Dermato

Split-thickness skin grafting is a well-known procedure for the treatment of small- and medium-sized burns. However, its effectiveness has been reported to be limited in the case of large and severe burns due to much lower real expansion offered by the grafts than the claimed expansion by graft mesh manufacturers. Recent computational studies have indicated that the collagen fiber orientation within the skin layers have a significant effect on the skin graft expansion. In this study, biofidelic anisotropic synthetic skin with one and two layers and all possible fiber orientations were developed, and incision patterns used in traditional graft meshing techniques were projected to fabricate novel synthetic skin grafts with a theoretical meshing ratio of 3:1. A biaxial tensile testing device was designed to simulate skin graft stretching in clinical settings, and a wide range of synthetic skin graft variants were mechanically tested. The measured quantities included induced nonlinear stress–strain, void area, and meshing ratio. In addition, the stress–strain responses were characterized using nonlinear hyperelastic models. The key observations include the generation of higher induced stresses in two-layer grafts. In the one-layer graft models, a 15° fiber orientation produced the highest expansion at a minimal stress value of 0.21 MPa. In the two-layer graft models, the 45°–15° fiber orientation generated the maximum expansion with minimum stress. A range of such findings were analyzed to determine the graft orientations that may allow enhanced expansion without generating much stress. This information would be indispensable not only for understanding the expansion potential of skin grafts, but also for further research and the development of skin grafts with enhanced expansion for severe burn injury treatment. Full article

Dermatofibrosarcoma protuberans (DFSP) is a rare mesenchymal tumor of intermediate malignant potential. The neoplasm is locally aggressive with a high rate of recurrence. It typically presents in adults. Atrophic congenital DFSP is extremely rare. The few reported cases have presented as a morphea-like plaque that persists for years, before progressing into a nodular form. To our knowledge, congenital atrophic DFSP has been only reported fourteen times, and of those, only nine were confirmed by molecular studies. Herein we report a congenital case of atrophic DFSP, which initially presented as a bruise-like atrophic plaque on the dorsal forearm, initially mistaken for child abuse. The clinical appearance, histopathology, and molecular features of this rare form of DFSP are reviewed. Our case highlights the importance of early detection and adequate sampling of congenital DFSP; early treatment allows for treating small lesions without large, disfiguring, and potentially disabling excisions. Full article

Advanced cutaneous squamous cell carcinoma (cSCC) can be a life-threatening disease for which effective and safe treatment in advanced stages is very limited. GP-2250 has been recently proven to have—in vitro and in vivo—antineoplastic effects on cancer cells. This study aims to investigate the potential anti-neoplastic effects of GP-2250 on the cSCC cell lines SCC13 and A431 through dose finding assessments, MTT cytotoxicity assays, cell migration assays, BrdU proliferation assays and FCM analysis. Our preliminary results have shown for the first time evidence for anti-neoplastic effects of GP-2250 on cSCC cells, enhancing cytotoxicity, attenuating cancer cell proliferation, inducing apoptosis and reducing tumour cell migration. Further investigations evaluating the modes of action of GP-2250 on cSCC cell lines are warranted in order to justify the use in vivo studies. Full article

Advances in Terahertz frequency electromagnetic radiation (THz) production technologies have produced an increasing interest in exploring possible applications. New applications will inevitably lead to increased incidental interaction of humans with THz radiation. Given that the wavelength of THz radiation is in the same order of magnitude as the dimensions of skin structures such as hair and sweat ducts, the possibility of interaction among these structures is of interest. The interaction was studied utilizing Finite Difference Time Domain (FDTD) simulations using a far-field excitation of 0.45 THz. No antenna-like effects were detected. Regions of increased specific absorption rate (SAR) due to reactive near-field effects with both the hair and sweat ducts were found in the order of 0.01–0.05 mm and 0.001–0.002 mm, respectively. Simulations using unwound sweat ducts yielded the same penetration pattern as the helical structure, indicating that the helical structure has no impact on the propagation of THz radiation in skin. Full article

