Blood-Count-Derived Inflammatory Markers as Predictors of Response to Biologics and Small-Molecule Inhibitors in Psoriasis: A Multicenter Study.

Background: Psoriasis is an immune-mediated chronic disorder associated with various comorbidities. Even though biologics and small-molecule inhibitors are the mainstay treatment for moderate-to-severe psoriasis, there is no current consensus regarding which agent should be used for a specific type of patient. This paper aims to test the reliability of blood-count-derived inflammatory markers in assessing treatment response to biologics and small-molecule inhibitors in psoriasis. Material and Methods: Bio-naïve adult patients diagnosed with chronic plaque psoriasis fulfilling the inclusion criteria were enrolled. They were divided into study subgroups based on treatment of choice, and blood-count-derived inflammatory markers were analyzed at baseline, three-month, six-month, and at twelve-month visits. Results: A total of 240 patients were included. The highest number of patients underwent treatment with ixekizumab. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI) all varied significantly (p < 0.005) between the four visits. The psoriasis area severity index (PASI) score correlated with PLR, d-NLR, and SII, while the psoriasis scalp severity index (PSSI) score correlated with AISI and SIRI. More than half of patients reached the target goal of PASI90 at the six-month visit. A total of 77 patients were super-responders, with the highest number undergoing treatment with ixekizumab. Higher baseline values of d-NLR and SIRI are independent predictors of the super-responder status. Conclusions: Blood-count-derived inflammatory markers can serve as indicators of treatment response to biologics in psoriasis, while d-NLR and SIRI were independent predictors of super-responders in our study.

An Overview of Methotrexate Indications in Skin Diseases.

Methotrexate is an immunosuppressive drug with remarkable therapeutic results in the treatment of autoimmune and proliferative skin diseases. Although it has been more than half a century since it was first introduced into the therapeutic arsenal of dermatologists, there are currently no standardized therapeutic protocols regarding the prescription of methotrexate in dermatology, with the exception of psoriasis treatment. This review aims to highlight the indications and benefits of methotrexate beyond psoriasis, with a focus on a wide range of inflammatory, vesiculobullous, and proliferative dermatological pathologies.

Skin Lesions with Loss of Tissue and Cutaneous-Onset Sepsis: The Skin Infection-Sepsis Relationship.

Infectious and inflammatory dermatoses featuring skin lesions with loss of tissue expose skin layers to microbial invasions, disrupt the normal skin microbiome, and potentially lead to sepsis. However, literature data on the incidence of cutaneous-onset sepsis are scarce. This retrospective observational study assessed hospital admissions for primary skin lesions without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients, 441 had infected lesions, 78 had sepsis caused by venous ulcers from microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, and erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, and E. coli; and K. pneumoniae and S. ß-hemolytic associated with sepsis, even if this was rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, and mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, and type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

Update on Obesity in Psoriasis Patients.

Psoriasis is a chronic inflammatory skin condition, with genetic, epigenetic, environmental, and lifestyle factors contributing to its onset and recurrence. Severe psoriasis has a great impact on quality of life, which is similar to that of insulin-dependent diabetes, depression, and ischemic heart disease, but with a lower mortality. There is an overlap between the rising incidences of autoimmune diseases and obesity. In recent years, research has shown that there is an association between psoriasis and obesity. Psoriasis is linked to obesity in a two-way manner, as each can precipitate the development of the other. Several adipose tissue-secreted adipokines were shown to be elevated in obese psoriasis patients, exhibiting similar mechanisms of action to those underlying the pathogenesis of psoriasis. Excess body weight can influence not only the treatment response in psoriasis, but also the adverse events, leading to decreased patient compliance. Specific human microbiome patterns have been identified for obesity and psoriasis and could represent a future therapeutic target in selected individuals.

Cutaneous Manifestations Associated with Diabetes Mellitus-A Retrospective Study.

Diabetes mellitus (DM) is one of the world's most important health problems, affecting more than half a billion of the world's population today, with an ever-increasing prevalence. Among the most common manifestations of diabetes are skin manifestations, with 30-70% of patients experiencing skin complications during the course of the disease. Conditions such as acanthosis nigricans, diabetic dermopathy, necrobiosis lipoidica, bacterial infections, fungal infections, skin xerosis, and metabolic prurigo are often associated with diabetes and often precede its diagnosis. We conducted a retrospective study on a group of 103 patients hospitalized between January 2018 and December 2022, in a clinic of a county hospital, using as criteria the diagnosis of diabetes mellitus complicated by cutaneous manifestations frequently associated with diabetes. The aim was to observe which are the most common manifestations and whether they correlate with data in the research literature. In the present study, manifestations such as diabetic foot (20% of patients), bacterial (35%) and fungal infections, and cutaneous xerosis (45%) were predominant. Often, the integumentary involvement may precede the diagnosis of the underlying disease. It is therefore very important to recognize, investigate and treat these manifestations as soon as possible.

