Molecular and cellular stratagem of brain metastases associated with melanoma.

Tumors of the central nervous system are the most prevalent complications of melanoma, especially in the late stage of disease. Melanoma, lung and breast cancer are the leading cause of secondary tumors in the brain, the majority of them having a poor outcome. Brain dissemination is developed in half of stage IV melanomas and these cases can increase up to 75%, having a major impact on the quality of life. This review will focus on recent findings that provide new ways to potentially prevent brain metastases in malignant melanoma. The key of these findings is based on the heterogeneity of the melanoma and of the brain metastases at genetic levels. This new era of technologies provides new tools in understanding the dissemination mechanisms of malignant cells. The cellular and molecular changes, the immune status of the patient and the blood-brain barrier permeability are key regulators of cancer cell dissemination. Understanding these mechanisms can render new hope in preventing brain metastases by focusing on melanoma and new pharmacologic approaches.

Role of modern imaging techniques for the in vivo diagnosis of lichen planus.

Lichen planus (LP) is a chronic inflammatory skin disease that can sometimes affect mucosal surfaces, with unknown pathogenesis, even though it appears to be an autoimmune disease. The diagnosis of lichen planus is usually based on histopathological examination of the lesions. Nowadays, the classical invasive diagnostic methods are replaced by modern non-invasive techniques. In this review, we present the main non-invasive imaging methods (dermoscopy, reflectance confocal microscopy, optical coherence tomography, ultrasound and diffuse reflection spectrophotometry) used in the diagnosis and therapeutic monitoring of lichen planus. Dermoscopy is a non-invasive method initially used for diagnosis of pigmented tumors but now is used also for inflammatory and infectious skin diseases. In lichen planus, the dermoscopy increases the accuracy of diagnosis, avoids skin biopsies commonly used and can be useful in the therapeutic monitoring by repeated investigation at different stages of treatment. Reflectance confocal microscopy (RCM) is a novel non-invasive imaging technique that is prevalently used for the diagnosis of skin tumors and inflammatory skin diseases. This technology has been mostly employed for bedside, real-time microscopic evaluation of psoriasis, lichen planus, contact dermatitis, revealing specific confocal features to support clinical diagnosis and assist with patient management. Optical coherence tomography (OCT) is an emergent imaging technique, developed over the last decade, based on the interaction of the infrared radiation (900-1,500 nm) and the living tissues. A limited information exists on the benefits of OCT technology for the in vivo diagnosis of LP but could be a useful auxiliary tool in the in vivo differential diagnosis, especially in clinical equivocal settings like mucosal lesions, and in monitoring the response to treatment. Our review shows the possibility of using modern imaging techniques for the in vivo diagnosis and also for evaluation of the treatment response.

Comparative study in leg telangiectasias treatment with Nd:YAG laser and sclerotherapy.

Telangiectasias and reticular veins of the lower extremities are common lesions. Sclerotherapy is considered the gold standard for treatment. The aim of our prospective randomized study was to compare the efficacy and safety of hypertonic 20% saline/2% lignocaine (HS) versus polidocanol 0.5% (POL) versus long-pulsed neodymium:ytrium aluminium garnet (Nd:YAG) laser (LAS) treatments of leg telangiectasias in women, using each patient as her own control. We included in this study 285 women with primary leg telangiectasias and reticular veins (C1AEpAS1PN) in order to be treated with sclerotherapy or laser. One leg was treated with either LAS, POL or HS. The other leg received, randomly, one other of these treatments. At the end there were 190 legs treated with each method. There were two sessions at 8-week interval. Assessment of vessel clearing and complications was conducted 2 months after each session using before and after photographs of the leg vessels using a six-point scale from 0 (no change) to 5 (100% cleared). For telangiectasias under 1 mm diameter LAS was better (RR=9.72, P<0.0001) than HS and also POL was better (RR=2.70, P=0.003); for telangiectasias over 1 mm diameter LAS and POL were better too (RR=2.70, P=0.003) respectively (RR=1.44, P=0.00756). For telangiectasias under 1 mm LAS treatment is clearly superior to POL treatment. For telangiectasias over 1 mm the hazard regression model showed a hazard ratio of 3.97 (P=0.047) for LAS and 4.96 (P=0.486) for POL vs. HS treatment. In conclusion, telangiectasias and reticular veins of the lower extremities can be successfully treated with Nd:YAG laser or sclerotherapy. Nd:YAG laser is recommended in treating small telangiectasias (under 1 mm diameter) while sclerotherapy with polidocanol is more efficient as long as telangiectasias diameter is growing.

