PpIX fluorescence combined with auto-fluorescence is more accurate than PpIX fluorescence alone in fluorescence detection of non-melanoma skin cancer: an intra-patient direct comparison study.

BACKGROUND: Previous research on fluorescence detection of non-melanoma had mixed results. An accurate non-invasive method for the detection of skin cancer is valuable to dermatologists because of the high incidence of skin cancer among the aging population. One notable difference between the methods of fluorescence detection previously studied was the use of the auto-fluorescence of the skin. Currently, there has not been a direct comparison between both methods of fluorescence detection. OBJECTIVE: To compare the accuracy of PpIX fluorescence and auto-fluorescence normalized PpIX fluorescence detection systems for the localization non-melanoma skin cancers (NMSC). METHODS: We conducted an observer blinded direct comparison of both methods. Thirty patients, 14 females and16 males, mean age 62 (SD = 9 years), skin type I to III and being suspected of having one or more NMSC, visited an independent treatment centre for dermatology. The patients were investigated using a fluorescence detection system capable of both normalized and non-normalized PpIX fluorescence measurements. Liposomal encapsulated 5-aminolevulinic acid was used as a photosensitizer. For each area being investigated, the associated normalized and non-normalized fluorescence measurements were directly compared. The results of the analysis were confirmed by clinical investigation using a dermatoscope. Both methods were evaluated based on the number of true and false positives and the number of true and false negatives. Specificity and sensitivity were calculated. Statistical significance of the findings was determined using Pearson's Chi-squared test. RESULTS: The non-normalized method was found to have a sensitivity of 27 % and a specificity of 39 % and the normalized method has a sensitivity of 97% and a specificity of 100%. This difference is statistically significant (p < 0.05). CONCLUSION: Using auto-fluorescence in PpIX fluorescence detection of NMSC is more accurate that PpIX fluorescence detection alone.

Cellular and molecular effects of pulsed dye laser and local narrow-band UVB therapy in psoriasis.

BACKGROUND AND OBJECTIVES: Pulsed dye laser (PDL) therapy is effective in clearing psoriasis plaques, but the mechanism of action is only partially understood. Local narrow-band ultraviolet B (NB-UVB), which has a better-defined mode of action, is an effective standard treatment for psoriasis. Our aim was to evaluate the cellular and molecular effects of PDL and to compare them with those of local NB-UVB in order to gain further insight into their mechanisms of action in psoriasis. STUDY DESIGN/PATIENTS AND METHODS: Nineteen patients with stable plaque-type psoriasis were treated either with PDL or NB-UVB. Lesional punch biopsies were obtained from all patients before treatment. Additional biopsies were obtained at 3 and 24 hours after PDL treatment in five of these patients. In 14 patients additional biopsies were taken after 7 and 13 weeks of treatment. Samples were histopathologically examined for the level of dermal T cell infiltrate, and the expression of epidermal beta-defensin 2, immune cell-derived tumor necrosis factor (TNF)-alpha, endothelial E-selectin, vascular endothelial growth factor receptor (VEGFR) 2 and 3, and the expression of interleukin (IL)-23 before and after treatment. RESULTS: The expression of VEGFR2, VEGFR3, and E-selectin was decreased in clinically high responders within 24 hours after PDL treatment. The expression of IL-23, TNF-alpha mRNA, and E-selectin protein were significantly reduced after two PDL treatments, whereas the expression of all epidermal markers and dermal T cell infiltrates had normalized after four treatments. The expression of epidermal activation markers and E-selectin were significantly reduced after 13 weeks of NB-UVB treatment. CONCLUSIONS: The expression of epidermal activation markers and the dermal T cell infiltrates were decreased after both treatments. The decreased expression of VEGFR2 and VEGFR3 followed by the down-regulation of TNF-alpha and IL-23p19 may be contributory factors in the efficacy of PDL in stable plaque-type psoriasis.

Skin fluorescence controlled photodynamic photorejuvenation (wrinkle reduction).

