Photodynamic therapy with green light for the treatment of vulvar lichen sclerosus - Preliminary results.

INTRODUCTION: The standard treatment for lichen sclerosus (LS) is symptomatic and is primarily based on the chronic use of corticosteroids, sometimes resulting in unsatisfactory effects. Therefore, other non-pharmacological methods are being sought, which are less aggravating for the patient. LS can be treated topically by using photodynamic therapy (PDT) based on 5-aminolevulinic acid (5-ALA). Unfortunately, therapy with the red light is often connected with severe local pain during the illumination. Green light can also be characterised by its ability to turn on photodynamic reactions in cells. MATERIALS AND METHODS: The aim of this study was an evaluation into the efficacy and tolerance of 5-ALA-PDT with a green light (540nm±15nm) in 11 patients with chronic LS that were characterised by severe itching. The disease lasted from 1.5 to 4 years. All the patients were treated with three sessions of PDT. RESULTS: Following treatment with PDT, a significant improvement of local status, as well as a reduction of the main symptom (pruritus), were observed. No patient complained of severe pain during the sessions that would have required an interruption of irradiation or local application of analgesics. CONCLUSIONS: Our preliminary results of using green light in PDT for superficial skin non-oncological lesions are very promising but require further studies.

Photodynamic therapy of vulvar lichen sclerosus et atrophicus in a woman with hypothyreosis--case report.

Lichen sclerosus et atrophicus (LSA) is disease of skin and mucosa, its pathogenesis remains unknown. Itching, pain and burning sensations and atrophy of vulva impair quality of life. Treatment is symptomatic. We report case of 30-year old woman with lesions in vulva in which series of topical PDT were carried out. We applied Levulan®Kerastick® for 4h and after that lesions were illuminated with red light. Along with above treatment patient started receiving Euthyrox®, because of recently diagnosed hypothyreosis. Significant relief from subjective symptoms was achieved and lesions in vulvar region disappeared. Combination of topical PDT with hormonal therapy allowed controlling course of disease and minimizing symptoms, and thus improved quality of life.

Distribution of the CTLA-4 single nucleotide polymorphisms CT60G>A and +49A>G in psoriasis vulgaris patients and control individuals from a Polish Caucasian population.

Psoriasis vulgaris is a multifactorial disease with an autoimmune component, and T lymphocytes seem to be involved in its aetiology. CTLA-4 molecule is an important down-regulator of T-lymphocyte activation, and several polymorphisms of the CTLA-4 gene were found to be associated with some autoimmune diseases. We examined whether single nucleotide polymorphisms (SNPs) in the CTLA-4 gene, CT60A>G and +49A>G, are associated with psoriasis vulgaris. Alleles of these two SNPs were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Both the CT60G>A and the +49A>G alleles and genotypes were distributed similarly in patients and controls. Although the two SNPs studied here in Poles were in linkage disequilibrium, all four possible two-locus haplotypes were found, one of them rare; of the remaining three, the haplotype +49G, CT60G was significantly (P = 0.019, OR = 0.58, 95%CI = 0.37-0.91) less frequent in the patient group with disease onset between the ages of 21 and 40 years than in controls and the other patient groups, whereas the frequencies of the other haplotypes were similar in patients and controls. To the authors' knowledge, this is the first study on CTLA-4 CT60 allele frequencies in psoriasis.

CTLA-4 gene polymorphisms and natural soluble CTLA-4 protein in psoriasis vulgaris.

CTLA-4 molecule is an important inhibitor of T-lymphocyte activation. Several single nucleotide polymorphisms (SNPs) in the CTLA-4 gene were found, and their associations with many human diseases were described. So far, however, such studies have not been performed in psoriasis vulgaris in Caucasoids. Therefore, we examined the distribution of three CTLA-4 SNPs: -1147C/T, -318C/T and +49 A/G in 116 patients with psoriasis vulgaris and 123 healthy blood donors using the polymerase chain reaction-restriction fragment length polymorphism method. For all three SNPs, the frequencies of alleles, genotypes and three-point haplotypes were very similar in patients and controls, suggesting no contribution of these genetic variants to psoriasis.

Inflammation in stasis dermatitis upregulates MMP-1, MMP-2 and MMP-13 expression.

