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Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2-5.5; p < 0.0001) in MMP to 28.7 (CI 3.9-211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2-7.9; p < 0.0001) to 23.3 (CI 17.0-31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

In the psoriatic non-lesional (PS-NL) skin, the tissue environment potentially influences the development and recurrence of lesions. Therefore, we aimed to investigate mechanisms involved in regulating tissue organization in PS-NL skin. Cytokine, chemokine, protease, and protease inhibitor levels were compared between PS-NL skin of patients with mild and severe symptoms and healthy skin. By comparing mild and severe PS-NL vs. healthy skin, differentially expressed cytokines and chemokines suggested alterations in hemostasis-related processes, while protease inhibitors showed no psoriasis severity-related changes. Comparing severe and mild PS-NL skin revealed disease severity-related changes in the expression of proteases, cytokines, and chemokines primarily involving methyl-CpG binding protein 2 (MECP2) and extracellular matrix organization-related mechanisms. Cytokine and chemokine expression in clinically resolved versus healthy skin showed slight interleukin activity, differing from patterns in mild and severe PS-NL skin. Immunofluorescence analysis revealed the severity-dependent nuclear expression pattern of MECP2 and decreased expression of 5-methylcytosine and 5-hydroxymethylcytosine in the PS-NL vs. healthy skin, and in resolved vs. healthy skin. Our results suggest distinct cytokine–chemokine signaling between the resolved and PS-NL skin of untreated patients with varying severities. These results highlight an altered inflammatory response, epigenetic regulation, and tissue organization in different types of PS-NL skin with possibly distinct, severity-dependent para-inflammatory states. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence and severity of adverse events following immunization (AEFIs) with COVID-19 vaccines in individuals with chronic skin diseases and comorbidities within a Central European cohort. Methods: An anonymous online survey was conducted between May 2022 and February 2023, targeting students and employees of universities in Wrocław, Poland. A total of 513 respondents were analyzed, focusing on AEFIs following the first, second, and third doses of COVID-19 vaccines and the effects of COVID-19 on conditions such as atopic dermatitis, psoriasis, vitiligo, acne vulgaris, rosacea, and various comorbidities. Results: COVID-19 vaccination effectively protected against severe disease across all doses. The analysis revealed no significant impact of either COVID-19 infection or vaccination on the course of selected skin diseases and comorbidities. The reporting of AEFIs to the Sanitary Inspection was notably low. The Moderna and Pfizer mRNA-based vaccines were associated with a higher reported number of AEFIs, particularly after the second and third doses, compared to AstraZeneca, which exhibited fewer adverse events after subsequent doses. Conclusions: COVID-19 vaccination is both safe and effective, even in patients with pre-existing skin conditions and comorbidities. Vaccine selection may benefit from considering individual health profiles, and better reporting of AEFIs is needed to enhance vaccine safety monitoring. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid is an autoimmune bullous disease that frequently affects a large skin surface area, but it can also present in localized areas. It has been hypothesized that bullous pemphigoid affects the systemic functioning of different organs because inflammatory cells and cytokines circulate throughout numerous organs. Results: Recent clinical and experimental studies have revealed an association between bullous pemphigoid and systemic organ disorders. To avoid the emergence of systemic organ diseases, the significance of systemic treatment in cases of severe bullous pemphigoid should be emphasized. Conclusions: Here, we discuss the specific molecular processes underlying typical systemic organ inflammatory diseases associated with bullous pemphigoids. [ABSTRACT FROM AUTHOR]

Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient's quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory. [ABSTRACT FROM AUTHOR]

Background and Objectives: Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting mainly elderly patients. Still, little is known about the pathogenesis of pruritus in BP or the factors that affect the clinical course of the disease. This study aimed to evaluate the factors influencing the clinical course of BP among older patients. Materials and Methods: A retrospective analysis of medical records of 55 patients with BP hospitalized in the dermatology department in 2015–2021 was conducted. The study focused on preliminary diagnosis, medical history, clinical examination (characteristics and location of cutaneous changes), laboratory investigation, and direct and indirect immunofluorescence. Results: Analysis of laboratory results in combination with the clinical course of BP showed that red blood cell count, hemoglobin, and hematocrit values were negatively associated with a risk of erosions and erythema, while MCHC values were positively correlated with a risk of associated pruritus. A correlation was found between neurological diseases and an increased risk of erosions. Conclusions: We have shown that age and neurological conditions, including stroke, affect the clinical course of BP. Further studies on a larger group of patients should be conducted to investigate the different factors affecting the clinical aspect of BP and to understand the relationship between them. [ABSTRACT FROM AUTHOR]

Autoimmune blistering diseases of the pemphigus and pemphigoid groups are immune-mediated disorders due to circulating pathogenetic autoantibodies. Multiple human leukocyte antigen (HLA) genes have been associated with predisposition to these disorders. HLA-Cw6 is involved in antigen presentation processes and has been linked to psoriasis. The aim of our study was to investigate the association between the presence of the HLA-Cw6 allele and susceptibility to pemphigus vulgaris and bullous pemphigoid. A genetic study in vitro with a cross-sectional design was performed enrolling forty patients with pemphigus vulgaris and forty patients with bullous pemphigoid. The detection of HLA-Cw6 was performed through the EUROArray test on DNA obtained from whole blood samples. The polymorphism was detected in 3/40 genotypes in the pemphigus vulgaris group and in 4/40 genotypes of patients with bullous pemphigoid, unveiling a non-statistically significant different frequency in pemphigus (p = 0.6368) and in pemphigoid (p = 0.62) compared to the reference frequency from the literature of 0.086. Further research is needed to better investigate the role of HLA-Cw6 in immune-mediated diseases and to identify novel genetic markers associated with susceptibility to autoimmune blistering diseases and with disease severity and response to immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

Prior to the introduction of COVID-19 vaccines, patients with severe mental illness (SMI) were at greater risk of COVID-19-related outcomes than the general population. It is not yet clear whether COVID-19 vaccines have reduced the risk gap. We systematically searched nine international databases and three Chinese databases to identify relevant studies from December 2020 to December 2023 to compare the risk of COVID-19-related outcomes for SMI patients to those without SMI after vaccination. Random effects meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CI). Subgroup analysis, sensitivity analysis, and publication bias analysis were conducted with R software 4.3.0. A total of 11 observational studies were included. Compared with controls, SMI patients were associated with a slightly increased risk of infection (pooled OR = 1.10, 95% CI, 1.03–1.17, I2 = 43.4%), while showing a 2-fold higher risk of hospitalization (pooled OR = 2.66, 95% CI, 1.13–6.22, I2 = 99.6%), even after both groups have received COVID-19 vaccines. Limited evidence suggests a higher mortality risk among SMI patients compared to controls post vaccination, but the findings did not reach statistical significance. SMI patients remain at increased risk compared to their peers in COVID-19-related outcomes even after vaccination. Vaccination appears an effective approach to prevent severe COVID-19 illness in SMI patients, and actions should be taken by healthcare providers to improve vaccination coverage in these vulnerable groups. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is the most common autoimmune bullous disease, whose main autoantigens are hemidesmosomal components BP180 and BP230. Although recent studies found no association between COVID-19 vaccines and BP, since mass vaccinations started, more than 90 vaccine-associated BP cases have been reported. To find an agreement among real-life clinical observations and recent epidemiologic data, we further investigated this topic. A total of 64 patients with BP onset in 2021 were demographically, clinically, and serologically characterized: 14 (21.9%) vaccine-associated patients (VA) developed BP within 5 weeks from the first/second vaccine dose. VA and vaccine-non-associated (VNA) patients had similar demographics and clinical and immunological characteristics. Noteworthy, the monthly distribution of BP onset during mass vaccinations paralleled vaccine administration to the elderly in the same catchment area. Additionally, in 2021, BP onsets in April–May and June–July significantly increased (p = 0.004) and declined (p = 0.027), respectively, compared to the three years before vaccination campaigns (2018–2020). Interestingly, VA and VNA patients showed statistically significant differences in the use of inhalers and diuretics. Our findings suggest that the COVID-19 vaccine may constitute an accelerating factor that, together with other triggering factors, could act in genetically predisposed individuals with possible sub-clinical autoreactivity against BP antigens, slightly accelerating BP onset. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) activate T cells, causing immune-related adverse events (irAEs). Skin manifestations are common among irAEs, but ICI-associated bullous pemphigoid (BP) is rare. Inhibiting programmed death (PD)-1 signaling, in addition to causing epitope spreading, may disrupt B and T cell balance, causing excessive autoantibody production against the skin's basement membrane, leading to BP. A 70-year-old woman developed late-onset multi-organ irAEs, including diarrhea, thyroid dysfunction, and BP, while receiving pembrolizumab, a PD-1 inhibitor. This highlights the long-term risk of irAEs, which can occur 2–3 years after starting ICIs. In cases of multi-organ irAE, C-reactive protein levels and neutrophil/lymphocyte ratio are often low. These characteristics were observed in our case. Few papers address multiple organ involvement, highlighting the need to consider irAEs in a multi-organ context. While it is known that drug-induced skin reactions worsen as blood eosinophil counts increase, in our case, the eosinophil count remained normal, suggesting that ICI-associated BP might have been controlled without discontinuing the ICI and through tapering of low-dose oral prednisone treatment. Additionally, in this case, significant CD4-positive T cell infiltration was observed in the immunostaining examination of the blisters, indicating that severe CD4-positive T cell infiltration induced by the ICI might have led to multi-organ involvement, including severe diarrhea. Few reports focus on blood eosinophil counts in BP cases or discuss CD4 and CD8 immunostaining in BP cases. Therefore, future research should explore the relationship between blood eosinophil counts, immunostaining results, and the prognosis of irAEs, including BP, in treatment courses. [ABSTRACT FROM AUTHOR]

Background/Objectives: Mycoplasma genitalium (MG) infections and antibiotic resistance are increasing in prevalence while treatment options are limited. Limited data exist regarding MG resistance in Israel. Our aim was to study the prevalence of MG resistance in a sexually transmitted infection (STI) clinic in Israel. Methods: We performed a single-center retrospective study among patients attending an STI clinic during 2019–2020. MG isolates were tested to detect their resistance to azithromycin and fluoroquinolones (FQs) using commercial kits (Allplex™ MG & AziR Assay, Allplex™ MG & MoxiR Assay). We collected patient data regarding the risk factors for STIs and resistance. A multivariate logistic regression model was used to identify the risk factors for resistance. Results: Of the 142 patients who tested positive for MG, 50 (35.2%) and 22 (15.5%) had resistant mutations to azithromycin and FQ, respectively, and 13 (9.2%) showed resistance to both agents. In a multivariate logistic regression model, men who have sex with men (RR 7.01 95% CI 3.00–16.33) and past STIs (RR 2.33 95% CI 1.01–5.34) were independent risk factors for azithromycin resistance. Conclusions: We found a high prevalence of azithromycin resistance and, to a lesser degree, FQ resistance. These findings may help design the treatment guidelines and support routine resistance testing in high-risk populations. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia is a complex multifaceted syndrome primarily characterised by chronic musculoskeletal pain, fatigue, and functional symptoms. Although FM is known to be associated with several comorbidities, the aim of this systematic review was to comprehensively examine the available evidence regarding the relationship between FM and dermatological manifestations. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched up to June 2023. After removing duplicate records, 21 articles were deemed eligible for inclusion in the qualitative synthesis. Results: Overall, the included studies revealed an increased frequency of FM among patients with cutaneous diseases, including psoriasis, chronic urticaria, contact allergy, acneiform disorders, hidradenitis suppurativa, and vitiligo. Additionally, the presence of comorbid FM may intensify skin conditions, which has a negative impact on quality of life and vice versa. Conclusions: Although the causal mechanisms of FM are still far from being understood, this systematic review suggests a relationship between FM and skin disorders. However, further research is encouraged in this area. [ABSTRACT FROM AUTHOR]

Autoimmune bullous diseases (AIBDs) are characterized by the formation of vesicles, bullous lesions, and mucosal erosions. The autoantibodies target the cellular anchoring structures from the surface of epidermal keratinocyte named desmosomes, leading to a loss of cellular cohesion named acantholysis. AIBDs are classified into intraepidermal or subepidermal types based on clinical features, histological characteristics, and immunofluorescence patterns. Pemphigus foliaceus (PF) is an acquired, rare, autoimmune skin condition associated with autoantibodies that specifically target desmoglein-1, leading to a clinical presentation characterized by delicate cutaneous blisters, typically sparing the mucous membranes. Several factors, including genetic predisposition, environmental triggers, malignancies, medication use, and vaccination (for influenza, hepatitis B, rabies, tetanus, and more recently, severe acute respiratory syndrome Coronavirus 2 known as SARS-CoV-2), can potentially trigger the onset of pemphigus. With the advent of vaccines playing a pivotal role in combatting the 2019 coronavirus disease (COVID-19), extensive research has been conducted globally to ascertain their efficacy and potential cutaneous adverse effects. While reports of AIBDs post-COVID-19 vaccination exist in the medical literature, instances of PF following vaccination have been less commonly reported worldwide. The disease's pathophysiology is likely attributed to the resemblance between the ribonucleic acid (RNA) antigen present in these vaccines and cellular nuclear matter. The protein produced by the BNT-162b2 messenger ribonucleic acid (mRNA) vaccine includes immunogenic epitopes that could potentially trigger autoimmune phenomena in predisposed individuals through several mechanisms, including molecular mimicry, the activation of pattern recognition receptors, the polyclonal stimulation of B cells, type I interferon production, and autoinflammation. In this review, we present a comprehensive examination of the existing literature regarding the relationship between COVID-19 and PF, delving into their intricate interactions. This exploration improves the understanding of both pemphigus and mRNA vaccine mechanisms, highlighting the importance of close monitoring for PF post-immunization. [ABSTRACT FROM AUTHOR]

Introduction: Chronic oral mucosal diseases (COMDs) can significantly impair the quality of life (QoL) of affected individuals. Monitoring the overall disease's impact and the efficacy of treatments requires the use of the Chronic Oral Mucosal Diseases Questionnaire-15 (COMDQ-15) as a standardized instrument for measuring QoL in these patients. Objective: This study aimed to assess QoL in patients with COMDs using an Indonesian version of the COMDQ-15. Methods: Seventy patients diagnosed with recurrent aphthous stomatitis (RAS), oral lichen planus, autoimmune blistering diseases (ABD), and cheilitis were included. Levels of QoL among different groups of disease were compared. Various potential factors influencing QoL were evaluated. Bivariate analysis was performed to identify factors associated with overall and specific aspects of QoL. Results: The mean total COMDQ-15 score was 20.83 ± 10.07. The highest scores were in the physical discomfort domain (8.76 ± 4.65), while the lowest was in the medication and treatment domain (2.13 ± 1.99). Physical discomfort was significantly associated with gender, major RAS, and cheilitis. Social and emotional aspects were significantly associated with age and ABD, while patient support was linked to employment status, RAS types, and cheilitis. Conclusions: The Indonesian version of the COMDQ-15 is a valid and reliable tool for assessing QoL in patients with COMDs. [ABSTRACT FROM AUTHOR]

The extracellular matrix of most bacterial biofilms contains polysaccharides, proteins, and nucleic acids. These biopolymers have been shown to mediate fundamental biofilm-related phenotypes including surface attachment, intercellular adhesion, and biocide resistance. Enzymes that degrade polymeric biofilm matrix components, including glycoside hydrolases, proteases, and nucleases, are useful tools for studying the structure and function of biofilm matrix components and are also being investigated as potential antibiofilm agents for clinical use. Dispersin B is a well-studied, broad-spectrum antibiofilm glycoside hydrolase produced by Aggregatibacter actinomycetemcomitans. Dispersin B degrades poly-N-acetylglucosamine, a biofilm matrix polysaccharide that mediates biofilm formation, stress tolerance, and biocide resistance in numerous Gram-negative and Gram-positive pathogens. Dispersin B has been shown to inhibit biofilm and pellicle formation; detach preformed biofilms; disaggregate bacterial flocs; sensitize preformed biofilms to detachment by enzymes, detergents, and metal chelators; and sensitize preformed biofilms to killing by antiseptics, antibiotics, bacteriophages, macrophages, and predatory bacteria. This review summarizes the results of nearly 100 in vitro and in vivo studies that have been carried out on dispersin B since its discovery 20 years ago. These include investigations into the biological function of the enzyme, its structure and mechanism of action, and its in vitro and in vivo antibiofilm activities against numerous bacterial species. Also discussed are potential clinical applications of dispersin B. [ABSTRACT FROM AUTHOR]

We aimed to examine the drug retention rate (DRR) of the interleukin-17 inhibitor ixekizumab in a real-world monocentric cohort of psoriatic arthritis (PsA) patients and to assess the predictors of drug discontinuation. Consecutive PsA patients who underwent treatment with ixekizumab from October 2019 to February 2023 were enrolled in this observational, retrospective, monocentric study. Clinical records were assessed at baseline and throughout the follow-up period. We collected sociodemographic data, smoking habits, body mass index, the presence of Human Leukocyte Antigen B27, comorbidities, disease involvement and duration, previous therapy, discontinuation of ixekizumab, reasons for discontinuation, and adverse events (AEs). DRR was evaluated as time to drug discontinuation and assessed through Kaplan–Meier curves. Baseline factors predicting drug discontinuation were investigated through logistic regression models. Eighty PsA patients were included in this study. Ixekizumab was administered at a dose of 160 mg by subcutaneous injection at baseline, followed by 80 mg every four weeks thereafter. Ixekizumab had a 38-month-cumulative DRR of 43.8%, accounting for both inefficacy and AEs. When considering only inefficacy, the DRR was 62.6%. Comorbidities (p = 0.665), obesity (p = 0.665), smoking (p = 0.884), disease duration ≤ 2 years (p = 0.071), axial (p = 0.131) and skin involvement (p = 0.460), and previous therapies, including conventional synthetic (p = 0.504) and biological (p = 0.474) Disease-Modifying Antirheumatic Drugs (bDMARDs), as well as the number of previous bDMARDs or targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs), did not significantly affect the DRR (p = 0.349). Multivariate analysis found no independent predictors of drug discontinuation. The most frequent AEs leading to discontinuation were skin reactions; no severe infections were observed. In our real-world study, comorbidities, disease duration, and previous therapies did not affect the DRR of ixekizumab. Ixekizumab had a favorable safety profile, with no severe AEs observed. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient's characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens–Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier's gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions. [ABSTRACT FROM AUTHOR]

We aimed to use the digital platform maintained by the local health service providers in Southeast Sweden for integrated monitoring of disparities in vaccination and morbidity during the COVID-19 pandemic. The monitoring was performed in the adult population of two counties (n = 657,926) between 1 February 2020 and 15 February 2022. The disparities monitored were relocated (internationally displaced), substance users, and suffering from a psychotic disorder. The outcomes monitored were COVID-19 vaccination, SARS-CoV-2 test results, and hospitalization with COVID-19. Relocated residents displayed an increased likelihood of remaining unvaccinated and a decreased likelihood of testing as well as increased risks of primary SARS-CoV-2 infection and hospitalization compared with the general population. Suffering from a major psychiatric disease was associated with an increased risk of remaining unvaccinated and an increased risk of hospitalization but a decreased risk of SARS-CoV-2 infection. From the digital monitoring, we concluded that the relocated minority received insufficient protection during the pandemic, suggesting the necessity for comprehensive promotion of overall social integration. Persons with major psychiatric diseases underused vaccination, while they benefitted from proactively provided testing, implying a need for active encouragement of vaccination. Further research is warranted on legal and ethical frameworks for digital monitoring in vaccination programs. [ABSTRACT FROM AUTHOR]

Patients with rheumatic diseases frequently operate with incomplete or incorrect information while planning for and experiencing pregnancy, often due to variability in provider care and knowledge. Risk assessment at each stage of pregnancy—pre-conception, during pregnancy, and postpartum—is focused on reducing maternal and neonatal complications. This review aims to compile updated, evidence-based guidance on how to minimize risk factors contributing to adverse pregnancy outcomes (APOs). Mitigation of known causes of infertility, appropriate testing and monitoring, achieving low disease activity on pregnancy-safe disease-modifying antirheumatic drugs (DMARDs) prior to conception, controlling hypertension (a frequent comorbidity among patients with certain rheumatic diseases), and the use of appropriate adjunctive medications (such as low-dose aspirin when preeclampsia risk is high) can optimize fertility and prevent adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Millions of children and adults worldwide suffer from undiagnosed and untreated celiac disease (CeD). The clinical picture of CeD is highly heterogeneous and comprises manifestations that can affect almost the whole body. This narrative overview is aimed at characterizing diseases and complaints that are associated with unrecognized CeD and that frequently involve sites other than the gastrointestinal (G.I.) tract, i.e., dental, otorhinolaryngological, and ocular complications; skin and hair abnormalities; afflictions of the bones, joints, and muscles; cardiovascular affectations; kidney diseases; neuro-psychiatric disorders; and gynecological–obstetrical manifestations. The association between CeD and extra-GI manifestations is frequently overlooked, which leads to a delay in diagnosis. Most CeD-mediated disorders can be treated with a strict gluten-free diet (GFD), but some of them are irreversible unless CeD is diagnosed in time. Some manifestations can be classified as risk factors for CeD, and CeD screening tests for affected patients should be selectively considered. Apart from gastroenterologists, specialists in other medical disciplines can play an important role in identifying people with unrecognized CeD and may help prevent its progress and long-term complications. Further comprehensive investigations are necessary to clarify the pathogenesis of extra-GI manifestations and the effect of a GFD. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis and psoriasis are chronic skin diseases that affect the mental health of patients. The relationship between AD and psoriasis and cognitive processes in patients remains unclear. The aim of the review was to answer the question of whether AD and psoriasis have an impact on cognitive decline in patients. Method: A systematic literature search was conducted on PubMed and EBSCO to identify case–control, cross-sectional, or cohort studies that evaluated the association between atopic dermatitis and psoriasis and cognitive impairment. Results: Most of the studies included in the review confirmed cognitive decline in patients with atopic dermatitis and psoriasis. Conclusions: It seems that atopic dermatitis and psoriasis may negatively affect cognitive processes such as working memory, concentration, attention, and speed of motor reactions. Psychological interventions targeting distorted cognitive processing could improve the quality of life of patients with atopic dermatitis and psoriasis. [ABSTRACT FROM AUTHOR]

This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology but also a significant risk factor for systemic diseases affecting cardiovascular, hepatic, renal, pulmonary, and skeletal systems, as well as associated with an increased incidence of anemia, depression, anxiety, and arthritis. The research highlights the complex interplay of cytokines, particularly IL-17 and IL-36, which are central to the pathophysiology of GPP and implicated in the exacerbation of systemic conditions. Key findings indicate a higher incidence of cardiovascular events in GPP patients compared to those with other severe forms of psoriasis, notably with a stronger correlation between myocardial infarction history and GPP development. Liver disturbances, frequently reversible upon psoriasis remission, suggest a cytokine-mediated link to hepatic health. Renal dysfunction appears elevated in GPP sufferers, with IL-17 and IL-36 potentially driving renal fibrosis. Similarly, interstitial lung disease and osteoporosis in GPP patients underscore the systemic reach of inflammatory processes initiated in the skin. The associations with anemia, depression, anxiety, and arthritis further complicate the clinical management of GPP, requiring a multidisciplinary approach. The study concludes that managing GPP effectively requires a holistic approach that addresses both the cutaneous and systemic dimensions of the disease, advocating for continued research into the mechanisms that connect GPP with broader health implications to refine therapeutic strategies. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient's quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis. [ABSTRACT FROM AUTHOR]

(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level. [ABSTRACT FROM AUTHOR]

Background: Previous research has indicated a potential correlation between hidradenitis suppurativa (HS) and psoriasis (PSO), two chronic inflammatory dermatological diseases. However, there is a lack of comprehensive evaluations that consider a variety of clinical and demographic factors, and the risk of developing HS in PSO patients remains unclear. Our study aims to examine HS risk over time among PSO patients versus matched controls while considering the influence of confounders to provide insights into the potential link between these two diseases. Method: In this multi-institutional cohort study using the TriNetX database, we matched 202,318 patients with PSO with an equivalent number of individuals without PSO, using propensity score matching. The study period extended from 1 January 2005 to 31 December 2018. We computed hazard ratios and their respective 95% confidence intervals (CIs) to evaluate the probability of HS manifestation over a period of 5 years in patients with PSO in comparison to those without PSO. Results: PSO patients demonstrated a consistently higher risk of developing HS than matched controls across all analytic models with the hazard ratios (HR) ranging from 1.43 (95% CI 1.30–1.56) to 5.91 (95% CI 2.49–14.04). Stratified analyses showed the increased HS risk was observed in both genders but only significant in those aged 18–64 years. Kaplan–Meier analysis indicated PSO patients had a higher cumulative probability of developing HS over time (HR 1.77, 95% CI 1.49–1.89). Conclusions: PSO was associated with increased HS risk, highlighting the importance of considering HS as a potential comorbidity in PSO patients and may have implications for early detection, prevention, and management strategies for both conditions. Shared inflammatory pathways, genetic components, and skin dysbiosis may contribute. Further research should elucidate underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background and Objectives: Lichen planus of the lip (LPL) is a chronic inflammatory condition that resembles actinic cheilitis, discoid lupus erythematosus, graft-versus-host disease, and lichenoid reaction to dental materials or drugs. The purpose of this study was to conduct a literature review on lichen planus lip involvement and to report a retrospective observational study that characterises and explores the clinical, histopathological, and evolution of the lesions in a group of patients with unique involvement of LPL. Materials and Methods: Clinical data of patients diagnosed with LPL was retrieved from the medical charts of the patients referred to the Oral Pathology Department of the "Carol Davila" University of Medicine and Pharmacy. A concurrent electronic literature research was carried out using PubMed and Web of Science from 2003 to 2023. Results: Eleven patients diagnosed with unique LPL were analysed (male/female ratio was 1.75, mean age 63.64 years ± 12.52). All patients presented lesions of the lower lip; the clinical forms were atrophic (six cases) and erosive (five cases), and the histopathological exam confirmed the diagnosis. After topical treatment with corticosteroids, most of the patients had complete remission. The literature review revealed 24 studies (sixteen case reports and eight case series) which comprised 84 patients. Isolated lip involvement was reported in 17 studies, and five articles with concomitant oral lichen planus, while two articles did not mention this criterion. Conclusions: Our study brings new data on isolated lichen planus of the lip that primarily affects the lower lip with predominance in male patients. It was reported worldwide in patients between 22 and 75 years old. Topical corticosteroids were the main treatment prescribed and they usually brought remission of the lesions. Lichen planus of the lip is a challenging diagnosis for oral health practitioner providers as well as for dermatologists. [ABSTRACT FROM AUTHOR]

Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce. Methods: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers—direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis. Results: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP. Conclusion: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense. [ABSTRACT FROM AUTHOR]

Background: Axial spondyloarthropathy(AS) is a chronic inflammatory disease primarily affecting the axial skeleton, often characterized by sacroiliitis. While pulmonary embolism (PE), a potentially lethal condition, has been linked to several autoimmune diseases, limited data exist regarding PE risk among patients with AS. Methods: This retrospective cohort study utilized the Clalit Healthcare Services (CHS) database, including 5825 patients with AS and 28,356 matched controls. Follow-up began at the date of first AS diagnosis for patients and at the matched patient's diagnosis date for controls and continued until PE diagnosis, death, or study end date. Results: Prevalence of PE before AS diagnosis in patients compared to controls was 0.4% vs. 0.2% (p < 0.01). The incidence rate of PE was 11.6 per 10,000 person-years for patients with AS and 6.8 per 10,000 person-years for controls. The adjusted hazard ratio (HR) for PE in patients with AS was 1.70 (p < 0.001). Subgroup analysis demonstrated excess risk for PE in patients with AS regardless of gender and age, with variations among AS treatment categories. Discussion: Our findings highlight a significant association between AS and PE, indicating an increased risk in patients with AS independent of age and sex and suggests a subclinical level of inflammation. Preliminary results suggest a protective role of immunosuppressing drugs. Further research into the impact of treatment strategies should be conducted and could inform clinical management and reduce the life-threatening risk of PE in Patients with AS. [ABSTRACT FROM AUTHOR]

Some 90 autoimmune disorders have been described in medical literature, affecting most of the tissues within the body. Autoimmune disorders may be difficult to treat, and there is a need to develop novel therapeutic strategies for these disorders. Autoimmune disorders are characterised by mitochondrial dysfunction, oxidative stress, and inflammation; there is therefore a rationale for a role for coenzyme Q10 in the management of these disorders, on the basis of its key role in normal mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. In this article, we have therefore reviewed the potential role of CoQ10, in terms of both deficiency and/or supplementation, in a range of autoimmune disorders. [ABSTRACT FROM AUTHOR]

The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research. [ABSTRACT FROM AUTHOR]

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. β-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). [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic skin hardening, which combines Raynaud's phenomenon and other vascular disorders, skin and internal organ fibrosis, immune disorders, and a variety of other abnormalities. Symptoms vary widely among individuals, and personalized treatment is sought for each patient. Since there is no fundamental cure for SSc, it is designated as an intractable disease with patients receiving government subsidies for medical expenses in Japan. Oxidative stress (OS) has been reported to play an important role in the cause and symptoms of SSc. HOCl-induced SSc mouse models are known to exhibit skin and visceral fibrosis, vascular damage, and autoimmune-like symptoms observed in human SSc. The antioxidant combination Twendee X® (TwX) is a dietary supplement consisting of vitamins, amino acids, and CoQ10. TwX has been proven to prevent dementia in humans with mild cognitive impairment and significantly improve cognitive impairment in an Alzheimer's disease mouse model by regulating OS through a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. We evaluated the effectiveness of TwX on various symptoms of HOCl-induced SSc mice. TwX-treated HOCl-induced SSc mice showed significantly reduced lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced highly oxidized protein products (AOPP) in serum and suppressed Col-1 gene expression and activation of B cells involved in autoimmunity. These findings suggest that TwX has the potential to be a new antioxidant treatment for SSc without side effects. [ABSTRACT FROM AUTHOR]

