An Update on Non-Invasive Skin Imaging Techniques in Actinic Keratosis-A Narrative Review.

Nonmelanocytic skin cancers (NMSCs) are currently the most common group of human cancers and include all tumors that are not melanomas. Increased exposure to sunlight over the past few years, the lack of regular and proper use of sunscreen, the aging of the population, and better screening techniques are the reasons for the escalation in their diagnosis. Squamous cell carcinoma (SCC) comprises nearly 37% of the tumors in this group and can originate from actinic keratosis (AK), which usually presents as pink, often scaly plaques, usually located on the face or scalp. Advances in dermatoscopy, as well as the development of other non-invasive skin imaging modalities such as high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT), have allowed for greatly increased sensitivity in diagnosing these lesions and monitoring their treatment. Since AK therapy is usually local, and SCCs must be removed surgically, non-invasive imaging methods enable to correctly qualify difficult lesions. This is especially important given that they are very often located on the face, and achieving an appropriate cosmetic result after treatments in this area is very important for the patients. In this review, the authors describe the use of non-invasive skin imaging methods in the diagnosis of actinic keratosis.

Characteristics of pruritus in various clinical variants of psoriasis: Final report of the binational, multicentre, cross-sectional study.

BACKGROUND: Pruritus, which is the most frequent subjective symptom of psoriasis, may cause significant discomfort, embarrassment and even interfere with patients normal daily activities. However, the perception of itch in various psoriasis subtypes remains unknown. OBJECTIVES: The aim of this study was to investigate and to characterize pruritus in different clinical variants of psoriasis. METHODS: This cross-sectional, binational, multicentre study included 295 subjects suffering from nine different clinical subtypes of psoriasis: large-plaque psoriasis (n = 45), nummular psoriasis (n = 32), guttate psoriasis (n = 31), scalp psoriasis (n = 32), inverse psoriasis (n = 23), erythrodermic psoriasis (n = 33), palmoplantar psoriasis vulgaris (n = 33), palmoplantar pustular psoriasis (n = 42) and generalized pustular psoriasis (n = 23). Measures included sociodemographic and anthropometric data, detailed pruritus characteristics including but not limited to pruritus intensity, frequency and extend, as well as psoriasis severity. RESULTS: The lifetime prevalence of pruritus in each clinical variant of psoriasis was similar and quite high, reaching up to 100% in some disease subtypes (i.e., nummular psoriasis, scalp psoriasis and generalized pustular psoriasis). Psoriasis severity correlated with pruritus intensity in scalp psoriasis, palmoplantar pustular psoriasis and generalized pustular psoriasis. The age, duration of psoriasis and BMI did not interfere with the intensity of itch. CONCLUSIONS: Pruritus is highly prevalent in each clinical variant of psoriasis. However, the sensation of itch is very individual, difficult to universally describe even in the same subtype.

Pathomechanism of Pruritus in Psoriasis and Atopic Dermatitis: Novel Approaches, Similarities and Differences.

Pruritus is defined as an unpleasant sensation that elicits a desire to scratch. Nearly a third of the world's population may suffer from pruritus during their lifetime. This symptom is widely observed in numerous inflammatory skin diseases-e.g., approximately 70-90% of patients with psoriasis and almost every patient with atopic dermatitis suffer from pruritus. Although the pathogenesis of atopic dermatitis and psoriasis is different, the complex intricacies between several biochemical mediators, enzymes, and pathways seem to play a crucial role in both conditions. Despite the high prevalence of pruritus in the general population, the pathogenesis of this symptom in various conditions remains elusive. This review aims to summarize current knowledge about the pathogenesis of pruritus in psoriasis and atopic dermatitis. Each molecule involved in the pruritic pathway would merit a separate chapter or even an entire book, however, in the current review we have concentrated on some reports which we found crucial in the understanding of pruritus. However, the pathomechanism of pruritus is an extremely complex and intricate process. Moreover, many of these signaling pathways are currently undergoing detailed analysis or are still unexplained. As a result, it is currently difficult to take an objective view of how far we have come in elucidating the pathogenesis of pruritus in the described diseases. Nevertheless, considerable progress has been made in recent years.

Role of Mast Cells in the Pathogenesis of Pruritus in Mastocytosis.

Pruritus can be defined as an unpleasant sensation that evokes a desire to scratch and significantly impairs patients' quality of life. Pruritus is widely observed in many dermatoses, including mastocytosis, a rare disease characterized by abnormal accumulation of mast cells, which can involve skin, bone marrow, and other organs. Increasing evidence highlights the role of mast cells in neurogenic inflammation and itching. Mast cells release various pruritogenic mediators, initiating subsequent mutual communication with specific nociceptors on sensory nerve fibres. Among important mediators released by mast cells that induce pruritus, one can distinguish histamine, serotonin, proteases, as well as various cytokines. During neuronal-induced inflammation, mast cells may respond to numerous mediators, including neuropeptides, such as substance P, neurokinin A, calcitonin gene-related peptide, endothelin 1, and nerve growth factor. Currently, treatment of pruritus in mastocytosis is focused on alleviating the effects of mediators secreted by mast cells. However, a deeper understanding of the intricacies of the neurobiology of this disease could help to provide better treatment options for patients.

Convolutional neural networks for the detection of malignant melanoma in dermoscopy images.

INTRODUCTION: Convolutional neural networks gained popularity due to their ability to detect and classify objects in images and videos. It gives also an opportunity to use them for medical tasks in such specialties like dermatology, radiology or ophthalmology. The aim of this study was to investigate the ability of convolutional neural networks to classify malignant melanoma in dermoscopy images. AIM: To examine the usefulness of deep learning models in malignant melanoma detection based on dermoscopy images. MATERIAL AND METHODS: Four convolutional neural networks were trained on open source dataset containing dermoscopy images of seven types of skin lesions. To evaluate the performance of artificial neural networks, the precision, sensitivity, F1 score, specificity and area under the receiver operating curve were calculated. In addition, an ensemble of all neural networks' ability of proper malignant melanoma classification was compared with the results achieved by every single network. RESULTS: The best convolutional neural network achieved on average 0.88 precision, 0.83 sensitivity, 0.85 F1 score and 0.99 specificity in the classification of all skin lesion types. CONCLUSIONS: Artificial neural networks might be helpful in malignant melanoma detection in dermoscopy images.

Landscape of current and future therapies of Merkel cell carcinoma.

Merkel cell carcinoma is rare and aggressive skin cancer, which occurrence is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus. In recent years, significant progress in understanding the mechanism of Merkel cell carcinoma pathogenesis has been observed. This neoplasm often expresses PD-L1, and MCPyV-specific T cells can express PD-1 thus PD-1/PD-L1 checkpoint therapies seem to be remarkably interesting treatment options. Many clinical trials are currently being conducted to confirm their effectiveness and safety for this group of patients. However, only about half of advanced Merkel cell carcinoma patients could achieve remission or disease stabilization through PD-1/PD-L1 checkpoint therapies thus innovative treatments are still needed. In this article, we have presented current and future directions in the development of Merkel cell carcinoma therapy.

Photodynamic Therapy in Pigmented Basal Cell Carcinoma-A Review.

This review summarizes the effectiveness of photodynamic therapy (PDT) in the treatment of the pigmented subtype of basal cell carcinoma (BCC) based on the current literature. PDT is a light-activated treatment, non-invasive, that selectively destroys tumor cells and tissues via the interaction of a photosensitizer, light, and molecular oxygen. It can induce cancer cell death through direct tumor vascular damage or via the induction of immune response. However, human skin is also an absorption and scattering medium since it contains hemoglobin and melanin that act as chromophores. Eumelanin can be considered a light-absorber and an intracellular antioxidant that can neutralize PDT-induced ROS and, therefore, decrease PDT success. Various factors, including tumor depth, the degree of pigmentation in malignant cells, and the individual's skin phototype, can impact the outcome of this intricate biochemical process. It has been widely recognized that PDT exhibits limited efficacy in the treatment of pigmented lesions. However, new combination techniques such as curettage or debulking before PDT show promising results in the treatment of pigmented BCC.

