الفهرس 
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Abstract
Photodynamic therapy (PDT) is a new modality of therapy being increasingly used for treatment of skin tumors and other dermatological disorders. With its range of application, it is certainly the therapy of the future.
Its mechanism of action is based on the presence and interaction of three key elements: light, a photosensitizer and oxygen. After exposure to specific wavelengths of light, the photosensitizer is excited from a ground state (S0) to an excited singlet state (S1). It then undergoes intersystem crossing to a longer-lived excited triplet state (T1).
Then, the photosensitizer at T1 state can undergo two types of reaction with surrounding molecules: either a type I reaction through hydrogen or electron transfer with the production of free radicals, or a type II reaction through energy transfer to oxygen, producing singlet oxygen (1O2).
The 1O2 species is highly active in biological systems and can only diffuse less than 0.02 μm in a cell before deactivation during its very short lifetime (τ <40 ns). Thus, 1O2-mediated damage occurs at the site of its generation and affects all intracellular components, including proteins,
lipids and DNA. Although it is considered that 1O2 is the major cytotoxic species and principal initiating pathway responsible for the damaging effects of PDT, free radicals also play an important role through type I reactions for the oxidative damage mediated by PDT.
A wide array of photosensitizers for PDT exists. They can be divided into porphyrins, chlorophylls and dyes. The most important photosensitizers used are porfimer sodium, 5-aminolevulinic acid (ALA),
benzoporphyrin derivative monoacid ring A (BPD MA), N-aspartyl chlorin e6 (Npe6), tin ethyl etiopurpurin (Sn ET2), temoporphin and
phthalocyanines.
Any light source, either laser or non-laser, with suitable spectral characteristics and a high output at an absorption maximum of the photosensitizer can be used for PDT. Laser light is suitable for small skin lesions whilst non-laser light is better for the treatment of large skin lesions as the field of illumination is larger.
Non-laser light sources used include metal halogen lamps, light emitting diodes (LEDs), blue light system and short arc xenon lamp.
Noncoherent light sources are superior to lasers in treatment of large skin lesions in addition to their low cost, smaller size, easy availability and different photosensitizers with varying absorption maxima can be used.
Laser light sources include the tunable argon-dye laser, pulsed lasers,
the neodymium: YAG laser, the flashlamp pumped pulsed dye laser and semiconductor diode lasers.
Advantages of lasers in PDT are maximum effectiveness if the wavelength of the laser corresponds with the peak absorption of the photosensitizer. Second, lasers can produce high irradiance to minimize the therapeutic exposure time. Finally, lasers can be readily coupled to fiberoptics, enabling light delivery to any organ, such as the bladder,
gastrointestinal tract, or lungs.
Currently, PDT has received approval for the treatment of dermatooncologic conditions like actinic keratoses, Bowen’s disease, squamous cell carcinoma, basal cell carcinoma, Kaposi’s sarcoma, Mycosis fungoides, Malignant melanoma, actinic chelitis, keratoacanthoma and disseminated actinic porokeratosis.
Summary
Non-oncological indications of PDT include acne vulgaris, psoriasis,
viral warts, localized scleroderma and photorejuvenation.
Other indications include fungal diseases, leishmaniasis, lichen planus, necrobiosis lipoidica, sebaceous hyperplasia, hidradenitis suppurativa and alopecia areata.
PDT for the treatment of actinic keratosis (AK) was approved by the US Food and Drug Administration (FDA) in 1999. It has a cure rate of
73-100%. These results are similar to those reported with conventional forms of treatment, albeit with fewer side effects and a faster recovery time.
Concerning Bowen’s disease (BD), studies carried out with ALA (in general ALA 20% in cream formulations with variable light sources)have shown cure rates of 88% to 100%.There remain limited data on the efficacy of topical PDT for primary cutaneous invasive SCC. Clearance rates for superficial lesions of 54–
100% have been observed following ALA-PDT in series of 5 to 35 lesions, but with recurrence rates ranging from 0% to 69% (weighted average 30%) and reduced efficacy for the few nodular lesions treated.
