PpIX Fluorescence Kinetics and Increased Skin Damage after Intracutaneous Injection of 5-Aminolevulinic Acid and Repeated Illumination  Monique R. Thissen  Journal of Investigative Dermatology  Volume 118, Issue 2, Pages 239-245 (February 2002) DOI: 10.1046/j.0022-202x.2001.01571.x Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 PpIX fluorescence at test sites. The PpIX fluorescence. intensity measured before administration of ALA (the tissue autofluorescence), immediately before irradiation at 3.5 h after the intracutaneous (○) and topical (▪▪) administration of ALA, and after irradiation with (•) 3, (□) 6, (▴) 9, (▪) 15, and (♦) 30 J per cm2 at 50 mW per cm2 (n = 6, mean ± SEM). The re-synthesis of PpIX is dependent on the fluence delivered after 3 and 6 J per cm2. The intensity of PpIX fluorescence increases after photobleaching during irradiation. With increasing fluence the re-synthesis of PpIX is strongly inhibited. Journal of Investigative Dermatology 2002 118, 239-245DOI: (10.1046/j.0022-202x.2001.01571.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Skin damage score. The visual skin damage score (▪) 48 h and (□) 96 h after irradiation using a variety of single and 2-fold irradiation schemes (n = 6, mean ± SEM). There is significantly more damage when the fluence is delivered in two fractions separated by an interval of 2 h than when an equal fluence is delivered in a single light fraction. Journal of Investigative Dermatology 2002 118, 239-245DOI: (10.1046/j.0022-202x.2001.01571.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Visual skin damage. The visual skin damage (left) 48 h and (right) 96 h after irradiation using a variety of single and 2-fold irradiation schemes. Damage after 2-fold irradiation (a, 15 + 15 J per cm2; b, 6 + 24 J per cm2) is more severe than after a single irradiation (c, 15 J per cm2; d, 30 J per cm2). Journal of Investigative Dermatology 2002 118, 239-245DOI: (10.1046/j.0022-202x.2001.01571.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Histopathologic skin changes. The histopathologic changes at 96 h after (left) single (30 J per cm2) and (right) 2-fold (15 + 15 J per cm2) irradiation at 50 mW per cm2. Damage after 2-fold irradiation is more pronounced and more deeply localized. The necrotic part of the epidermis/dermis (a) has already been shed and neo-epidermis has been formed (b). In the dermal layer complete vascular thrombosis (c) and vasculitis (d) are observed. Journal of Investigative Dermatology 2002 118, 239-245DOI: (10.1046/j.0022-202x.2001.01571.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 PpIX fluorescence outside test sites. The PpIX fluorescence intensity measured at (○) a distant test site and (•) a point immediately adjacent to a test site that had received ALA. There is no significant difference between the maximum intensity and kinetics of PpIX fluorescence between local and distant sites, indicating that (ALA and) PpIX is not transported cutaneously. Journal of Investigative Dermatology 2002 118, 239-245DOI: (10.1046/j.0022-202x.2001.01571.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions