The Association of Telangiectasias with Other Peripheral Vascular Lesions of Systemic Sclerosis.

Purpose: Systemic sclerosis (SSc) is a relatively rare collagenosis manifested as microvasculopathy, excessive cutaneous and visceral fibrosis in a background of autoimmune alteration. Autoimmune vasculopathy in SSc occurs early and begins with endothelial cell activation followed by blood vessel intimal proliferation in a context of defective angiogenesis. The alteration of peripheral micro and macrocirculation in SSc is evident through vascular lesions, such as Raynaud's phenomenon, telangiectasias, acrocyanosis, digital ulcers, gangrene, peripheral pulse deficiency. Our paper details the results of the study on the association between telangiectasias and other types of immune-mediated peripheral vascular lesions that can be identified in SSc. The presence of these peripheral vascular lesions can provide information about the magnitude of the peripheral vasculopathy. Patients and Methods: A total of 37 patients diagnosed with SSc, recruited from a university clinic in Bucharest between February 2019 and March 2020, were enrolled in an observational study. We evaluated the presence of telangiectasias, as a stigma of autoimmune microvasculopathy, and their association with other immune-mediated peripheral vascular lesions that may be present in SSc. Results: The presence of telangiectasias was identified in the absence, but especially in the presence of acrocyanosis and digital ulcerations, and patients with peripheral pulse deficiency almost always had telangiectasias. Less than a quarter of the patients with digital ulcers progressed unfavorably to gangrene, and only one required amputation, telangiectasias being present not only in the patient with amputation but in all patients with gangrene. Conclusion: We appreciate that telangiectasias may be the clinical expression of peripheral vasculopathy characteristic of SSc, they can often be present in association with other peripheral vascular lesions and may represent a valuable indicator for the gangrene risk of digital ulcerations in SSc.

Pathogenesis of Musculotendinous and Fascial Injuries After Physical Exercise - Short Review.

Purpose: The identification of sports and physical exercises with injury risk is necessary to preserve the capacity of athletes and people who perform physical education and also to prevent the installation of functional deficiencies. Methods: We have selected the articles related to the pathogenic mechanisms involved in musculotendinous and fascial injuries produced as a result of physical exercise. Results and Discussions: The lesional pathogenesis is complex and incompletely clarified. Recent theories put in a new light the mechanisms of muscle pain and tendinopathy production. The accumulation of lactate anion, known to be a residue that induces fatigue and muscle pain, has been reconsidered by some authors. It appears that lactate anion is an excellent fuel for the myocardial fiber. Moreover, the accumulation of lactic acid after intense physical exercise could prevent the inexcitability of the sarcolemma induced by the increased concentration of interstitial K+. Most of the time, overuse injuries are not limited to muscles. They can cause myofascial, myotendinous or purely muscular injuries. The muscular fascia is more susceptible to injuries produced under the action of large external forces. Also, fascia is more sensitive to pain compared to muscle when external forces act eccentrically. Overloading the tendon and putting it under tension repeatedly is followed by ruptures of the tendon fibers. The regeneration of the degenerated tendon is defective in the context of the inflammation produced by the injury. Tendon fibers undergo a process of fibrosis, scarring, adhesion and heterogeneous calcification. Oxidative stress is responsible for inflammation, degeneration and apoptosis of tenocytes. Conclusion: The benefits brought by physical education and sports are indisputable, but their practice requires a coordinated program to prevent possible traumatic and overuse injuries.

Immunologic and nonimmunologic sclerodermal skin conditions - review.

Scleroderma-like cutaneous lesions have been found in many pathological conditions and they have the clinical appearance of sclerotic or scleroatrophic lesions. Affected skin biopsies described histopathological changes similar to those of scleroderma located strictly on the skin or those of systemic sclerosis. These skin lesions can be found in inflammatory diseases with autoimmune substrate (generalized morphea, chronic graft versus host disease, eosinophilic fasciitis), tissue storage diseases (scleredema, scleromyxedema, nephrogenyc systemic fibrosis, systemic amyloidosis), metabolic diseases (porphyrya cutanea tarda, phenylketonuria, hypothyroidism, scleredema diabeticorum), progeroid syndromes. Given the multiple etiologies of sclerodermal lesions, a correct differential diagnosis is necessary to establish the appropriate treatment.

Basal Cell Carcinoma Perineural Invasion and Suggestive Signs of Perineural Invasion-Findings and Perspectives.

Basal cell carcinoma (BCC) is a malignant tumor with a rising incidence and is the beneficiary of several innovative evaluation techniques. Histopathology remains the gold standard for assessment, having the possibility of addressing multiple high-risk factors such as perineural invasion (PNI). The current study included a number of 244 BCC patients and targeted the identification of positive PNI and its suggestive signs, and whether they correlated or not with other high-risk tumor signs. PNI was found in 20.1% of patients, with 30.7% of patients having perineural chronic inflammation (PCI), which is a suggestive sign of PNI. PNI was also found in larger tumors, with deeper Clark levels, in high-risk BCCs and high-grade tumors. PNI and PCI are both important for pathology reporting, aiding in treatment choice and further patient management, with possibly positive outcomes concerning morbidity and mortality.

Multimodal Considerations Concerning Basal Cell Carcinoma Clefting - Profile of Structural and Aggressive Traits - Perspectives.

Although basal cell carcinoma is a well-known tumor with confirmed clinical and histopathology traits, prognosis factors and treatment options, new facets of this tumor emerge as innovative approach methods develop. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) allow a basal cell carcinoma's in vivo analysis of its depth of invasion, tumor margins prior to surgical approach and the tumor's response to a non-invasive treatment, evaluating simultaneously the tumor's vasculature. By RCM and OCT analysis, basal cell carcinoma has registered a groundbreaking discovery regarding a small (but with predictive factor potential) trait - the cleft, developing in between the tumor islands/nodules/chords and the surrounding tumor stroma; it was considered to date as a consequence of the tissue's histopathology processing. RCM and OCT revealed that the "clefting artifact", as it is frequently found in the medical literature, is not actually an artifact of laboratory processing, but a tumor trait found in vivo, with apparent mucin deposits. This review aims at merging the methods of evaluating basal cell carcinoma, both non-invasive (dermoscopy, RCM, OCT) and invasive ones (histopathology - with newly proposed classification), with special emphasis on the cleft issue - its assessment with the aforementioned techniques, with potential implications in the patient's prognosis.

Interrelationship and Sequencing of Interleukins4, 13, 31, and 33 - An Integrated Systematic Review: Dermatological and Multidisciplinary Perspectives.

The interrelations and sequencing of interleukins are complex (inter)actions where each interleukin can stimulate the secretion of its preceding interleukin. In this paper, we attempt to summarize the currently known roles of IL-4, IL-13, IL-31, and IL-33 from a multi-disciplinary perspective. In order to conduct a comprehensive review of the current literature, a search was conducted using PubMed, Google Scholar, Medscape, UpToDate, and Key Elsevier for keywords. The results were compiled from case reports, case series, letters, and literature review papers, and analyzed by a panel of multi-disciplinary specialist physicians for relevance. Based on 173 results, we compiled the following review of interleukin signaling and its clinical significance across a multitude of medical specialties. Interleukins are at the bed rock of a multitude of pathologies across different organ systems and understanding their role will likely lead to novel treatments and better outcomes for our patients. New interleukins are being described, and the role of this inflammatory cascade is still coming to light. We hope this multi-discipline review on the role interleukins play in current pathology assists in this scope.

The Influence of Living in Rural Areas on the Evolution and Management of Pediatric Ovarian Cystic Lesions: A Retrospective Study on a Cohort from South Eastern Romania.

Background: The incidence of ovarian cystic lesions (OCLs) in pediatric patients has been increasing in recent years. An early diagnosis is mandatory for a favourable prognosis but it depends on the primary medical care services and on the socioeconomic status of the patient. The present study aims at assessing the prevalence and the age-specific frequencies of pediatric OCLs, as well as identifying disparities between subjects in the urban and the rural areas, in order to explore the extent to which OCLs occurrence, diagnosis, evolution and treatment differ in the case of patients living in rural areas. Methods: A 3-year retrospective study was conducted between 2017 and 2019. All the female patients aged between 0 and 18 with OCLs ≥10 mm (N = 488), diagnosed and treated at "Sf.Ioan" Clinical Emergency Hospital for Children in Galati were included in the study. The Chi2 test was used for comparing the distributions of frequencies, and the t-Student test was used for comparing the means of any two normally distributed variables. The statistical significance threshold (p) was set at 0.05. Results: The prevalence of OCLs ≥10 mm was 14.85%, 47.13% of the subjects originating in rural area (p = 0.62). Different from the urban areas, the rural ones are characterised by a lower proportion of patients with BMI ≥25 (p = 0.002), larger OCLs mean size (p = 0.278), a more frequent complex aspect on ultrasonography (p = 0.01), and a smaller number of general physician referrals (p = 0.005). Moreover, a higher proportion of rural patients were intraoperatively diagnosed with OCLs (p = 0.044), had complicated OCLs (p = 0.012) and had their OCLs surgically treated OCLs (p < 0.01). Conclusion: Taking into consideration the socio-economic situation of south eastern Romania, patients living in rural areas have proven exposed to a higher risk of presenting with larger, complex and complicated OCLs, which most often require surgical treatment.

Hearing Loss Secondary to Systemic Sclerosis Vasculopathy: Case Study with a Short Review.

Systemic sclerosis (SSc) is a collagenosis with a substrate of chronic inflammation, which is determined by autoimmunity. The pathogenesis of this disease involves microvasculopathy (small vessel pathology) followed by excessive cutaneous and visceral fibrosis. Although acoustic and vestibular impairment is not classified as being a secondary pathology of SSc, several studies have identified cases of SSc that associate hearing loss and especially vertigo and tinnitus. This paper presents data from the medical literature that have identified vestibular and auditory symptoms among patients with SSc, associating the clinical case presentation of a patient suffering from SSc, which is associated with hearing loss. The need for additional studies on larger groups of patients is underlined, in order to clarify the impact of vasculopathy and fibrosis on the acoustic and vestibular analyzer in patients with SSc.

CREST Syndrome in Systemic Sclerosis Patients - Is Dystrophic Calcinosis a Key Element to a Positive Diagnosis?

Introduction: CREST syndrome is a clinical entity associated with systemic sclerosis, which meets at least three of the five clinical features: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Three of these clinical features (Raynaud's phenomenon, sclerodactyly and esophageal dysmotility) are often present in classical subsets of SSc: limited and diffuse, and their presence in association does not define CREST syndrome. Calcinosis seems to be less common in SSc and its association with other clinical features is characteristic of CREST syndrome. Therefore, it can be appreciated that calcinosis is the key element of CREST syndrome. Methods: This study included a number of 37 candidates with SSc, diagnosed with the help of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria. Results and Discussions: These three elements (calcinosis, Raynaud's phenomenon, esophageal dysmotility) were recorded both in the limited subset of SSc, but especially in the subset of diffuse SSc, contrary to the data in the literature. Conclusion: We appreciate that CREST syndrome is a clinical entity that can overlap with both subsets of SSc. Given the divergent views of the authors on the classification of CREST syndrome, future studies may contribute to a reassessment of SSc classification.

Paraclinical Aspects in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.

Once-Daily Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults and Adolescents Aged 12 Years and Over: A Short Review of Current Clinical Perspectives.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with high prevalence and a complex pathophysiology. This relapsing and remitting skin disorder has many negative consequences on the patient's quality of life and that of his family. Until now, moderate-to-severe AD treatment was a symptomatic one, using skin emollients, topical corticosteroids, phototherapy, antihistamines and systemic drugs - immune suppressants and other systemic treatments (dupilumab). Starting from 2021, abrocitinib, a Janus kinase-1 inhibitor, was approved for the treatment of moderate-to-severe cases of AD in Europe, in adults. Multiple phase three studies (JADE MONO-1 [NCT03349060]; JADE MONO-2 [NCT03575871]; JADE TEEN [NCT03796676]; JADE COMPARE; GOODERHAM; JADE EXTEND) have yielded positive results in adults and adolescents suffering from this disease, with efficacy, a good tolerance, safe profile, and with generally mild side effects. The positive results were obtained even starting from the first stages of the oral drug administration. The low frequency of side effects and the advantage of having an orally administered medication makes abrocitinib an important additional tool for the treatment of moderate-to-severe forms of AD.

Old and new therapeutic strategies in systemic sclerosis (Review).

Systemic sclerosis (SSc) is a chronic inflammatory disease with autoimmune determinism having an incompletely known pathogenesis. Although not all links in the pathogenic chain are known, studies have shown that vasculopathy is the initial event and is followed by extensive fibrosis of the skin and internal organs. New therapeutic strategies have been developed in recent years, thanks to innovative research which has increased understanding of the disease mechanisms. No curative treatment for SSc is currently known. Therefore, the therapeutic target in SSc is its symptomatology. Peripheral vasculopathy can be improved by administering vasodilators. Endothelin receptor antagonists and 5-phosphodiesterase inhibitors have a double benefit, both on peripheral and on pulmonary vasculopathy. Several molecules with antifibrotic effects are currently available; however, further studies are needed to confirm their beneficial effects. Immunosuppressants manage to control the cutaneous and visceral fibrotic process, thereby remaining as first-line drugs in the treatment of SSc. Although biological therapy using rituximab and tocilizumab has shown promising results in pulmonary fibrosis, ongoing studies are needed to determine their exact impact. The authors have differing views on the triggering role of glucocorticoids and the benefits of angiotensin-converting enzyme inhibitors in renal scleroderma. Some aspects of this disease such as calcinosis and pruritus, asthenia, or joint and muscle damage, remain difficult to manage.

Cutaneous adverse reactions in a lung cancer patient treated with pembrolizumab: A case report.

Lung cancer is the main cause of oncological death in the US and worldwide, constituting a significant public health problem. The incidence of lung cancer is on the increase. In the present study, the diagnostic process was carried out and treatment options were considered to determine the therapeutic response of a patient diagnosed with lung cancer. The case of an early stage lung cancer patient who benefited from surgical treatment was presented. The pathology report stated the complete diagnosis to be pleomorphic lung cancer with an adenocarcinoma component, pT2aN0M0, with focal positivity for thyroid transcription factor 1 (TTF1), without epidermal growth factor receptor (EGFR) mutations and ALK recombinations, having an initial clinical stage of IB and programmed death ligand-1 (PD-L1) positivity with a tumor proportion score of over 70%. The patient underwent radiotherapy treatment and was administered osteoclast inhibitors and immunotherapy, with no favorable therapeutic effect and with the presence of secondary cutaneous adverse effects to pembrolizumab. As a main cause of death, lung cancer registers a low general survival rate even in patients with targeted therapies or immunotherapy. By better identifying the patients at risk, one can establish a more efficient personalized treatment; the future objective of scientific studies is the follow-up of adverse effects of new therapies.

Basal cell carcinoma: Comprehensive clinical and histopathological aspects, novel imaging tools and therapeutic approaches (Review).

Basal cell carcinoma (BCC) is one of the most common malignant tumors worldwide, involving the skin. It is also part of keratinocyte carcinomas, alongside its squamous counterpart. It has low mortality and extremely low metastatic rates (although when present, it indicates a poor patient prognosis); it also has a high morbidity rate through local destruction and recurrence, particularly when perineural invasion is observed, clinically or histopathologically. BCC development is the result of environmental and patient factors, with genetics and ultraviolet radiation playing major roles. The clinical and histopathological aspects vary according to tumor subtype, being classified as high-risk tumors (nodular, superficial, pigmented and infundibulocystic BCC with adnexal differentiation) and fibroepithelial subtypes, or as high-risk tumors (micronodular, infiltrating, sclerosing/morphoeic and basosquamous subtype or the type with sarcomatoid differentiation). Dermoscopy is now complimented by novel in vivo diagnostic tools (optical coherence tomography, reflectance confocal microscopy, high-resolution ultrasonography, Raman spectroscopy or terahertz pulse imaging), improving the diagnostic accuracy and providing tumor depth and lateral margins without the use of invasive techniques. Novel treatment approaches for the treatment of BCC have recently been investigated with the use of hedgehog pathway inhibitors, such as Vismodegib. These approaches aim for complete resolution, minimal side-effects, high patient satisfaction with the optimal cosmetic results, particularly in key areas, such as the face. The present review article summarizes and discusses the comprehensive clinical and histopathological aspects of BCC, and presents novel imaging tools and therapeutic approaches that have been identified.

Nevi, biologics for psoriasis and the risk for skin cancer: A real concern? (Case presentation and short review).

Psoriasis is a systemic inflammatory cutaneous disease that affects approximately 2% of the world's population. Systemic treatments and biologic treatment therapies are a powerful option for patients with moderate to severe psoriasis. Some studies from the literature indicate an overall small, but increased, risk of neoplasia in patients with psoriasis treated with phototherapy or systemic medication. The relationship between psoriasis and malignancy is not very well established; there are few studies with conflicting results. We present the case of a 31-year-old male patient, diagnosed with psoriasis, who was deemed eligible for systemic therapy. Treatment with methotrexate was initiated, but without a satisfactory outcome. Given the patient's resistant disease involving 15% of his body surface, his desire to have a clear skin, besides his being naïve to biologic therapy, he was proposed to start treatment with secukinumab 300 mg monthly. The patient experienced complete clearance of lesions and was followed-up on the basis of clinical and biological parameters. There are limited data concerning the relationship between melanocytic lesions, psoriasis and melanoma. Immunologic pathways implicated in psoriasis induce a reduction in the number of melanocytic nevi. Nevertheless, little is known concerning the association of melanocytic nevi with psoriasis. Thorough skin examination, meaning clinical and dermoscopic evaluation of melanocytic lesions, must be encouraged in patients treated with systemic therapies such as biologic agents.