BACKGROUND: Identical skin fluorescence can be obtained after one hour spraying with 0.5% liposome-encapsulated 5-ALA and after 0.5 hour application of 20% 5-ALA in a cream base. In this study the clinical outcome and side effects using the 0.5% 5-ALA in Caucasian skin are investigated and compared to earlier reported non-ablative treatments for wrinkles and improvements of skin texture using 20% ALA photodynamic photorejuvenation. METHODS AND MATERIALS: 37 healthy Caucasian female patients participated in a randomized, prospective split face study. Two different intense pulsed light (IPL) treatment modalities were investigated; both employed a pre-treatment of approximately one hour of spraying with 0.5% liposome encapsulated 5-ALA. One modality combined type I photorejuvenation with wrinkle reduction (C-PDT) using a waveband from 530 to 750 nm and short pulse durations (7 J/cm(2), 2 x 2.5 ms, delay 10 ms). The other modality (PDT alone) emitted a band of wavelengths from 400 to 720 nm, three passes were performed (3.5 J/cm(2), 30 ms pulse duration). RESULTS: After a series of three C-PDT or PDT-alone treatments, the patients obtained statistically significant (P< 5 x 10-5) reductions in periorbital and perioral wrinkles. Using the Fitzpatrick wrinkle scale, periorbital wrinkles were reduced by 1.2 grades (SD: 1.1) and 1.1 (SD: 1.1), respectively and perioral wrinkles were reduced by 0.8 grades (SD: 1.0) and 0.7 (SD: 0.9) respectively. The difference in treatment efficacy between. C-PDT and PDT alone treated sides was not statistically significant (P = 0.224). CONCLUSION: The present study shows that statistically significant improvements in wrinkle reduction and skin texture, equivalent to previously reported results obtained with 20% ALA, can be obtained with 0.5% liposome encapsulated 5-ALA. Only minor and infrequent side effects were registered at the 0.5% 5-ALA treated areas. Skin fluorescence monitoring during pre-treatrnent with 5-ALA may improve clinical efficacy, reduce time consumption and increase safety of the treatment.

Fluorescence detection and diagnosis of non-melanoma skin cancer at an early stage.

BACKGROUND: The occurrence of non-melanoma skin cancer (NMSC), including actinic keratosis (AK) is increasing all over the world. The detection and diagnosis of NMSC is not optimal in clinical practice. Complementary methods for detection and accurate demarcation of NMSC at an early stage are needed in order to limit the damage caused by tumours. OBJECTIVE: The purpose of the present study was to use a large area skin fluorescence detection system to detect early NMSCs (clinical visible as well as non-visible lesions) in the face, neck, chest, back and hands of patients treated with UV and outdoor workers. METHODS: Fluorescence detection with a purpose-made digital camera and software (Dyaderm combined with 5-aminolevulinic acid (5-ALA) encapsulated in liposomes. RESULTS: In 93 consecutively referred patients positive skin fluorescence was detected in 61 patients. After histological examination the positive fluorescence appeared to be correlated to benign lesions in 28 patients (sebaceous gland hyperplasia in 22 patients) and to (pre-) malignant lesions in 33 patients (actinic keratosis in 29, BCC in 3 and SCC in 1 patient). False negative fluorescence was found in only one lesion. In five patients the FD technique used in this study appeared to be more sensitive for the identification of (pre-) malignant lesions than the clinical examination. This is in contrast with FD techniques used in previous studies. CONCLUSION: Diagnostic skin fluorescence using liposomal encapsulated 5-ALA and a specialised computerised detection and visualisation system offers the possibility for detection of NMSC at an early, pre-clinical stage. The technique is well suited to examine large areas of skin. It also identifies areas of most interest for performing confirmatory skin biopsies, as well as pre-operative assessment of boundaries of skin malignancies, and finally, the technique is applicable in the control and follow-up of skin cancer treatment.

A comparative study on the efficacy of treatment with 585 nm pulsed dye laser and ultraviolet B-TL01 in plaque type psoriasis.

