Histological Skin Remodeling Following Autologous Fibroblast Application.

The aim of this study was to quantify the effectiveness of intradermal application of autologous fibroblasts on lean tissue structures. The histological sections of the skin were analysed and evaluated for the expansion potential of autologous fibroblasts in the control skin patch area and the nearby pre-treated skin patch into which we had injected expanded autologous fibroblasts nine month earlier. The results show that the pre-injection of fibroblasts into the dermis leads to a long-term rejuvenation of the skin, as evaluated from the histological appearance and from the significantly increased density of fibroblasts in the pre-injected skin vs. controls, from around 60% to over 80%, determined as the percent of lean tissue by a novel image analysis approach. Interestingly, the rate of the in vitro fibroblast expansion from the pre-injected area of the skin was reduced in comparison with the controls, consistent with the view that fibroblasts exhibit a limited cell-division potential and that fibroblasts from the pre-injected skin already experienced expansion nine month earlier prior to the injection into the skin. We conclude that autologous fibroblast application results in a significant long-term augmentation of the lean tissue elements of the skin.

Subcutaneous parasitic infection in Slovenia: a case report.

Filariasis is a parasitic disease caused by infection with roundworms of the Filarioidea superfamily. Depending on the species of roundworm, the disease can present itself in one of three forms. It can affect the lymphatic system, the subcutaneous tissue, or serous cavities. We present the case of a male patient from central Europe with a subcutaneous manifestation similar to filariasis. Laboratory findings showed eosinophilia and elevated levels of IgE antibodies, and histological examination of skin biopsy material showed granulation tissue with lymphoid and plasma cell infiltration. When the lesion was examined under a microscope following an excision, live wormlike parasites about 3.5 cm long were detected. Such parasitic infections are usually encountered in tropical regions and sometimes reported in travelers returning from endemic countries. Our patient, however, had never left Europe, which is what makes this case so interesting.

A case of segmental form of type 1 mosaic Darier's disease.

Darier's disease is a rare genetic disorder with autosomal dominant inheritance. It is characterized by hyperkeratotic papules in seborrheic areas. Associated abnormalities include nail abnormalities and changes in the mucous membranes. Exacerbation of the disease occurs with exposure to high temperatures, sun, and sweating, resulting in a worsening clinical picture in summer months. The unilateral zosteriform pattern is a rare variant that is clinically manifested by a unilateral outbreak of erythematous keratotic papules without any other associated symptoms. Here we present a 52-year-old male with a zosteriform pattern of Darier's disease. We also discuss the most important clinical and pathohistological characteristics of the disease and various treatment options.

Topical Imiquimod for Management of Recurrent Lentigo Maligna Melanoma in Situ.

Topical imiquimod is a medication approved for the treatment of external genital and perianal warts, actinic keratosis, and superficial basal cell carcinoma. There have also been reports of its successful use in patients with lentigo maligna melanoma in situ. An 80-year-old female patient was diagnosed with lentigo maligna melanoma in situ which was then surgically removed. After several recurrences, nonsurgical treatment using topical 5% imiquimod was introduced. At 9-month follow-up the skin was completely healed with no evidence of cancer recurrence. In select cases, topical imiquimod seems to be an effective alternative to surgical treatment of melanoma in situ (MIS). Further studies are necessary to assess the successfulness of this treatment method.

