Comparative study of photodynamic therapy vs CO2 laser vaporization in treatment of condylomata acuminata: a randomized clinical trial

BACKGROUND: Most conventional therapies for condylomata acuminata (CA) are traumatic and have high recurrence rates. OBJECTIVES: To investigate the efficacy and safety of topical application of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for the treatment of CA. METHODS: Sixty-five patients with CA were allocated into the treatment (ALA-PDT) group and treated with 20% ALA solution under occlusive dressing for 3 h followed by irradiation with the helium-neon laser at a dose of 100 J cm(-2) and a power of 100 mW. Another 21 CA patients were allocated into the control group and treated with the CO(2) laser. The treatment was to be repeated 1 week later if the lesion was not completely removed after the first treatment. RESULTS: After one treatment, the complete removal rate was 95% in the ALA-PDT group and 100% in the control group. After two treatments with ALA-PDT, the complete removal rate in the treatment group was 100%. The recurrence rate for ALA-PDT group was 6.3% which was significantly lower than that in control group (19.1%, P < 0.05). Moreover, the proportion of patients with adverse effects in the ALA-PDT group (13.9%) was also significantly lower than that in control group (100%, P < 0.05). The side-effects in patients treated with ALA-PDT mainly included mild burning and/or stinging restricted to the illuminated area. CONCLUSIONS: The present study shows that topical application of ALA-PDT is a simpler, more effective and safer therapy with a lower recurrence for treatment of CA compared with conventional CO(2) laser therapy.     

A randomized clinical comparative study of cryotherapy plus photodynamic therapy vs. cryotherapy in the treatment of multiple condylomata acuminata

Background: Cryotherapy cannot destroy subclinical human papillomavirus‐infected cells of condylomata acuminata (CA). The topical application of aminolevulinic acid (ALA) results in a shallow penetration depth in CA lesions ( 1 ). Objectives: To compare the efficacy and safety of cryotherapy plus ALA‐photodynamic therapy (PDT) with cryotherapy in the treatment of multiple CA. Methods: Eighty patients with multiple CA received cryotherapy plus ALA‐PDT (n=40) or cryotherapy plus placebo‐PDT (n=40). After cryotherapy, a 20% ALA or a placebo solution was applied to the CA area 3 h before illumination with red light (635 nm, 100 mW/cm², 100 J/cm²). The treatment was repeated 7 days after the first treatment if the lesions were not completely resolved. The complete response rate, recurrence rate and adverse effects in the two groups were analyzed. Results: After two treatments, the complete response rates in the combined group (cryotherapy plus ALA‐PDT) and cryotherapy group were 32.4% (36/111) and 32.6% (43/132) in the anal area (P>0.05), 100% (32/32) and 54.5% (18/33) in the urethral meatus (P<0.05), and 94.2% (129/137) and 50.5% (56/111) in the external genitals (P<0.05), respectively. The recurrence rates in the combined group and cryotherapy group were 24.3% (27/111) and 31.1% (41/132) in the anal area (P>0.05), 9.4% (3/32) and 39.4% (13/33) in the urethral meatus (P<0.05), and 3.6% (5/137) and 31.5% (35/111) in the external genitals (P<0.05), respectively. The adverse effects in each group included mild to moderate pain, edema, erosion and hypopigmentation, without any infection, ulcers, scarring or urethral malformations. Conclusion: Cryotherapy plus ALA‐PDT is a more effective regimen for the treatment of multiple CA compared with cryotherapy alone.     

