Defining the short-term and long-term skin manifestations of COVID-19: insights after more than three years of the pandemic.

AIM: This review aimed to assess the impact of coronavirus disease 2019 (COVID-19) on skin health to establish a classification of the skin lesions that occur most frequently during the disease and whether a particular category of skin damage is more likely to occur both in the short term and in the long term. METHODS: We conducted a literature search of the PubMed database. Ultimately, 109 articles were included in this review. The exact phrases∕syntax and connectors used for the database search∕query were as follows: "Coronavirus and skin", "COVID-19 and skin", "SARS-CoV-2 and skin", "Coronavirus cutaneous manifestations", "COVID-19 cutaneous manifestations", "SARS-CoV-2 cutaneous manifestations", "Coronavirus dermatology", "SARS-CoV-2 and dermatology", "COVID-19 and dermatology", "COVID-19 and skin eruption", "Coronavirus and skin rash", "COVID-19 and hair", "Coronavirus and hair", "Coronavirus and nails", "SARS-CoV-2 and hair", and "SARS-CoV-2 and nails". Only articles with abstracts referring strictly to cutaneous manifestations of COVID-19 were chosen. Articles without abstracts were not considered. RESULTS: We established six of the most frequently reported clinical patterns associated with COVID-19 and their probability of occurring during COVID-19 disease evolution based on the current literature reports. We did not identify the particular types of skin lesions that are most prone to long-term persistence; most such cases are rare, and no conclusion can be drawn based on them. CONCLUSIONS: Apart from classified COVID-19-related skin disorders, this pandemic has been a challenge for dermatologists and a wide range of cutaneous side effects related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treatments have been reported. We are aware of other polymorphic clinical presentations, with novel data being reported periodically, but the pathophysiological mechanisms and evolution are largely unknown.

CYP27B1 Enzyme in Psoriasis: A Preliminary Study of Immunohistochemical Observations.

Connections between vitamin D and psoriasis have been a matter of interest for the past decades, with its active metabolite, 1,25(OH)2 vitamin D, being valued for antiproliferative and immunomodulatory effects. However, none of vitamin D's actions could be possible without the CYP27B1 enzyme that bio-activates this metabolite of interest. In order to see if there is any link between the enzyme expression and the disease's particularities, we conducted a preliminary study that involved 11 skin biopsies of patients with mild (n = 4) or moderate to severe psoriasis (n = 7). The cell proliferation antigen Ki67 and the CD45RO+ marker were also assessed. Compared with healthy skin, in psoriasis, it is reported that the enzyme's expression seems to be more ubiquitous, but a clear correlation between the disease's severity and the CYP27B1 expression was, to our knowledge, lacking. We found that, in patients with very mild psoriasis, the enzyme expression was observed in the epidermal stratum basale in a similar manner as in healthy skin specimens. Contrary, for higher severity scores, a divergent result was observed, with the enzyme being either variably spread in the epidermal stratum spinosum or completely absent. Unlike malignant diseases, a significant connection between CYP27B1 and Ki67 (p = 0.313) or CYP27B1 and CD45RO+ (p = 0.657) does not seem to be relevant in psoriasis.

Vitamin D May Be Connected with Health-Related Quality of Life in Psoriasis Patients Treated with Biologics.

Suboptimal states of vitamin D may play a role in psoriasis evolution, but the interconnections have been studied over the past years with controversial results. Although a peerless therapy among moderate to severe types of psoriasis, the therapeutic effectiveness of biological therapy may vary unforeseeably between patients and leads to biologics switch. We conducted a pilot study in patients diagnosed with psoriasis and treated with biologics, the purpose of which was to explore the prevalence of suboptimal states of vitamin D, especially in the group of patients characterized by the failure of previous biologics, and to investigate the associations between vitamin D levels and psoriasis, regarding aspects such the severity of the disease and quality of life. Their current result of latent tuberculosis infection (LTBI) was also considered concerning a feasible relationship with vitamin D levels. From July to December 2021, 45 patients corresponding to our inclusion criteria were assessed. Variables such as Psoriasis Area and Severity Index (PASI) score and the Dermatology Life Quality Index (DLQI) score, as well as vitamin D serum concentrations and their LTBI result, were recorded for them. Lower serum concentrations of vitamin D were not more common in patients characterized by failure to previous biologics (p = 0.443), but we concluded a weak correlation between the DLQI score and vitamin D (rho = -0.345, p-value = 0.020), although a statistically insignificant result was obtained between vitamin D and the PASI score (rho = -0.280, p-value = 0.062), and with the LTBI result (rho = -0.053, p-value = 0.728). These results establish a connection between higher levels of vitamin D and a better outcome of psoriasis from the perspective of the patient's quality of life, with no significant association with psoriasis severity and no significant prevalence of suboptimal states among patients that failed previous biologics compared to those with a continuously good response.