The incidence of skin lesions in contrast media-induced chemical hypersensitivity.

Contrast agents are used in radiology to increase the sensibility and specificity of radiological techniques. Some of these compounds have side effects that include organ toxicity (with kidney being the most affected organ) and hypersensitivity reactions. We performed multiple PubMed searches from January, 2008 to January, 2018 for studies regarding adverse reactions to compounds used as contrast agents in imagistic techniques. The initial research identified 929 records written in English. After further excluding 223 non-human studies, 292 articles that had irrelevant designs as reviews, meta-analysis, commentaries, editorials and case reports, 414 studies were selected for retrieval. After reading the abstracts, we excluded 363 studies as they had little relevance to the study. In total, 51 full-articles were assessed for eligible studies to be included. Finally, 20 articles were included in the analysis. In our systematic literature search the incidence of overall skin immediate reactions to iodinated contrast media (ICM) had an incidence between 1.15 and 0.12%, depending on the cohort analyzed in the studies. The percentage of cutaneous manifestations in the cohort that experienced immediate hypersensitivity reactions was between 33.33 and 87.7%. The most frequent skin manifestations were urticaria, rashes, pruritus and limited facial edema. Non-iodinated contrast agents have a safer profile compared with ICM, the incidence of immediate adverse reactions being very low in gadolinium-based contrast agents and other agents used for contrast-enhanced ultrasound. The incidence of delayed reactions was between 10.1 and 0.03%. In the studies analyzed by us the main adverse reactions due to delayed hypersensitivity phenomena were cutaneous manifestations that were present between 70.27 and 100% of the cases. Regarding the risk factors for developing immediate adverse reactions, being female was a predisposing factor accompanied by history of allergy and history of reactions to contrast media. An accurate anamnesis of the patients and a correctly conducted pretreatment can limit the incidence and the severity of the adverse reactions and also can avoid the life occurrence of life-threatening reactions.

Assessment of dermal papillary and microvascular parameters in psoriasis vulgaris using in vivo reflectance confocal microscopy.

In vivo reflectance confocal microscopy (RCM) is a modern, non-invasive imaging technique, which allows for real-time examination of the upper layers of the skin at a resolution similar to that of classic microscopy. In addition, it has the advantage of real-time evaluation of blood flow and dynamic monitoring of cutaneous changes while preserving tissue integrity. The present study reported on the in vivo RCM technique as an objective method for the noninvasive assessment of psoriasis vulgaris that is potentially applicable in clinical studies and in monitoring the evolution of lesions under treatment. In psoriasis lesions, RCM virtual horizontal sections at the level of the dermo-epidermal junction featured numerous and prominent dermal papillae that were not surrounded by bright rings of basal cells. Micromorphological examination of the lesions using this technique revealed that mean values of the section area, the perimeter and the Feret's diameter of the dermal papillae were significantly higher in psoriatic lesions than in normal skin. An increased number of capillary vessels per lesional dermal papilla as compared to healthy skin was observed. Furthermore, micromorphological parameters of dermal capillaries were increased in psoriatic skin. These observations point to the utility of in vivo RCM as a promising technique for the non-invasive diagnosis of psoriasis vulgaris, for monitoring the evolution of lesions at a micromorphological level under various treatments and for gaining a better understanding of the pathophysiological processes that occur in the evolution of this disease.

Age-dependent endocrine disorders involved in the pathogenesis of refractory acne in women.

