methyl aminolevulinate (MAL) is an ester of ALA that is more lipophilic and has been shown to localize to abnormal tissue more than ALA. Irradiation of ALA or MAL produces reactive oxygen species which have a cytotoxic effect.¹ The excitation spectrum of porphyrins has a major peak in the blue light range (417 nm) with a smaller peak of absorbance in the red light range (635 nm).² Several studies have demonstrated >75 percent complete response rate in 69-78 percent of patients treated with PDT.³

Several different protocols exist for using photosensitizing agents. The ALA and blue U system has been licensed for a drug incubation period of 18-24 hours prior to illumination. However, several recent studies have shown similar efficacy when applied for 1-3 hours prior to light exposure for the treatment of photodamage and actinic keratoses. In contrast, treatment of superficial basal cell carcinomas requires two treatments with four-hour incubation times. The protocol followed by our office is application of ALA for 3-4 hours prior to blue light exposure for up to 1000 seconds.⁴

Major side effects of PDT include localized stinging, burning, and pain during treatment with erythema and edema peaking within 24 hours, and lasting for up to four weeks after treatment.⁵ Severe cutaneous reactions as in our patient are likely attributable to longer incubation times and larger areas of treatment. We propose that caution should be taken when