Reflectance Confocal Microscopy and Dermoscopy of Facial Pigmented and Non-Pigmented Actinic Keratosis Features before and after Photodynamic Therapy Treatment.

Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment regardless of the clinical stage. New imaging techniques, such as in vivo reflectance confocal microscopy (RCM), significantly increase the accuracy of diagnosis and allow noninvasive evaluation of the therapeutic efficacy of the ongoing treatment. Our objective was to evaluate the prevalence of specific (video)dermoscopy and RCM features of pigmented and classical subtypes of AK before and after photodynamic therapy (PDT) treatment. We included patients with facial grade II AKs (25 pigmented, 275 non-pigmented) were included in the study. Skin lesions were evaluated by (video)dermoscopy and RCM at the baseline and three months after PDT. In classic AK, the most frequent dermoscopic findings were fine wavy vessels (96%), scale (92%), microerosions (48%), and "strawberry" pattern (36%), while pigmented AK was characterized mostly by "rhomboidal pattern" (80%), scale (60%), white globules (48%), "jelly sign", and superficial pigmentation (40%). RCM's most characteristic classic AK findings were abnormal honeycomb pattern in the spinous layer, epidermal inflammatory infiltrate, and solar elastosis that were present in 96% of lesions. Pigmented AKs presented mostly with dark central areas of parakeratosis (72%), mottled pigmentation (72%), dermal inflammatory infiltrate (64%), solar elastosis (60%), and abnormal honeycomb pattern in the spinous layer (56%). Dermoscopically, PDT resulted in complete disappearance of the "rhomboidal pattern" in both classical and pigmented AKs, "starburst pattern" and "jelly sign" in classical AKs, and inner gray halo, "rosette sign" and central crust in pigmented AKs. Three months after one PDT session, RCM evaluation showed mostly solar elastosis in both classical and pigmented AK subtypes, epidermal inflammatory infiltrate in classical AKs, and dermal inflammatory infiltrate in pigmented AKs. New noninvasive imaging techniques such as RCM and (video)dermoscopy can help practitioners better visualize the efficacy of the ongoing PDT treatment in either classical or pigmented AK subtypes.

YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance.

Malignant melanoma, with its increasing incidence and high potential to form metastases, is one of the most aggressive types of skin malignancies responsible for a significant number of deaths worldwide. However, melanoma also demonstrates a high potential for induction of a specific adaptive anti-tumor immune response being one of the most immunogenic malignancies. Yin Yang 1 (YY1) transcription factor is essential to numerous cellular processes and the regulation of transcriptional and posttranslational modifications of various genes. It regulates programmed cell death 1 (PD1) and lymphocyte-activation gene 3 (LAG3) by binding to its promoters, as well as suppresses both Fas and TRAIL by negatively regulating DR5 transcription and expression and interaction with the silencer region of the Fas promoter, rendering cells resistant to apoptosis. Moreover, YY1 is considered a master regulator in various stages of embryogenesis, especially in neural crest stem cells (NCSCs) survival and proliferation as it acts as transcriptional repressor on cancer stem cells-related transcription factors. In addition, YY1 increases the metastatic potential of melanoma through negative regulation of microRNA-9 (miR-9) expression, acts as a cofactor of transcription factor EB (TFEB) and contributes to autophagy regulation, mainly due to increased transcription of genes related to autophagy and lysosome biogenesis. Therefore, focusing on the detailed biology and administration of therapies that directly target YY1 or crosstalk pathways in malignant melanoma could facilitate the development of new and more effective treatment strategies and improve patients' outcomes.