Oral and Vulvar Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin (1). Simultaneous involvement of the oral mucosa is extremely rare, but it may be the only affected area (2). A 55-year-old woman was referred to the Department of Oral Medicine, School of Dental Medicine University of Zagreb due to whitish lesions on the right ventrolateral part of the tongue and buccal mucosa with desquamative gingivitis (Figure 1, a-c). The lesions were asymptomatic but indurated on palpation. Histology was conclusive for oral lichen sclerosus (OLS). The lesions on gingiva were successfully treated with betamethasone ointment, three times a day for two weeks. One year earlier, she had been referred to the Department of Dermatology and Venereology with progressive pruritus and dyspareunia, white patches, obliteration of the labia minora, and stenosis of the introitus (Figure 2). Histology was conclusive for vulvar LS (Figure 3, a and b). She was successfully treated for 5 months with clobetasol propionate 0.05% ointment. The patient was taking levothyroxine to treat hypothyroidism associated with Hashimoto's thyroiditis and was otherwise healthy. Oral LS is clinically characterized by the appearance of white macules, papules, or plaques mostly appearing on labial mucosa but also on buccal, palate mucosa and on the lower lip (2,3). On the genitals, it typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring (1). While vulvar LS is often associated with pruritus, dyspareunia, and dysuria, OLS is often asymptomatic, although pain, soreness, pruritus, and tightness when opening the mouth can be present (1,2). Oral manifestations of LS, as well as association of anogenital and oral LS, are rarely reported in the literature (4-6). Tomo et al. searched the Medline database for papers reporting oral LS cases with histological diagnosis confirmation from 1957 to 2016 and found only 34 cases of oral LS with histopathologic confirmation of the diagnosis (4). Kakko et al. reported 39 histologically proven cases of OLS (2). Attilli et al. (5) reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement. They reported that LS was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in only 7 cases (5). Some believe that many cases of clinically diagnosed lichen planus may actually be LS and that isolated oral mucosal LS may not be as rare as is generally thought (2). While vulvar LS can occur at any age with increasing incidence with age, the median age of patients with OLS was 34 years and most of the patients were female (1,2,5). Due to the small number of patients in the literature, treatment recommendations for OLS are not available. In case of symptomatic oral lesions, topical or intralesional corticosteroids are considered to be the first-line treatment (2). First-line treatment for anogenital LS is a potent to very potent topical corticosteroid ointment, and second-line therapies include topical calcineurin inhibitors 1% pimecrolimus and 0.1% and 0.03% tacrolimus (1). For treatment-resistant genital LS, oral retinoids, methotrexate, and possibly local steroid injections for single lesions are mainly applicable for women (1). There is limited evidence for systemic treatments for both conditions. If it is not treated, genital LS is associated with a greater degree of scarring and an elevated risk of progression to squamous cell cancer; however, malignant transformation of OLS has not been reported (1-6). Due to the very rare presentation in the oral cavity, it is important to notice these lesions during a dental exam.

Health Behavior Changes in Cutaneous Melanoma Survivors.

Aim of this study was to investigate changes in health behavior of melanoma survivors with emphasis on safe sun behavior (SSB) and skin self-examination (SSE). We also identified factors with significant impact on SSE improvement. We performed a cross-sectional (epidemiological) survey based on a structured questionnaire. 150 patients from three medical institutions were invited and 144 patients responded. Statistical analysis was performed with SPSS version 23.0, with the level of significance set to 0.05. After being diagnosed with cutaneous melanoma, patients significantly improved preventive health behavior: 68.1% showed improvement in SSE, and 91.5% of patients improved SSB. There was statistically significant (P<0.001) improvement in the frequency of skin examination, examination of poorly visible areas (between the toes, genitals), and obtaining help in examination. Use of melanoma images remained scarce. Results for SSB were even better, and statistically significant improvement was recorded in all areas: using higher UV protection filters, wearing sunglasses, headgear, long sleeves, and trousers, and especially in staying in deep shade during hours of heavy UV radiation. The only factor with a positive influence on expected improvement in SSE was female gender. On the other hand, there were two factors that had a negative impact on SSE: patients with melanoma stage 1 and patients who had already self-examined themselves before their melanoma diagnosis. Preventive health behavior improved significantly after diagnosis of cutaneous melanoma. Patients markedly improved SSB and substantially enhanced SSE. We believe that it is reasonable to improve SSE further, encouraging patients by increasing their feeling of self-efficacy.

Health Behaviour Changes of Cutaneous Melanoma Survivors in Slovenia - A Qualitative Study.

INTRODUCTION: Most data related to cutaneous melanoma survivors' health behaviour comes from epidemiological studies and is predominantly concerned with safe-sun behaviour and self-examination. Data regarding other changes of health behaviour are scarce and so are qualitative studies in this realm. The aim of our research is to acquire insight into the experiences of patients with cutaneous melanoma in Slovenia. How did they react to the diagnosis, which changes did they introduce in their health behaviour and how do they assess the role of family doctors? METHODS: Using the qualitative approach of collective case reports, a demographically diverse group of patients with different forms and stages of cutaneous melanoma was selected. Semi-structured interviews conducted by a psychologist were recorded and transcribed verbatim. For data processing, the approach of Qualitative Content Analysis was applied. RESULTS: We integrated interviewees' experiences after the diagnosis of cutaneous melanoma in several subcategories: either they did not introduce any changes or they mentioned changing their habits when exposed to the sun and performing skin self-examination; they also emphasized their ways of dealing with stress and raising awareness about melanoma among family members and friends. The role of family doctors in the prevention and care appears unclear; even contradictory. CONCLUSION: We obtained insight into the experiences of Slovenian patients with cutaneous melanoma. The interviewees prioritised safe behaviour in the sun, strengthening of psychological stability and raising awareness about melanoma. Findings will be used in the creation of a structured questionnaire for national epidemiological survey.

Coexistence of genital lichen sclerosus and genital warts.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin. Anogenital warts are benign proliferative lesions caused by human papillomavirus (HPV), which is found in > 95% of lesions. We present two cases of the coexistence of LS and genital warts: one patient with and one without a previous history of genital warts. According to our knowledge and a literature search, only a few cases of the coexistence of LS and genital warts have been reported.