With this work, we aimed to review the principal benign and malignant tumors (including vascular, keratinocytic/epidermal, melanocytic, hematopoietic, and lymphoid origin), primarily affecting the leg’s skin. The lesions’ location can also help focus on a spectrum of differential diagnoses in clinical practice. All the diseases present the same clinical presentation characterized by erythematous to violaceous nodules. Despite the same clinical presentation, each disease’s prognostic outcome and therapeutic management can be somewhat different. Since clinical diagnosis may sometimes be challenging, histology and immunohistochemistry play a fundamental role in recognizing and staging these types of lesions. Molecular studies can help to determine the exact nature of lesions with no specific characteristics. Kaposi’s sarcoma is an angioproliferative neoplasm that typically occurs in the lower limbs and can enter into differential diagnosis with several other rarer skin diseases. The principal differential diagnosis concerns primary cutaneous lymphomas, of which mycosis fungoides represent the most frequent primary cutaneous T-cell lymphoma. Other rare forms include primary cutaneous B-cell lymphomas, which can be divided into indolent and aggressive forms, such as the primary cutaneous diffuse large B-cell lymphoma, leg type, and lymphomatoid papulomatosis (LyP). In the case of indolent lesions, skin-directed therapies, limited-field radiotherapy, and surgical approaches can be good options. At the same time, different management, with systemic chemotherapy and allogenic bone marrow transplant, is required with aggressive neoplasms, such as blastic plasmacytoid dendritic cell neoplasia or advanced mycosis fungoides. The dermatologist’s role can be crucial in recognizing such diseases and avoiding misdiagnosis, giving the pathologist the correct clinical information for an accurate diagnosis, and starting the suitable therapy. Full article

Merkel cell carcinoma (MCC) is an uncommon form of skin neoplasm with poor histological differentiation and an aggressive disease process, leading to high recurrence and mortality. There are multiple risk factors in which being in an immunocompromised state is a significant factor, and the discovery of Merkel cell polyomavirus (MCPyV) since 2008 has strengthened causal associations between MCC and immunosuppression. Individuals who have undergone kidney transplantation are therefore more susceptible to having MCC, secondary to post-transplant immunosuppression which plays a vital role in reducing the risk of transplant kidney rejection. Over recent years a rise in the incidence of MCC following kidney transplantation is noted, with increased reporting of such cases. Whilst localized MCC is observed, MCC metastasis to the lymphatic system, brain, bone, liver, lung, and heart has been previously observed in patients with transplanted kidneys. Kidney metastasis is less common and has been only reported in recent years with greater frequency. The management of aggressive, metastatic MCC has historically been palliative, and prognosis is poor. Recently, the use of immune checkpoint inhibitors for metastatic MCC in multi-center phase II clinical trials have shown promising survival outcomes and have been approved for use in countries such as the United States as a first-line treatment. In this review we will explore the potential pathophysiological processes of MCC manifesting post-kidney transplantation. We will then evaluate the epidemiology of MCC within the context of kidney transplantation, before discussing the various clinical presentations, diagnostic measures, surveillance strategies, and current treatment options as well as future directions to best manage MCC in kidney transplant recipients. Full article

Psoriasis is a common genetic autoimmune disorder with a global prevalence of 2–3%. The clear pathogenesis of psoriasis is not fully understood, but hyperproliferation and inflammation of the epidermis with marked infiltration of immune cells have been indicated in psoriasis with such cells producing different types of cytokines- interleukin. As such a new member of the IL-1 cytokine family, in some research, IL-33 has been linked with psoriasis showing high serum concentration of IL-33 in human psoriatic plaques compared to normal healthy skin. Despite this, the association between IL-33 and psoriasis is not clear. Herein, in this review, we aim to investigate the correlation between serum IL-33 levels and psoriasis. We conducted meta-analysis using fixed or random-effects models to calculate pooled standard mean differences. We found that the mean IL-33 serum levels were reported between 0.35 pg/mL to 586 pg/mL in the psoriatic group and 0 pg/mL to 87.7 pg/mL in the healthy control group. Out of five, four individual studies included in the analysis reported statistically significant differences in IL-33 levels, the pooled estimate (SMD = 0.340 95% CI: −0.308 to 0.988), however, did not indicate a significant relation between IL-33 and psoriasis. This analysis revealed no significant difference between serum IL-33 levels in the psoriatic population in comparison to healthy controls. This may be because we did not include any animal studies, lab-based studies, any other markers mixed together, or any other cases of diseases mixed together. However, further research is warranted to confirm the reported association as this analysis is limited by the low-quality and observational nature of the included studies. Full article

Daily photoprotection (PhP) is essential in preventing harmful effects from solar ultraviolet radiation (UVR) exposure. For that reason, we interviewed students aged from 4 to 20 years old about their knowledge on sun exposure and PhP habits. Age, sex, family income, and skin phototype were statistically related to the proposed questions. Our results show that Brazilian youngsters do not have the habit of wearing long-sleeved clothing (<15% in summer), sunglasses (0.0%), or hats (2.1%). More than 40% had no knowledge about ultraviolet index (UVI), while another 30% misinterpreted what it is. Less than half of all students wear sunscreen when out in the sun. Despite this low PhP use-rate, more than 90% know that UVR causes skin cancers. Low income was the factor that showed the greatest number of significant relationships with respect to the lack of PhP. The findings suggest that current traditional PhP campaigns are not efficient. We propose that PhP should be part of school curricula from elementary school onwards. After all, the lack of educational programs predisposes these youngsters to an increased chance of skin diseases in the future. Full article

Acne tarda is defined as acne that develops (late-onset acne) or continues (persistent acne) after 25 years of age. The disease is more common in women. The etiology of acne tarda is still controversial, and a variety of factors such as endocrinological disorders including hyperandrogenism and hyperandrogenemia, stress, modern western diet, ultraviolet irradiation, drugs and cosmetics have been implicated. In particular, women with acne tarda and other symptoms of hyperandrogenism such as hirsutism and androgenetic alopecia have a high probability of endocrine abnormalities such as polycystic ovarian syndrome, primary ovarian insufficiency, Cushing’s syndrome and late-onset adrenogenital syndrome. Virilization is a relatively uncommon feature of hyperandrogenemia and its presence often suggests an androgen-producing tumor. Treatment is similar to that of acne in adolescence; however, long-term treatment over years or decades may be required. A thorough history, a focused clinical examination and an interdisciplinary approach together with gynecologists and endocrinologists are extremely helpful in diagnostic evaluation and therapy of patients with acne tarda. Full article

X-ray diffraction is one of the powerful tools in the study of a variety of structures in the stratum corneum at the molecular level. Resolving structural modifications during functioning is an important subject for clarifying the mechanism of operating principles in the function. Here, the X-ray diffraction experimental techniques used in the structural study on the stratum corneum are widely and deeply reviewed from a perspective fundamental to the application. Three typical topics obtained from the X-ray diffraction experiments are introduced. The first subject is concerned with the disruption and the recovery of the intercellular lipid structure in the stratum corneum. The second subject is to solve the moisturizing mechanism at the molecular level and the maintenance of normal condition with moisturizer, being studied with special attention to the structure of soft keratin in the corneocytes in the stratum corneum. The third subject is the so-called 500 Da rule in the penetration of drugs or cosmetics into skin, with attention paid to the disordered intercellular lipid structure in the stratum corneum. Full article

There is increasing evidence of adverse events associated with the use of COVID-19 vaccines. Here, we report a case of the SARS-CoV-2-vaccination-related onset of pityriasis rubra pilaris (PRP) and provide an analysis of previously reported cases in the medical literature. A 67-year-old male presented with a 1-year history of histopathologically proven PRP that first developed 14 days after receiving a COVID-19 booster vaccination. Skin symptoms improved under ustekinumab medication after unsuccessful previous treatment approaches using systemic corticosteroids, brodalumab, and risankizumab. Among the published cases of post-COVID vaccination PRP, 12 (75%) males and 4 (25%) females were reported. The median age of the reported patients was 59 years. In 10 out of 16 patients (62.5%), PRP was diagnosed after the first vaccine dose, in 4 (25%) after the second dose, and in 2 of 15 patients (12.5%) after the third dose. The median time between COVID-19 vaccination and the onset of PRP was 9.5 days (range: 3–60 days). The majority of patients required systemic treatment, including systemic retinoids and methotrexate. PRP might be a rare adverse event after COVID-19 vaccination, particularly affecting older males. Even though most reported patients with COVID-19-vaccination-related PRP could be successfully treated with PRP standard medications, therapy refractory cases may also occur. Thus, clinicians must be aware of this rare but potentially severe complication. Full article

Cutaneous squamous cell carcinoma (cSCC) is one of the most prevalent neoplasms worldwide. Important risk factors for cSCC include sun exposure, immunosuppression, pale skin, and aging. White people are more likely to develop cSCC, and men are more affected than women. In advanced cases, surgery and/or radiotherapy are no longer effective. Due to a historical lack of treatment options, some medications have been used in these patients without sufficient recommendation. There is an urgent need to identify patients at an increased risk of recurrence and spread early for timely diagnosis and treatment. Despite extensive data on the high-risk features and prognostication, considerable variation remains globally regarding high-risk cSCC and the delivery of oncology services. The current comprehensive review evaluated and summarized contemporary knowledge of various management options for cSCC to simplify the integrated treatment plans. Full article

