Photodynamic therapy of acne vulgaris using 5‐aminolevulinic acid 0.5% liposomal spray and intense pulsed light in combination with topical keratolytic agents

Background Increasing antibiotic resistance of Propionibacterium acnes and growing awareness on the side effects of topical and systemic drugs in the treatment of acne vulgaris by physicians and patients have paved the way for a search into new efficacious and safe treatment modalities such as photodynamic therapy (PDT). Although the efficacy of PDT using 20% 5‐aminolevulinic acid (ALA) cream has been established, phototoxic side effects limit its use. The 5‐ALA concentration can be lowered by a factor of 40 by changing the vehicle of 5‐ALA from a moisturizing cream to liposome encapsulation. Objectives Assessment of the efficacy and the safety of PDT using 5‐ALA 0.5% in liposomal spray and intense pulsed light (IPL) in combination with topical peeling agents (Li‐PDT‐PC) in acne vulgaris. Materials and Methods 32 patients suffering from acne participated in this randomized, prospective, single blind study. All patients were treated with Li‐PDT‐PC. During the study nine patients were additionally treated with topical or systemic antibiotics (Li‐PDT‐PC‐AT). These patients were removed from the study although their results were recorded. Results After a mean period of 7.8 months and a mean number of 5.7 treatments the mean total number of lesions dropped from 34.6 lesions to 11.0 lesions, resulting in a mean improvement of 68.2%. Side effects were minimal. Additionally, an intention to treat analysis was conducted. Conclusion Photodynamic therapy of acne vulgaris using 5‐ALA 0.5% liposomal spray and IPL in combination with topical peeling agents is safe and efficacious, even in patients with acne recalcitrant to standard therapy.     

Prospective study of topical 5‐aminolevulinic acid photodynamic therapy for the treatment of severe adolescent acne in Chinese patients

Acne vulgaris is one of the most common skin diseases in adolescents. In the present study, we aimed to evaluate the effectiveness and safety of topical 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) for the treatment of severe acne in Chinese adolescent patients. Twenty‐one Chinese adolescent patients aged 12–18 years with Pillsbury III–IV severe facial acne were treated with three courses of ALA‐PDT. A 5% ALA lotion was applied topically for 60 min followed by irradiation with light‐emitting diode light at 633 nm with a light intensity of 75–80 mW/cm² and a light dose of 90–96 J/cm². Clinical assessment was conducted before and after each treatment, and at each follow‐up session. The total effective rates were 85.71%, 90.48%, and 95.23% after the three PDT sessions, and at the 4‐ and 8‐week follow ups, respectively. ALA‐PDT is an effective treatment for severe adolescent acne vulgaris, and is associated with mild and reversible side‐effects.     

Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris

BACKGROUND: Photodynamic therapy (PDT) is useful for the treatment of epidermal neoplasia but may also have use in the treatment of inflammatory dermatoses. The purpose of this study was to evaluate the safety and efficacy of PDT in the treatment of acne on the face. METHODS: Eight patients with mild-to-moderate acne vulgaris on the face were treated with one session of topical aminolevulinic acid (ALA)-PDT using a red light. Each patient's face was divided into two areas (right side and left side) for ALA-PDT and untreated control. Twenty percent topical ALA was applied with 4 h occlusion, and 18 J/cm(2) red light (630+/-63 nm) was administered. Each patient's acne was visually assessed by a spot count of both inflamed and non-inflamed lesions at baseline and at 1, 3, and 6 months following PDT. RESULTS: At 1, 3, and 6 months, the mean percentage reduction in inflamed lesions count was 27.6%, 37.9%, and 41.9%, respectively, in the ALA-PDT-treated area, whereas in the control area, it was 8.0%, 14.7%, and 15.4%, respectively, compared with the baseline. This showed a higher reduction of a spot count of inflamed lesions in the ALA-PDT-treated area, which was statistically significant (P<0.05). There was a slightly higher reduction of a spot count of non-inflamed lesions in the ALA-PDT-treated area, which was statistically not significant (P>0.05). The adverse effects were minimal. CONCLUSION: ALA-PDT with red light was found to be effective in the reduction of the number of inflamed lesions in patients with mild-to-moderate acne vulgaris, with no significant short-term adverse effects.     