Eosinophils are a type of granulocyte key to immune system modulation seen in a number of disease processes. Nearly every major organ system can be connected to peripheral eosinophilia through a number of different disease processes, ranging from benign conditions to malignancy. In this paper, we review both common and rare causes of peripheral eosinophilia, their symptoms, and a framework for the workup of peripheral eosinophilia of unknown etiology. [ABSTRACT FROM AUTHOR]

Background: Studies assessing the psychological impact of the COVID-19 pandemic on populations highlight the emergence of mental health difficulties, especially if a mental health disorder is already present. Patients with severe mental illnesses (SMIs) may be even more vulnerable to the psychosocial effects of the pandemic. However, little is known regarding the possible impact of the pandemic on SMI patients supported by community-based mental health day centers. Methods: A two-year prospective study comprising 29 individuals with SMI was conducted by the Skitali Mental Health Day Center in Ioannina, Northwest Greece. The described group of examined patients consisted mainly of psychotic patients (65.5%). Patients were assessed using the Health of Nations Outcome Scale and the Global Assessment of Functioning scale, and scores prior to and after the onset of the pandemic were compared. Results: The results indicated that participants did not present any significant decline in their overall clinical status during the COVID-19 pandemic and the national lockdown measures. Conclusions: This finding is relevant because previous research has shown that the pandemic may negatively impact adherence to treatment and service attendance and that the symptomatology of patients with SMIs may further deteriorate. It is suggested that the operation of mental health day centers during collective stressful events should be preserved, but further research is needed to evaluate their role in maintaining continuity of care during such events. [ABSTRACT FROM AUTHOR]

Hidradenitis Suppurativa (HS) is a debilitating cutaneous disease characterized by a vicious cycle of chronic inflammation and tissue destruction that stems from disruption of the skin microbiome and abnormal activation of both the innate and adaptive immune system. A hallmark of HS pathophysiology is dysregulation of both the innate and adaptive immune system. The role of immune system dysregulation in HS development has motivated researchers to explore the utility of biologic immunomodulators. In 2015, adalimumab, a tumor necrosis factor-α inhibitor, was approved by the Food and Drug Administration (FDA) for treatment of moderate-to-severe HS in the US. In 2023, secukinumab, an interleukin-17A (IL-17A) inhibitor, was approved by the European Medicines Agency for treatment of moderate-to-severe HS in Europe. Ongoing clinical trials have shown promising clinical responses to targeted therapies against other pro-inflammatory cytokines including IL-17, IL-12, IL-1, IL-36, IL-6, IL-10, interferon γ, C5a, and Janus kinase (JAK). We provide an update on the efficacy and clinical usage of targeted biologics in HS treatment. [ABSTRACT FROM AUTHOR]

Psoriasis is a widespread chronic inflammatory skin disease, that negatively affects physical and emotional well-being and quality of life, as shown by the generally low Dermatology Life Quality Index (DLQI). Psoriasis is burdened by associated comorbidities and some patients manifest concurrent oral lesions, although the existence of oral psoriasis remains controversial. Psoriasis-specific and nonspecific oral lesions and Oral Health-Related Quality of Life (OHRQoL), self-assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, were retrospectively reviewed in adult untreated psoriasis patients with ≥15 teeth, who were non-smokers and had no dental or periodontal infections. Sample (age, gender, comorbidities) and descriptive variables (Body Surface Area-BSA, Psoriasis Area and Severity Index-PASI, Dermatology Life Quality Index-DLQI, severity of psoriasis, distribution of lesions and predominant involvement, years since diagnosis) were correlated with DLQI and OHIP-14 and compared by baseline DLQI and OHRQoL classes. Charts from 90 participants were included. No oral lesions were detected, and excellent/good OHRQoL was found in 94% of the participants. DLQI scores displayed positive significant associations with PASI and BSA, while OHIP-14 with hypertension and IMID, and age. PASI and BSA were significantly higher in participants with DLQI > 10 and also differed significantly among OHQRoL ranks, as well as mucosal involvement and comorbidities. Specifically, among subjects revealing an Excellent OHQRoL, 92.6% were non-IMID, 75% non-hypertensive, 89.7% non-diabetic subjects, 86.8% of non CVD-subjects. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic skin disease that significantly reduces the quality of life (QoL) of patients. The aim of this study was to assess whether dietary antioxidants can support the effect of cosmetic treatment in improving the QoL of patients with rosacea. Basic data about participants (N = 160) were collected using a self-reported survey. QoL was assessed using the standardized Dermatology Life Quality Index (DLQI) questionnaire. An interventional cosmetic treatment was performed using cavitation peeling and sonophoresis with a commercial capillary repair serum. The study was registered as a clinical trial (NCT06271135). To assess antioxidant diet quality, for the first time, a new dietary antioxidant quality index (DAQI) was developed, which consisted of 12 items: dietary total antioxidant capacity, dietary polyphenols, phytosterols, lignans, vitamin C, vitamin E, β-carotene, zinc, iron, copper, manganese and selenium. It was found that the highest tertiles of DAQI diminished the odds about 40–45% of the moderate, large and extremely large effect of rosacea on QoL and about 8–11% of the occurrence of rosacea symptoms compared with the lowest tertile. This study showed that rosacea has a negative impact on QoL, but a comprehensive approach to treatment, including antioxidant cosmetic treatment and dietary antioxidants, can improve the QoL of patients with rosacea. [ABSTRACT FROM AUTHOR]