Epidemiological Study of Autoimmune Bullous Dermatoses in Northeastern Romania.

BACKGROUND: Autoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. ABDs are characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Most epidemiological studies have focused on a single ABD. More than that, there are few data about the incidence and prevalence of autoimmune blistering diseases in Romania. METHODS: In this study, between 2015 and 2019, we retrospectively investigated a total of 225 patients with autoimmune bullous diseases from the northeastern region of Romania. The diagnosis was based on the clinical and histo- and immunohistological findings. RESULTS: Pemphigus was the most frequently encountered ABD, with an incidence of 8.16/1,000,000 inhabitants, representing 58.7% (132 cases), followed by 24% cases of bullous pemphigoid (54 cases), 15.4% of patients were diagnosed with dermatitis herpetiformis (37 cases), and 0.9% other subepidermal autoimmune bullous dermatoses. The average age of onset of pemphigus vulgaris was 59.4 years, the majority of patients being male, while the average age of patients diagnosed with bullous pemphigoid was 73.8 years, the majority being female. CONCLUSIONS: Pemphigus vulgaris is the most frequently encountered ABDs in the northeast of Romania, with a higher incidence than in Western European countries, and this may be due to specific peculiarities of the geographical area, as well as to a genetic susceptibility of the population in this region.

Why Are Patients Unhappy with Their Healthcare? A Romanian Physicians' Perspective.

BACKGROUND: Medical professional liability complaints are not triggered by a single factor, but rather by multiple factors, each having more or less implications, such as the characteristics of the physician, the medical system, the patients, the complexity of their pathology, and the inherent limits of medicine. Knowledge about the factors that initiate the complaint procedure is essential to identify the targeted measures to limit their prevalence and impact. The purpose of this study was to identify the reasons behind the malpractice complaints and the factors that may influence the initiation of complaints by the patients. MATERIAL AND METHODS: This study was conducted using an online questionnaire, addressed to Romanian doctors, with questions about the reasons for patient dissatisfaction and complaints, the factors that predispose a physician to being complained against, and the protective factors against patient complaints. RESULTS: The study group included 1684 physicians, of whom 16.1% were themselves involved in a complaint, and 52.5% knew of a colleague who was complained against. The opinions of the participants regarding the reasons for the complaints, the predisposing factors to complaints, and the factors that contributed to the reported incident showed a strong link between professional liability complaints and the physician-patient/patient's family relationship. The relationship between fellow physicians is additional to this. CONCLUSION: This study reveals that the improvement in the relational aspects of medical practice (physician-patient relationship and relationship between physicians) has the highest potential to decrease the number of malpractice complaints. Its practical relevance is related to the need for training physicians in the relational aspects of medical practice during academic years and throughout their career.

Assessment of Basal Cell Carcinoma Using Dermoscopy and High Frequency Ultrasound Examination.

Basal cell carcinoma (BCC) is the most common form of cutaneous neoplasia in humans, and dermoscopy may provide valuable information for histopathological classification of BCC, which allows for the choice of non-invasive topical or surgical therapy. Similarly, dermoscopy may allow for the identification of incipient forms of BCC that cannot be detected in clinical examination. The importance of early diagnosis using the dermoscopy of superficial BCC forms is proven by the fact that despite their indolent clinical appearance, they can be included in high-risk BCC forms due to the rate of postoperative recurrence. Nodular pigmentary forms of BCCs present ovoid gray-blue nests or multiple gray-blue dots/globules associated with arborized vessels, sometimes undetectable on clinical examination. The management of BCC depends on this, as pigmentary forms have been shown to have a poor response to photodynamic therapy. High frequency ultrasound examination (HFUS) aids in the diagnosis of BCC with hypoechoic tumour masses, as well as in estimating tumour size (thickness and diameter), presurgical margin delineation, and surgical planning. The examination is also useful for determining the invasion of adjacent structures and for studying local recurrences. The use of dermoscopy in combination with HFUS allows for optimisation of the management of the oncological patient.

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.

Atopic Dermatitis-Beyond the Skin.

Atopic dermatitis is a chronic inflammatory disease that can arise during the first months of life or at maturity and have a significant negative impact on the quality of life. The main pathogenic mechanism is the breakdown of cutaneous barrier integrity, which is associated with systemic inflammatory immunologic disorders. Atopic dermatitis involves numerous immunologic, allergic, respiratory, and ophthalmologic comorbidities that develop through similar intricate pathogenic phenomena. The atopic march represents the evolution in time of various allergic diseases, of which food allergies often cause the first manifestations of atopy, even from a very young age. Chronic inflammation translated through specific markers, next to increased immunoglobulin E (IgE) serum levels and heterogenous clinical manifestations, argue for the inclusion of atopic dermatitis in the systemic disease category.

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.

Prevalence and Characteristics of Psoriasis in Romania-First Study in Overall Population.