PDT with MAL and red light has proven to be effective for basal cell carcinomas (BCCs), attaining success rates close to 95% in superficial BCC and 73-94% in cases of nodular BCC. The recurrence rate for superficial BCC is approximately 22%, similar to that found with conventional therapies such as cryotherapy, which has a recurrence rate of around 19%. With respect to nodular BCC, however, the recurrence rate is around 14% compared to 4% with surgery, the standard treatment for nodular BCC. The principal indications include the treatment of multiple lesions, particularly in elderly patients, the treatment of patients for whom surgery is contraindicated and in situations in which the lesions are located in sites that hamper the healing process such as on the lower limbs.
The use of systemic PDT such as sodium porfimer showed efficacy in the treatment of superficial and nodular lesions of Kaposi sarcoma (KS)with few adverse effects and excellent final cosmetic results.
Various clinical studies have shown encouraging results for cutaneous T-cell lymphoma with PDT. However, there are no controlled trials yet and treating lesions locally would probably not prevent new lesions from coming up. However PDT can be a useful additional treatment modality for patients with therapy-resistant lesions of cutaneous T-cell lymphoma.
There is little information on the efficacy of ALA-PDT in the treatment of primary and metastatic malignant melanoma, and the results are contradictory. The high pigmentation of melanoma tissues may be the limiting factor by inhibiting light penetration. PDT is not really an acceptable modality for melanoma in view of its high propensity for rapid spread.
Systemic and topical sensitization with hematoporphyrin followed by visible light irradiation resulted in clinical improvement of psoriatic plaques and palmopustular psoriasis.
The difficulty in substrate application and insufficient light sources are drawbacks limiting the practicability of PDT in psoriasis, especially in disseminated psoriasis lesions.
Certain positive results were observed with PDT as an antiviral modality. Disorders due to papilloma viruses could be a potential area of PDT application. But PDT appears a relatively painful therapy option,
with outcomes dependent on adequate paring and the use of a keratolytic agent pre-PDT.
The application of photosensitizers for the treatment of fungal infections is a new and promising development within the field of photodynamic treatment.
Phototherapy has been shown to be an effective treatment for acne,
and there has been a renewed interest in PDT as a treatment modality for this condition. The main advantages of PDT in comparison with other treatment modalities are its excellent cosmetic results and its high remission rates despite low invasiveness.
One of the most recent methods introduced in the dermatologic practice is the process of photorejuvenation with PDT. Photorejuvenation using PDT should be considered as an off-label application. The effect of rejuvenation induced by PDT is secondary and should be used in patients with multiple AKs on the face.
The good cosmetic result which is obtained due to selective tissue destruction is one of the main PDT advantages. from the pharmacological point of view, sensitizers show low toxicity and almost no interaction with other medications, making PDT a safe treatment modality. PDT is easy to apply in curved skin areas where surgery is difficult to carry out. It can be also administered for seriously ill patients in whom surgery with general anesthesia is not recommended. Treatment sessions can be easily performed and repeated if necessary on an outpatient basis which saves money and is convenient for patients.
The side effects of PDT are burning, stinging or prickling sensations,
restricted to the area exposed to light. These sensations usually decrease if exposure to the light source is paused or terminated. This phototoxic reaction may be variable in intensity and enhanced in patients who expose themselves to the sun or to powerful artificial lights during the first 2 days after topical application. Excessive phototoxic reaction excessive burning, vesicle formation, crusting and peeling may present as a severe and undesirable end of the spectrum.
Hyperpigmentation and hypopigmentation have been reported as adverse affects of PDT. Also, patients developing urticaria and contact dermatitis after treatment with MAL are known. Topical PDT treatments are intrinsically very safe. Though, theoretically, extensive topical application can lead to systemic absorption, if, somehow, all the ALA contained in a Kerastick is completely absorbed.
Contraindications for PDT include cutaneous photosensitivity,
porphyria, and allergies to ALA or to any of its components. Patients who have concomitant disorders that are provoked or aggravated by light should be evaluated cautiously. It is not known whether ALA or its metabolites are excreted in breast milk, therefore, caution should be exercised when treating women who are breastfeeding.