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Dovepress Photodynamic therapy in dermatology true for other skin tumors, PDT is less effective in deep or tumor-stage lesions. One prospective study (n=29) reported an objective response in 75% of plaque or patchy lesions after monthly treatments for 6 months.90 However, a recent study observed two of five patients who appeared to have had a complete response initially, but relapsed at follow- up (10.0±10.5 months).91 MAL-PDT was successful in treatment-refractory mycosis fungoides (four patients with complete remission and one with partial remission).92 In conclusion, several consecutive treatments of PDT can be considered as an adjunct for treatment of mycosis fungoides, particularly for patch and plaque-stage mycosis fungoides, with good cosmetic results in sensitive skin areas. Other tumors PDT has also been reported in the treatment of Kaposi’s sar- coma, extramammary Paget’s disease, and cutaneous B cell lymphoma.93 Other proliferative disorders, such as vascular malformations, have also been treated with impressive results, likely due to the antiangiogenic effects of PDT.94 PDT in inflammatory diseases Acne vulgaris The most common dermatologic disorder, acne vulgaris, is thought to be primarily caused by the obstruction of seba- ceous glands, leading to proliferation of bacteria, mainly Propionibacterium acnes. P. acnes naturally produces porphyrins (protoporphyrin IX and coproporphyrin III), so light sources alone (blue light . red light) can have a direct therapeutic photodynamic effect.95 It is hypothesized that once applied to the skin, ALA and MAL are preferen- tially taken up by the pilosebaceous unit and augment the response to light therapy. The available treatments for acne currently include salicylic acid, topical retinoids, benzoyl peroxide, sulfur, alpha hydroxy acids, and various light therapies.96,97 ALA-PDT and MAL-PDT with a light-emitting diode are commonly used as off-label treatments for acne. In gen- eral, inflammatory lesions respond well to PDT, whereas comedonal/noninflammatory lesions tend to show no signifi- cant change (Table 1). The literature has focused primarily on MAL-PDT followed by red light because targeting of the sebaceous glands is optimized with this regimen. In practice, however, this treatment tends to be painful, with increased edema and milium formation. It should be noted that a 180-minute incubation time maximizes production of porphyrin in the sebaceous glands and leads to longer remis- sion of acne (Figure 3). In a split-face study, there was no Clinical, Cosmetic and Investigational Dermatology 2014:7 significant difference in efficacy between ALA-PDT plus red light (34 J/cm2) and MAL-PDT plus red light (34 J/cm2) with 3-hour incubation times.98 Nonetheless, regimens using short incubation times (30–60 minutes) followed by blue light and/or IPL persist because they tend to be well tolerated. In these cases, frequent treatments are recommended. Such regimens have an advantage in Fitzpatrick skin types IV–VI because post-inflammatory hyperpigmentation is reduced. There may even be a role for ALA-PDT followed by IPL in the reduction of comedonal acne. ALA-PDT in acne The efficacy of PDT in acne was first described in a study of 22 patients, where 20% ALA was applied topically to the back with 3-hour occlusion followed by red light irradiation. This regimen was shown to reduce inflammatory acne lesions after multiple treatments (four treatments at one-week intervals) when compared with the other treatment groups (ALA alone, red light alone, untreated control) and compared with single PDT treatment in the respective study groups. After application of ALA, immunofluorescence revealed accumulation of porphyrin in areas of acne. Improvement initially was observed at 3 weeks following treatment, and was marked histologically by atrophic sebaceous glands, a granulomatous reaction, obliterated follicles, and perifol- licular fibrosis. By the end of the study, there was complete destruction or a 45% decrease in sebaceous gland size. In this particular study, red light alone did not produce a therapeutic effect.99 Other small studies have also confirmed that inter- val treatment of ALA with varying occlusion times (3 and 4 hours) followed by red light is a highly effective treatment for acne (Table 1).99–102 The mechanism of ALA-PDT is thought to be due to selective destruction of the sebaceous unit after uptake of the photosensitizer, so the longest wavelengths capable of activating porphyrins (red light, 635 nm) have been utilized to target the sebaceous glands in the dermis. Most studies have focused on ALA with red light, but a few studies have also suggested that blue light PDT has increased efficacy compared with blue light alone in the treatment of acne.103 Nonetheless, in vitro studies comparing ALA followed by blue light (415 nm) or red light (635 nm) and examining the bactericidal effects on P. acnes, found that red light phototherapy was less effective for the eradica- tion of P. acnes than blue light phototherapy with and without ALA.104 Therefore, there may still be a role for combined blue and red light activation of ALA in the treatment of acne. submit your manuscript | www.dovepress.com Dovepress 151PDF Image | applications of photodynamic therapy dermatology
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