Long‐term follow‐up of photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid patch: 12 months data

Background Photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid (5‐ALA) patch shows high efficacy rates in the treatment of mild to moderate actinic keratosis (AK) in short term trials. Objectives The purpose of the trial was to follow up patients after successful 5‐ALA patch‐PDT at 3 month intervals over a total period of 12 months. Patients who had received placebo‐PDT or cryosurgery served for comparison. Patients/methods Three months after therapy, 360 patients from two separate randomized parallel group phase III studies (one superiority trial vs. placebo‐PDT, one noninferiority trial vs. cryosurgery) were suitable for the follow‐up study. Patients had to show at least one successfully treated AK lesion after initial therapy. A total of 316 patients completed the follow‐up. Results Twelve months after a single treatment, 5‐ALA patch‐PDT still proved superior to placebo‐PDT and cryosurgery (P < 0·001 for all tests). On a lesion basis, efficacy rates were 63% and 79% for PDT, 63% for cryosurgery and 9% and 25% for placebo‐PDT. Recurrence rates of patch‐PDT proved superior to those of cryosurgery (per protocol set: P = 0·011, full analysis set: P = 0·049). While 31% of cryosurgery lesions were still hypopigmented after 1 year, the 5‐ALA patch‐PDT groups showed hypopigmentation in 0% (superiority trial) and 3% (noninferiority trial) of the treated lesions. Conclusion Twelve months after a single 5‐ALA patch‐PDT the majority of lesions were still cleared with an excellent cosmetic outcome. 5‐ALA patch‐PDT proved to be superior to cryosurgery in the noninferiority study setting.     

Fractionated aminolevulinic acid–photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer

Background Photodynamic therapy (PDT) is an accepted treatment for superficial basal cel carcinoma (sBCC) and Bowens disease. In Rotterdam, extensive preclinical research has lead to an optimized twofold illumination scheme for aminolevulinic acid–PDT (ALA‐PDT). Objective To provide additional evidence of ALA‐PDT for sBCC, Bowens disease (BD), nodular BCC (nBCC) and actinic keratosis (AK) using a 2‐fold illumination scheme after a single application of ALA. Methods Five hundred fifty‐two lesions (430 sBCC, 20 nBCC, 32 BD, 70 AK) were treated with ALA‐PDT using a twofold illumination scheme. ALA was applied topically for 4 h. Lesions were treated with two light fractions of 20 and 80 J/cm² separated by a 2‐h dark interval. Results After a minimum follow‐up of 12 months, in average follow‐up of 2 years, an overall complete response of 95% was seen for all lesions. For sBCC, the complete response at 2 years was 97% (for AK 98%, for BD 84% and for nBCC 80% after 2 years). A sub‐analysis of the results of lesions larger than 2 cm showed CR at 2 years of 89% for all lesions (n = 57). Cosmetic outcome was good to excellent in 95% of the treated lesions. Conclusion ALA‐PDT using a twofold illumination scheme of 20 plus 80 J/cm² separated by a 2‐h dark interval leads to high complete response rates at 2 years and can be regarded as an evidence‐based treatment modality for superficial growing non‐melanoma skin cancer and the (pre)malignant AK. The Rotterdam fractionated approach should be included in future guidelines.     

Photodynamic therapy using topical 5‐aminolaevulinic acid vs. surgery for basal cell carcinoma

