Clinical results of photodynamic therapy for superficial skin malignancies or actinic keratosis using topical 5-aminolaevulinic acid

Abstract

Photodynamic therapy (PDT) with topical application of 5-aminolaevulinic acid (ALA, 20% w/w) was used to treat superficial basal cell carcinoma (BCC, 16 patients), Morbus Bowen (one patient), basal cell naevus syndrome (BCNS, three patients), actinic keratosis (AK, two patients), chronic inflammation (CI, one patient), and metastasized BCC (one patient). The interval between ALA application and illumination was 3-6 h. The incident light dose was 50-100 J cm 2, mostly 75 J cm -2, at 633 nm wavelength. This was based on the fluorescence excitation spectrum, measured on the skin of human volunteers. In a few cases, 514.5 nm light was used. A complete response (CR) rate of 79% (median follow-up 13 months) was obtained with 42 BCC lesions._The treatment of five areas with AK, two areas with CI and one area with M. Bowen yielded three CR for AK and five partial remissions (PR). Photodynamic therapy of metastasized BCC, after either topical or oral ALA, was not successful. Treatment of BCNS was satisfactory with 100% CR in one patient (22 lesions), PR in a second patient (20 lesions), and good palliation in a third patient (>250 lesions). The treatment was well tolerated, although the illumination had to be interrupted occasionally due to pain. Healing usually occurred in 2 weeks. Cosmetic results were good to excellent. 5-Aminolaevulinic acid application over 16-19 h and repeated treatments made it possible to obtain CR of non-superficial lesions. The selective tumour fluorescence was then lost, however, due to fluorescence of normal skin, but the cosmetic outcome did not deteriorate. 5-Aminolaevulinic acid PDT may be a good alternative outpatient treatment, especially in elderly patients and for large treatment areas. The excellent cosmetic outcome warrants further study in younger patients. More work is necessary to establish optimal ALA-treatment schemes.

Quantitative Model Calculation of the Time-dependent Protoporphyrin IX Concentration in Normal Human Epidermis After Delivery of ALA by Passive Topical Application or Iontophoresis¶

“…hair follicles) may be important routes for iontophoretic and passive transport of molecules into the skin (6,7), although significant nonfollicular transport occurs as well (30). After 4–5 h passive topical application of ALA we have seen small spots with enhanced PpIX fluorescence, apparently from hair follicles (31). We have also studied fluorescence microscopy of frozen sections after topical ALA application to rat skin pretreated with depilation cream.…”

Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and hexyl 5-aminolaevulinate on normal human skin

“…Furthermore, at the same time we found higher fluorescence of PpIX by fluorescence measurements after ALA and MAL application than after HAL. Small spots with enhanced PpIX fluorescence (probably from hair follicles 56 or sebaceous glands 57 ) were seen after HAL application. After topical application of ALA on human skin, high levels of PpIX fluorescence were found in the epidermis, with little PpIX in the dermis, cutaneous musculature and vasculature 38 .…”

Quantification of Topically Delivered 5-Aminolevulinic Acid by Iontophoresis Across Ex Vivo Human Stratum Corneum¶

“…Hence, intraepidermal delivery of ALA by passive diffusion, e.g. from a gel, requires a high ALA concentration and long application times (8–12). Iontophoresis, on the other hand, could provide an effective alternative means to deliver the compound across the SC at a predetermined, enhanced rate, thereby allowing the use of a lower ALA concentration, and possibly also to channel the photosensitizer prodrug more rapidly and uniformly into the target tissue.…”