Background: Psoriasis is a chronic inflammatory disease characterized by an excessive hyperproliferation of keratinocytes and a combination of genetic, epigenetic, and environmental influences. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. Objectives: The study of the prevalence of psoriasis will allow the estimation of the number of people suffering from this condition at the national level, as well as the development and validation of a questionnaire to estimate the prevalence and the risk factors associated with the disease. Methods: A quantitative research was conducted at a national level among the target population in order to validate the questionnaire and estimate the national prevalence. Results: Declaratively, the prevalence of psoriasis in the studied group (N = 1500) is 4%, the first symptoms appearing around the age of 50, with a certified diagnosis being made on average at 55 years. The prevalence of psoriasis vulgaris was 4.99%. Conclusions: The results obtained will be useful in guiding future initiatives and communication campaigns related to this condition, and the methodological approach used will provide the opportunity to make recommendations for improving similar initiatives in the future.

Molecular markers associated with potentially malignant oral lesions (Review).

According to literature data, potentially premalignant oral lesions are the basis of over 85% of cell carcinomas. Despite multiple advances achieved during the last few decades in the diagnosis and treatment of oral squamous cell carcinomas, there has not been a significant change in the prognosis and 5-year survival rate. The prevention of malignant transformation of these tumors by diagnosis and targeted treatment would be the ideal scenario. These potentially premalignant oral lesions represent an important subject for either the clinical or the research field, due to the higher malignant transformation observed in the last few years at different ages. To date, histopathological examination based on TNM criteria is considered the 'golden standard'. However, this type of examination has its limitation due to staining procedures and photonic microscope examination. Identification of cellular and molecular markers specific to these oral lesions with potentially malignant transformation could lead to early detection, accurate diagnosis, prevention of the development of oral squamous cell carcinoma (OSCC) and facilitate a targeted therapeutic approach. In this review, we focused on a series of molecules that are implicated in the malignant transformation of these lesions and considered potential biomarkers.

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.

Erratum: Dynamics of digital ulcers in systemic sclerosis.

[This corrects the article DOI: 10.3892/etm.2020.8572.].

Inflammatory marker alteration in response to systemic therapies in psoriasis.

Substantial research has focused on the presence of biomarkers involved in both the pathogenesis of psoriasis and its comorbidities. The identification of these biomarkers has a crucial role in establishing the diagnosis and prognosis, in understanding the physiopathological mechanism and in determining the therapeutic response. The aim of this study was to emphasize the alteration in inflammatory markers in response to systemic therapies in psoriasis. Evolution of inflammatory marker alteration was studied in 194 patients with psoriasis, aged between 7 and 87 years. Two groups were set up: the first comprised of patients treated with methotrexate (n=51), while the second comprised patients treated with biological therapy (n=143). Each group was evaluated for blood values of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fibrinogen before and after treatment, the fluctuation of these values according to the treatment, the interrelation between inflammatory markers and inflammatory activity of the disease and the evolution of the disease after treatment. In group I, 46 out of 51 patients had elevated levels of acute phase reactants before treatment. After treatment with methotrexate 7.5 mg/week, 12 out of 46 patients had elevated blood levels of ESR and 18 out of 46 patients of CRP and fibrinogen. Before treatment with biological therapy, 138 patients out of 143 presented abnormal high range for acute phase reactants. After treatment with biological therapy, 18 patients out of 138 had elevated blood levels of ESR and 37 patients out of 138 had elevated CRP and fibrinogen. A favorable evolution was noted in 98 patients out of 138. It was concluded that the systemic treatment with both methotrexate and biological therapy showed a marked decline in the patients with abnormal values of CRP, ESR and fibrinogen, indirectly showing a decline in the inflammatory activity of psoriasis.

Use of imaging techniques for melanocytic naevi and basal cell carcinoma in integrative analysis (Review).

Early detection of skin cancer is essential in order to obtain an improved prognosis. Clinicians need more objective and non-invasive examination methods to support their decision whether to biopsy or not tumoral lesions. These may include several imaging techniques such as dermoscopy, videodermoscopy, also known as sequential digital dermoscopy (SDD), computer-aided diagnosis (CAD), total body photography, imaging and high-frequency ultrasonography (HFUS), reflectance confocal microscopy, multiphoton tomography, electrical impedance spectroscopy, Raman spectroscopy, stepwise two-photon-laser spectroscopy and quantitative dynamic infrared. This review summarizes the current developments in the field of melanocytic lesions, such as naevi and basal cell carcinoma (BCC) imaging techniques. The aim was to collect and analyze data concerning types, indications, advantages and disadvantages of modern imaging techniques for in vivo skin tumor diagnosis. Two main methods were focused on, namely videodermoscopy and HFUS, which can be included in daily dermatologists' practice. In skin tumors HFUS allows the assessment of tumoral lesions with depth smaller than 1.5 cm, being described a correlation between ultrasonographic depth and the histologic index.