Background Photodynamic therapy (PDT) is an attractive modality for the treatment of BCC, based on its generally favorable efficacy, adverse effect profile and its excellent cosmetic outcome. Objectives The purpose of the study is to compare the efficacy and cosmetic outcome of photodynamic therapy with topical 5‐aminolaevulinic acid (ALA‐PDT) vs. simple excision surgery for superficial and nodular basal cell carcinoma (BCC). Methods A total of 72 patients, 32 with 48 lesions, were treated with ALA‐ PDT, and 40 with 46 lesions treated by excision were included in this prospective, comparative, controlled, clinical study. The patients have been followed for 16–37 months (mean 25 months). The PDT was performed in combination with 5‐aminolaevulinic acid twice, one month apart. Surgical excision was performed under local anesthesia with a 3‐mm margin, followed by histological examination. The cosmetic outcome was evaluated by the physician according to a 4‐point scale. Results Overall 94 BCC were treated. Complete healing rates did not differ significantly between groups, P = 0.64 (46/48 [95.83%] lesions treated with PDT vs. 44/46 [95.65%] lesions with surgery). In the first 12 months of follow‐up, 4 lesions had recurred, 2 of which were in the PDT group while 2 lesions after surgery. The mean follow‐up was 25 months. The recurrence rate in the ALA‐PDT group was 4.16% vs. 4.34% in the surgery group, p = 0.64. The cosmetic outcome was superior for ALA‐PDT at all time points. At 12 months, 100% lesions treated with ALA‐PDT had an excellent or good cosmetic outcome, according to the investigator, compared with 88.86% with surgery, P = 0.01. Conclusion ALA‐PDT offers a similarly high efficacy, and a better cosmetic outcome than simple excision surgery in the treatment of BCC.     

BF‐200 ALA gel vs. MAL cream for BCC

Basal cell carcinoma (BCC), also known as rodent ulcer, is the most common type of non‐melanoma skin cancer worldwide. It affects about 3–10% of people. This study from the U.K. and Germany aimed to find out if BF‐200 ALA gel would work as well as (is non‐inferior to) the already authorised MAL cream in the treatment of non‐aggressive BCC lesions. Both medications are applied topically (on the skin) to the tumour, which is then illuminated with a certified lamp. The illumination causes a chemical reaction that affects the cancer cells so that they eventually die. This kind of procedure is called photodynamic therapy (PDT). Patients in the study were put into the two groups by chance (randomized): 138 in the BF‐200 ALA group and 143 in the MAL group. The treatment scheme for both drugs was the same. Initially, patients had two PDTs one week apart. Four and 12 weeks after the second PDT, patients visited the doctor again, who assessed the treated lesions and patient's health. If all lesions were gone by week 12, the patient entered the 5‐year follow‐up study. In case of remaining lesions, patients received two more PDTs before entering the follow‐up. During the follow‐up, doctors monitor the health of the patients and assess if any of the treated lesions come back. The study found that there was no difference between the two groups, which means that BF‐200 ALA gel worked as well as the already approved MAL cream. In 113 of 121 patients (93.4%) treated with BF‐200 ALA and 101 of 110 patients (91.8%) treated with MAL, lesions disappeared completely. 87% of the BF‐200 ALA‐treated patients rated their satisfaction with the PDT as “very good or good”; 86% of the MAL‐treated patients said the same. Almost all patients experienced mild to moderate local side effects related to the study medications. Common side effects at the application site, which affected more than 1 of 10 patients, were pain, skin reddening (erythema), itching (pruritus), and tissue swelling (oedema). Side effects were similar for both medications. At 12‐month follow‐up, lesions reappeared in 8.4% of the BF‐200 ALA‐treated patients and in 8.5% of the MAL‐treated patients. The follow‐up is still ongoing; further results will be reported after the end of the study. This study showed that BF‐200 ALA gel is as effective and well‐tolerated as MAL cream in the treatment of non‐aggressive BCC. Based on these findings, the European Medicine Agency (EMA) granted approval for BF‐200 ALA for the treatment of non‐aggressive BCC.     

