Correlations between Gut Microbiota and Hematological, Inflammatory, Biochemical and Oxidative Stress Parameters in Treatment-Naïve Psoriasis Patients.

Psoriasis is an inflammatory dermatosis with a complex pathogenesis, significantly impacting the quality of life of patients. The role of oxidative stress and gut microbiota in the pathogenesis of this disease is increasingly studied, appearing to underlie the comorbidities associated with this condition. We present the first prospective observational study conducted in Romania evaluating the interrelationship between gut microbiota and hematological, inflammatory, biochemical, and oxidative stress parameters in treatment-naïve psoriasis patients. Significant differences were observed in terms of microbiota composition, with lower levels of Firmicutes and Enterobacteriaceae in the psoriasis group compared to the control group. Moreover, a negative correlation was found between the serum triglyceride levels in patients with psoriasis and the Enterobacteriaceae family (p = 0.018, r = -0.722), and a positive correlation was found between the serum glucose levels and the Firmicutes/Bacteroides ratio (p = 0.03, r = 0.682). Regarding the oxidant-antioxidant status, a significant correlation was found between the FORT level and Lactobacillus (p = 0.034, r = 0.669). Lastly, the Firmicutes level negatively correlated with the DLQI level, independent of the clinical severity of the disease (p = 0.02, r = -0.685). In conclusion, even though the number of included patients is small, these results may serve as a starting point for future research into the involvement of the microbiota-inflammation-oxidative stress axis in psoriasis development.

The Importance of In Vivo Reflectance Confocal Microscopy in a Case of Desmoplastic Melanoma.

Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma.

Digitally Enhanced Methods for the Diagnosis and Monitoring of Treatment Responses in Actinic Keratoses: A New Avenue in Personalized Skin Care.

Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist's life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens.

Oxidative Stress and Inflammation Levels in a Population of Eastern European Naïve Versus Treated Psoriasis Patients.

Psoriasis is a chronic inflammatory disease, with a major impact on the patients' quality of life. Oxidative stress (OS) is represented by the imbalance between oxidant and antioxidant mechanisms of the organism, with increased levels being described in the majority of chronic diseases. We present the first prospective study in Romania to evaluate the redox balance changes (using a CR3000 analyzer) in patients with moderate-severe psoriasis based on treatment regimens: treatment-naïve (A), treatment with novel targeted agents (B) and methotrexate (C). The study group included 53 Caucasian patients divided into three groups (A- 27 patients, B - 15 patients, and C - 11 patients) for which OS, antioxidant status, standard blood count, and inflammatory status were evaluated. Our findings demonstrate that patients with psoriasis display high levels of OS, with elevated Free Oxygen Radical Test (FORT) (p-value for group A (pA)<0.0001, p-value for group B (pB)=0.0019 and p-value for group C (pC)=0.0063) and reduced Free Oxygen Radical Defense (FORD) (pB=0.018) values noted in our subjects. Higher erythrocyte sedimentation rate (ESR) values were detected in groups B (pB=0.00012) and C (pC<0.00001). Psoriasis treatments alleviate FORT and FORD levels, but their impact is not sufficient to restore the oxidative balance to normal ranges. Moreover, despite adequate treatment, patients with psoriasis display elevated inflammation levels. Future research should explore in more detail the interplay between OS and inflammation in psoriasis, namely the long-term impact on the redox balance of biotherapies.

Antimicrobial Biomaterials for Chronic Wound Care.

Chronic wounds encompass a myriad of lesions, including venous and arterial leg ulcers, diabetic foot ulcers (DFUs), pressure ulcers, non-healing surgical wounds and others. Despite the etiological differences, chronic wounds share several features at a molecular level. The wound bed is a convenient environment for microbial adherence, colonization and infection, with the initiation of a complex host-microbiome interplay. Chronic wound infections with mono- or poly-microbial biofilms are frequent and their management is challenging due to tolerance and resistance to antimicrobial therapy (systemic antibiotic or antifungal therapy or antiseptic topicals) and to the host's immune defense mechanisms. The ideal dressing should maintain moisture, allow water and gas permeability, absorb wound exudates, protect against bacteria and other infectious agents, be biocompatible, be non-allergenic, be non-toxic and biodegradable, be easy to use and remove and, last but not least, it should be cost-efficient. Although many wound dressings possess intrinsic antimicrobial properties acting as a barrier to pathogen invasion, adding anti-infectious targeted agents to the wound dressing may increase their efficiency. Antimicrobial biomaterials may represent a potential substitute for systemic treatment of chronic wound infections. In this review, we aim to describe the available types of antimicrobial biomaterials for chronic wound care and discuss the host response and the spectrum of pathophysiologic changes resulting from the contact between biomaterials and host tissues.