Gut Microbiota Imbalance in Metastatic Colorectal Patients Treated With EGFRI and Long-Term Antibiotic Therapy for Cutaneous Toxicity: A Pilot Study.

Patients with metastatic colorectal cancer (mCRC) frequently experience epidermal growth factor inhibitors (EGFRI)-induced skin side effects. Antibiotic treatment with doxycycline is often required in order to manage the skin and mucosal toxicity. Since these patients already have significant gut dysbiosis, the long-term antibiotic treatment may destabilize their gut microbiome. Objectives The assessment of intestinal dysbiosis in patients undergoing treatment with EGFRI, who require antibiotic treatment with doxycycline in order to manage adverse skin effects. Methods We conducted a prospective pilot study between 2020 and 2021 involving 10 patients with mCRC. These patients were undergoing treatment with EGFRI and required either short-term or long-term treatment with doxycycline in order to manage skin toxicity. Results The patients with mCRC who were treated with doxycycline for 8 weeks showed overexpression of Escherichia coli, Candida, and Geotrichum species compared to the patients who only received doxycycline treatment for two weeks. Conclusions The elevated levels of Escherichia coli and Candida species in the patients who received doxycycline for eight weeks compared to the patients who received the treatment for two weeks could provide a starting point for the development of a standardized guideline regarding the use of pre-active or reactive antibiotic treatment. We also highlight the importance of analyzing the intestinal microbiome of these patients. The identification of overexpressed species, as well as the deficiency of certain protective species, could guide the administration of probiotics to cover and repair the affected intestinal flora.

Cutaneous Toxicity in Oncologic Patients Receiving Epidermal Growth Factor Receptor Inhibitors.

BACKGROUND: In recent years, oncology studies have focused on molecular targeted therapy, based on the development of numerous agents with a role in inhibiting the epidermal growth factor receptor (EGFR). When overexpressed, EGFR plays an extremely important role in the growth of certain tumour cells. Compared to classical chemotherapy, the systemic adverse effects of the molecular targeted therapy are much lower. However, between 80 to 100% of the patients treated with EGFR inhibitors develop a separate class of adverse effects, namely skin reactions. OBJECTIVES: Early identification of skin toxicity, dynamic monitoring of patients during EGFRI treatment, correlation of clinical data and their management. METHODS: We conducted a prospective study from 2018 to 2021 on patients who had received any EGFRI from all over Oltenia region. We were able to identify 31 oncologic patients who had received EGFRI for metastatic colorectal cancer, lung cancer or head and neck cancer. All of them were completely dermatologically examined, dynamically monitored for each oncological cycle. RESULTS: The dermatological follow-up throughout the study allowed the classification of skin toxicity according to the onset of manifestations after EGFRI treatment, the reporting of serious adverse effects and their management. Within the study group, 29 out of the 31 patients treated oncological with EGFRI therapy experienced at least one cutaneous adverse effect, the majority of which showed clinical polymorphism of lesions. CONCLUSIONS: The lack of dermatological treatment often leads to dose reduction or even to the discontinuation of the cancer treatment. Severe forms were also identified and their rapid treatment allowed the continuation of the cancer therapy and increased quality of life for all patients.

Gastric cancer - histopathological correlations between tumor and non-tumor gastric mucosa changes.