Propranolol: a novel treatment for angiolymphoid hyperplasia with eosinophilia

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic disease that manifests as dermal or subcutaneous red or brown papules or nodules, most commonly on the head and neck. Histologically, ALHE is characterized by vascular proliferation with epithelioid endothelial cells with surrounding lymphocytic and eosinophilic infiltrate. There may be an accompanying serum eosinophilia and local lymphadenopathy. We report a case of a 32‐year‐old woman who presented with multiple erythematous nodules in the periauricular area and the vertex of her scalp. The nodules had been present for several months. Surgical removal of one of the lesions confirmed the histological diagnosis of ALHE. The patient was started on oral propranolol (40 mg once daily) in an effort to reduce the vascular component of the lesions. Within 6 weeks, the patient noted that several of the lesions had decreased in size, and all were less erythematous. Propranolol was subsequently stopped within a few months of initiating treatment. One lesion recurred over a year later, and propranolol was then restarted. No new lesions occurred after 2 years of follow‐up.     

Treatment efficiency of combining photodynamic therapy and ionizing radiation for Bowen’s disease

Background Topical 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) is widely used for treating Bowen’s disease (BD), but recurrence and tumour cell persistence after ALA‐PDT is sometimes problematic. Radiation therapy (RT) is also effective for BD, but is limited by its side‐effects, such as refractory ulcers. Objective The objective of the study was to observe a synergic effect of combination therapy with ALA‐PDT and RT for BD cases that did not respond effectively to prior ALA‐PDT. Methods Subjects were BD patients whose lesion did not show complete remission or showed recurrence after prior ALA‐PDT. A total of four cases involving four lesions were studied (three male and one female, mean age 69.5). ALA ointment (20%) was applied to the lesions. After 4 to 6 h, subjects received combination therapy consisting of excimer‐pumped dye laser radiation at 630 nm (50 J/cm²) followed by electron‐beam radiation (3 Gy). The combination therapy was repeated every 2 to 3 days for a total of four treatments. The lesions were evaluated clinically or histologically after the final combination therapy session. Results Following combination therapy, all of the lesions disappeared. Recurrence was not detected during the observations periods, which averaged 14.0 months in duration. Conclusion Our results indicate that the cure rate of BD could be improved by combination therapy with ALA‐PDT and RT. Compared with conventional RT, the synergetic effect of this therapy might reduce the dose of radiation required, thereby also reducing skin side‐effects such as refractory ulcers.     

High and sustained efficacy after two sessions of topical 5-aminolaevulinic acid photodynamic therapy for basal cell carcinoma: a prospective, clinical and histological 10-year follow-up study

Background Prolonged follow‐up data on topical photodynamic therapy (PDT) in basal cell carcinoma (BCC) are necessary for a full evaluation of its effect and for comparison with conventional treatment methods. Objectives To assess 10‐year long‐term PDT efficacy in primary and recurrent BCC and to evaluate clinical and histopathological factors which may be associated with treatment failure. Methods We performed a longitudinal study on 60 histologically verified BCCs in 44 patients treated with curettage and one or two sessions of dimethylsulphoxide (DMSO)‐supported topical 5‐aminolaevulinic acid (ALA)‐based PDT. Treated lesions were investigated by clinical and histopathological examination at regular intervals. The main outcomes were 10‐year lesion complete response rate using a time‐to‐event analysis, histological treatment failure and cosmesis. Results Overall complete response rate for all lesions was 75% (95% confidence interval 64–87%); 60% after one and 87% after two treatment sessions. The response rate was 78% for primary lesions; 63% after one and 90% after two sessions. The cosmetic outcome was rated as good or excellent in 91–100% of evaluated cases. Treatment failure was documented in 15 (25%) of 60 lesions; clinical investigation identified 14 of them. All failures were noted within 3 years of treatment. Male gender, recurrent tumour and one treatment session were factors significantly associated with treatment failure. The only lesion larger than 2·0 cm relapsed. Conclusions Two sessions of DMSO‐supported topical ALA‐PDT and curettage can provide long‐term effective treatment results with favourable cosmetic outcome in primary, small BCC.     