The high metastasis and mortality rates of melanoma in the era of chemotherapy have decreased significantly over the last 10 years. The success is owed largely to the introduction of targeted therapy of oncogenes and immunotherapies, such as checkpoint inhibitors. The aim of the present retrospective, monocentric study is to investigate the impact of chemotherapy or immunotherapy in 550 patients with metastatic melanoma between the years of 2010 and 2019, looking at overall survival while considering BRAF/NRAS/c-KIT mutation status. A total of 17 patients were found to have a c-KIT mutation in exon 11, 13 or 17, including 58.3% with acral lentiginous melanoma, with 53% localized primarily in the lower limbs. In 13.3% of the 231 NRAS-mutated melanomas, primary tumor location was found to be in UV-exposed skin such as on the head and neck, thus about 50% lower than in the 302 patients with wild-type (BRAF-/NRAS-/cKIT-negative) melanoma. Patients with NRAS-mutated melanomas had a significantly lower probability of survival compared to patients with wild-type melanomas, irrespective of the recommendations of the clinical guideline on drug therapy for metastatic melanoma that have been in force since 2010. In contrast to patients with wild-type melanoma who showed a higher probability of survival receiving immune checkpoint inhibitors, the overall survival of patients with NRAS-mutated metastatic melanoma was not more favorable after therapy with immune checkpoint inhibitors compared to chemotherapy treatment. Full article

The effects of orally consumed probiotics on skin wrinkles and dryness are not fully known. A randomized, placebo-controlled, triple-blinded study was conducted with 148 healthy Korean female volunteers aged between 33 and 60 years, who were administered 1.75 × 10⁹ colony-forming units (CFUs) of Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) (N = 74) or matching placebo (N = 74) for 12 weeks. Facial wrinkles (with 3-dimensional (3D) imaging), skin hydration, transepidermal water loss (TEWL), elasticity, and gloss were assessed at baseline and after every 4 weeks of the intervention. Questionnaire-based subjective evaluations of product efficacy and usability were also analyzed. The consumption of Bl-04 was safe and ameliorated significantly facial skin wrinkle parameters (total wrinkle area and volume, average depth of wrinkles, and arithmetic average roughness (Ra)) versus placebo at 4 weeks, but there were no differences at Week 8 or 12 between groups. Skin hydration, TEWL, elasticity, and gloss were similar between treatment groups, as were the subjective evaluation scores. Oral consumption of Bl-04 indicated promising short-term effects on skin appearance from the winter toward the spring. In future study designs, special attention should be paid to environmental conditions as well as to the skin condition and age of the participants. Full article

There has recently been an increased interest in the use of novel automated technologies for the early detection of skin malignancies. We performed a retrospective analysis of the clinical effectiveness of electrical impedance spectroscopy (EIS) in detecting malignancies in an everyday clinical setting. After a thorough visual examination and dermoscopy, 909 abnormal lesions suspicious for malignancy were detected in 481 patients who presented in a private dermatology practice between 2015 and 2017 and evaluated with the EIS system. The histopathological results of the excised lesions were compared to the Neviscore, the output of the device. In total, 443 lesions (49%) received a negative Neviscore and were thus benign. On the other hand, 466 lesions received a positive Neviscore, indicating aberrations of the physiological cell structure. Of the 909 lesions, 45% were excised after visual and EIS examination. Of the excised lesions, 16% were diagnosed histopathologically as malignant. The EIS detected melanomas with 100% accuracy. The number needed to excise decreased from 17.5 to 7.8. The predictive value for a negative Neviscore was 98.9% (true negative results). EIS was found to be a valuable adjunct support tool when making clinical assessments of potentially malignant lesions. Full article

The purpose was to evaluate the prognostic performance of the derived neutrophil–to-lymphocyte ratio (dNLR) in patients with metastatic cutaneous melanoma (CM) treated with immune checkpoint inhibitors (ICI). We retrospectively investigated 41 CM patients with stage IV disease who had the indication for treatment with ICI. dNLR as well as NLR were routinely determined prior to the start of ICI treatment. The dNLR and NLR were calculated as follows: dNLR = absolute neutrophil counts (ANC)/white blood cell count −ANC and NRL = ANC/absolute lymphocyte counts, respectively. Follow-up of the patients was performed in line with current guidelines. In univariate analysis, dNLR (p = 0.027 and p = 0.032) as well as NLR (p = 0.0023 and p = 0.0036) were the only parameters which were significantly associated with the best overall response (BOR) and disease control rate (DCR) on ROC curve analyses. NLR negatively correlated with CM-specific survival (r = −0.32, p = 0.043). CM-specific deaths were significantly associated with the absence of immune-related adverse events (p = 0.043), elevated S100 calcium-binding protein B (S100B) at baseline (p = 0.0006), and dNLR (p = 0.024). In multivariate analyses, NLR was the only significant independent predictor for BOR (p = 0.014; odds ratio: 1.7; and 95% CI 1.11 to 2.61) and DCR (p = 0.019; odds ratio: 1.5; and 95% CI 1.07 to 2.19). Regarding CM-specific death, however, normal baseline S100B was the only significant independent predictor (p = 0.0020; odds ratio: 0.074; and 95% CI 0.014 to 0.38) for survival. Our data demonstrate that baseline NLR seems to be superior to dNLR in the prediction of ICI response in CM patients. Full article