Nevus Sebaceous of Jadassohn in Adults-Can Reflectance Confocal Microscopy Detect Malignant Transformation?

Nevus sebaceous of Jadassohn (NSJ) is a rare congenital lesion that affects the adnexal structures of the skin. It is typically located on the scalp and face of females and presents as a well-defined, slightly elevated, yellow lesion. It is also linked to a high risk of secondary tumors, which are more frequently benign than malignant. In vivo reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides a horizontal image of the skin with a resolution similar to histology. We report a case of basal cell carcinoma (BCC) developed in an NSJ with its dermoscopic, confocal, and histopathological features. A 49-year-old female presented with a well-circumscribed, 1 cm-diameter verrucous, yellowish lesion surrounded by a poorly defined, slightly erythematous, translucent plaque, located on the scalp in the temporoparietal region, which had been present since birth, grew at puberty, and changed its appearance in the last three years. Dermoscopy of the central lesion revealed yellow globules grouped into clusters, with peripheral linear and arborescent thin vessels, surrounded by several translucent nodular lesions with fine, arborizing vessels. RCM examination showed large, monomorphic cells with a hyperreflective periphery and a hyperreflective center located on the central lesion, corresponding to sebocytes, surrounded by multiple dark silhouettes lined with hyperreflective bands of thickened collagen, corresponding to tumor islands. The histopathological findings confirmed the diagnosis of BCC developed on an NJS. RCM can be a useful technique for the non-invasive examination and monitoring of these lesions, taking into account their transformation risk and preventing unnecessary excisions that might have a detrimental aesthetic impact on patients.

Correlations between Histopathological and Confocal Reflectance Microscopy Aspects in a Patient with Bowenoid Papulosis.

Bowenoid papulosis is a cutaneous disease that is part of the spectrum of genital in situ carcinomas, caused primarily by infection with oncogenic strains of the HPV virus. The potential to transform into squamous cell carcinoma requires the diagnosis and treatment of the lesions. We present the case of a 34-year-old non-smoker without medical history who presented to our clinic for the appearance of multiple, asymptomatic, well-defined, flat, pigmented violaceous papules at the root of the penis in evolution for a year. Reflectance confocal microscopy (RCM) suggested the diagnosis of bowenoid papulosis, which was confirmed by histopathological examination. The treatment with Imiquimod 5% (3 times/week) and Isoprinosine (4 g/day) was initiated, followed by monitoring of the lesions by repeated RCM examination. The evolution of the patient at 6 weeks of therapy was favourable, with clinical remission of lesions and improvement in RCM aspects of the evaluated skin. In conclusion, RCM represents a useful noninvasive examination method that allows not only the diagnosis but also the follow-up of the treatment response in order to decide the appropriate length of therapy.

Subepidermal Low-Echogenic Band-Its Utility in Clinical Practice: A Systematic Review.

High-frequency ultrasonography (HF-USG) is a relatively new imaging method that allows the evaluation in a non-invasive manner of the skin layers and skin appendages. It is a diagnostic tool with increasing usefulness in numerous dermatological pathologies. High reproducibility, non-invasiveness and short diagnostic time make this method an increasingly used tool in dermatological practice. The subepidermal low-echogenic band is a relatively newly described parameter that seems to be a marker not only of intrinsic and extrinsic skin aging, but also of inflammatory processes taking place at the skin level. This systematic review aims to evaluate the role that SLEB has in the diagnosis and monitoring of the treatment of some inflammatory and non-inflammatory dermatological conditions, as well as its utility as a disease marker.

In Vivo Characterization of Mucin and Amyloid Deposits in Primary Basal Cell Carcinoma through Reflectance Confocal Microscopy: A Correlation with Histopathology.

