Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is increasingly employed for skin cancer, yet ALA dosing is crude. Using iontophoresis, we developed a rapid and quantifiable system for topical ALA delivery, with measurement of subsequent PpIX fluorescence and phototoxicity. ALA was iontophoresed from a 2% solution into upper inner arm skin of 13 healthy volunteers. Six doses of ALA were delivered with a series of charges varying from 3-120 milliCoulombs (mC); four additional doses were given with a charge of 60 mC. Five hours post-iontophoresis, sites were irradiated with broad-band yellow-red light, the series of six ALA doses receiving 100 J/cm2, while the four identical doses received 6.25, 12.5, 25, and 50 J/cm2, respectively. Resultant erythema was measured by reflectance spectroscopy. The time course of PpIX fluorescence was ALA-dose-dependent. With charge < or = 24 mC, PpIX fluorescence peaked at 3 h and returned to zero at 9-10 h, whereas charges > 24 mC had a sustained peak at 5-10 h, falling to zero by 24 h. Pre-irradiation, PpIX fluorescence correlated with ALA dose (r = 1.0). PpIX fluorescence fell immediately post-irradiation (p < 0.0001); recovery levels at 3 h correlated with ALA dose (p < 0.0001). Delayed erythema correlated with ALA dose and irradiation dose (p < 0.0001, p < 0.01, respectively). Both PpIX fluorescence intensity pre-irradiation and fall in PpIX fluorescence post-irradiation correlated with erythema (r = 0.98). Hence, PpIX synthesis is ALA-dose-dependent, and phototoxicity can be predicted from ALA dose, irradiation dose, and photobleaching of PpIX. This reproducible system allows accurate dosimetry in topical PDT and facilitates study of ALA metabolism.

This review supports PDT as an efficacious treatment for acne and a good adjunctive treatment for mild to severe acne, especially in patients who have not responded to topical therapy and oral antibacterials, and are not great candidates for isotretinoin. Further studies are warranted to evaluate the optimal photosensitizers, light sources, incubation times, and number of treatments for PDT use in acne.

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Actinic keratoses (AKs) are atypical, precancerous proliferations of keratinocytes that develop because of chronic exposure to ultraviolet (UV) radiation. Treatment of AK can be lesion-directed or field-directed. Field cancerization theory postulates that the skin surrounding AK is also at increased risk for possible malignant transformation since it has been exposed to the same chronic UV light. Field-directed therapies thus have the potential to address subclinical damage, reduce AK recurrence rates, and potentially reduce the risk of squamous cell carcinoma (SCC) development. Published clinical studies have found lesion clearance rates ranging from 81 to 91% for photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL). Clinical studies have also been published on various topical treatments. Complete clinical clearance (CCC) was significantly higher in patients treated with a combination of 5-fluorouracil and salicylic acid (5-FU-SA) than in the vehicle group across multiple studies, and CCC ranged between 46 and 48% following treatment with imiquimod. Additionally, treatment with diclofenac sodium (DFS) found reduction in lesion sizes to range from 67 to 75%. Reported results have been similar for another non-steroidal anti-inflammatory drug (NSAID), piroxicam, which has more cyclooxygenase (COX)-1 activity than DFS. Active treatments with ingenol mebutate were also significantly more effective than vehicle at clearing AK lesions. All treatments resulted in mild, localized skin reactions. PDT using conventional light sources was associated with increased severity of pain and/or discomfort, while PDT using daylight as the light source was associated with less pain and occasionally no pain at all. Though no widely accepted algorithm for the treatment of AKs exists, field-directed therapy can be particularly useful for treating photo-exposed areas containing multiple AKs. Additional research with more direct comparisons between these field-directed therapies will help clinicians determine the best therapeutic approach. Here, we provide a balanced and comprehensive narrative review of the literature, considering both light-based and topical therapies with a focus on their field-therapy aspects, and propose a therapeutic algorithm for selecting an appropriate treatment in the clinical setting.

Three subjects were excluded because they were irradiated for skin cancer (2 non-users, 1 user).

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Melanoma is the deadliest form of skin cancer and remains a diagnostic challenge in the dermatology clinic. Several non-invasive imaging techniques have been developed to identify melanoma. The signal source in each of these modalities is based on the alteration of physical characteristics of the tissue from healthy/benign to melanoma. However, as these characteristics are not always sufficiently specific, the current imaging techniques are not adequate for use in the clinical setting. A more robust way of melanoma diagnosis is to “stain” or selectively target the suspect tissue with a melanoma biomarker attached to a contrast enhancer of one imaging modality. Here, we categorize and review known melanoma diagnostic biomarkers with the goal of guiding skin imaging experts to design an appropriate diagnostic tool for differentiating between melanoma and benign lesions with a high specificity and sensitivity.

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