M.D. Gold - Photodynamic Therapy in Dermatology

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Michael H. Gold

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PDT research turned to other potential photosensitizers following these initial reports, mainly those related to porphyrins. In 1911, Hausman et al. [] later reported that hematoporphyrin was also selectively absorbed into other cells, including embryonic, traumatized skin, and neoplastic areas.

From these clinical investigations, the principles of PDT in human cancer cells had now been firmly established. A photosensitizer, which in this case was hematoporphyrin, could be absorbed and concentrated into the cancerous cells, and when activated by a proper light source and in the presence of oxygen, could be cytotoxic to these cells. In 1978, Dougherty et al. [.

Because of the unique nature of the skin and its accessibility for study with both natural light or artificial light sources, dermatological research became a prime focus for PDT research at this time. HPD, however, remained phototoxic in the skin for several months, making its practical use in dermatology difficult. In 1990, Kennedy et al. [] changed the face of PDT forever when they introduced the first topical porphyrin derivative, known as aminolevulinic acid (ALA). This photosensitizer is known as a prodrug and is converted in the skin to its active form. They found that ALA could penetrate through the stratum corneum of the skin and be selectively absorbed by actinically damaged skin cells. They also described that ALA could be selectively absorbed by nonmelanoma skin cancer cells as well as the pilosebaceous units in the skin. Kennedy then described the PDT reaction of ALA. Once the ALA is applied to the skin, it is absorbed through the stratum corneum, and converted to its active form, Protoporphyrin IX (PpIX).

ALA, the natural precursor of PpIX in the heme pathway, is shown in Fig. ].

The heme biosynthetic pathway (Fig. ) is maintained under a very close feedback loop apparatus, not allowing for buildup of heme or its precursors, such as PpIX, in tissues. Exogenous ALA forming PpIX is cleared from the body much more rapidly than its predecessor photosensitizer, HPD. Therefore, the potential for phototoxicity from ALA-induced PpIX is much reduced, only to days instead of several months. And, ALA penetrates only actinically damaged skin, thus increasing the specificity of ALA-PDT.

PDT has taken on two separate pathways, as noted in the Preface, since Kennedys introduction of topically applied ALA. In the US, research has centered on 20% 5-ALA (Levulan Kerastick, Dusa Pharmaceuticals, Wilmington, MA) and its ability to treat AKs, photorejuvenation, inflammatory acne vulgaris, sebaceous gland hyperplasia, and hidradenitis suppurativa, among other entities. In Europe, research has centered on the methyl ester of 5-ALA, 16.8% MAL (Metvix in Europe, Metvixia in the US, Galderma Laboratories, Ft. Worth, TX), and its uses in treating nonmelanoma skin cancers and AKs. Interest in photorejuvenation and inflammatory acne vulgaris has seen a recent surge with MAL [].

This textbook will explore the various photosensitizing drugs, the various indications for each drug, and the research which has been performed with the drugs, allowing the reader the opportunity to determine if PDT can play a vital role in their daily practice of dermatology. Each chapter and each of the authors have been chosen to bring their expertise to this project I am confident we have achieved our goal.

PDT has truly become a global therapeutic option for many patients we treat in dermatology. The hope of this textbook was to bring to you, the reader, some of the brightest and best minds in the PDT field, from all over the world, and to utilize their strengths in presenting what we hope is, the most up-to-date and sophisticated PDT reference on the market.