The Accumulation of Protoporphyrin IX in Plaque Psoriasis After Topical Application of 5-Aminolevulinic Acid Indicates a Potential for Superficial Photodynamic Therapy

Abstract

The success reported for the treatment of superficial skin carcinomas by photodynamic therapy with topical application of the photosensitizer precursor 5-aminolevulinic acid has therapeutic implications for the treatment of other skin disorders. This paper describes the accumulation of the photosensitizing agent protoporphyrin IX in areas of plaque psoriasis by monitoring of the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present results from 15 patients with a total of 42 plaques and show that the characteristic fluorescence emission of protoporphyrin IX increases in intensity within the 6-h period following application of 5-ami-nolevulinic acid, suggesting that there is a potential for superficial photodynamic therapy. The rate of increase and maximum intensity of fluorescence emission was not directly related to the applied quantity of the precursor. The variability of the fluorescence intensity was as great between plaques at different sites on the same patient as between different patients. Also, the effect of plaque occlusion following application appeared insignificant. Although there was only limited enhancement of emission from areas of skin surrounding the plaque, a significant buildup of sensitizer was detected after several days in some areas of psoriasis that received no application.

Optimum porphyrin accumulation in epithelial skin tumours and psoriatic lesions after topical application of δ-aminolaevulinic acid

“…Fluorescence studies on the kinetics of the ALA-induced porphyrins showed maximum levels in BCC and PS 4-6 h after ALA application with 3-15-fold higher levels than in normal skin (Svanberg et al, 1994;Stringer et al, 1996). These data are supported by our analysis.…”

“…In general, the available data on ALA-induced porphyrin levels in human tissues are based on fluorescence studies Svanberg et al, 1994;Szeimies et al, 1994;Malik et al, 1995;Martin et al, 1995;Peng et al, 1995;Stringer et al, 1996) (Table 4) and only some biochemical studies were performed (Fritsch et al, 1997c(Fritsch et al, , 1998. It was shown by fluorescence microscopy that the major factor limiting the efficacy of topical ALA-PDT is the penetration depth of ALA and ALA-induced NS 4.7 ± 0.8 88.3 ± 2.8 0 ± 0 0.6 ± 0.5 0 ± 0 0.7 ± 0.4 4.0 ± 0.9 7.9 ± 1.3 BCC 15.7 ± 1.1* 92.2 ± 1.2 0 ± 0 2.1 ± 0.6 0 ± 0 0.6 ± 0.3 1.1 ± 0.4 5.3 ± 1.3 SCC 16.7 ± 2.1* 92.6 ± 1.7 0 ± 0 1.9 ± 0.7 0 ± 0 0.4 ± 0.3 3.6 ± 1.1 7.1 ± 1.6 PS 21.9 ± 2.7* 83.8 ± 7.6 0 ± 0 1.5 ± 1.3 0.5 ± 0.4 2.1 ± 1.3 4.3 ± 2.7 8.9 ± 2.5…”

“…Intravenous injection or oral administration of ALA was shown to optimize the homogeneous intralesional accumulation of porphyrins in PS, BCC and oral cavity SCC (Grant et al, 1993;Peng et al, 1995;Stringer et al, 1996). In mice or rats bearing colon or mammary carcinomas and in hamsters bearing an amelanotic melanoma, systemically administered ALA led to earlier (1 h) and higher tumour/skin ratios (6-30) of porphyrins than did topical ALA application Hua et al, 1995;Sroka et al, 1996;Fritsch et al, 1997a).…”

Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles

“…We have found that high quantities of porphyrins were accumulated in a tumour implanted in the contralateral side of a topically treated tumour (data not shown), indicating that, if ALA is not transferred to remote sites by direct contact, an efflux of porphyrins to distant tumours may exist, very likely through the bloodstream. Similar results were obtained by Stringer et al (1996), when psoriasis plaques were treated with ALA and remote plaques displayed significant fluorescence, afterwards.…”

Enhancing Protoporphyrin IX induced Photodynamic Therapy with a Topical Iron Chelating Agent in a Normal Skin Model

“…This was investigated as there have been reports in the literature [44] which describe porphyrins in untreated areas of skin indicating that some systemic effect may be produced when ALA is applied topically. There was no evidence of this in this study however, indicating that application of a simple light occlusive dressing to the treatment area alone should be sufficient to prevent clinical cutaneous photosensitivity even when hyperaccumulating even greater amounts of PpIX with an iron chelating agent.…”