Gastric cancer is a widely geographically distributed malignancy with high prevalence, therefore being a serious health problem that needs standardized methods for early diagnosis and treatment. The aim of the study was to evaluate the correlation of some epidemiological and clinical data with the histological features. The study group was made up of 66 patients that underwent surgical removal of the gastric neoplasm, and the pathological exam showed the morphological features of the tumor, as well as the ones of the unaffected mucosal tissue. Topographically, the highest incidence of the tumor was registered in the gastric antrum, but in recent years, an increased incidence of the superior gastric pole localization was recorded. The macroscopic aspects reveal that the ulcerated type 2 Borrmann is the most frequent, and alongside type 3 Borrmann, the ulcer-infiltrative type represents most of the gastric antrum cancers. The analysis of the tumor invasion showed that most carcinomas underwent surgery when the tumor invaded the serosa (pT3) or even the perigastric tissues (pT4). In our research, we chose Goseki's microscopic classification because of its best coverage of the histological heterogeneity of the gastric carcinomas, providing information about the percentage of the cellular and secretory differentiation with direct impact on the invasion of the tumor. In more than 70% of the cases, the patients showed lesions of severe chronic atrophic gastritis of the non-tumor mucosa. Lately, the incidence of Helicobacter pylori has been 5.5%, lower than indicated by mainstream literature. We observed that the incidence of type 3 incomplete intestinal metaplasia, as the most commonly involved factor in the etiopathogenesis of gastric neoplasms, was encountered in 36.3% of the cases, this percentage rising proportionally with age and being frequently associated with antrum tumors. In conclusion, the permanent analysis of the relation between epidemiological data and some histological features might be relevant for the characterization of the tumoral process or the non-tumor gastric mucosa, leading to an evaluation of the prognosis.

The role of non-invasive scores in determining the liver fibrosis in NAFLD and psoriatic patients.

According to recent data, psoriatic patients have an increased prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome, compared with the general population. In some published studies, the severity and presence of psoriasis disease were correlated with the severity of NAFLD. In the current study, we aimed to compare the sensibility and specificity of the non-invasive scores and liver biopsy in determining fibrosis in patients with NAFLD and moderate to severe psoriasis. We performed the scientific research from June 2014-December 2017 and we included 71 patients: 40 patients with NAFLD and 31 patients with moderate to severe psoriasis according to Psoriasis Area and Severity Index (PASI) score and NAFLD, who received Etanercept treatment for at least one year. Based on the clinical and laboratory data, we calculated the following scores for fibrosis: body mass index (BMI), aspartate aminotransferase (AST)∕alanine aminotransferase (ALT) ratio, diabetes (BARD) score, Fibrosis-4 (FIB-4) score, and NAFLD fibrosis score (NFS). For liver biopsy, we used the Menghini technique. By calculating Kendall's test, we also observed a strong direct correlation between the degree of fibrosis and FIB-4 (tau=0.558) and NFS (tau=0.490) scores, with a critical statistical impact, and the lack of a correlation with the BARD score (tau=0.095; p=0.332). The hepatic biopsy allowed the more accurate establishment of the role of the non-invasive tests in the diagnosis of the lesions of steatosis, steatohepatitis, and hepatic fibrosis. The non-invasive tests are most useful for the exclusion of the evolution lesions and for the confirmation of the advanced stages of the disease. Among these, the NFS score proved a high statistically significant correlation (p<0.0001) with the fibrosis histological lesions.

Molecular and cellular stratagem of brain metastases associated with melanoma.

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

Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report.