Single vs. fractionated photodynamic therapy for face and scalp actinic keratoses: a randomized,intraindividual comparison trial with 12‐month follow‐up

Objective To compare the efficacy and tolerability of a single ALA‐PDT illumination scheme with that of a fractionated ALA‐PDT illumination scheme in face and scalp actinic keratoses (AKs). Methods Eligible patients received either a single ALA‐PDT illumination or a fractionated illumination scheme randomly allocated to alternate sides of face/scalp. The side allocated to a single illumination received 75 J/cm². This side received 2 sessions performed 7 days apart. Lesions on the fractionated illumination scheme side received 20 and 80 J/cm², 4 and 6 hours after a single ALA application. Patients were evaluated at baseline, at 3 and 12 months after treatment. Efficacy end point included the individual AK lesion clearance rate. Results Thirty three patients with 266 lesions were enrolled in the study. Three months after treatment the overall lesion complete response rate was 89.05% for the single scheme and 96.12% for the fractionation scheme while at the 12‐months follow‐up response rate decreased to 85.4% for the single illumination and to 93.79% for the fractionated illumination group. Looking at lesion response based on lesion grade fractionated photodynamic therapy (PDT) resulted in larger rates of cured grade I as well as grade II lesions. Recorded adverse events were transient and did not demand additional therapy. Conclusions Our results demonstrate that higher responses are achieved with fractionated PDT compared with single illumination PDT. The study data indicate that fewer treatment sessions may be needed with fractionated PDT increasing that way the comfort of the patient regarding number of visits, treatment cost and treatment‐related downtime.     

Non‐invasive management of non‐melanoma skin cancer in patients with cancer predisposition genodermatosis: a role for confocal microscopy and photodynamic therapy

Background Patients with genodermatosis such as Gorlin syndrome (GS) and Xeroderma pigmentosum (XP) require a close follow‐up for early diagnosis and treatment of skin cancer. We aimed to evaluate the efficacy of methyl‐aminolevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinomas (BCCs) from patients with GS and XP, and to determine the utility of reflectance confocal microscopy (RCM) in the diagnosis and the evaluation of therapeutic response. Patients and methods We included four patients with GS and two siblings with XP. Single or multiple lesions in localized areas were treated with 1–3 cycles of MAL PDT. RCM was performed before and 3 months after the treatment in target lesions in all the patients. Patients were followed up for 3 years. Results In XP patients, we treated 13 pigmented BCCs on the face. All the lesions responded to the treatment and six lesions showed a complete clinical clearing. In GS patients, facial or trunk areas with multiple BCCs were treated (up to 200). Complete clinical remission was obtained in 25–67% of the lesions. Some nodular and pigmented lesions failed to achieve a complete remission. RCM could identify already described confocal features for BCC. Tumour remissions could be assessed by this technique. Conclusions Methyl‐aminolevulinate PDT may be useful for the treatment of superficial BCC in GS and XP. In some nodular lesions, PDT may complement surgery reducing tumour size. RCM may be regarded in the future as a complementary technique in BCC for the diagnosis and post‐treatment assessment to non‐invasive therapeutic modalities.     

Photodynamic therapy for dermatologic conditions in the pediatric population: a literature review

Photodynamic therapy (PDT), using topical aminolevulinic acid (ALA), has been used for years to treat a variety of dermatologic conditions, including actinic keratosis, superficial basal cell carcinoma, and in situ squamous cell carcinoma. While there is a wide range of neoplastic and non‐neoplastic skin diseases for which ALA‐PDT is used in adults, there is a knowledge gap when it comes to its use in children. This review highlights what is currently known regarding the use and efficacy of this therapy in the pediatric population. A PubMed search was conducted to identify studies including pediatric patients undergoing monotherapy PDT with topical aminolevulinate (published 2005–2016). Twenty pediatric articles were identified. ALA‐PDT has been used successfully in children to reduce the number and size of basal cell tumors, inflammatory acne lesions, plantar warts, and linear porokeratoses. ALA ‐ PDT may be an attractive alternative to surgery for children with basal cell nevus syndrome, or to conventional destructive and/or topical methods used for plantar warts or linear porokeratoses. PDT can be considered for inflammatory acne when topical treatments have failed and systemic medications are not an option. Pain associated with treatment and insurance coverage may be a barrier to use.     