Stasis dermatitis is a common disorder, which is a consequence of impaired venous drainage of the legs. It is characterized histologically by proliferation of small blood vessels in the papillary dermis. This neovascularization may lead occasionally to the formation of discrete papules due to inflammatory processes. In order to evaluate the role of matrix metalloproteinases (MMPs) in the acute phase of chronic venous insufficiency, we examined the production of MMP-1, -2, -13 and tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in lesional skin of stasis dermatitis. A total of 19 patients affected by stasis dermatitis were included in this experimental study. Polymerase chain reaction, western blot and immunohistochemical studies on tissue specimen were performed. In lesional skin of stasis dermatitis, there was elevated gene expression and immunoreactivity for MMP-1, -2 and -13 in comparison to healthy controls. In contrast, genexpression and immunoreactivity for TIMP-1 and -2 were diminished in stasis dermatitis in comparison with healthy controls. Overexpression and production of MMP-1, -2 and -13 without inhibitory effects could be the result of cytokine mediated induction. Matrix metalloproteinases (MMPs) may play an important role in the remodeling of lesional skin in stasis dermatitis.

Increased interleukin-7 levels in the sera of psoriatic patients: lack of correlations with interleukin-6 levels and disease intensity.

Interleukin (IL)-7 is a multifunctional cytokine which is involved in the regulation of keratinocyte-T lymphocyte interactions; the latter is an important factor in the pathogenesis of psoriasis. In vitro, IL-7 is able to induce release of cytokines, including IL-6; IL-6 expression is known to be enhanced in psoriatic patients. Serum levels of IL-7 and IL-6 were measured by ELISA in 40 psoriatic patients and compared with cytokine levels in 18 healthy individuals. Serum levels of IL-7 were also evaluated in 24 psoriatic patients during the remission of the disease after effective treatment. The IL-7 and IL-6 serum levels were significantly higher in psoriatic patients than in healthy subjects and the IL-7 serum levels did not significantly decrease after treatment. Serum levels of IL-7 did not correlate with PASI scores; however, a significant positive relationship was observed between IL-6 levels and PASI scores. There was no correlation between increased levels of IL-7 and IL-6 in the sera of psoriatic patients, suggesting the lack of a direct link between these two cytokines in the psoriatic process. In conclusion, increased IL-7 serum levels suggest that IL-7, like IL-6, may be involved in the pathogenesis of psoriasis, but in contrast with IL-6, serum IL-7 levels could not be used as a marker of disease activity in psoriatic patients.

Soluble E-selectin serum levels correlate with disease activity in psoriatic patients.

E-selectin is an adhesion molecule expressed on vascular endothelial cells in several inflammatory skin diseases, including psoriasis. It is responsible for the adherence between microvascular endothelium and neutrophils, monocytes, eosinophils and subsets of T cells. Soluble E-selectin (sE-selectin) serum levels were measured by ELISA in 32 psoriatic patients before treatment and compared with both post-treatment sE-selectin levels in 16 patients and sE-selectin values in 10 healthy individuals. Soluble E-selectin serum levels were significantly increased in psoriatic patients compared with healthy persons. Moreover, a significant correlation was demonstrated between sE-selectin values and PASI scores. No relationship was found between sE-selectin levels and duration of psoriasis. Soluble E-selectin serum levels decreased significantly after treatment of psoriasis. This phenomenon was more evident in patients with more severe psoriasis. In conclusion, sE-selectin serum levels correlate with the extent of psoriatic lesions and could be used as marker of the disease activity in psoriatic patients.

Lipodermatosclerosis and the significance of proteolytic remodeling in the pathogenesis of venous ulceration (Review).

The preceding stage of venous ulceration represents a scleroderma-like hardening of the skin called lipodermatosclerosis. Clinical stages such as lipodermatosclerosis and venous ulceration, which succeed one another are highly associated to chronic venous insufficiency. Lipodermatosclerosis is characterized by fibrous scar tissue of the reticular dermis built up of collagen bundles and loss of cellular components, whereas venous ulceration is characterized by total loss of epidermis and partially of matrix structures in the upper dermis. There is a growing recognition that an excessive proteolytic activity by proteases, in particular that of matrix metalloproteinases and fibrinolytic factors of the plasminogen activation system may be a key feature in the pathophysiological understanding of venous leg ulcer formation. Lipodermatosclerosis displays an intense ongoing proteolytic process by elevated matrix metalloproteinase activity, as recently shown on different molecular and biological levels. Elevated expression on mRNA and protein level of matrix metalloproteinases and fibrinolytic factors of the plasminogen activation system have been detected in liposclerotic skin lesions. In addition, matrix metalloproteinases were proteolytically activated confirmed by zymography experiments and collagen degradation assays. Therefore it is well conceivable, that proteolytic enzymes of matrix metalloproteinases could initiate an elevated turnover of the extracellular matrix with subsequent breakdown of the matrix scaffold finally resulting in venous ulceration.