A Trial of Short Incubation, Broad-Area Photodynamic Therapy for Facial Actinic Keratoses and Diffuse Photodamage

Touma, Dany J.; Yaar, Mina; Whitehead, Sara J.; Konnikov, Nellie; Gilchrest, Barbara A.

doi:10.1001/archderm.140.1.33

Cited by 229 publications

(156 citation statements)

References 45 publications

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“…The inflammatory response associated with PDT is often accompanied by the dermal formation of collagen which leads to an improved skin appearance in the treated area. This has been reported by several authors and becomes especially evident when performing field-directed PDT [82][83][84][85]. In the recent pivotal study evaluating BF-200 ALA in field-directed PDT, the cosmetic outcome was diligently studied and reported on a Phase III level [80].…”

Section: Cosmetic Outcomementioning

confidence: 85%

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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BF-200 ALA is a combination of a nanoscale-lipid vesicle formulation and the prodrug 5-aminolevulinic acid (5-ALA). The nanoemulsion stabilizes the prodrug and enhances its penetration through the stratum corneum. It has shown excellent therapeutic results in both lesion and field-directed photodynamic therapy of actinic keratosis (AK). AK is an early form of epidermal neoplasia and a precursor of invasive cutaneous squamous cell carcinoma. It is characterized by the combination of visible neoplastic lesions and surrounding tissue also harboring tumorigenic UV-induced mutations: a concept called field cancerization. A selective, field-directed treatment is ideal to meet the requirements of field change. Here, we review the clinical data on BF-200 ALA for AK along with a summary of molecular mechanisms and future perspectives. Actinic keratosis (AK), also known as solar keratosis, is caused by chronic exposure to sunlight or other ultraviolet light sources [1,2] and may progress to invasive squamous cell carcinoma (SCC) [3]. It is the most common lesion with malignant potential to arise on the skin. AK is mostly seen in Caucasians in skin areas that have extensive sun exposure throughout their lives [4]. Epidemiological data show a high occurrence rate of AK. Regions with higher ultraviolet exposure have a higher prevalence of AK. For the USA, the prevalence was estimated to range from 11 to 26%, while in Australia it ranged from 40 to 60%. In Europe, a prevalence of 15% in men and 6% in women has been documented [5]. Over the age of 70 years, 34% of men and 18% of women were found to have actinic keratotic lesions [6]. Next to fair skin type, an advanced age and lifelong sun exposure immunosuppression/-deficiency plays another important risk factor [5].Mostly, AK develops slowly and early in the disease process, they may disappear only to reappear later. Recurrence of the disease may include partial elimination of the initial lesion, subclinical lesion progression to visible status, or development of new lesions [7]. On top of this, an AK may progress to invasive SCC, the second-most common form of skin cancer [8,9]. The actual percentage of progress to invasive SCC remains unknown, and estimates vary from 5 to 20% within 10 to 25 years with reported annual transformation rates varying greatly from as low as 0.25% to as high as 16% [10]. The regression rate for a single untreated lesion is 15 to 63% after a year; recurrence rates range from 15 to 53% [11]. In general patients develop multiple AKs in one area and predicting which course each individual lesion will follow is impossible. Nonetheless, AK lesions are reliable markers for patients who are most predisposed to developing invasive SCC [4,[12][13].AK lesions typically appear in areas most frequently exposed to the sun such as the face, back of the hands, or bald scalp; 75% of lesions are found on the head, neck and forearms [14]. The lesions vary in appearance as well as size and can include erythematous scaly macules, rough pigmented patches and hyperker...

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Section: Cosmetic Outcomementioning

confidence: 85%

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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“…Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a photosensitizing agent, using a variety of lasers and light sources, ultraviolet enhances the treatment of photodamaged skin and associated AK. 2,3 However, the histologic changes that occur after ALA-PDT have not been fully assessed.…”

Section: Introductionmentioning

confidence: 99%

Photorejuvenation induced by 5-aminolevulinic acid photodynamic therapy in patients with actinic keratosis: A histologic analysis

Park

Sohn

Lee

et al. 2010

Journal of the American Academy of Dermatology

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Background: Repeated exposure to ultraviolet radiation from the sun results in premature photoaging. Photodynamic therapy (PDT) has been shown to be effective for treatment of photoaging, although the data from most studies have been based on clinical observation.Objectives: We investigated whether 5-aminolevulinic acid (ALA)-PDT induced histologic changes suggesting photorejuvenation.Methods: Fourteen patients with one to three actinic keratoses on the face were treated twice with ALA-PDT by using a 1200 W metal halogen lamp at 1-month intervals. Skin biopsy before and 1 month after the PDT was performed. Twenty-five pairs of specimens were obtained. We examined the specimens with routine and immunohistochemical staining and evaluated the parameters associated with photoaging by using image analysis.Results: After ALA-PDT, the mean epidermal thickness and dermal inflammatory infiltrate were reduced. The total collagen volume in the dermis significantly increased with expression of type I and III procollagen. The level of transforming growth factor b and transforming growth factor b type II receptors in the epidermis also increased. The elastotic material with co-localizing fibrillin-1 and tropoelastin expression in the dermis decreased after treatment. The expression of matrix metalloproteinases-1, -3, and -12 also decreased.Limitations: The study was limited by the small sample size.Conclusions: ALA-PDT resulted in histological changes indicating restoration of photoaged skin. These data suggest that ALA-PDT could be effective for photorejuvenation. ( J Am Acad Dermatol 2010;62:85-95.)

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“…However, because patients must make two office visits ͑on the first day for drug application, and on the second day for light exposure͒, this regimen was inconvenient. When Touma et al 5 demonstrated in 2004 that shorter ALA incubation times ͑1, 2, or 3 h͒ were effective for treatment of AK, clinicians began experimenting informally with reduced contact times in their practices. Many now routinely employ a 2-h drug-light interval, and therapeutic efficacy has been reported with even shorter contact times, for example after 30, 45, or 60 min ͑Refs.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

et al. 2010

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Abstract. Topical 5-aminolevulinic acid ͑ALA͒ is widely used in photodynamic therapy ͑PDT͒ of actinic keratoses ͑AK͒, a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX ͑PpIX͒ accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements ͑5 replicates͒ were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin. © 2010 Society of Photo-Optical Instrumentation Engineers.

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A Trial of Short Incubation, Broad-Area Photodynamic Therapy for Facial Actinic Keratoses and Diffuse Photodamage

Cited by 229 publications

References 45 publications

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Photorejuvenation induced by 5-aminolevulinic acid photodynamic therapy in patients with actinic keratosis: A histologic analysis

Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

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