Long‐term (6 and 12 months) follow‐up of two prospective,randomized, controlled phase III trials of photodynamic therapy with BF‐200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

Summary Background Two phase III trials of photodynamic therapy (PDT) with BF‐200 ALA, a recently approved nanoemulsion formulation of 5‐aminolaevulinic acid (ALA) demonstrated high clearance rates in mild‐to‐moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. Objectives To evaluate long‐term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF‐200 ALA, MAL or placebo. Methods The follow‐up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF‐200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Results Recurrence rates were similar for BF‐200 ALA and MAL, with a tendency to lower recurrence rates for BF‐200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF‐200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF‐200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF‐200 ALA. The slightly lower recurrence rates after BF‐200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.     

Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment

Background Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid‐face) and size of the lesion. Objectives Following reports that such difficult‐to‐treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL‐PDT. Methods An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL‐PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24‐month follow‐up is reported here. Ninety‐four patients with 123 lesions were enrolled and treated with MAL‐PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult‐to‐treat BCC according to the protocol. Results The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow‐up, rising to 85% at 12 months follow‐up, and 94% at 24 months follow‐up. Conclusions Topical MAL‐PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL‐PDT preserves the skin and shows favourable cosmetic results.     

Photodynamic therapy with 5‐aminolevulinic acid in actinic cheilitis: an 18‐month clinical and histological follow‐up

Background Actinic cheilitis (AC) may bear the initial and superficial changes of actinically induced squamous cell carcinoma (SCC) and may progress into fully developed SCCs. Early and effective treatment is important. Objective To assess the clinical and histological long‐term outcome in AC after two ALA‐PDT sessions. Methods Patients with histologically proven grade 1 and 2 AC received two ALA‐PDT sessions at 2 weeks interval. Subjects with complete clinical response at 3 months were evaluated further clinically and histologically at months 6, 12 and 18. Long‐term study outcome was defined as clinical and histological AC recurrence among patients with complete clinical response 3 months after treatment. Cosmetic outcome was assessed by the investigators at the final follow‐up visit at 18 months. Results Of the 40 patients enrolled, 38 completed the study. Complete clinical response at 3 months was achieved in 26 patients. At 6 months, clinical and histological recurrence occurred in three patients and at 12 months, one more patient showed clinical and histological recurrence. At 18 months, overall clinical recurrence rate was 15.38% (4/26), while overall histological recurrence rate was 34.61% (9/26). Cosmetic outcome was rated as excellent in more than 80% of evaluated cases. Conclusion PDT represents a moderately effective treatment modality in AC. Optimization of treatment procedure and protocols is still needed for higher response rates to be achieved. Moreover, the high treatment cost should be given consideration. Further long‐term follow‐up studies are needed for assessment of clinical and histological very late recurrences that could be expected after PDT.     

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.     

Photodynamic therapy with BF‐200 ALA for the treatment of actinic keratosis: results of a prospective,randomized, double‐blind,placebo‐controlled phase III study

Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) provides a therapeutic option for the treatment of actinic keratosis (AK). Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration. A new stable nanoemulsion‐based ALA formulation, BF‐200 ALA, is currently in clinical development for PDT of AK. Objectives To evaluate the efficacy and safety of PDT of AK with BF‐200 ALA. Methods The study was performed as a randomized, multicentre, double‐blind, placebo‐controlled, interindividual, two‐armed trial with BF‐200 ALA and placebo. A total of 122 patients with four to eight mild to moderate AK lesions on the face and/or the bald scalp were included in eight German study centres. The efficacy of BF‐200 ALA after one and two PDT treatments was evaluated. BF‐200 ALA was used in combination with two different light sources under illumination conditions defined by European competent authorities. Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (per‐protocol group: 64% vs. 11%; P < 0·0001) and lesion complete clearance rate (per‐protocol group: 81% vs. 22%) after the last PDT treatment. Statistically significant differences in the patient and lesion complete clearance rates and adverse effect profiles were observed for the two light sources, Aktilite^® CL128 and PhotoDyn^® 750, at both time points of assessment. The patient and lesion complete clearance rates after illumination with the Aktilite^® CL128 were 96% and 99%, respectively. Conclusions BF‐200 ALA is a very effective new formulation for the treatment of AK with PDT. Marked differences between the efficacies and adverse effects were observed for the different light sources used. Thus, PDT efficacy is dependent both on the drug and on the characteristics of the light source and the illumination conditions used.     