The practicalities of photodynamic therapy in acne vulgaris

A staple clinical skill in a dermatologist’s repertoire is the ability to treat acne vulgaris effectively. Light‐based therapies such as photodynamic therapy (PDT) widen the therapeutic options available for acne. Numerous review articles have agreed on the answer to core questions such as: ‘Does PDT work?’ and ‘Which acne lesions respond best to PDT?’ They conclude that PDT is especially useful in inflammatory acne and may be superior to light therapy alone. This literature review seeks to offer guidance regarding treatment‐specific queries about the photosensitizer, route of administration, treatment intervals, light sources and patient selection. Ovid Medline, PubMed and EMBASE database searches were executed between January 2007 and March 2008. Due to the scarcity of data, all five randomized trials, four of which were at least investigator blinded and controlled, 12 open clinical studies, two case reports and two abstracts published in English were considered. Four hundred and nineteen patients were recruited. As the quality of the data was suboptimal in a significant number of articles, the conclusions are drawn in very broad strokes: topical short‐contact (90 min or less) 5‐aminolaevulinic acid or methyl aminolaevulinate using a noncoherent light source at 2–4‐week intervals for a total of two to four treatments produces the greatest clinical effect. Papulopustular acne is more responsive and all Fitzpatrick skin types are eligible. However, patients with skin types I–III have a reduced risk of postinflammatory hyperpigmentation seen in darker skin types. These treatment parameters demonstrate a good side‐effect profile resulting in acne remission for at least 3 months to a year in a relatively cost‐effective manner. Well‐designed nonsplit‐face randomized controlled trials would offer further guidance, especially for queries surrounding the light source and illumination schemes.     

光动力疗法联合清痘修复精华液治疗中重度痤疮疗效评价

目的:评价5-氨基酮戊酸光动力疗法联合薇诺娜清痘修复精华液治疗中重度痤疮的临床疗效及安全性。方法:选取60例中重度痤疮患者随机分为2组:光动力组(对照组)和光动力联合清痘修复液组(治疗组),共治疗4周;在治疗后第2、4、6周对两组患者进行疗效评价,治疗结束后第3个月随访评估复发情况。结果:治疗2、4、6周后治疗组治愈率分别为67%,80%和93%,对照组治疗率分别为40%,60%和73%,两组差异显著(P0.05)。治疗后随访治疗组复发率为7.14%,显著低于对照组的31.82%(P0.05)。结论:ALA-PDT联合薇诺娜清痘修复精华液治疗中重度痤疮疗效好,复发率低且不良反应轻微。     

Efficacy of ALA-PDT vs blue light in the treatment of acne

BACKGROUND: Photodynamic therapy (PDT) is based on the principle of using light excitation of a wavelength-specific endogenous or exogenous photosensitizer to destroy the target tissue, and has shown efficacy in the treatment of certain non-melanoma skin cancers. PDT using aminolevulinic acid (5-ALA) has attracted attention in the treatment of acne vulgaris. METHOD: Twenty patients with moderate to severe acne vulgaris on the face were treated with four sessions of topical ALA-PDT with blue light (415 nm) on the right side of the face compared with blue light alone on the left side of the face, each treatment being 1 week apart. Ten percent of topical ALA was applied to acne spots on the right side of the face with a 1-h incubation period and the entire face was treated with 48 J/cm(2) of 415 +/- 5 nm light from an articulated LED planar array. Evaluation was performed by counting acne lesions at baseline, 4, 8, 12 and 16 weeks after the beginning of the treatment. Biophysical measurements included sebum levels and the erythema, and melanin indices. RESULT: At the given assessment times 4, 8, 12 and 16 weeks after the beginning of the treatment, the mean percent reduction in inflamed lesions counts tended to be higher in the ALA-PDT areas; it was 32%, 50.9%, 65.9% and 71.1%, respectively, compared with the blue-light-alone treatment, which was 20.7%, 27%, 57.7% and 56.7%, respectively, but without any statistical significance (P=0.092). There was no demonstrable significant change in sebum excretion, erythema or the melanin index after treatment. The side effects were pain, stinging, peeling, erythema, pruritus, oozing and pustules. These side effects were stronger on the ALA-PDT-treated side. CONCLUSION: From this study, the trend for ALA-PDT with blue light to be superior to blue light alone was observed, but it did not reach statistical significance. ALA-PDT had more side effects.     