Basal cell carcinoma (BCC) is the most common keratinocyte carcinoma and the most prevalent skin cancer in humans, worldwide. BCC is histologically characterized by the proliferation of basaloid cells, arranged in globular masses of varying size, often separated from the surrounding stroma by optically empty spaces. Although attributed to tumor retraction during tissue processing for the preparation of pathology slides, these spaces are also seen on cryostat sections. The aim of this study is to in vivo characterize amyloid and mucin deposits in primary BCC lesions through RCM, followed by histopathological correlation. We included twenty-two consecutive subjects totaling thirty-one primary BCCs. Each lesion underwent the same evaluation protocol which included: clinical and dermoscopic images, RCM imaging, excisional biopsy under local anesthesia, and histopathological examination (colloidal iron and cytokeratin 34betaE12 stains). Hypo-reflective peritumoral clefts and hyper-reflective globules were measured on RCM images and compared to mucin and amyloid deposits seen on histology slides. The mean differences between RCM and histology measurements in both mucin and amyloid were not statistically significant. There were medium and strong correlations between RCM and histology regarding mucin and amyloid deposits, respectively.

Vasculitis-Like Hemorrhagic Herpes Zoster and HIV Infections: An Intricate Association.

Herein, we report the case of a 69-year-old patient who presented to our dermatology clinic for a skin eruption characterized by grouped hemorrhagic vesicles and erosions covered by hemorrhagic crusts on an erythematous background located on the lower right limb. The lesions were small, clustered, and variable in size (diameters between one and 10 mm) and located at the level of the L4-L5 dermatomes. The rash had started three to five days after the complete COVID-19 vaccination scheme with the BNT162b2 Pfizer BioNTech vaccine and had been accompanied by a flu-like syndrome. The histopathological examination established the diagnosis of leukocytoclastic vasculitis potentially in the context of a cytopathic zoster phenomenon. The atypical aspect of the zosterian eruption required additional laboratory work-up to identify possible causes of immunosuppression, i.e., screening for the presence of the human immunodeficiency virus (HIV) infection, solid cancers, as well as measurement of serum immunoglobulin concentrations, which revealed that the subject was HIV-positive. Antiviral treatment was started, with a favorable evolution of the lesions, and the patient was referred to an infectious diseases clinic for initiation of antiretroviral therapy (ART).

The CSIESA: A Novel Score for the Assessment of Intrinsic and Extrinsic Skin Aging Based on Reflectance Confocal Microscopy Imaging.

Skin aging is an intricate physiological process governed by intrinsic and extrinsic factors. Increasing life expectancy has turned skin aging into a growing concern for the general population. Clinical examination of the skin does not fully describe the skin aging process. This study aims to evaluate the healthy skin of five different age groups in order to develop an easy-to-use confocal score for quantifying signs of skin aging and test the correlation between this new score and the already described clinical score, SCINEXA (score of intrinsic and extrinsic skin aging). Thirty-five subjects split into five age groups: <35; 36−45; 46−55; 56−65, and >65 years old were enrolled. Clinical signs were quantified using the SCINEXA score, and known confocal variables of skin aging were evaluated. Three different semi-quantitative scores were calculated: epidermal disarrangement score (EDS), epidermal hyperplasia score (EHS), and dermal score (DS). The EDS showed a stable trend up to the age of 65 and a dramatic increase in older subjects. EHS was characterized by an ascending trend from younger subjects to middle-aged ones. The DS was progressive with age, with a different proportion of distinct collagen types. The confocal CSIESA (confocal score for the assessment of intrinsic and extrinsic skin aging) score correlated well with the SCINEXA score. Reflectance confocal microscopy is a powerful, non-invasive technique for microscopically quantifying aging signs.

Feasibility of Reflectance Confocal Microscopy Monitoring in Oily, Acne-Prone Facial Skin Treated with a Topical Combination of Alpha and Beta-Hydroxy Acids, Anti-Inflammatory Molecules, and Herculane Thermal Water: A Blinded, One-Month Study.

