Plum-blossom needle tapping enhances the efficacy of ALA photodynamic therapy for facial actinic keratosis in Chinese population: a randomized, multicenter, prospective, and observer-blind study.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a reliable treatment for actinic keratosis (AK), but its effect needs to be enhanced in thick lesions. Plum-blossom needle is a traditional Chinese cost-effective instrument for enhancing the transdermal delivery of ALA. However, whether it could improve the efficacy of AK treatment has not yet been investigated. OBJECTIVE: To compare the efficacy and safety of plum-blossom needle-assisted PDT in facial AK in the Chinese population. METHODS: In this multicenter, prospective study, a total of 142 patients with AKs (grades I-III) were randomized into the plum-blossom needle-assisted PDT group (P-PDT) and control PDT group (C-PDT). In the P-PDT group, each AK lesion was tapped vertically by a plum-blossom needle before the application of 10% ALA cream. In the C-PDT group, each lesion was only wiped with regular saline before ALA cream incubation. Then, 3 hours later, all the lesions were irradiated with light-emitting diode (LED) at a wavelength of 630 nm. PDT was performed once every 2 weeks until all lesion patients achieved complete remission or completed six sessions. The efficacy (lesion response) and safety (pain scale and adverse events) in both groups were evaluated before each treatment and at every follow-up visit at 3-month intervals until 12 months. RESULTS: In the P-PDT and C-PDT groups, the clearance rates for all AK lesions after the first treatment were 57.9% and 48.0%, respectively (P < 0.05). For grade I AK lesions, the clearance rates were 56.5% and 50.4%, respectively (P = 0.34). For grade II AK lesions, the clearance rates were 58.0% and 48.9%, respectively (P = 0.1). For grade III AK lesions, the clearance rates were 59.0% and 44.2%, respectively (P < 0.05). Moreover, grade III AK lesions in the P-PDT group required fewer treatment sessions (P < 0.05). There was no significant difference in the pain score between the two groups (P = 0.752). CONCLUSION: Plum-blossom needle tapping may enhance the efficacy of ALA-PDT by facilitating ALA delivery in the treatment of AK.

Efficacy of 5-Aminolevulinic Acid (ALA)-Photodynamic Therapy (PDT) in Refractory Vulvar Lichen Sclerosus: Preliminary Results.

BACKGROUND As a chronic inflammatory skin disease of unknown etiology, vulvar lichen sclerosus (VLS) mainly affects postmenopausal and perimenopausal women. The main clinical manifestations of VLS include itching, burning pain, and sexual dysfunction, which can lead to a decline in quality of life. The existing treatment options include topical corticosteroid ointment, estrogen, and traditional Chinese medicine; however, their therapeutic effects on VLS remain unsatisfactory. MATERIAL AND METHODS Thirty patients with VLS and routine treatment failure were treated with 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT). A 20% ALA water-in-oil emulsion was applied to the vulvar lesions and sealed with plastic film for 3 h. Patients were irradiated at a power density of 60 to 90 mW/cm² with a red light at a wavelength of 635±15 nm for 20 min, delivering a total dose of 100 to 150 J/cm² per session. The treatment was repeated 3 times every 2 weeks. The objective parameters, female sexual function index (FSFI) and quality of life (QoL) scores, were used before and after treatment to evaluate the clinical curative effect. RESULTS All patients completed 3 treatment cycles of ALA-PDT and follow-up visits. The clinical symptoms of pruritus completely disappeared in 27 cases, and itching improved from severe to mild in 3 cases. The pathological changes of all patients were objectively improved. FSFI score decreased significantly after treatment (P<0.001). The main adverse effects of ALA-PDT were pain, erythema, and swelling. These adverse effects were temporary and tolerable. The QoL score was significantly improved after treatment (P<0.001). CONCLUSIONS ALA-PDT is an effective and safe approach for the treatment of VLS.

Light-Emitting Diode-Based Photodynamic Therapy for Photoaging, Scars, and Dyspigmentation: A Systematic Review.