An adverse reaction after hyaluronic acid filler application: a case report.

Among several skin fillers developed in recent decades, hyaluronic acid (HA) fillers have become the material of choice. They are safe, long-lasting, not immunogenic, and cost effective, and they can be removed with hyaluronidase. Unfortunately, early and delayed complications can also occur following HA filler injection. Here we report the case of a hyaluronic filler-related complication in a 50-year-old female patient. The locations affected were the forehead, glabella, and nose. Three days after HA filler application in the upper lip, glabellar region, and nasal root, with no immediate diverse reaction at the time of application, an erythematous, livedoid rash with a well-defined border occurred at the site of the injection in the glabellar region, including the area from the nasal root to the scalp and left upper eyelid. Because an infection or allergy was suspected, she was first given an antibiotic for 6 days p.o. and later also a corticosteroid systemically with good results. Two years later (in 2017) the patient decided to repeat the treatment with HA injections in the glabellar region and experienced no adverse reactions.

Comparison of in vitro and in vivo ultraviolet protective properties of PET textile samples.

BACKGROUND: Many studies have been devoted to the problem of harmful effects of UV radiation on human skin. The incidence rate for all forms of skin cancer is rising quickly. Considering this fact, there is currently a need for diligent preventive work, not only from dermatologists but also from other doctors and scientists. Textiles represent simple and effective protection against UV radiation. Good protective clothing can reduce UV radiation on the surface of skin by at least 95%. Even though numerous studies present the effects of various textile parameters on UV protection, not many have been conducted for determining the degree of agreement between in vivo and in vitro measurements of UPF. METHODS: This study presents the effect of various constructional parameters on UPF values (determined using spectrophotometry). The phenomenon of minimal erythema doses on the skin of test subjects was tested based on in vitro calculated UPF values. RESULTS: Despite some differences in values, the study nevertheless showed a good correlation between both methods and confirms the congruity of in vivo and in vitro UPF values. CONCLUSIONS: It is clear that both methods are needed for a more precise look at the UV protection offered by textiles.

Topical effectiveness of a cosmetic skincare treatment for acne-prone skin: a clinical study.

BACKGROUND: Physiological acne is a milder form of clinical acne and is very frequent in adult women (18 years of age and older). Acne therapy is usually unnecessary in such cases, and so appropriate cosmetic treatments are sought. OBJECTIVES: To determine the effectiveness of a topical cosmetic hydrating skincare treatment for adult acne-prone skin (Normaderm, Vichy, France) against the clinical signs of physiological acne: few inflammatory and retentional lesions, uneven (grainy) skin relief, dilated pores, and occasional and/or local hyperseborrhea. METHODS: Within the study, the tested product's keratolytic, antimicrobial, and antiseborrheic properties, and its overall ability to improve the clinical signs of physiological acne present in adult subjects were evaluated through objective and clinical evaluation methods by the investigators and through self-evaluation questionnaires by the subjects themselves. The study group was composed of 50 adult women between 18 and 35 years of age with combination or oily acne-prone skin, who were chosen according to previously defined inclusion criteria. They applied the product tested twice daily on thoroughly cleansed skin for a period of 2 months. The results were evaluated after 30 (±2) and 60 (±2) days. RESULTS: The number of inflammatory and retentional lesions on the forehead, cheeks, and chin decreased after 60 days of use (an average of 30.7% and 70.7%, respectively). The level of sebum secretion on the forehead decreased by 33.4% and the level of skin scaling decreased by 38.5% after 60 days of use. The moisture content in the horny layer on the forehead, cheeks, and chin increased by an average 39.7%. The decrease in pore size and content after 60 days of use was very noticeable. The subjects evaluated all the studied characteristics of the product tested very positively, with results already showing after 30 days of use. CONCLUSIONS: The results of the study confirm that the product tested is suitable for the cosmetic care of adult acne-prone skin, either as an independent cosmetic hydrating skincare treatment, as a complementary cosmetic part of acne therapy, or as a subsequent cosmetic regimen to sustain the results of the acne therapy for a longer period of time.

Sex differences in survival of cutaneous melanoma are age dependent: an analysis of 7338 patients.