In vivo fluorescence kinetics and photodynamic therapy in condylomata acuminata

BACKGROUND: Topical application of 5-aminolaevulinic acid (ALA) to condylomata acuminata leads to accumulation of protoporphyrin IX (PpIX); therefore ALA-induced photodynamic therapy (ALA-PDT) appears to be a potential treatment. OBJECTIVES: To investigate in vivo the PpIX fluorescence time course after topical application of ALA in order to determine the optimal time for irradiation, and to assess the efficacy of subsequently performed ALA-PDT. METHODS: Fluorescence kinetics was studied in 12 male patients with condylomata acuminata. Confirmation of diagnosis was established with conventional histology and polymerase chain reaction. Lesions were treated with 20% ALA and irradiated at the optimal time with a dose of 70 J cm-2 or 100 J cm-2 light. An additional session with 100 J cm-2 was administered 1 week later to lesions that persisted. RESULTS: The in vivo study of fluorescence kinetics indicated that the optimal time for irradiation varied among patients from 6 to 11 h. The overall cure rate was 72.9%, 12 months after treatment. CONCLUSIONS: Topical ALA-PDT is a potentially effective treatment for condylomata acuminata.     

Topical 5-aminolaevulinic acid-photodynamic therapy for the treatment of urethral condylomata acuminata

BACKGROUND: Electrocoagulation and laser evaporation for urethral condylomata acuminata have high recurrence rates and can be associated with urethral malformations. OBJECTIVES: To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) on urethral condylomata acuminata and to examine the histological changes in lesions of condylomata acuminata after ALA-PDT. METHODS: Patients with urethral condylomata (n = 164) were given topical ALA followed by intraurethral PDT through a cylindrical fibre. Patients included 11 individuals with 16 penile or vulval condylomatous lesions which were biopsied before or after treatment; the histological changes were then evaluated by light microscopy and electron microscopy. RESULTS: The complete response rate was 95% and the recurrence rate was 5% after 6-24 months of follow-up. Light microscopy revealed keratinocytes in the middle and upper layers of the epidermis showing marked vacuolation and some necrocytosis 1 and 3 h after PDT. Necrosis in all layers of the epidermis was noted 5 h after PDT. Electron microscopy of keratinocytes revealed distinct ultrastructural abnormalities of mitochondria and the endoplasmic reticulum, and membrane damage. Apoptotic bodies were detected 3 h after PDT and a large number of keratinocytes exhibited necrosis 5 h after PDT. CONCLUSIONS: Results suggest that, compared with conventional therapies, topical ALA-PDT is a simple, effective, safe and well-tolerated treatment for urethral condylomata acuminata that is associated with a low recurrence rate. The mechanism might be the triggering of both apoptosis and necrosis by ALA-PDT in human papillomavirus-infected keratinocytes.     

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.     

Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acid

Photodynamic therapy (PDT) has been used for inflammatory skin disorders as well as superficial skin cancers such as solar keratosis and Bowen's disease. Whether PDT with topical application of aminolevulinic acid (ALA) and exposure to visible light has a similar immunosuppressive action to ultraviolet phototherapy was investigated using a murine contact hypersensitivity (CHS) model. The number of epidermal Langerhans cells (LC) was decreased with their morphological changes 1 day after PDT with the minimal level at 5 days and gradual recovery thereafter. Conversely, the number of CD11c(+) I-A(+) cells was significantly increased in the draining lymph nodes after PDT. This suggests that LC moved from PDT-treated skin, resulting in the decrement of epidermal LC and migration to lymph nodes. CHS response to DNFB applied on the PDT-treated skin with 20% ALA and 40 J/cm(2) visible light was significantly suppressed (local immunosuppression). When mice were treated with 80 J/cm(2) of PDT, CHS response to the antigen applied on untreated distant skin was also significantly suppressed (systemic immunosuppression). The locally or systemically immunosuppressed mice by PDT were attempted to sensitize again with DNFB on non-treated skin, but elicitation responses were significantly suppressed. However, these mice were able to be sensitized with another hapten, oxasolone. Thus, a hapten-specific immunological unresponsiveness (tolerance) was induced in mice by topical ALA-PDT. These findings suggest that PDT has a potential immunological contribution to clinical efficacy for inflammatory diseases identical to ultraviolet phototherapies.     

Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy

Background  There remains the need for more effective therapeutic options to treat acne vulgaris. Interest in light-based acne treatments has increased, but few randomized, controlled clinical trials assessing the value of photodynamic therapy (PDT) for acne have been reported.
Aims  We sought to examine the efficacy of PDT using 5-aminolevulinic acid (ALA) and pulsed dye laser therapy in the treatment of acne.
Patients/methods  We conducted a randomized, controlled, split-face, single-blind clinical trial of 44 patients with facial acne. Patients were randomized to receive three pulsed dye laser treatments to one side of the face after a 60–90 min ALA application time, while the contralateral side remained untreated and served as a control. Serial blinded lesion counts and global acne severity ratings were performed.
Results  Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin. Erythematous macules (remnants of previously active inflammatory lesions) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin. There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion. Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts, while only 7% of patients responded in terms of noninflammatory lesion counts.
Conclusions  PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne.     

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.     

Variable pulsed light is less painful than light-emitting diodes for topical photodynamic therapy of actinic keratosis: a prospective randomized controlled trial

BACKGROUND: Photodynamic therapy (PDT) of actinic keratosis (AK) using methylaminolaevulinate (MAL) is an effective and safe treatment option, but the procedure is painful. OBJECTIVES: To evaluate the efficacy and pain associated with variable pulsed light (VPL), a prospective, randomized, controlled split-face study was performed. METHODS: Topical MAL-PDT was conducted in 25 patients with AK (n = 238) who were suitable for two-sided comparison. After incubation with MAL, irradiation was performed with a light-emitting diode (LED) (50 mW cm(-2); 37 J cm(-2)) vs. VPL (80 J cm(-2), double pulsed at 40 J cm(-2), pulse train of 15 impulses each with a duration of 5 ms, 610-950 nm filtered hand piece) followed by re-evaluation up to 3 months. RESULTS: The pain during and after therapy was significantly lower with VPL irradiation [t (d.f. = 24) = 4.42, P < 0.001]. The overall mean +/- SD infiltration and keratosis score at 3 months after treatment was 0.86 +/- 0.71 (LED system) vs. 1.05 +/- 0.74 (VPL device) (no statistically significant difference; P = 0.292). Patient satisfaction following both treatment modalities did not significantly differ at the 3-month follow up (P = 0.425). CONCLUSIONS: VPL used for MAL-PDT is an efficient alternative for the treatment of AK that results in complete remission and cosmesis equivalent to LED irradiation but causes significantly less pain.     

棒状光源盐酸5-氨基酮戊酸光动力治疗肛管内尖锐湿疣

目的:评价棒状光源盐酸5-氨基酮戊酸光动力疗法治疗肛管内尖锐湿疣的临床疗效。方法:棒状光源盐酸5-氨基酮戊酸治疗肛管内尖锐湿疣男性患者46例,每周1次,共4次。结果:35例(76.1%)患者疣体完全清除,无感染、溃疡、瘢痕、痔疮病例。随访12周复发5例,复发率为14.3%。疼痛程度可视模拟评分(VAS)为(6.96±1.41)分。结论:棒状光源盐酸5-氨基酮戊酸治疗肛管内尖锐湿疣疗效好,中度疼痛,复发率低,不良反应少。     

Role of photodynamic therapy in psoriasis: a brief review

Background and purpose: Photodynamic therapy (PDT) is a light treatment modality which involves either systemic or local application of a photosensitizing compound, which preferentially deposits in the target cells, and is then followed by selective illumination of the lesion with visible light. The purpose of this study was to review the literature to examine the success, side effects, and different protocols used thus far to treat psoriasis using PDT. Methods: A thorough review of the literature was performed and analyzed. Results and conclusions: After a thorough review of the literature, PDT remains a potential treatment for psoriasis. Clinical improvement has been observed in most studies. The major limiting factor seen in many of the studies was the side effect of pain and burning sensations associated with PDT. This highlights the need for other photosensitizers with better tolerability profiles.     

Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study

BACKGROUND: There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES: To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six-point rating scale. Data were analysed on an intention-to-treat basis, including all 30 patients. RESULTS: There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.     

