Skin ageing Kohl, E.; Steinbauer, J.; Landthaler, M. ...
Journal of the European Academy of Dermatology and Venereology,
08/2011, Letnik:
25, Številka:
8
Journal Article
Recenzirano
Similar to the entire organism, skin is subject to an unpreventable intrinsic ageing process. Additionally, skin ageing is also influenced by exogenous factors. Ultraviolet radiation in particular ...results in premature skin ageing, also referred to as extrinsic skin ageing or photoageing, which is the main cause of the changes associated with the ageing process in sun‐exposed areas. Despite their morphological and pathophysiological differences, intrinsic and extrinsic ageing share several molecular similarities. The formation of reactive oxygen species and the induction of matrix metalloproteinases reflect the central aspects of skin ageing. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for the further degradation of the extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin ageing and the detection of its mechanisms have furthered the development of various therapeutic and preventive strategies.
Topical photodynamic therapy (PDT) is a widely used non‐invasive treatment for certain non‐melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High ...efficacy is demonstrated for PDT using standardized protocols in non‐hyperkeratotic actinic keratoses, Bowen’s disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain‐minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.
Summary
Background
Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair‐skinned individuals. The World Health Organization ...distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC.
Objectives
To demonstrate noninferiority of BF‐200 ALA (a nanoemulsion gel containing 5‐aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF‐200 ALA was no worse than that for MAL, within a statistical margin of Δ = −15%.
Methods
The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5‐year follow‐up. Of 281 randomized patients, 138 were treated with BF‐200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm−2). The results shown include clinical end points and patients’ reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013‐003241‐42).
Results
Of the BF‐200 ALA‐treated patients, 93·4% were complete responders compared with 91·8% in the MAL group. The difference of means was 1·6, with a one‐sided 97·5% confidence interval of −6·5, establishing noninferiority (P < 0·0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%.
Conclusions
Treatment of nonaggressive BCC with BF‐200 ALA‐PDT is highly effective and well tolerated with proven noninferiority to MAL‐PDT. It demonstrates low recurrence rates after 1 year of follow‐up.
What's already known about this topic?
Photodynamic therapy (PDT) using BF‐200 aminolaevulinic acid (ALA) gel is registered and highly effective in the treatment of mild‐to‐moderate actinic keratosis and field cancerization.
BF‐200 ALA gel was recently approved for the treatment of superficial and/or nodular basal cell carcinoma (BCC) unsuitable for surgical treatment.
PDT using methyl aminolaevulinate (MAL) cream is approved for the treatment of thin or nonhyperkeratotic and nonpigmented actinic keratoses, Bowen disease, and superficial and nodular BCCs when other therapies are considered less appropriate.
What does this study add?
BF‐200 ALA‐PDT is confirmed to be significantly noninferior to MAL‐PDT for the treatment of nonaggressive BCC.
Treatment‐emergent adverse events were comparable between the two patient groups, with similar or slightly lower recurrence rates for BF‐200 ALA gel compared with MAL cream after 12 months.
Plain language summary available online
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Oxygen in acute and chronic wound healing Schreml, S.; Szeimies, R.M.; Prantl, L. ...
British journal of dermatology (1951),
August 2010, Letnik:
163, Številka:
2
Journal Article
Recenzirano
Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even ...though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.
In addition to established indications in non‐melanoma skin cancer in immunocompetent patients, photodynamic therapy (PDT) has been studied for the treatment, and possible prevention, of superficial ...skin cancers in immunosuppressed patients. As a topical photosensitizer can be applied over large areas, PDT is also increasingly used for field cancerization in photodamaged skin, with evidence of potential to delay the development of actinic keratoses and basal cell carcinoma, although direct evidence of prevention of invasive squamous cell carcinoma remains limited. PDT has been studied in patch/plaque‐stage cutaneous T‐cell lymphoma, with efficacy more likely in unilesional disease. Accumulating evidence supports the use of PDT in acne and several other inflammatory/infective dermatoses including cutaneous leishmaniasis, although protocols are still to be refined. Despite proven efficacy, PDT is not widely used in viral/genital warts, where pain during treatment can be intense. PDT is a therapeutic option for photorejuvenation, with improvement in fine wrinkles, mottled hyperpigmentation, roughness and sallowness reported.