Is the step‐up therapy of topical 5‐aminolevulinic acid photodynamic therapy effective and safe for the patients with recalcitrant facial flat wart?

Facial flat wart, caused by human papilloma virus type 3 and less often, type 10, 27, and 41, often brings many cosmetic problems to children and young adults. Considering the disturbing cosmetic problem, the treatment of facial flat wart is always frustrating and often unsuccessful, although there are many treatment modalities. Considering the possible serious side effects of 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT), we designed step‐up therapy of ALA‐PDT on different clinical phases of facial flat wart. As a new protocol of ALA‐PDT, we found the step‐up therapy of ALA‐PDT could also receive excellent effects with the lower side effects. Meanwhile, the tolerance of patients to ALA‐PDT could improve with subsequent treatment sessions and escalating doses of ALA‐PDT.     

Treatment of superficial basal cell carcinoma with 7.8% 5‐aminolaevulinic acid nanoemulsion‐based gel (BF‐200 ALA) and photodynamic therapy: Results in clinical practice in a tertiary hospital

Photodynamic therapy (PDT) is an effective treatment option for the treatment of superficial basal cell carcinoma (sBCC). Recent publications have demonstrated that PDT with 7.8% 5‐aminolaevulinic acid nanoemulsion‐based gel (BF‐200 ALA‐PDT) is an effective and safe alternative for the treatment of sBCC). To investigate the efficacy and safety of 7.8% 5‐aminolaevulinic acid nanoemulsion‐based gel (BF‐200 ALA)‐PDT for the treatment of sBCC. A non‐controlled, open‐label single centre study was conducted. Patients received one PDT cycle with two PDT sessions one‐week apart. In case that clinical‐dermoscopy evaluation of treatment outcome revealed remaining lesions, a second PDT cycle was performed. The clinical results at the dermoscopy and fluorescence diagnosis level were histologically confirmed in all patients. Treatment response was evaluated 3, 6, and 12 months after last PDT session. A total of 31 patients (12 men and 19 women), with a median age of 63.74 years were included in this study. 3‐month after PDT‐session, 23/31 patients were complete responders (74.19%) after two BF‐200 ALA ‐PDT sessions. Esthetic outcome was considered good‐to‐excellent. 5 Aminolevulinic acid 7.8% nanoemulsion‐based gel (BF‐200 ALA) PDT is an effective therapy option for the treatment of sBCC. Complete clearance rates were higher in those patients who received only one PDT cycle. These results show a similar tendency as shown in other publications.     

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.     

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo

Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) or its methylester [methyl‐5‐aminolaevulinate (MAL) or 5‐amino‐4‐oxopentanoate] was recently ranked as first‐line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF‐200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. Objectives To evaluate the efficacy and safety of PDT of AKs with BF‐200 ALA in comparison with a registered MAL cream and with placebo. Methods The study was performed as a randomized, multicentre, observer‐blind, placebo‐controlled, interindividual trial with BF‐200 ALA, a registered MAL cream and placebo in a ratio of 3 : 3 : 1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P < 0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3 months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P < 0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment‐related adverse events were observed for the narrow‐ and broad‐spectrum light sources. Conclusions BF‐200 ALA is a very effective, well‐tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.