Randomized, double-blind, prospective study to compare topical 5-aminolaevulinic acid methylester with topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratosis

BACKGROUND: 5-aminolaevlinic acid methylester (MAL) and 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) are both effective treatment options for actinic keratosis (AK). While MAL is significantly more expensive than ALA, no studies have directly compared their efficacy in the treatment of extensive scalp AK. OBJECTIVES: To compare the efficacy and adverse effects of MAL-PDT with ALA-PDT in the treatment of scalp AK. METHODS: Sixteen male patients aged 59-87 years with extensive scalp AK were randomized into a double-blind, split-scalp prospective study. Two treatment fields were defined (right and left frontoparietal scalp) and treated 2 weeks apart. These fields were randomized to receive either MAL or ALA as first or second treatment. MAL cream was applied for 3 h; 20% ALA cream was applied for 5 h. A blinded observer assessed efficacy comparing AK counts before and 1 month after treatment. Pain was assessed using a visual analogue scale at 3, 6, 12 and 16 min. RESULTS: Fifteen patients completed treatment to both fields. There was a mean reduction from baseline in AK counts with the use of ALA-PDT of 6.2 +/- 1.9 compared with 5.6 +/- 3.2 with MAL-PDT (P = 0.588). All patients experienced pain which was of greater intensity in the ALA-treated side at all time points: 3 min (P = 0.151), 6 min (P = 0.085), 12 min (P = 0.012) and 16 min (P = 0.029). Similarly, duration of discomfort post-procedure persisted for longer following treatment with ALA when compared with MAL-PDT (P = 0.044). CONCLUSIONS: This study demonstrates that both ALA-PDT and MAL-PDT result in a significant reduction in scalp AK. There is no significant difference in efficacy. However, ALA-PDT is more painful than MAL-PDT in the treatment of extensive scalp AK.     

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.     

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.     

Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies

Background  Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self-adhesive patch (PD P 506 A) containing 5-aminolaevulinic acid (5-ALA) was developed to facilitate PDT.
Objectives  To investigate efficacy and safety of the patch in comparison with placebo–PDT (superiority design, observer-blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04).
Methods  Two separate confirmatory randomized parallel-group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients).
Results  Twelve weeks after treatment, 5-ALA patch–PDT proved to be superior to placebo–PDT ( P  < 0·001) and cryosurgery ( P  = 0·007). Efficacy rates on a lesion basis were 82% (AK 03) and 89% (AK 04) for PDT, 77% for cryosurgery and 19% (AK 03) and 29% (AK 04) for placebo–PDT. Local reactions at the treatment site occurred in almost all patients treated with 5-ALA patch–PDT or cryosurgery. Headache was the only side-effect not related to the treatment site which occurred in more than one patient.
Conclusions  PD P 506 A is an innovative, easy-to-handle 5-ALA patch for PDT of mild to moderate AK lesions. Compared with current PDT procedures, pretreatment (e.g. curettage) is not needed and handling is considerably facilitated. A single PDT treatment results in efficacy rates being statistically significantly superior to placebo and cryosurgery.     

光动力疗法联合CO2激光治疗肛管内尖锐湿疣疗效观察

目的：评价光动力疗法（PDT）联合CO2激光治疗肛管内尖锐湿疣（CA）的疗效与安全性。方法：分析92例肛管内CA患者,其中ALA—PDT联合CO2激光治疗组47例,CO2激光对照治疗组45例,比较两组的治愈率、复发率及不良反应。结果：治疗组和对照组术后疣体清除率均为100％,但治疗组治疗后复发率（17．02％）较对照组（56．66％）显著降低（P〈0．01）,两组之间不良反应发生率无明显差异（P〉0．05）;治疗组患者术后复发时间较对照组有显著延迟（P〈0．01）。结论：光动力疗法联合CO2激光治疗肛管CA复发率低,优于单纯的激光治疗。