Surgery – Miscellaneous – Methods
Reexamination Certificate
1998-05-26
2001-08-07
Peffley, Michael (Department: 3739)
Surgery
Miscellaneous
Methods
C606S001000, C607S088000
Reexamination Certificate
active
06269818
ABSTRACT:
TECHNICAL FIELD
The invention is in the field of diagnostic methods and light-activated treatments for skin disease, particularly the use of visible light for treatment of a diagnostically distinct form of psoriatic plaque exhibiting elevated endogenous porphyrin levels.
BACKGROUND ART
The emission of light at longer wavelengths after absorption of incident photons by chromophores is termed fluorescence. Under certain conditions, when human skin is illuminated with ultraviolet or visible light, cutaneous fluorescence can be detected. This phenomenon may be termed “autofluorescence” when it occurs in the absence of exogenously administered fluorescent compounds (Anderson, 1982; Zeng, 1993
a
).
Autofluorescence is believed to originate from various endogenous fluorophores, including nicotinamide adenine dinucleotide, elastin, collagen, flavins, amino acids and porphyrins. Porphyrins are naturally produced as intermediates in the biosynthetic pathway of heme. Protoporphyrin IX is the immediate precursor of heme. Spectrophotometry may be useful for distinguishing between porphyrins and other endogenous fluorophores based on the emission spectra of the fluorescent light.
Autofluorescence emission spectra and fluorescence images can be generated and recorded when incident light is shone on skin. An ultraviolet A emitting Wood's lamp may be used to assess cutaneous fluorescence for dermatologic diagnosis (Kochevar et al 1993). Macrospectrophotometry is a simple, flexible and efficient method of detecting cutaneous porphyrins illuminated with appropriate wavelengths of light; the technique is painless, takes only a few seconds and does not require a skin biopsy (Zeng et al., 1993).
Autofluorescence photographic images have been used to evaluate treatment responses in acne (Lucchina et al 1996, Martin R. J. et al 1973). Analysis and comparison of emission spectra has also been studied as a noninvasive diagnostic tool for skin diseases (Zeng et al 1995; Lohman 1988, Steremborg et al 1995).
Punctate red fluorescence on the nose and forehead under Wood's lamp illumination was reported as early as 1927 (Bommer, 1927), and has been linked to the presence in acne of porphyrins generated by Propionibacterium acnes (Cornelius, 1967; McGinley, 1980; Lee et al 1978; Konig et al, 1992; Johnson, 1987; Lucchina, 1996). The presence of red skin autofluorescence at the centre of experimentally produced or grafted tumours has been reported for rats (Policard, 1924; Gougerot, 1939; Rochese, 1954), mice (Konig, 1989), rabbits (Ghadially, 1960) and for chemically-induced squamous cell carcinoma in the cheek pouch of the hamster (Harris, 1987). In the latter case, the tumours were examined microscopically and the red fluorescence was shown to be restricted to the surface keratin layer (Harris, 1987). Similar red autofluorescence has also been reported for human oral and oropharyngeal squamous cell carcinoma (Harris, 1987; Dhingra, 1996; Konig, 1994), dysplastic areas of the oral mucosa (Ingrams et al., 1997) as well as normal human tongue (Harris et al, 1987).
In studies where spectroscopic analysis was performed, the fluorescence emission peak was centred around 636-640 nm (Konig et al., 1994; Dhingra, 1996). Konig et al. (1994) believed it was related to bacterial synthesis of porphyrins whereas Dhingra et al (Dhingra, 1996) hypothesized that the red autofluorescence could be caused by a build-up of endogenous porphyrins by tumor cells.
Macrospectrophotometry may be used to detect skin porphyrin in patients receiving exogenous porphyrins, or porphyrin precursors, for photodynamic therapy, and to follow the time course accumulation of porphyrins in photodynamic therapy (Lui, 1996; Rhodes, 1997; Stringer, 1996). The intensity of the fluorescence emission peaks has been shown to correlate with the amount of exogenous porphyrin precursor applied on the skin (Rhodes, 1997).