Delta-aminolevulinic acid-based photodynamic therapy for acne on the body

Intractable acne on the body was clinically treated with photodynamic therapy (PDT) combining oral administration of delta-aminolevulinic acid (ALA) with polychromatic visible light from a metal halide lamp. The total number of body acne patients was 51. A 10 mg/kg B.W. of ALA was administered to the patients, and the acne lesions were exposed to the light emitted from the metal halide lamp. The wavelengths of the light ranged from 540 to 800 nm. The diameter of the irradiated area and the irradiating distance from the lamp were 100 mm and 130 mm, respectively. Under the irradiation conditions, the total fluence rate and the energy-density uniformity of the light were 69.2 mW/cm2 and 11.5%. The total light energy dose in one session was 60-80 J/cm2 for the body. All patients underwent two sessions of PDT and received no other treatments after PDT or during the follow-up period. The interval between the two PDT sessions was 2-4 weeks. The physician's clinical assessment scores as worsened, unchanged, improved, and markedly improved were 0 (0%), 4 (7.8%), 16 (31.4%), and 31 (60.8%) patients, respectively. Adverse effects of very slight discomfort, burning, and stinging were reported during the irradiation. The blood tests of patients before and after oral administration of ALA demonstrated that no liver dysfunction occurred in this study with ALA dosages within 10 mg/kg B.W. Consequently, orally administered ALA-PDT with a metal halide lamp was considered to be effective for treatment of acne on the body.     

Incomplete efficacy of 5-aminolevulinic acid (5 ALA) photodynamic therapy in the treatment of widespread extramammary Paget's disease

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an effective treatment for several conditions such as Bowen's disease, subsets of basal cell carcinomas and actinic keratosis. Surgical resection is the first-choice therapy for extramammary Paget's disease (EMPD), but extensive resection is highly invasive and recurrences are frequent. We report two cases of genital EMPD treated by PDT with partial efficacy. The first patient, a 78-year-old male, suffered from pubic and scrotal Paget's disease for 6 years despite numerous treatments. The second patient, a 78-year-old female, had vulvar involvement for 2 years that was resistant to multiple treatments. The disease was recurrent and chronic with important pruritus and significant impact on the quality of life. Methyl 5-aminolevulinate was applied for 3 h, and irradiation was applied with red light (630 nm) using a total light dose of 37 J/cm(2) for a period of 10 min. The patients were treated every 2 to 4 weeks for a total of at least three treatments. Both patients experienced a partial transient reduction in their symptoms. One patient had a partial transient remission (< 50% reduction of the involved surface), whereas in the other patient, PDT failed to reduce the surface area of the lesions.     

Comparative split-face study of 5-aminolevulinic acid photodynamic therapy with intense pulsed light for photorejuvenation of Asian skin