BACKGROUND: Light-emitting diodes (LEDs) may be used as an activating light source for photosensitizers in photodynamic therapy (PDT), a form of noninvasive phototherapy. Photodynamic therapy for aesthetic dermatologic conditions has demonstrated skin rejuvenating effects. OBJECTIVE: To evaluate the safety and efficacy of PDT using LEDs to treat aesthetic dermatologic conditions including photoaged skin, scarring, and dyspigmentation. MATERIALS AND METHODS: A search of PubMed and EMBASE databases was conducted through May 31, 2019, to identify studies that used LEDs as a light source for PDT and evaluated cosmetic improvements as the primary outcome measure. RESULTS: A total of 24 original articles were included in the authors' systematic review. The available evidence supports methyl aminolevulinate or 5-aminolevulinic acid incubation followed by LED treatment for global improvement of skin quality, including smoother texture, reduction of rhytides, and improvement of scars. Histologic analysis for global skin improvement demonstrated increased collagen fibers and decreased elastin fibers after LED-mediated PDT. CONCLUSION: Light-emitting diode-based PDT seems to have beneficial effects for photoaging, scars and dyspigmentation. A paucity of high-quality studies using LED-based PDT for aesthetic outcomes was found, highlighting the need for well-designed randomized control trials on this topic.

A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination.

BACKGROUND: Blue light photodynamic therapy (PDT) is effective for actinic keratosis, but many patients experience stinging pain during illumination. OBJECTIVE: To compare a conventional regimen (1 hour of 5-aminolevulinic acid [ALA] preincubation, followed by blue light) versus a new modified regimen in which blue light is started immediately after ALA application. METHODS: A clinical trial with a bilaterally controlled, intrapatient study design was conducted with 23 patients. Topical 20% ALA was applied to the entire face and/or scalp. On 1 side of the body, blue light was started immediately and continued for either 30, 45, or 60 minutes (simultaneous PDT). On the contralateral side, the blue light began 1 hour after ALA application and lasted 1000 seconds (conventional PDT). Pain was evaluated on a scale from 0 to 10. Actinic keratosis lesion counts were determined by clinical examination and photography. RESULTS: All patients experienced significantly less pain during simultaneous illumination than during the conventional regimen. At 3 months after treatment, lesion clearance was nearly identical on the 2 sides, as determined by statistical testing of noninferiority ± 15% margin. LIMITATIONS: Although bilaterally controlled, the study was relatively small. Additional studies are recommended. CONCLUSION: The modified PDT regimen is essentially painless, yet it provides treatment efficacy similar to a conventional regimen.

Photodynamic therapy activated by intense pulsed light in the treatment of actinic keratosis.

BACKGROUND: Actinic keratosis (AK), a hyperkeratotic lesion induced by solar exposure, is the precancerous lesion that most frequently develops into squamous cell carcinoma. Cryotherapy, topical fluorouracil 5, topical diclofenac 3% gel and, more recently, ingenol mebutate are used in addition to surgery. However, these treatments have varying degrees of effectiveness and are not always tolerated due to side effects. In recent years, photodynamic therapy (PDT), has asserted itself as a new effective and safe method for the treatment of actinic keratoses with almost no side effects. The aim of this study is to verify whether a third treatment may now be added to the "Conventional -PDT" and "Daylight-PDT": PhotoDynamic Therapy activated by Intense Pulsed Light (IPL-PDT). METHODS: Thirty-one patients, 24 males and 7 females, in most cases elderly, were included in the trial. As in the previous methods, also in IPL-PDT, 5-methylaminolevulinic acid (MAL) was applied topically for a period of 3 hours. Thereafter, the occlusive dressing and the topical cream, were removed and the neoformation was irradiated with IPL, with a 640 nm filter with variable power. Irradiation was performed in single or multiple sessions, depending on the type of keratosis, to completely cover the lesion and the apparently healthy surrounding areas, i.e. the cancerization field. RESULTS: Results were evaluated 3, 6 and 9 months after treatment. Treatment achieved a 95% complete clearance rate, with a 5% partial relapse, 9 months after the last treatment. CONCLUSIONS: The above method is a valid alternative to methods already in use. The results obtained demonstrate the efficacy and tolerability of the treatment described which, due to its versatility and speed of use, is preferable to the methods used so far.

Plum-blossom needle assisted photodynamic therapy for the treatment of oral potentially malignant disorder in the elderly.

