Modeling pulsed dye laser treatment of psoriatic plaques by combining numerical methods and image-derived lesion morphologies.

OBJECTIVES: Knowledge of the physical effects of pulsed dye laser (PDL) treatment of psoriatic lesions is essential in unraveling the remedial mechanisms of this treatment and hence also in maximizing in its disease-modifying potential. Therefore, the main objective of this study was to provide estimates of these physical effects (for laser wavelengths of 585 and 595 nm), with the aim of identifying pathogenic processes that may be affected by these conditions. METHODS: We modeled the laser light propagation and subsequent photothermal heating by numerically solving the transient diffusion and heat equations simultaneously. To this end, we used the finite element method in conjunction with an image-derived psoriatic lesion morphology (which was defined by segmenting blood vessels from a confocal microscopy image of a fluorescently labeled section of a 3 mm punch biopsy of a psoriatic lesion). The resulting predictions of the generated temperature field within the lesion were then used to assess the possibility of stalling or arresting some suspected pathogenic processes. RESULTS: According to our results, it is conceivable that perivascular nerves are thermally denatured, as almost all locations that reach 60°C were found to be within 18 µm (at 585 nm) and 11 µm (at 595 nm) of a blood vessel wall. Furthermore, activation of TRPV1 and TRPV2 channels in perivascular neuronal and immune cells is highly likely, since a critical temperature of 43°C is generated at locations within up to 350 µm of a vessel wall (at both wavelengths) and sustained for up to 700 ms (at 585 nm) and 40 ms (at 595 nm), while a critical temperature of 52°C is reached by locations within 80 µm (at 585 nm) and 30 µm (at 595 nm) of a vessel wall and sustained for up to 100 ms (at 585 nm) and 30 ms (at 595 nm). Finally, we found that the blood vessel coagulation-inducing temperature of 70°C is sustained in the vascular epithelium for up to 19 and 5 ms at 585 and 595 nm, respectively, rendering partial or total loss of vascular functionality a distinct possibility. CONCLUSIONS: The presented approach constitutes a useful tool to provide realistic estimates of the photothermal effects of PDL treatment of psoriatic plaques (as well as other selective photothermolysis-based treatments), yielding information that is essential in guiding future experimental studies toward unraveling the remedial mechanisms of these treatments.

Effects of pulsed dye laser treatment in psoriasis: A nerve-wrecking process?

Pulsed dye laser (PDL) therapy can be effective in treating psoriasis, with a long duration of remission. Although PDL therapy, albeit on a modest scale, is being used for decades now, the underlying mechanisms responsible for the long-term remission of psoriasis remain poorly understood. The selective and rapid absorption of energy by the blood causes heating of the vascular wall and surrounding structures, like perivascular nerves. Several studies indicate the importance of nerves in psoriatic inflammation. Interestingly, denervation leads to a spontaneous remission of the psoriatic lesion. Among all dermal nerves, the perivascular nerves are the most likely to be affected during PDL treatment, possibly impairing the neuro-inflammatory processes that promote T-cell activation, expression of adhesion molecules, leukocyte infiltration and cytokine production. Repeated PDL therapy could cause a prolonged loss of innervation through nerve damage, or result in a 'reset' of neurogenic inflammation after temporary denervation. The current hypothesis provides strong arguments that PDL treatment affects nerve fibres in the skin and thereby abrogates the persistent and exaggerated inflammatory process underlying psoriasis, causing a long-term remission of psoriasis.

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.

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 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.