One week's holiday sun exposure induces expression of photoaging biomarkers.

INTRODUCTION: Skin aging is accompanied by the upregulation of the expression of various matrix metalloproteinases (MMPs). It was shown that exposure to ultraviolet radiation (UVR) may induce skin expression of MMPs and dysregulation of the transforming growth factor beta (TGF-ß)/Smad pathway. The aim of our study was to compare the effects of short holiday UVR exposure and lifetime UVR exposure, on the expression of MMP-8, TGF-ß1, and Smad2 in human skin biopsies. MATERIAL AND METHODS: Skin biopsies were taken from the outer upper arm of 15 elderly people with significant photoaging (mean age 64.1 years) (Group 1) and from 15 healthy young adult volunteers (mean age 24.1 y) who participated in a six-day sun holiday. Biopsies were taken twice: 24 hours before leaving for holiday (Group 2a) and 24 hours after returning (Group 2b). The expression of TGF-ß1, Smad2, and MMP-8 was examined by immunochemistry and measured semiquantitatively by two independent pathologists. RESULTS: The mean expression of TGF-ß1 in dermal fibroblasts and keratinocytes in Group 1 and Group 2b was significantly lower than in Group 2a (0.54% ± 0.44% and 0.48% ± 0.51% vs. 1.48% ± 0.72%, respectively). The percentage of Smad2 (+) cells in Group 1 and Group 2b was lower than in Group 2a (2.13% ± 1.39% and 1.81% ± 1.16% vs. 4.13% ± 1.58%, respectively). The MMP-8 expression in Group 2b was 1.36% ± 0.68% and was significantly higher than in Group 1 (0.34% ± 0.42%) and Group 2a in which the protein was not detected (p < 0.001). CONCLUSIONS: We conclude that the decrease in the expression of TGF-ß1 and Smad2 is a persistent biomarker of skin photoaging, while the increased expression of MMP-8 in keratinocytes can be regarded as a marker of acute sun exposure.

Can biologic treatment induce cutaneous focal mucinosis?

Skin mucinosis is a rare skin disease which clinically manifests as firm papules and waxy nodules. We report a case of a 66-year-old female psoriatic patient who developed skin mucinosis during biological therapy. Because of a previous lack of response to the local and conventional systemic treatment of psoriasis, the patient received biological therapy (infliximab from June 2008 to May 2009 - initial clinical improvement and loss of treatment effectiveness in the 36(th) week of the therapy; adalimumab from June 2009 to January 2010 - lack effectiveness; ustekinumab from March 2012 to the present). Throughout 2 months we observed a manifestation of the skin mucinosis as well-demarcated, yellow and brown, papulo-nodular lesions of 5-10 mm in diameter, localized on the back. Histopathological examination with alcian blue staining demonstrated mucin deposits in the dermis. On the basis of clinical and histopathological findings, the diagnosis of cutaneous focal mucinosis was established. We present the case because of the extremely rare occurrence of the disease. Scarce literature and data suggest that there is an association between focal mucinosis and thyroid dysfunction, as well as possible adverse effects of biological therapy with TNF-α antagonists.

Atopic dermatitis patients carrying G allele in -1082 G/A IL-10 polymorphism are predisposed to higher serum concentration of IL-10.

INTRODUCTION: Atopic dermatitis (AD) is a chronic skin inflammatory disease in which Th2-derived cytokines play an essential role. Aim of the study was to assess interleukin 4, 10 and 13 (IL-4, IL-10 and IL-13) serum concentrations in AD patients and to correlate the values with the occurrence of genotypes of selected polymorphisms in genes encoding these cytokines. MATERIAL AND METHODS: Seventy-six AD patients (mean age 11.4 years) and 60 healthy controls were enrolled in the study. Blood samples were analyzed for IL-4, IL-10 and IL-13 concentrations with ELISA assay and genotyping for -590C/T IL-4, -1082A/G IL-10 and -1055C/T IL-13 polymorphisms with PCR-RFLP. RESULTS: The obtained results revealed statistically higher serum concentration of IL-10 and IL-13 in AD patients when compared to healthy controls (10.30 pg/ml vs. 8.51 pg/ml for IL-10 and 5.67 pg/ml vs. 4.98 pg/ml for IL-13). There were no significant differences between AD patients and controls in regard to IL-4 serum level (5.10 pg/ml vs. 7.1 pg/ml). Analyzing the association between level of the examined cytokines and genotype polymorphisms -590 C/T for the IL-4 gene, -1082 A/G for the IL-10 gene and -1055 C/T for the IL-13 gene, we found a statistically higher IL-10 serum level among carriers of the G allele in the -1082 G/A IL-10 polymorphism both in AD and control groups. We did not find any significant differences between serum level of IL-4 and IL-13 in regard to genotype occurrence in examined polymorphisms: -590 C/T for the IL-4 gene and -1055 C/T for the IL-13 gene. CONCLUSIONS: The obtained results confirm the genetic background of IL-10 synthesis in the Polish population.

Sonic hedgehog pathway dysregulation in skin basal-cell carcinoma of a Polish population.