Oral leukoplakia (OLK) is one of the most common oral potentially-malignant disorders (OPMD) with complex causes, a long disease course and a high tendency for recrudescence. Although a variety of methods exist for treating this disease, canceration rates remain high. Herein, we described a case of 72-year-old male patient with OLK of the palatine mucous membrane who had achieved complete remission after being treated with five sessions of plum-blossom needle (PBN) assisted 5-aminolevulinic acid-photodynamic therapy (ALA-PDT). The patient had since been subsequently placed under close observation (>12 mo). To date, there has been no recurrence. PBN assisted PDT might be suitable for the treatment of OPMDs in patients presenting with epithelial hyperkeratosis.

Hyperbaric Oxygen Combined with 5-Aminolevulinic Acid Photodynamic Therapy Inhibited Human Squamous Cell Proliferation.

The photodynamic therapy (PDT) depends on the presence of molecular oxygen. Thus, the efficiency of PDT is limited in anoxic regions of tumor tissue and vascular shutdown. It is reported the use of hyperbaric oxygen (HBO) may enhance the efficiency of PDT. However, there are rarely studies about utilizing HBO plus PDT for treatment with human squamous cell carcinoma (SCC). Therefore, this study aimed to investigate and compare the therapeutic effect of combined therapy and PDT alone treatment. Multiple cellular and molecular biology techniques were used in the current study such as CCK-8, Western blotting, flow cytometry, monodansylcadaverine (MDC) staining and immunofluorescence assay. The results of combination index indicated that HBO combination with PDT synergistically inhibited A431 cells proliferation in vitro. In addition, we found that HBO significantly enhanced PDT-induced cell apoptosis via increasing the active caspase-3, active caspase-9, Apaf-1 and Bax levels and down-regulating Bcl-2. Meanwhile, the result of MDC and immunofluorescence assay confirmed that HBO increased PDT-induced autophagosome formation in A431 cells. Interestingly, autophagy inhibitor 3-methyladenine (3-MA) further increased combination-induced cell apoptosis by increasing the levels of active-caspase 9 and Apaf-1. Our results showed that HBO combined with PDT markedly induced A431 cells apoptosis and autophagy. Nevertheless, autophagy play a pro-survival role against apoptosis. Thus, HBO combination with PDT may constitute a promising approach to treat human squamous cell carcinoma in the future.

PDT and BF-200 ALA: The therapy option for the treatment of Poikiloderma of Civatte.

Poikiloderma is a chronic skin condition affecting middle-age men and women that comprises cutaneous atrophy, telangiectasias, and changes in the pigmentation of the skin usually of mottled appearance (both hyper- and hypopigmentation). There is no specific medical treatment for Poikiloderma of Civatte (PC), but the use of photoprotector/sunscreen + SPF 50 to avoid prolonged sun exposure is highly recommended in these patients. Some authors recommend the use of topical corticoids in early stages; however, the results have not been satisfactory. Multiple topical (retinoids, dimethyl sulfoxide, or calcineurin inhibitors), systemic (cyclophosphamide), and physical (dermabrasion, phototherapy, and fractional photothermolysis) treatments have been described with unequal and inconsistent responses or unsatisfactory. This report underlies the combination of BF-200 ALA and photodynamic therapy (PDT) with positive results at the clinical level: significant improvement of pigmentary changes and telangiectasias after two PDT sessions.

Photodynamic therapy as an alternative treatment for mycosis fungoides: a systemic review and meta-analysis.

INTRODUCTION: Mycosis fungoides is the most common cutaneous T cell lymphoma. Selection of appropriate treatment for mycosis fungoides (MF) is based on prognostic factors and overall clinical stage at diagnosis. In the past decade, clinical success has been reported using photodynamic therapy (PDT) as an alternative target-specific therapy to treat mycosis fungoides. This review aimed to summarize the current advances in management of mycosis fungoides by administration of photodynamic therapy. EVIDENCE ACQUISITION: Twenty-four articles, published between 1994 and 2017, were reviewed to assess the efficacy of PDT for MF. EVIDENCE SYNTHESIS: Methyl-aminolevulinic acid has increased lipophilic properties; red light at around 630 nm achieves deepest and best tissue penetration. However, the total number of PDT sessions depends on the clinical response. CONCLUSIONS: Further multicenter clinical studies are warranted to assess the cost-effectiveness of PDT.

5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

Staphylococcus aureus (S. aureus) is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT), which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA), a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT) to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

New therapeutic approaches in the treatment of anogenital lichen sclerosus: does photodynamic therapy represent a novel option?