This study identified sex differences in clinical presentation and survival for primary cutaneous melanoma without clinical evidence of metastasis at diagnosis from 1976 to 2008 in southern Germany. Melanoma-specific survival curves and estimated survival probabilities were generated using the Kaplan-Meier method. Multivariate survival analyses were carried out using the Cox modeling. Male patients had significantly thicker and more frequently ulcerated tumors and a lower 10-year disease-specific survival (DSS) and recurrence-free survival probability compared with females among patients of 43 years old or younger (DSS: 86.1 vs. 93.2%, P<0.001) and 44-60 years old (DSS: 83.5 vs. 90.1%, P<0.001). The survival advantage of female patients in terms of 10-year DSS and 10-year recurrence-free survival was not observed after an age of 60 years (P=0.21 and 0.51, respectively). Sex was of prognostic importance for DSS and survival after recurrence [hazards ratio (HR): 1.3; 95% confidence interval (CI): 1.1-1.6; P=0.002 and HR: 1.2; 95% CI: 1.0-1.5; P=0.018, respectively]. Stratified by age groups, sex remained of prognostic importance for DSS only in patients of 43 years or younger, and 44-60 years old (HR: 1.5; 95% CI: 1.0-2.1; P=0.03 and HR: 1.4; 95% CI: 1.1-2.0; P=0.02, respectively). Sex is an independent prognostic factor in surviving melanoma. The sex difference in survival with a better outcome for women is confined to melanoma patients of 60 years and younger. In addition, in younger age groups, male patients present with prognostically unfavorable features of primary melanoma. A female survival advantage is also known for other solid tumors such as colon and lung cancer; however, age dependency has not been studied.

Diagnosis and categorization of acral melanocytic lesions using teledermoscopy.

We performed a multicentre study to test the validity of teledermoscopy for diagnosing acral melanoma and to evaluate inter-observer agreement on the classification of acral melanocytic lesions. Dermoscopic images of 77 acral melanocytic lesions (71 common melanocytic naevi and 6 melanomas) were sent by email to 11 dermatologists with different degrees of experience in dermoscopy. The observers analysed the images on a computer monitor to diagnose acral melanoma or atypical lesions and to categorize all lesions. All 11 observers, regardless of their degree of experience, obtained high values for sensitivity (mean 0.91, SD 0.09) and specificity (mean 0.95, SD 0.04) with regard to the diagnosis of melanoma. The inter-observer agreement was good to excellent (kappa 0.49-0.88) for the categorization of acral melanocytic lesions. All six melanomas were correctly classified as 'atypical pattern' and all observers recommended surgical excision. Teledermoscopy represents a useful tool for the diagnosis of acral melanoma and for the categorization of patterns that suggest benign or potentially malignant acral melanocytic lesions.

Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet.

BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma.

The urokinase-type plasminogen activator (uPA) and its inhibitors type 1 (PAI-1) and type 2 (PAI-2) are considered to have a key role in the process of invasion and metastasis. We investigated the differences in uPA, PAI-1 and PAI-2 concentrations in primary cutaneous melanoma and normal skin and correlations with well-established melanoma prognostic factors. The study was performed on 43 patients (19 men, 24 women; mean age 57 years) with histologically confirmed primary melanomas <1.5 mm thick. The uPA concentrations were determined in 36 pairs of triton extracts, and the PAI-1 and PAI-2 concentrations in 43 pairs of cytosols prepared from the tumour and adjacent normal tissue samples (matched pairs). The uPA, PAI-1 and PAI-2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Significantly higher concentrations of both uPA and PAI-1 were measured in melanomas than in normal surrounding skin (uPA: 1.08 vs 0.48 ng/mg total protein (mgp), p<0.001; PAI-1: 14.07 vs 2.07 ng/mgp, p<0.001). The melanoma uPA, PAI-1 and PAI-2 concentrations correlated significantly (p<0.05) with normal skin (r=0.73, 0.54, 0.38 respectively). The uPA concentrations positively correlated with those of PAI-1 measured in melanomas (r=0.45, p<0.01). PAI-1 values were significantly lower (p<0.001) in the melanomas of Breslow thickness < or =0.75 mm, Clark invasion 0.75 mm, Clark invasion of > or =II and < or =III, with microscopic ulceration and vascular invasion (22.25, 17.67, 27.67, 37.77, respectively). Determination of uPA and PAI-1 can provide significant additional prognostic information for melanoma patients.

"Compound blue nevus": a reappraisal of "superficial blue nevus with prominent intraepidermal dendritic melanocytes" with emphasis on dermoscopic and histopathologic features.

We describe 5 cases of "compound blue nevus" (CBN) ("superficial blue nevus with prominent intraepidermal dendritic melanocytes," "Kamino nevus"). Dermoscopically in 2 of 4 cases the bluish pigmentation characteristic of blue nevi was centrally replaced by a black lamella, with black dots and brown globules also observed in one case, thus revealing a structural asymmetry suggestive of melanoma. Histopathologically, pigmented parakeratosis was the underlying histopathologic finding of black lamella and dots/globules. Immunohistochemistry highlighted the unique histopathologic feature of CBN, namely, single dendritic melanocytes at the dermoepidermal junction with striking intraepidermal prolongations. Our findings confirm that CBN is a distinctive variant of blue nevus that may mimic cutaneous melanoma both clinically and dermoscopically.