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wan and Lin Dovepress with Leishmania major.91,152 Clinicians can consider PDT as a safe and efficacious treatment option for cutaneous leishmaniasis. Other infections Erythrasma is the cutaneous manifestation of Corynebacterium minutissimum, characterized by heterogeneous coral-red fluo- rescence due to presence of endogenous porphyrins in the bacteria. PDT with red light irradiation and without an exog- enous photosensitizer achieved complete clearance in 23% of lesions (3/22) and partial clearance in 82% of lesions (18/22).153 Reports of unsuccessful ALA-PDT in the treatment of Candida albicans intertrigo have been documented.139 PDT in proliferative disease Photoaging/antiaging/photorejuvenation Photoaging is characterized by increased skin elastosis associated with degraded collagen. Clinically, one can observe irrevers- ible skin hyperpigmentation, ephelides, lentigines, abnormal elastic fibers, telangiectasias, sebaceous gland hyperplasia, and rhytids.154,155 Histopathologically, dilated blood vessels and increased pigment are found accumulated in the papillary dermis.156–160 Current treatments for photorejuvenation include retinoids, laser resurfacing, chemical peels, and various light therapies (Table 3). Photorejuvenation has been frequently observed in patients undergoing PDT for other disease entities, and therefore has become an area of further investigation. PDT with blue light ALA-PDT with blue light has been reported to improve skin elasticity, as well as skin texture, pigmentation, fine lines, and complexion.161–163 Deep wrinkling and mottled hyperpigmentation have not been reported to change fol- lowing treatment. PDT with red light One study (n=20) revealed a statistically significant improve- ment (P,0.05) after administration of MAL-PDT and red light with respect to mottled hyperpigmentation, fine lines, skin roughness, and sallowness, but no improvement of deep wrinkles, superficial angiogenesis, facial erythema, and seba- ceous gland hyperplasia. To quantify epidermal and dermal changes during PDT, an analysis using high-resolution echog- raphy showed increased skin thickness, which the authors postulated to be caused by increased collagen synthesis.164 One investigator-blinded study with a 2-month follow-up revealed moderate improvement in fine lines, tactile rough- ness, and skin tightness, especially on the half of the face that had a 3-hour incubation with MAL compared with a one-hour incubation. In contrast with other studies, there was no change in mottled hyperpigmentation, and consistent with other reports, no improvement of telangiectasias.165 A larger clinical split-face trial (n=94) demonstrated superiority in terms of improvement in global photodamage using MAL-PDT with red light versus placebo.166 Opposing studies exist, however, including one study that compared blue light versus red light and MAL-PDT. In this study, no difference in efficacy was observed in photodamaged skin.167 PDT with intense pulsed light One retrospective split-face study (n=20) compared pretreat- ment with 5-ALA (5-ALA first treatment, IPL only for last two treatments) on one half of the patient’s face versus IPL treatment alone. After three treatments, greater subjective improvement was observed in the ALA-IPL arm in terms of global photoaging, mottled pigmentation, and fine lines.168 Pretreatment with ALA did not improve observed sallow- ness or tactile roughness at one-month follow-up after five treatments. Following this, another split-face study (n=13) reported similar results, with improved appearance of crow’s feet (55% versus 29.5%), tactile skin roughness (55% versus 29.5%), mottled hyperpigmentation (60.3% versus 37.2%), and telangiectasias (84.6% versus 53.8%) in the ALA-IPL group.169 A major advantage of IPL compared with irradiation with a light-emitting diode is less time expenditure and less painful effects of heat delivery due to shorter intense expo- sure times.170 Clinicians should be aware that heat delivered by IPL may cause destruction of hair follicles, so it should be used with caution, especially in men with facial hair. Mechanisms supporting PDT-induced photorejuvenation have been proposed. Studies involving punch biopsies after ALA- IPL demonstrate an increase in type I collagen. Interestingly, Orringer et al used biomarkers to examine the molecular effects of ALA-PDT and PDL, and showed upregulation of Ki-67 (an immunohistochemical biomarker of keratinocyte proliferation), along with elevated levels of procollagen I and procollagen III, indicating new formation of collagen.159 Other proliferative conditions PDT has been shown to reduce type I collagen synthesis and fibroblast activity in vitro, thus potentially having a role in the treatment of scars.171 Several groups have dem- onstrated improvement in the skin flexibility of hypertro- phic scars using MAL-PDT.172,173 One recent study (n=20) demonstrated that three treatments of MAL-PDT were effective in reducing formation of keloid scars, which were Clinical, Cosmetic and Investigational Dermatology 2014:7 156 submit your manuscript | www.dovepress.com DovepressPDF Image | applications of photodynamic therapy dermatology
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