Acne is a disorder of the pilosebaceous unit, common among adolescents, which may be extended to adulthood. The aim of this study was to assess the prevalence of hormonal disorders in women with acne resistance to conventional therapy. We included 72 women aged between 15 and 36 years (divided in two age groups) who presented to our clinic between May and October 2014, suffering from moderate and severe forms of papulopustular and nodulocystic acne. The subjects were non­responsive to classic dermatological treatment or had clinical manifestation of hyperandrogenism. Based on age, we divided the women into two groups, group I with 40 patients aged 15­22 years and group II with 32 patients aged 23-36 years. Using ELISA, a hormonal profile was performed for each patient in days 1­3 of the menstrual cycle including, total testosterone, dehydroepiandrosterone sulfate (DHEA­S), follicle­stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, and plasma cortisol. For statistical analysis we used Stata 13 software. We compared the hormonal profile of the two groups and identified significant differences for: testosterone levels (mean value, 0.64±0.35 vs. 0.97±0.50 ng/ml; p<0.0001), DHEA­S levels (mean value, 0.85±0.27 vs. 1.05±0.33 mg/24 h; p=0.001), prolactin levels (mean value, 281.85±91.113 vs. 353.969±102.841 mIU/ml; p=0.002) and LH levels (14.8±6.7 vs. 20.1±8.2 mIU/ml; p=0.002) were higher in group â…¡. No statistically significant differences were found for estradiol (p=0.588) and cortisol (p=0.182) levels. In conclusion, refractory acne can be the first sign of systemic illness including polycystic ovary syndrome. Thus, for a correct therapeutic approach it is necessary to interpret the clinical and biochemical elements in correlation with the medical history.

Rare case of disseminated fusariosis in a young patient with graft vs. host disease following an allogeneic transplant.

Fusarium infection is a severe fungal infection caused by fungi of the genus Fusarium. It most commonly occurs in immunocompromised patients with malignant hematological comorbidities or secondary to hematopoietic stem cell transplant. The classical route of contamination is through inhalation but infection may also occur through contiguity with a skin lesion. This report describes the case of a 24-year-old woman who developed graft-vs.-host disease (GVHD) at 220 days after receiving an allogeneic stem cell transplant from a sibling donor for Hodgkin disease. On day 330 after transplant the patient presented with fever and several painful subcutaneous, tender, red nodules with ulcerative and necrotic features on the pelvic region and right leg, extensive glass infiltrative lesions in the lungs and pansinusitis; however, the patient did not have onychomycosis. Following skin biopsy, culture of cutaneous lesions, computed tomography (CT) scanning of the lungs and CT scanning and magnetic resonance imaging of facial sinuses the patient was diagnosed with disseminated Fusarium species infection. Despite intensive treatment with voriconazole, the patient succumbed with respiratory insufficiency on day 400 after transplant. This case is noteworthy because the patient did not have any additional risk associated with the allogeneic transplant; there was no transplant mismatch, no severe neutropenia and no prior clinical signs of onychomycosis. The association of skin lesions with GVHD lesions increased the initial immunosuppression and delayed diagnosis.

Investigator-blind, placebo-controlled, randomized comparative study on combined vacuum and intense pulsed light versus intense pulsed light devices in both comedonal and papulopustular acne.

INTRODUCTION: The aim was to compare the treatment effectiveness of intense pulsed light (IPL) and vacuum versus IPL with placebo for mild to moderate comedonal and inflammatory acne. PATIENTS AND METHODS: We randomized 180 patients with mild to moderate comedonal and inflammatory acne into three groups: Group A - 60 patients treated with vacuum and IPL, Group V - 60 patients treated with IPL, and Group 0 (control group) - 60 patients who received topical treatment with Sebium H2O Micellaire Solution. We evaluated the results using the Leeds revised acne-grading system and Cardiff Acne Disability Index. RESULTS: There was a significant reduction in the number of papules, pustules, and comedones in Groups A and V compared with those in the control group (p < 0.001) with a more rapid decrease of the papules from Group A compared with that from Group V. We found an improvement in the clinical aspect (p < 0.001) when we compared Groups A and V with controls. Patients belonging to Group A were more satisfied compared with those belonging to Group V (p = 0.004) and significantly more satisfied compared with those belonging to Group 0 (p < 0.001). In conclusion, we consider that both the devices are efficient, the combination of vacuum and IPL representing a therapeutic option for the comedonal acne.