Sonic hedgehog (Shh) pathway impairment plays a key role in the pathogenesis of basal-cell carcinomas (BCC), the most frequent skin tumor among Caucasians. Shh, Smo, and Gli2 family proteins are necessary for adequate and controlled cell proliferation. The aim of this study was to evaluate Shh, Smo, and Smo expression in BCC skin biopsies taken from sun-exposed areas. 41 BCC skin biopsies and 22 healthy skin specimens (the control group) taken from the same areas served as material for the study. All specimens were immunohistochemically stained with monoclonal antibodies directed against the chosen proteins. Shh and Smo expression (cytoplasmic pattern) were recorded semiquantitatively using a four-grade score (0-3). Gli2 expression (nuclear pattern) was determined using an image analysis system (semiautomatic function). The immunoexpression of the Shh and Smo proteins significantly increased in the BCC group, as compared with the normal controls (for Shh, the mean intensity was 1.67 in BCC vs. 1.17 in the control group, p < 0.001; for Smo, the mean intensity was 1.46 in BCC vs. 0.99 in the control group, p < 0.001). The staining for Gli2 in the BCC group was completely negative, but indicated the presence of Gli2 in the control patients (1.15 Gli2+ cells/100 cells). Sonic hedgehog pathway dysregulation may play an important role in skin cancerogenesis leading to BCC development.

Effective treatment of nodular amyloidosis with carbon dioxide laser.

BACKGROUND: Nodular amyloidosis is a rare form of localized cutaneous amyloidosis that is characterized by nodules located on the extremities, trunk, genitalia, or face. In treatment regimens, many approaches have been described, including carbon dioxide (CO2) laser therapy. OBJECTIVE: We present a case of a 60-year-old white male with a 20-year history of disseminated waxy, purpuric, yellowish, and bullous skin lesions on the trunk and extremities. The skin changes were accompanied by pain during palpation and were temporarily pruritic. METHOD: Based on histologic and direct immunofluorescence test findings, the diagnosis of cutaneous nodular amyloidosis was established. Skin lesions were treated with a CO2 laser. During surgery, treated tissue was found to be slightly friable, and there was a little problem with hemostasis that correlated with amyloid infiltration of the dermis and blood vessels. However, after 8 weeks, we observed clinical improvement of all treated areas with the presence of atrophic scars. In the regions of laser therapy, no recurrence of the disease was observed during a 12-month follow-up. CONCLUSION: Based on these results, we conclude that CO2 laser has a beneficial effect in the treatment of nodular amyloidosis; however, surgery procedures may be associated sometimes with tissue friability and poor hemostasis.

An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes.

BACKGROUND: Vitamin D and folate are influenced by ultraviolet radiation (UVR), and both are implicated in skin carcinogenesis. Polymorphisms in the genes involved in the metabolism of these two compounds may alter the risk of basal cell carcinoma (BCC). OBJECTIVE: To assess the frequency of four polymorphisms in the gene encoding the vitamin D receptor (VDR) (FokI, BsmI, TaqI and ApaI) and two in the gene encoding methylenetetrahydrofolate reductase (MTHFR) (677C/T and 1286A/C) in 142 patients of Polish origin with BCC and the same number of controls. The expression of VDR and MTHFR proteins in the skin, and the vitamin D status of a subset of patients and controls were also measured. PATIENTS/METHODS: The polymorphisms were assayed by PCR-RFLP, the VDR and MTHFR proteins by immunoblotting and vitamin D status as 25-hydroxyvitamin D (25(OH)D) level in the serum by RIA. RESULTS: The presence of the TT genotype in the FokI VDR polymorphism resulted in a >10-fold higher risk of BCC development. The CT genotype in 677C/T MTHFR polymorphism and CC genotype in 1286A/C MTHFR polymorphism also significantly increased the risk of BCC development. The expression of the VDR and MTHFR proteins was significantly higher in BCCs of the patients than in the healthy skin of the controls. The median serum level of 25(OH)D was significantly higher in the control group compared with the patients with BCC. CONCLUSIONS: Certain VDR and MTHFR gene polymorphisms increase the risk of BCC development in individuals of Polish origin.

Risk factors in Central Poland for the development of superficial and nodular basal cell carcinomas.

INTRODUCTION: In the last decades the number of skin carcinomas has dramatically increased, which is mainly connected with changes in lifestyle, especially with common use of artificial light sources such as sunbeds. Basal cell carcinoma (BCC) is the most common form of skin cancer in white populations. Basal cell carcinomas are divided into subtypes, depending on their clinical picture and histology. The main groups are nodular (nBCC) and superficial (sBCC) ones. The major recognized risk factors for basal cell carcinoma (BCC) are exposure to chronic and intermittent burning doses of sunlight. Other risk factors leading to the development of the nBCC and sBCC subtypes of BCC are not well established. MATERIAL AND METHODS: An analysis of 123 patients with either nBCC or sBCC, living in Lodz, Poland, regarding various intrinsic and environmental parameters was undertaken following the histological diagnosis of BCC. RESULTS: No statistical differences were observed between the BCC subtype and sex, age, hair colour, eye colour, smoking, family history of skin cancer, occupation, or past episodes of sunburn. While sBCCs tended to occur on unexposed body sites in phototype I/II subjects who mainly avoided direct sunlight, nBCCs tended to occur on sun-exposed body sites in phototype III subjects who were frequently in direct sunlight. CONCLUSIONS: Thus the development of particular BCC subtypes is partially dependent on phototype and personal sun behaviour.