Rowell syndrome is defined as the association between lupus erythematosus, erythema multiforme-like lesions and characteristic immunological changes including positive tests for rheumatoid factor, speckled antinuclear antibody, positive anti-Ro or anti-La antibodies. The present report presents the case of a 45-year-old female patient who was previously diagnosed in January 2010 with terbinafine-induced subacute cutaneous lupus erythematosus and was admitted for a skin eruption consisting of erythematous-papular erythema multiforme-like lesions, primarily on the trunk and limbs. The associated symptoms consisted of fatigability, myalgia and gonalgia. In October 2015, the illness reoccurred ~1 week after the initiation of Helicobacter pylori eradication treatment. Anti-Ro antibodies, rheumatoid factor and antinuclear antibody tests were positive. Given the patient's medical history, clinical manifestations, and laboratory, histopathological and immunofluorescence microscopy findings, a diagnosis of Rowell syndrome was made. Systemic corticosteroids (methylprednisolone; 0.5 mg/kg/day) and immunomodulatory therapy (azathioprine; 50 mg/day) were administered with the associated medication (omeprazole, 20 mg/day; KCl, 1 g/day) and topical dermocorticoids (fluticasone propionate 0.05% cream; 1 application/day), with a favorable outcome. The major diagnostic criteria for Rowell syndrome are the presence of lupus erythematosus (acute, subacute or systemic), erythema multiforme-like lesions and positive testing for antinuclear antibodies. The minor diagnostic criteria for Rowell syndrome are chilblains, the presence of anti-Ro antibodies and positive testing for rheumatoid factor. A diagnosis of Rowell syndrome is made if the patient exhibits all major criteria and at least one minor criterion. The present case met all diagnostic criteria, excluding the presence of chilblains. Notably, in this case there was a co-occurrence of subacute lupus erythematosus and Rowell syndrome lesions, which was drug-induced.

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

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

Morphopathological stigmata in acne fulminans.

Acne fulminans is the most aggressive and destructive form of acne vulgaris, being also known as acne maligna. The onset is acute and systemic involvement is always present. Most commonly, acne fulminans (AF) occurs in male adolescents as a brutal complication of a preexisting mild or moderate acne. The etiology of AF remains incompletely elucidated. The skin lesions are polymorphic, the symptoms and clinical signs vary, and thus the diagnosis is not easy. In making a certain diagnosis of AF, histopathology has a decisive role. In this respect, we will present some of the most suggestive aspects of histopathology, immunohistochemistry and electron microscopy in a 16-year-old patient clinically diagnosed with AF. This patient presented on admission nodular inflammatory and ulcerative necrotic lesions on the face and chest, extremely, accompanied by significant myalgias and arthralgias.

Motor unit changes in normal aging: a brief review.

Aging is explored by multiple lines of research, in a pursuit of understanding this natural process. The motor response is usually the main dependent variable in studies regarding physical or cognitive decline in aging. It is therefore critical to understand how the motor function changes with age. The present review, aims at presenting briefly some of the most recently published works in the field, focusing on the three key components of the motor unit. The changes that the skeletal muscle undergoes aging sarcopenia, alteration of fiber type distribution and also intimate metabolic transformations. The neuromuscular junction suffers at cellular and molecular level, with possible implications of various cell components, mediators and oxidative stress. Motoneuron loss and change in their physiological properties accompany remodeling in the motor units. The applicability of knowledge in this field lies in possible interventions intended to counteract these age-related losses.

Specific features of a rare form of disseminated necrobiosis lipoidica granuloma annulare type: a case report.

Necrobiosis lipoidica (NL) is a rare dermatosis that has been shown to precede the onset of diabetes mellitus in 15% of patients. It is more common in women; the average age of the onset is 30 years. Skin lesions of classic NL begin as a small papule, typically on the bilateral pretibial area. Progressively, these papules become indurated plaques with an atrophic, yellow center and multiple telangiectatic vessels, and brown-violaceous borders. We present the case of a 57-year-old male with type II diabetes mellitus from 2004, class II obesity, hepatosteatosis and metabolic disturbances who presents a disseminated eruption from 2010, formed by indurated plaques with flattened centers and a tendency of atrophy and raised, sharply demarcated, red-violaceous borders, having a variable diameter between 1.5 and 5 cm. The laboratory findings revealed elevated glucose levels between 250 and 300 mg%, high levels of transaminases and lipids. Diagnosis of disseminated necrobiosis lipoidica granuloma annulare-type was histopathologically confirmed. For the treatment, we have used topical corticosteroids and Tacrolimus 0.1% and systemic vasodilators. We consider this rare case interesting because has some peculiarities, as: disseminated lesions extend over the characteristic areas for necrobiosis lipoidica, the characteristic features of lesions similar to granuloma annulare, gender (male) and the onset of the disease over fifth decade.