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is an inflammatory, mucocutaneous disorder that affects male and especially female with a debilitating impact on the quality of life. Common localization is the anogenital area. If not treated LSA can leave scars, functional impairment and can evolve in squamous cell carcinoma. The first line of treatment is represented by topical, ultra-potent corticosteroids, but often patients are unresponsive; moreover this therapy is frequently associated to relapses of the disease after discontinuation. METHODS: In this prospective observational study, the efficacy of three different treatments - topical calcineurin inhibitors, avocado and soya beans extracts, and methyl aminolevulinate photodynamic therapy (MAL-PDT) - was evaluated, and an effort has been made to define a therapeutic algorithm according to the severity of the disease. RESULTS: Of the 150 patients who were referred to the outpatient clinic for a dermatological and gynecological visit, 33 met the inclusion criteria. Sixteen (88%) patients showed an improvement of the lesion and a reduction of the itch; 3 (16.7%) patients with sever itch and fissurated lesions were evaluated for the MAL-PDT therapy. A total of 9 patients, after accurate examination of the lesions, were treated with MAL-PDT. The totality of the patients experienced a resolution of the lesions. CONCLUSIONS: In the early stages the use of ASE can represent a valid alternative that is well tolerated by the patients reducing the itching, dryness and improving the mucosal texture. The use of MAL-PDT represents a valid treatment in the moderate-severe stages of LSA.

The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain.

Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n = 53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n = 35, 5-ALA-SFC; n = 18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141.

Treatment of Acne in Pregnancy.

Acne vulgaris is a common disease of the pilosebaceous unit and affects adolescents and adults. Because high-quality guidelines regarding treatment of acne in pregnancy are scarce, management of this condition can be challenging. We describe the safety profile of common therapies and outline approaches based on available evidence. Topical azelaic acid or benzoyl peroxide can be recommended as baseline therapy. A combination of topical erythromycin or clindamycin with benzoyl peroxide is recommended for inflammatory acne. Oral erythromycin or cephalexin is generally considered safe for moderate to severe inflammatory acne when used for a few weeks. A short course of oral prednisolone may be useful for treating fulminant nodular cystic acne after the first trimester. In general, topical and oral antibiotics should not be used as monotherapy, but combined with topical benzoyl peroxide to decrease bacterial resistance. Oral retinoids are teratogenic and absolutely contraindicated for women who are pregnant or considering pregnancy. Although some complementary therapies including micronutrients and nonpharmacologic treatments seem to be well tolerated, limited data exist regarding their safety and efficacy, and they are not currently recommended during pregnancy. The risk-to-benefit ratio, efficacy, acceptability, and costs are considerations when choosing a treatment for acne in pregnancy.

Interstitial 5-ALA photodynamic therapy and glioblastoma: Preclinical model development and preliminary results.

OBJECTIVE: Photodynamic therapy (PDT) has become a well-established modality for the treatment of many cancers. Photodynamic eradication of tumor cells depends on the presence of a photosensitizer, oxygen and light. However, oxygen depletion during PDT is a well known problem. Modulation of light delivery could address this issue by counteracting tumor hypoxia, thereby improving tumor cell killing. This preclinical study was designed to validate an animal model incorporating 5-aminolaevulinic acid (5-ALA)-PDT using U87 glioblastoma cells. We aimed to evaluate the effects of light modulation for inducing specific tumoral lesions in this model (i.e., necrosis or apoptosis). MATERIALS AND METHODS: U87 glioblastoma cells were stereotactically engrafted into the brains of male fox1 rnu/rnu rats. Light delivery was studied after 5-ALA injection (100 mg/kg i.p.). 26J of 635 nm light was interstitially delivered to U87 tumor-bearing rats at a radiant power of either 30 mW (high fluence rate) or 4.8 mW (low fluence rate). In each group, half of the population received illumination in 2 fractions with a refractory interval of 120 s, whereas the other half received continuous illumination. RESULTS: Twenty-two animals received 5-ALA-PDT, and the level of necrosis was scored. In the high-fluence-rate group, we observed a greater degree of tumor necrosis in rats receiving fractionated delivery than in rats receiving continuous illumination. Similar differences were not observed in the low-fluence-rate group, which exhibited only sparse necrosis. Higher morbidity and mortality rates were observed in the high-fluence-rate group. CONCLUSION: We have developed a reproducible and reliable rodent model for interstitial 5-ALA PDT. We found that the effects of 5-ALA-PDT are dependent on light delivery conditions. Although the low-fluence-rate treatment was better tolerated, 5-ALA-PDT induced more necrosis using fractionated delivery at a high fluence rate. These results require confirmation with further studies involving larger populations and additional fractionation schemes.

Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis?

Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; -2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo.

The Two Faces of Fractionated Photodynamic Therapy: Increasing Efficacy With Light Fractionation or Adjuvant Use of Fractional Laser Technology.

"Fractionated photodynamic therapy (PDT)" is a new term being used by dermatologists to describe advances in PDT technology including fractionated light or the adjuvant use of fractional lasers. Although dermatologists have used PDT since the early 1990s for the treatment of photodamage and precancerous lesions, newer developments in technology have allowed for the treatment of non-melanoma skin cancers (NMSCs), in ammatory disorders, and even uses in the eld of anti-aging. Recent developments in fractionated light therapy have allowed for PDT with dark intervals and two-fold illumination schemes to increase cellular damage and apoptosis. Combining PDT with fractional laser technology has allowed for enhanced dermal penetration of topical photosensitizers including 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), as well as increased ef cacy of treatment. These advances in PDT technology will allow for increased convenience, decreased treatment time, only one application of topical photosensitizer, and decreased cost to the patient and dermatologist. J Drugs Dermatol. 2016;15(11):1324-1328..

Daylight photodynamic therapy with 1.5% 3-butenyl 5-aminolevulinate gel as a convenient, effective and safe therapy in acne treatment: A double-blind randomized controlled trial.

While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester, 1.5% 3-butenyl ALA-bu gel, using daylight only as the potential visible light source. Forty-six acne patients were randomly assigned to either ALA-bu or vehicle application group in a double-blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA-bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8, interleukin-1ß, matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy.

Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A One-Year Follow-up Study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AK) is lower on the distal extremities compared with head and neck areas. A recent pilot study demonstrated increased efficacy of ALA PDT when the skin is warmed during ALA incubation. Prolonged clearance rates on the heated extremity were noted in 3 subjects that were evaluated after the study ended. The aim of this study was to evaluate the longevity of clearance rates after temperature-modulated PDT for the treatment of AKs on the extremities. MATERIALS AND METHODS: A total of 18 subjects (20 pairs of extremities) with at least 10 AKs on the upper or lower extremities were enrolled in the single-center study. Twenty percent ALA was applied to both extremities and heated during the 1-hour incubation period, followed by exposure to 10 J/cm 417-nm blue light. Lesions were photographed, counted, and templated at baseline, 1 week, and 3, 6, 9, and 12 months after treatment. RESULTS: A total of 17 subjects completed the 1-year study. The total number of lesions counted at baseline was 724 Grade 1 and 2 AKs (median 15 on each extremity). The lesion count at 3 and 12 months was 70 (9.6%) and 72 (9.9%), respectively. Grade 3 AKs did not resolve with treatment. The median baseline temperature of the treated extremities was 31.6°C. The median maximum temperature during the 1-hour incubation period was 41.2°C. The median clearance at 3 months was 90% and the same was maintained at 12 months. No new AK lesions formed in the treated areas within the 12-month follow-up period. CONCLUSION: Warming the skin after application of ALA is well tolerated, does not increase side effects, and increases the long-term efficacy of PDT for the treatment of AKs. The authors suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice.

In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe(2+)) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug.

Daylight photodynamic therapy with methyl-aminolevulinate for the treatment of actinic cheilitis.

Actinic cheilitis (AC) is a common premalignant condition that requires an effective treatment to reduce the risk of malignant transformation. Photodynamic therapy (PDT) has been recently added to the armamentarium available for AC treatment. Daylight PDT (D-PDT) is a novel PDT modality in which the activation of the topical photosensitizer is induced by the exposure to natural daylight instead of artificial light sources without preliminary occlusion. This simplified procedure was found to be more tolerated as compared to conventional PDT. We report our preliminary experience on the use of D-PDT using methyl-aminolevulinate cream in 10 patients with refractory AC of the lower lip. Patients received two consecutive D-PDT sessions with an interval of 7-14 days. At 3 months after therapy, a complete response was observed in seven patients, with sustained results in five patients over an observational period of 6-12 months. Treatment was well tolerated.