BACKGROUND: Narrow-band ultraviolet-B and pulsed dye laser (PDL) affect psoriasis but via different pathways. OBJECTIVE: To compare the results of PDL with ultraviolet-B light therapy (UVB) and to look for synergism of both therapies in patients with plaque type psoriasis. METHODS: In each eligible individual, four similar target plaques were selected, and halves of these plaques were treated using PDL, UVB, or a combination of PDL and UVB or were not treated. Results were recorded single-blind using the Physician's Global Assessment score at study enrolment and Week 13. Nonparametric, paired statistical tests were used to test for differences within and between therapies.The results were also analyzed after dichotomization of the changes in the Physician's Global Assessment score into responsive and nonresponsive to treatment. RESULTS: A significant improvement of the psoriasis lesions was noted at Week 13 (P<.001) with each therapy. No significant differences were noted between the therapies. Synergism of PDL and UVB was not observed. CONCLUSIONS: PDL is safe for treating plaque type psoriasis, but its efficacy is limited to a subgroup of patients. Combining PDL with UVB has no additional benefit.

Concomitant treatment of psoriasis of the hands and feet with pulsed dye laser and topical calcipotriol, salicylic acid, or both: a prospective open study in 41 patients.

BACKGROUND: Psoriasis of the hands and feet is a chronic disease which is often resistant to the usual topical therapies. It has considerable morbidity and seriously affects the quality of life of patients. OBJECTIVE: We sought to prospectively evaluate the efficacy and safety of pulsed dye laser (PDL) treatment of psoriasis of the hands and feet. METHODS: In all, 41 patients with therapy-resistant psoriasis of the hands and feet were treated once every 4 to 6 weeks with PDL at 585-nm wavelength, 450-microsecond pulse duration, 7-mm spot diameter, and 5- to 6.5-J/cm2 fluence. Calcipotriol ointment and salicylic acid 5% to 10% ointment were used as keratolytic agents. Treatment efficacy was evaluated by blinded comparison of photographs of the lesions taken before and after PDL treatment in each patient. RESULTS: A good to very good improvement in the lesions was observed in 76% of the patients after treatment. An average duration of remission was 11 months. Side effects were transient purpura, moderate discomfort during the treatment, transient hyperpigmentation or hypopigmentation, and incidental transient crustae. LIMITATIONS: This was an open prospective study with a limited number of patients who were concomitantly treated with calcipotriol and salicylic acid ointment. Patients with photointolerance, on medication with phototoxic or photoallergic drugs, and with widespread psoriasis were excluded. CONCLUSIONS: Concomitant treatment with PDL and topical calcipotriol, salicylic acid, or both was a satisfactory modality for treating psoriasis of the hands and feet. There was a subjective improvement in the symptoms and quality of life in all patients.

A case study to evaluate the treatment of vitiligo with khellin encapsulated in L-phenylalanin stabilized phosphatidylcholine liposomes in combination with ultraviolet light therapy.

Vitiligo destroys the melanocytes in the epidermis; the inactive melanocytes in the outer root sheaths are not affected. Phosphatidylcholine liposomes are able to target molecules contained in them into the hair follicles. Khellin is activated by UVA and previous studies have shown that a combination of khellin and UVA (KUVA) can be effective in the treatment of vitiligo. The aim of this study was to determine in an open trial the efficacy and safety of treatment with khellin encapsulated in L-phenylalanine stabilized phosphatidylcholine liposomes in combination with UVA/UVB light therapy(KPLUV) in 74 subjects with vitiligo. After a mean treatment period of 12 months (range 10-14 months) 72% of the treated locations had a repigmentation response of 50% to 100%. Repigmentation of 75-100% was achieved on the face in 63%, the back in 59%, the arms in 58%, the trunk in 57%, the legs in 56% and on the hands in 4% of the patients. Side effects were not seen with KPLUV. The patients in the control group, only treated with UVA/B-light, hardly showed any repigmentation. This indicates that the exposure of the skin to UV light alone is not responsible for the results of KPLUV.