Porphyrins that absorb light may induce photochemical reactions that can be toxic to living cells. Such toxicity may be due to the local generation of reactive oxygen species (Arakane et al., 1996). The toxicity generated by light activation of pharmacologically elevated levels of porphyrins is the basis for photodynamic therapy which may be used to treat a variety of conditions, including cancer (see U.S. Pat. Nos. 5,211,938; 5,234,940; 5,079,262; all to Kennedy et al.) The low levels of natural porphyrins present in most tissues are not known to cause deleterious photochemical effects (Goerz et al., 1995).
Very low levels of porphyrins have been shown to be present in biopsies of human skin containing the epidermis and dermis (Goerz et al., 1995; Pathak 1963), as well as whole epidermis isolated by suction blister (Gog, 1973). Protoporphyrin IX was the predominant porphyrin type (Goerz et al., 1995; Gog, 1973) except in porphyria cutanea tarda patients, where uroporphyrin was predominant (Malina, 1978). Goerz et al., 1995, report that skin does not normally contain sufficient levels of porphyrins to allow one to perform photodynamic therapy, and consequently photodynamic therapy requires exogenous addition of photosensitizer.
Psoriasis is a hyperproliferative and inflammatory disease characterized by red scaly plaques on the skin. Current accepted or experimental methods of using light to treat psoriasis involve either the use of potentially carcinogenic ultraviolet light alone or the administration of exogenous photosensitizer, or a precursor of a photosensitizer (such as aminolevulinic acid), followed by light exposure. Blue and red light can activate protoporphyrin IX and this has been used to improve psoriasis when exogenous aminolevulinic acid (ALA) is applied on the skin to induce protoporphyrin IX synthesis (Boehncke, 1994; Nelson, 1995). However, photosensitizers or photosensitizer precursors such as ALA may have adverse side effects when administered topically or systemically. For example, they may induce photosensitivity on clinically normal skin.
SUMMARY OF THE INVENTION
In one aspect, the invention provides a diagnostic method for identifying psoriatic plaques having elevated porphyrin levels, comprising assaying psoriatic plaques for autofluorescent light. Autofluorescent light may be visualized under ultraviolet or visible light illumination. For example, red autofluorescence in some psoriatic plaques may be directly visualized under ultraviolet light using a Wood's lamp. The autofluroescence of psoriatic plaques may also be analysed using spectrophotometry, such as laser-induced macrospectrophotometry or micro-spectrophotometry, to detect the fluorescent emissions of a porphyrin, such as an emission peak around 630-635 nm that may be indicative of protoporphyrin IX.
Throughout this specification, any reference to “endogenous” porphyrin with reference to a psoriatic plaque refers to porphyrins which are present in a psoriatic plaque not as a result of the application of exogenous porphyrins (such as Photofrin
BPD-MA or others) or their precursors (such as ALA). Thus, endogenous porphyrins referred to herein arise within the plaque and do not include porphyrins present in the plaque as a result of application of a porphyrin to the patient or which could arise within a plaque as a result of administration of a porphyrin precursor to the patient. Endogenous porphyrin levels are ‘elevated’ when they are higher than in normal skin, particularly when such levels are detectable as red autofluorecence.
In another aspect of the present invention, psoriatic plaques with elevated endogenous porphyrin levels may be treated with visible light. The spectrum of the visible light used may be optimized to match the absorption spectrum of a porphyrin detected in the plaque. For example, blue light may be used to treat plaques with elevated levels of protoporphyrin IX.
Optionally, endogenous porphyrin levels in a psoriatic plaque may be elevated by administering a topical composition to the psoriatic plaque to modify some of its characteristics including, but not restricted to: the pH, iron levels, the degree of hydration (eg
Bissonnette Robert
Lui Harvey
MacAulay Calum
McLean David I.
Zeng Haishan
Kearney R.
Peffley Michael
The University of British Columbia
Townsend and Townsend / and Crew LLP
LandOfFree
Photoactivation of endogenous porphyrins for treatment of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Photoactivation of endogenous porphyrins for treatment of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Photoactivation of endogenous porphyrins for treatment of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2509184