Rare case of metachronous tumor: Nasopharyngeal and colorectal carcinoma.

The study presents an unusual case of a patient with a personal history of a rectal malignant tumor in 2013, who after a period of 6 years, was diagnosed with an advanced nasopharyngeal carcinoma, locally and regionally invasive. It is possible that the colorectal malignant tumor affected the development of the nasopharyngeal carcinoma, or the other way around, depending on the presence of genetic instabilities. These two types of malignant tumors share a series of genes that can influence their progression, i.e., SPINK-6 and Bcl-2. The particularity of this case stems from the development of a metachronous tumor, a rectal adenocarcinoma and nasopharyngeal carcinoma, two malignant tumors with different patient prognosis and disease progression. Research needs to be continued on the multidisciplinary therapeutic management of nasopharyngeal cancer and the ways of identifying this cancer type in its early stages, considering that most patients come from a rural environment, have poor medical education, a number of comorbidities, and who frequently ignore the signs, symptoms and sometimes the treatment offered.

Predictive value of immunological markers in systemic sclerosis.

Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high titers of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc.

Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review).

Interleukin 6 (IL-6), a cytokine produced by various cells of the human body (macrophages, lymphocytes, astrocytes, ischemic myocytes, endothelial cells) has both pro-inflammatory and anti-inflammatory properties, being a key component in regulating various physiologic and pathological processes. The structure of this molecule and the receptor system it possesses are important due to the different activities that IL-6 can exert; through trans-signaling pro-inflammatory activities are mediated, while through classic signaling, IL-6 is responsible for anti-inflammatory and regenerative activities. IL-6 signaling is involved in coronary artery disease and the global COVID-19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS-CoV-2, and is also associated with smoking or obesity-classic cardiovascular risk factors which promote inflammatory states. IL-6 levels are proportionally correlated with dyslipidemia, hypertension and glucose dysregulation, and they are associated with poor outcomes in patients with unstable angina or acute myocardial infarction. IL-6 targeting for treatment development (not only) in cardiovascular disease and COVID-19 is still a matter of ongoing research, although tocilizumab has proven to be effective in reducing the proatherogenic effects of IL-6 and is suggested to improve COVID-19 patient survival.

Epidemiological profile of systemic sclerosis in the southeast region of Romania.

Systemic sclerosis (SSc) is a collagenosis, in which the microvasculature of the skin and internal organs becomes affected, followed by excessive deposition of connective tissue. It has been included in the group of rare diseases, and it seems to have had an increasing incidence over the last two decades. Statistics show, not only an increase in the incidence of SSc, but that of autoimmune diseases as a whole. The present study aimed to outline the epidemiological profile of SSc in the southeast region of Romania and to identify similarities and differences concerning the epidemiology of this disease in other countries. The current observational study was carried out on a group of 22 patients who were diagnosed with SSc and who were hospitalized at a university clinic in Bucharest. Our research revealed a higher prevalence of women suffering from SSc, with higher numbers suffering from the diffuse subset of this disease. In addition, we found that the majority of patients came from urban areas. SSc has an important impact on the quality of life of patients, thus opening the opportunity for studies to be carried out on larger populations of patients in order to identify epidemiological similarities and differences in various countries, as well as finding new experimental models useful for future research.

Etiological factors of systemic sclerosis in the southeast region of Romania.

Systemic sclerosis (SSc) is a relatively rare autoimmune disease with skin and visceral involvement, having a yet unknown etiopathogenesis. Research has shown that professional exposure to various polluting chemicals such as dyes, aliphatic and aromatic organic solvents, inhalable silica dust or certain heavy metals, can be triggering factors for this disease when they overlap a predisposing genetic profile. Smoking is still a debated factor involved in the etiology of SSc, as authors have divergent opinions on this matter. The present study was designed to analyze the etiological factors identified in the group of 37 patients with diffuse and limited SSc from the southeast region of Romania and the results were compared to the literature data. In the group of patients included in this study, occupational exposure and smoking history were not present in all patients, and a hereditary factor was identified only in an isolated case. The majority of patients suffered from a major negative psychological event or from long-term stressful situations and these factors were associated with smoking history or occupational exposure; this suggests that SSc is initiated in a set of cumulative triggering factors.