Summary
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.
See also the Commentary by Hauschild
Summary
Background
Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun‐damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective ...therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial.
Objectives
To evaluate the efficacy, safety and cosmetic outcome of BF‐200 ALA (a nanoemulsion formulation containing 10% aminolaevulinic acid hydrochloride) combined with the BF‐RhodoLED® lamp for the field‐directed treatment of mild‐to‐moderate AK with PDT.
Methods
The study was performed as a randomized, multicentre, double‐blind, placebo‐controlled, parallel‐group, phase III trial with BF‐200 ALA and placebo in seven centres in Germany. A total of 94 patients were enrolled in this study; 87 were randomized (55 patients received BF‐200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF‐RhodoLED (635 nm ± 9 nm) until a total light dose of 37 J cm−2 was achieved.
Results
BF‐200 ALA was superior to placebo with respect to patient complete clearance rate (91% vs. 22%, P < 0·0001) and lesion complete clearance rate (94·3% vs. 32·9%, P < 0·0001) after a maximum of two PDTs. The confirmatory analysis of all key secondary variables supported this superiority” should not be skipped since this is an important result. Treatment‐emergent adverse events (TEAEs) were experienced by 100% of the BF‐200 ALA group and 69% of the placebo group. The most commonly reported TEAEs were TEAEs of the application site. The cosmetic outcome was improved in the BF‐200 ALA group compared with placebo.
Conclusions
Field‐directed therapy with BF‐200 ALA and BF‐RhodoLED lamp is highly effective and well tolerated for multiple mild‐to‐moderate AK lesions, providing greatly improved skin quality.
What's already known about this topic?
BF‐200 ALA is an exceptionally effective, well‐tolerated drug for photodynamic therapy (PDT) of actinic keratosis (AK).
AK affects extended skin areas and requires field‐directed treatment.
PDT with BF‐200 ALA is most effective with narrowband light‐emitting diode lamps.
What does this study add?
This study evaluates the safety and efficacy of BF‐200 ALA when used together with the BF‐RhodoLED lamp for the field‐directed treatment of AK.
This trial demonstrates a strong rejuvenation effect of PDT with BF‐200 ALA on an entire treatment field.
Our results show that field‐directed therapy with BF‐200 ALA and BF‐RhodoLED lamp is highly effective and well tolerated for multiple mild‐to‐moderate AK lesions.
Linked Comment: Gilaberte. Br J Dermatol 2016; 175:668–669.
Plain language summary available online
Summary
Background Methyl aminolaevulinate–photodynamic therapy (MAL‐PDT) is an effective treatment in facial/scalp actinic keratosis (AK).
Objectives The aims of this study were to compare ...efficacy, safety, cosmetic outcome and patient preference of MAL‐PDT vs. cryotherapy in patients with AK at other locations.
Methods A multicentre, controlled, randomized, open, intraindividual, right–left comparison was performed. Patients with nonhyperkeratotic AK were treated once with MAL‐PDT and cryotherapy on either side of the body. At week 12, lesions showing noncomplete response were retreated. The primary efficacy variable was the lesion response at week 24. Investigator’s assessment of cosmetic outcome, patient’s preference in terms of cosmetic outcome and a patient preference questionnaire were also analysed at week 24.
Results In total, of 121 patients with 1343 lesions (98% located on the extremities and the remainder on the trunk and neck) were included. Both treatments provided a high mean percentage reduction in lesion count at week 24 with significantly higher efficacy for cryotherapy: 78% for MAL‐PDT and 88% for cryotherapy (P = 0·002, per protocol population). Investigator’s assessment of cosmetic outcome was significantly better for MAL‐PDT than cryotherapy (P < 0·001), 79% of lesions having an excellent cosmetic outcome with MAL‐PDT vs. 56% with cryotherapy at week 24. The cosmetic outcome achieved by MAL‐PDT compared with cryotherapy was also preferred by patients (50% vs. 22%, respectively, P < 0·001), and 59% of patients would prefer to have any new lesions treated with MAL‐PDT compared with 25% with cryotherapy (P < 0·001). Both treatment regimens were safe and well tolerated.
Conclusions MAL‐PDT showed inferior efficacy for treatment of non‐face/scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL‐PDT conveyed the advantages of better cosmesis and higher patient preference.
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