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT) using intense pulsed light (IPL) as a light source (IPL-ALA-PDT) has been used for photorejuvenation, but it is unclear if this protocol can be applied to darker skin types. We performed this study to assess our IPL-ALA-PDT protocol for photorejuvenation in Asian skin. To determine an appropriate dose, ALA ointment (0-20%) was applied to the upper arm of five healthy volunteers and the fluorescence intensity (FI) was measured using a spectrofluorometer. Non-linear regression analysis of FI 2 h after ALA application with global fitting gave a typical sigmoid dose-response curve with R2 = 0.9705 and saturation after 5% ALA. The entire faces of 16 Japanese women with photodamage were then treated with IPL (500-670 and 870-1400 nm, 23-30 J/cm2) 2 h after application of 5% ALA to one side of the face. Three treatments were delivered at 4-week intervals with follow-up visits. Comparative analysis of photorejuvenation showed noticeable improvements on both sides of the face, although the reduction in the photoaging score from baseline did not differ significantly between the two sides in all subjects. Despite this finding, 75% of the patients felt that the IPL-ALA-PDT-treated side of the face showed greater improvement than the IPL-treated side. However, all IPL-ALA-PDT-treated sides showed adverse effects such as erythema and pain. Therefore, we conclude that the IPL-ALA-PDT protocol requires optimization for photorejuvenation in Asians.     

Acne-photodynamic therapy with intra-lesional injection of 5-aminolevulinic acid

Photodynamic therapy (PDT) is a treatment option for acne patients who fail to respond to conventional therapy. Although potent, we experience side effects such as erythema, exfoliation and dyspigmentation. In attempt to specify treatment and shorten the incubation time, we injected 5-aminolevulinic acid (ALA) to the individual lesion. The results of intralesional injection ILI-PDT and conventional PDT are compared in this study.     

Repeated 5-aminolevulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma

5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) in the standard manner is ineffective for pigmented basal cell carcinoma (pBCC), because melanin absorbs the photoactivating light interred for protoporphyrin IX. The objective of this study was to assess the therapeutic outcome of pBCCs with repeated ALA-PDT following removal of pigmentation with electro-curettage. After electro-curettage, 16 pBCCs were treated with a combination of topical application of 20% ALA in O/W emulsion and topical instillation of 10% ALA solution, followed by photoactivating light. ALA-PDT was performed more than three times. Fourteen of 16 pBCCs showed CR. Two pBCCs showing PR or NR were excised. Repeated ALA-PDT following electro-curettage was effective for pBCC.     

不同浓度氨基酮戊酸光动力治疗囊肿痤疮疗效观察

目的探索5-氨基酮戊酸光动力疗法(ALA-PDT)治疗囊肿痤疮时5-氨基酮戊酸(ALA)的最适浓度。方法采用随机方法将116例囊肿痤疮患者分为3个治疗组,给予ALA的浓度分别为5%、7.5%、10%,均采用波长632.8 nm的红光照射,每周1次,共4次。结果在治疗结束后2周、1个月、3个月,7.5%和10%浓度组间疗效差异均无统计学意义(P均0.05),而这两组与5%浓度组比较,差异均有统计学意义(P均0.05)。不良反应为红斑、肿胀,部分患者出现轻微渗出及暂时性色素沉着,所有患者均未出现溃疡和瘢痕。结论结合临床有效率及安全性,ALA-PDT治疗囊肿痤疮宜采用7.5%的浓度。     

Phototoxic reactions in healthy volunteers following photodynamic therapy with methylaminolevulinate cream or with cream containing 5-aminolevulinic acid: a phase II, randomized study

Background: Photodynamic therapy (PDT) is the selective destruction of abnormal cells through activation of a photosensitizer in the presence of oxygen. Local phototoxic reactions and pain are the most common limiting side effects.
Purpose: The primary objective was to compare the local phototoxic response following PDT with methylaminolevulinate (MAL) and 5-aminolevulinic acid (ALA). The secondary objectives were to compare the two treatments regarding pain, detection of substance P, change in fluorescence intensity from before to 5 h after cream application and adverse events not related to local phototoxicity.
Methods: Thirty-four healthy volunteers were treated by PDT using MAL 160 mg/g cream and ALA cream 20% randomly assigned to treatment areas on the inside of each upper arm. A composite score of local phototoxic events (erythema, edema, hyperpigmentation) was calculated.
Results: The area under the curve (AUC) analysis of composite scores showed a significantly higher AUC for ALA-PDT ( P ≤0.0001). ALA- and MAL-PDT showed equivalent local side-effect frequencies, except for a higher frequency of hyperpigmentation after 28 d using ALA-PDT ( P =0.006).
Conclusion: MAL- and ALA-PDT are nearly equivalent regarding individual side-effect frequencies, but MAL-PDT has a more favorable phototoxicity pattern as seen by AUC analysis and the lower frequency of long-lasting hyperpigmentation.     