The Significance of Autoantibodies in Juvenile Dermatomyositis.

Juvenile dermatomyositis is a chronic and rare autoimmune disorder classified into the spectrum of idiopathic inflammatory myopathies. Although this entity is mainly characterized by the presence of pathognomonic cutaneous lesions and proximal muscle weakness, the clinical manifestation can be highly heterogeneous; thus, diagnosis might be challenging. Current treatment recommendations for juvenile dermatomyositis, based mainly upon case series, include the use of corticosteroids, immunomodulatory, and immunosuppressive agents. Recently, several specific autoantibodies have been shown to be associated with distinct clinical phenotypes of classic dermatomyositis. There is a need to further evaluate their relevance in the formation of various clinical features. Furthermore, while providing more personalized treatment strategies, one should consider diversity of autoantibody-related subgroups of juvenile dermatomyositis.

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature.

Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, long-term, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.

Characteristics of Pruritus in Various Clinical Variants of Psoriasis: Results of the Multinational, Multicenter, Cross-Sectional Study.

Psoriasis is a chronic, inflammatory skin disease present in about 3% of the world's population. The clinical symptoms manifest diversely, therefore one can distinguish several subtypes of psoriasis. The majority of patients with psoriasis experience pruritus, which is an unpleasant sensation that decreases patients' quality of life. The knowledge on pruritus in different subtypes of psoriasis is limited. We have performed a cross-sectional, prospective, and multicenter study to evaluate the relationship between clinical subtypes of psoriasis (large-plaque, nummular, guttate, palmoplantar, inverse, erythrodermic, palmoplantar pustular, generalized pustular psoriasis, and psoriasis of the scalp) and the prevalence, intensity, and clinical manifestation of itch. We introduced a questionnaire assessing various aspects of pruritus to a total of 254 patients. Out of these, 42 were excluded. Pruritus was present in 92.9% of the remaining patients and its prevalence did not depend on the clinical subtype. A correlation between the severity of psoriasis and the intensity of itch was explicitly noticeable in palmoplantar pustular psoriasis and scalp psoriasis (p < 0.05). The itch sensation was individual and differed among subtypes of psoriasis. In conclusion, pruritus is a frequent phenomenon, and its presentation is different in various subtypes of psoriasis.

Influence of an Alkoxylation Grade of Acrylates on Shrinkage of UV-Curable Compositions.

Commercially available UV curable restorative materials are composed of inorganic filler hydroxyapatite, multifunctional methacrylate, photoinitiator and alkoxylated acrylate. Especially, the application of alkoxylated monomers with different alkoxylation grade allows the reduction of polymerization shrinkage which plays the major role by application of low shrinkage composites as high quality restorative dental materials or other adhesive materials in the form of UV-polymerized self-adhesive acrylics layers (films). There are several ways to reduce polymerization shrinkage of restorative compositions, for example, by adjusting different alkoxylated acrylic monomers, which are integral part of investigated UV curable restorative composites. This article is focused on the studies of contraction-stress measured as shrinkage during UV-initiated curing of restorative composites containing various commercially available alkoxylated acrylates. Moreover, studies with experimental restorative materials and recent developments typical for UV curing technology using special photoreactive monomers are described.

Novel Photoreactive Pressure-Sensitive Adhesives (PSA) Based on Acrylics Containing Additionable Photoinitiators.

A new class of additionable ultraviolet photoinitiators that can be used, through addition, for modification of the acrylic polymer chain and their influence of main properties of acrylic pressure-sensitive adhesives (PSAs) is described here. The photoinitiators studied are based on benzophenone, dibenzofuran and anthraquinone chromophores. The propyleneimine carbonyl is the reactive additionable group incorporated in the photoinitiator structure. First, the solvent-borne acrylic pressure-sensitive adhesive was synthesized and characterized. Then, a photoinitiator suitable for addition to the acrylic polymer chain possessing a carboxyl group was added before UV-irradiation. A mechanism of UV-initiated cross-linking reaction of acrylic PSA with additionable photoinitiators was done as well. The influence of the concentration and type of photoinitiator, UV-crosslinking time and UV-dose on peel adhesion, shear strength and tack of solvent-borne acrylic pressure-sensitive adhesives cross-linked by UV light was studied and presented here. It was found that the tack depends on the UV-dose and photoinitiator concentration. An increase of UV dose results in an increase of shear strength of acrylic pressure-sensitive adhesive (PSA) formulations.