Oily, acne-prone skin is a common skin type which may be monitored in vivo using reflectance confocal microscopy (RCM). The aim of the study was to assess the feasibility of RCM in evaluating the effectiveness of a topical combination of alpha- and beta-hydroxy acids, anti-inflammatory and antibacterial molecules, and Herculane thermal water on acne-prone skin. Thirty-five subjects with oily, acne-prone skin were prescribed topical combination products and were evaluated by clinical, Wood's lamp, and RCM imaging at baseline and after 28 days. At 28 days, the RCM-evaluated number of dilated infundibula, infundibula filled with keratotic material, and infundibula with thickened bright borders, as well as the density of the inflammatory infiltrate, were significantly decreased. Wood's light images at 28 days showed a significantly reduced number of C. acnes-colonized infundibula, and both the median area and the intensity of the red-orange fluorescence were decreased. The reduction in the clinical score was concurrent with the improvement in the RCM parameters, suggesting that this non-invasive imaging technique is appropriate for efficiency evaluations of topical acne treatments.

A Case of Multinucleate Cell Angiohistiocytoma with New Reflectance Confocal Microscopy Findings.

Multinucleate cell angiohistiocytoma (MCAH) is a rare, benign, vascular or fibrohistiocytic tumor usually presenting as single or multiple, reddish-brown papules mostly affecting the limbs and dorsum of the hands of middle-aged females. Since 1985, relatively few MCAH cases have been reported. In vivo reflectance confocal microscopy (RCM) findings of MCAH have never been described. We report a case of MCAH with new non-invasive imaging findings through RCM in correlation with dermoscopy and histopathology. A 66-year-old woman with an unremarkable family and personal history of an atypical nevus presented with a lesion on her right breast. It had appeared 12 months earlier and progressively enlarged. Physical examination revealed a 20 × 11.6 mm, non-tender, reddish-brown maculo-papular lesion with blurred margins. Dermoscopy showed diffusely arranged reddish areas, coalescing whitish patches, truncated and dotted vessels, and a peripheral brown reticulated pattern. RCM revealed a poorly outlined lesion with a normal honeycomb pattern, numerous vessels at the dermal-epidermal junction, and isolated, large, mildly reflective, bizarre structures with angulated edges. These findings correlated well with histological features, which established the diagnosis of MCAH. Even though histopathology remains the gold standard in the diagnosis of MCAH, non-invasive tools such as RCM can help rule out other entities, therefore reducing surgery-associated morbidity.

Healthcare Disparities in the Management of Indolent Mycosis Fungoides.

Mycosis fungoides represents the most common cutaneous T-cell lymphoma, clinically manifested with evolving skin lesions, including patches, plaques, tumors, and erythroderma. Early diagnosis remains difficult to establish because it mimics several benign skin conditions, but maintaining a high index of suspicion for the disease is essential in preventing the progression of a potentially fatal disease. We report the case of a 69-year-old female who presented in our dermatology clinic in 2018 with scaly, indurated, itchy erythematous-violaceus patches and plaques, and tumors disseminated throughout the skin evolving for nine years. Skin biopsy supplemented with immunohistochemical staining established the diagnosis of mycosis fungoides. Due to the equivocal clinical presentation and the lack of extracutaneous manifestations, the patient received conventional therapy according to the stage of the disease. The rapidly progressive evolution of the cutaneous lesions in the last year of the disease determined the patient's death despite instituting systemic chemotherapy. Patient follow-up and a multidisciplinary approach are essential to diagnose and manage this disease in its early stages. This will prevent the progression to a life-threatening malignancy and the use of immunosuppressive therapy, which can cause serious side effects.

Diagnosis and Treatment Challenges of an Atypical Case of Pemphigus vulgaris During the COVID-19 Pandemic.

Pemphigus defines a group of rare autoimmune blistering diseases that affect the skin and mucous membranes, with pemphigus vulgaris being the most common form that has increased morbidity and mortality in the absence of an early diagnosis and treatment. We report the case of a 24-year-old male with an atypical form of pemphigus vulgaris with cutaneous onset and subsequent involvement of the oral cavity. The management of the patient initially consisted of long-term systemic corticosteroid therapy. Following a mild form of SARS-CoV-2 infection and a flare-up of the disease in this context, which was not controlled with high doses of systemic corticosteroids, targeted therapy with rituximab was initiated but immediately stopped due to the manifestations of urticaria and angioedema. Considering the magnitude of these reactions, dapsone systemic therapy i.e., a steroid-sparing agent with minimal risk of infections, was started and managed to control the underlying disease. The management of this case of pemphigus vulgaris was challenging for both the patient and his physician, as the patient developed COVID-19 which caused disease complications and implied additional costs. This case highlights the importance of an accurate diagnosis given the atypical onset of the disease and the financial limitations with the impossibility of performing all confirmatory diagnostic tests.