Photodynamic therapy of interdigital mycoses of the feet with topical application of 5-aminolevulinic acid

BACKGROUND: Findings of in vitro studies have demonstrated that dermatophytes and yeasts can be effectively photosensitized after topical delivery of 5-aminolevulinic acid (ALA). This procedure, called photodynamic therapy (PDT), seems to lack mutagenic activity and hazard of selection of drug-resistant strains. METHODS: Twenty percent ALA preparation in Eucerin cream was applied under an occlusive dressing to skin lesions of nine patients with clinical and microbiological evidence of interdigital mycosis of the feet. After 4 h, lesions were irradiated with 75 J/cm(2) of broad-band red light. Interdigital lesions of the other foot served as control (treated with only light or only ALA). After 7 days from the first treatment, no further treatment was delivered if lesions were not clinically evident and direct microscopic examination was negative. Otherwise, three additional weekly treatments were delivered. Four weeks after the last treatment, patients had a final follow-up clinical and laboratory examination. RESULTS: Clinical and microbiological recovery was seen in six out of nine patients after one (four cases) or four (two cases) treatments. However, after 4 weeks, recurrences were seen in four patients. Overall tolerability was always good. CONCLUSION: Under the conditions employed in the present study, ALA-PDT had good therapeutic effects on interdigital mycosis of the feet. However, recurrences were quick. In vivo environmental conditions, i.e. temperature, humidity and pH of the interdigital skin, could induce a poor cell uptake of ALA and a deficient biosynthesis of photosensitizing protoporphyrin IX. In addition, the irregular tridimensional shape of this peculiar anatomical area could lead to a non-uniform delivery of light and/or ALA cream. However, the present results can stimulate further studies on the PDT of superficial skin mycoses.     

Topical 5‐aminolevulinic acid photodynamic therapy for recalcitrant facial flat wart in Chinese subjects

The facial flat wart (verruca plana) is not only a contagious viral disease, but also causes a disturbing cosmetic problem. Because 5‐aminolevulinic acid photodynamic therapy has successfully treated human papilloma virus‐related diseases, we employed 20% 5‐aminolevulinic acid and a light emitting diode on three recalcitrant facial flat wart patients. Most lesions achieved complete remission after three or four sessions. However, a few non‐elevated lesions did not respond to this method. An ablative therapeutic mode is required in addition to 5‐aminolevulinic acid photodynamic therapy in such lesions. Therefore, we utilized an Er:YAG laser and 20% 5‐aminolevulinic acid photodynamic therapy for one session and achieved an excellent result. Patients should be informed of the possible side‐effects of this treatment, such as erythema, exfoliation and post‐inflammatory hyperpigmentation, and the requirement for sun protection.     

Photodynamic therapy with intralesional 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: a comparative study

Despite the availability of many treatment modalities for acne vulgaris (AV), few of which provide excellent results. Photodynamic therapy (PDT) was shown to be an effective treatment especially when used with topical 5-aminolevulenic acid (ALA). We compared the efficacy and safety of PDT using intralesional ALA (IL-ALA) with intense pulsed light (IPL) and IPL alone in the treatment of AV. This study was carried on 30 patients with nodulocystic and inflammatory AV on the face and back. The right side of the body was treated with IL-ALA plus IPL, while the left side was treated with IPL alone. All patients experienced a reduction in number of acne lesions on both sides of the body, but the reduction was significantly more in PDT side than IPL only side. Recurrence of the lesions was significantly more likely in the IPL only side. There was no statistically significant difference between the face and back lesions in drug side effects and recurrence of the lesions. We concluded that photodynamic therapy in this cohort is effective in the treatment of AV when combined with IL-ALA. It gives superior results compared with IPL alone with minimal and tolerable side effects and less recurrence rates.