Onium salts improve the kinetics of photopolymerization of acrylate activated with visible light.

The aim was study the influence of onium salts on the kinetics of photopolymerization in the visible light region. Trimethylolpropane triacrylate TMPTA was selected as a monomer, and activated by 1,3-bis(phenylamino)squaraine (SQ) used as a photosensitizer in addition to tetramethylammonium n-butyltriphenylborate (B2). The iodonium salt [A-I-B]+X- functioned as a second radical initiator, bearing a different substitution pattern for the cation. The ternary system was formulated with different concentrations of both borate and diphenyliodonium salts. Differential scanning calorimetry was used to investigate the polymerization reaction over the photoactivation time carried out at 300 nm < λ < 500 nm irradiation. When the squaraine dye/borate salt was used as photoinitiator, a slow polymerization reaction was observed and a lower monomer conversion. The addition of a third component (onium salt) increased the polymerization rate and conversion. Ternary photoinitiator systems showed improvement in the polymerization rate of triacrylate leading to high conversion in a short photoactivation time. The photoinitiating ability of bi- and tri-component photoinitiators acting in the UV-Vis region for initiation polymerization of triacrylate was compared with those of some commercially used photoinitiating systems. It was also found, that, the parallel electron transfer from an excited state of the sensitizer to [A-I-B]+X-, and an electron transfer from a ground state of R(Ph)3B-N(CH3)4 + to an excited state of the sensitizer results in two types of initiating radical.

Beyond PD-1 Immunotherapy in Malignant Melanoma.

For many years, the standard therapy for malignant melanoma was based mainly on surgical resection. Unfortunately, this treatment is curative only in the early localized stage of this malignancy. The metastatic stage of malignant melanoma still remains a huge therapeutic challenge. Despite the many new therapeutic options that have become available over the last years, there is a constant need for safer and more effective treatment modalities. There has been a dynamic development of various anti-cancer immunotherapies directed against new molecular targets. A number of clinical trials are currently being conducted to confirm their effectiveness and safety. In this review of the literature, we summarize the contemporary knowledge on promising new immunotherapies beyond the currently available treatment options for malignant melanoma, including oncolytic immunotherapy, selective inhibitors of indoleamine 2,3-dioxygenease, anti-PD-(L)1 (programmed death ligand 1) drugs, immune checkpoint protein LAG-3 antibodies, inhibitors of histone deacetylase (HDAC) and inhibitors of B7-H3.

Delusions of Parasitosis: An Update.

Delusional parasitosis, also known as delusional infestation or Ekbom syndrome, is a relatively infrequent psychotic disorder characterized by an unwavering false belief that there is a parasitic infestation of the skin, despite the absence of any medical evidence that could support this claim. Delusional parasitosis can be categorized into primary, secondary, and organic forms. Sometimes, close relatives also experience identical delusions. This phenomenon was reported to occur in 5-15% of cases, and is known as shared psychotic disorder-delusional parasitosis with folie à deux. Patients with delusional parasitosis frequently seek help from many physicians. Close multidisciplinary cooperation between clinicians is often key to shortening the time taken to diagnose this disorder. Initiation of psychopharmacological therapy is a challenge, as many patients refuse any psychiatric treatment because of the stigma associated with mental illness and because of their firm belief that they have a parasitic infestation, not a psychiatric condition. For many patients, a sense of a lack of understanding leads to isolation and the development of depression symptoms, which is why it is crucial to earn the trust of such patients while taking care of them.