The Involvement of Oxidative Stress in Psoriasis: A Systematic Review.

Psoriasis is a chronic, immune-mediated inflammatory dermatosis characterized by the appearance of erythematous plaques, covered by white scales, occasionally pruritogenic, and distributed mainly on the extensor areas. Oxidative stress is defined as an imbalance or a transient or chronic increase in the levels of free oxygen/nitrogen radicals, either as a result of the exaggerated elevation in their production or the decrease in their ability to be eliminated by antioxidant systems. Although the pathogenesis of psoriasis remains far from elucidated, there are studies that delineate an involvement of oxidative stress in this skin disorder. Thus, a systematic search was computed in PubMed/Medline, Web of Science and SCOPUS and, in total, 1293 potentially eligible articles exploring this research question were detected. Following the removal of duplicates and the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 995), 298 original articles were selected for full-text review. Finally, after we applied the exclusion and inclusion criteria, 79 original articles were included in this systematic review. Overall, the data analyzed in this systematic review point out that oxidative stress markers are elevated in psoriasis and share an association with the duration and severity of the disease. The concentrations of these biomarkers are impacted on by anti-psoriasis therapy. In addition, the crosstalk between psoriasis and oxidative stress is influenced by several polymorphisms that arise in genes encoding markers or enzymes related to the redox balance. Although the involvement of oxidative stress in psoriasis remains undisputable, future research is needed to explore the utility of assessing circulating serum, plasma, urinary and/or skin biomarkers of oxidative stress and of studying polymorphisms in genes regulating the redox balance, as well as how can these findings be translated into the management of psoriasis, as well in understanding its pathogenesis and evolution.

Poroid Hidradenoma: Dermoscopic and In Vivo Reflectance Confocal Microscopic Description.

Poroid hidradenoma (PH) is a rare, benign adnexal neoplasm usually presenting as a solitary, well circumscribed, asymptomatic papule or nodule that appears reddish and is occasionally tender. Since 1990, only a few cases of PH have been reported. We present a case of PH on the medial surface of the thigh and describe, for the first time, the dermoscopic and reflectance confocal microscopic (RCM) features in correlation with histology. A 67-year-old woman with unremarkable family or past medical history presented with a nodular lesion on the medial surface of the right thigh. The lesion had appeared 4 months earlier and rapidly enlarged. Physical examination revealed a 7 × 5 mm, non-tender, reddish nodule with clinically distinct margins. Dermoscopy showed central blue-grey pigmented areas, a polymorphous vascular pattern with arborizing, glomerular and hairpin vessels surrounded by white halos. RCM revealed an ovoid, well-outlined tumor, with a central area containing cells with distinctive morphologies, two types of tumor cells, tubular hypo-reflective structures, and rectilinear vessels in the stroma. These findings correlated with histological features, which established the diagnosis of PH. Even though the diagnosis of PH remains histopathological, non-invasive tools, such as RCM, can help rule out several malignancies, therefore reducing surgical-associated comorbidity.

Artificial Intelligence-Based Approaches to Reflectance Confocal Microscopy Image Analysis in Dermatology.

Reflectance confocal microscopy (RCM) is a non-invasive imaging method designed to identify various skin diseases. Confocal based diagnosis may be subjective due to the learning curve of the method, the scarcity of training programs available for RCM, and the lack of clearly defined diagnostic criteria for all skin conditions. Given that in vivo RCM is becoming more widely used in dermatology, numerous deep learning technologies have been developed in recent years to provide a more objective approach to RCM image analysis. Machine learning-based algorithms are used in RCM image quality assessment to reduce the number of artifacts the operator has to view, shorten evaluation times, and decrease the number of patient visits to the clinic. However, the current visual method for identifying the dermal-epidermal junction (DEJ) in RCM images is subjective, and there is a lot of variation. The delineation of DEJ on RCM images could be automated through artificial intelligence, saving time and assisting novice RCM users in studying the key DEJ morphological structure. The purpose of this paper is to supply a current summary of machine learning and artificial intelligence's impact on the quality control of RCM images, key morphological structures identification, and detection of different skin lesion types on static RCM images.