Psoriasis can have a significant impact on quality of life and productivity, especially with increased severity. However, there is limited evidence on biologics' efficacy in highly severe cases compared to moderate-to-severe ones. This study aimed to evaluate the effectiveness and safety of novel biological therapies in very severe psoriasis. We conducted a retrospective analysis on patients ≥ 18 years old affected by very severe psoriasis who had received a biological agent for at least 16 weeks. We used PASI to assess disease severity and effectiveness at weeks 16, 52, 104, and 156. Safety was evaluated by tracking treatment discontinuation rates and adverse events. This study included 29 males and 11 females, with a mean age of 55.80 years (SD 13.82). Cardiometabolic diseases were the most common comorbidities (25.00%). Twenty-eight (70.00%) patients had psoriasis involvement in at least one difficult-to-treat area. All patients completed 16 weeks of treatment. The mean PASI was 31.60 (SD 2.57) at baseline, 3.48 (SD 4.13) at week 16, 0.58 (SD 1.70) at week 52, 0.77 (SD 1.66) at week 104, and 1.29 (SD 2.12) at week 156. PASI90 and 100 were achieved by 52.50% and 30.00% of patients at week 16, by 96.15% and 80.77% at week 52, by 93.33% and 66.67% at week 104, and by 85.71% and 42.86% at week 156. PASIs ≤ 2 were achieved by 50.00% of patients at week 16, 88.46% at week 52, 86.67% at week 104, and 85.71% at week 156. Only two patients discontinued biologics due to complete remission, and mild AEs were reported by four patients. Our findings show that biologics are effective and well tolerated for treating very severe psoriasis, maintaining long-term effectiveness. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory cutaneous condition characterized by several comorbidities, including musculoskeletal disorders. While the association with psoriatic arthritis has been widely addressed in literature, the aim of the present systematic review was to identify all available evidence on the relationship between psoriasis and fibromyalgia, a musculoskeletal syndrome primarily characterized by chronic widespread pain. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched for literature up to March 2023. After the removal of duplicate records, a total of 11 articles were deemed eligible for inclusion in a qualitative synthesis. Our results suggested that psoriatic patients had a higher prevalence of fibromyalgia (8–30%), with a very high impact on symptoms of psoriasis. Moreover, fibromyalgic patients had a slightly increased prevalence of psoriasis (2.2–6.7%) compared to the control groups. Finally, several studies demonstrated the substantial impact of fibromyalgia on psoriatic outcome measures in patients with concomitant psoriatic arthritis. In conclusion, available data support a potential interplay between psoriasis and fibromyalgia, but further research is encouraged in this area. [ABSTRACT FROM AUTHOR]

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field. [ABSTRACT FROM AUTHOR]

In the last decade, new treatments for atopic dermatitis (AD) have emerged. We aimed to describe trends of the diagnosis, disease course, and treatment of AD over a decade (2012–2021) using data from Maccabi Healthcare Services (a 2.7-million-member healthcare provider in Israel). The AD prevalence was stable (4.0% on 31 December 2021 vs. 4.3% on 31 December 2012). The annual AD incidence was also stable (5.8/1000 in 2012 and 5.7/1000 in 2021). AD-related treatment use was highest in the first year post-diagnosis, and it included, among children (n = 87,414) vs. adults (n = 36,865), low-potency topical corticosteroids (TCS) (41.8% vs. 27.1%), mid-potency TCS (30.1% vs. 28.1%), high-potency TCS (34.9% vs. 60.3%), topical calcineurin inhibitor (10.8% vs. 10.1%), phosphodiesterase-4-inhibitor (0.3% vs. 0.7% overall; approved in 2019), phototherapy (0.1% vs. 2.3%), and systemic/biologic treatments (13.0% vs. 13.3%). Among children diagnosed in 2012 and followed through to 2021 (n = 5248), 21.5% had ≥1 AD diagnosis/treatment 10 years later (among 3223 adults: 38.3%). We conclude that the incidence and prevalence rates of AD were comparable to those in similar database studies and remained relatively stable over the past decade. The results underscore the burden of medication use among children and adults, particularly in the first year after AD diagnosis, and the low rate of AD diagnosis among patients originally diagnosed as children 10 years earlier. [ABSTRACT FROM AUTHOR]

Psoriasis is an autoimmune-mediated disease with several comorbidities in addition to typical skin lesions. Increasing evidence shows the relationships between psoriasis and renal functions, but the relationship and causality remain unclear. We aimed to investigate the associations and causality between psoriasis and four renal functions, including the estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), urine albumin to creatinine ratio (UACR), and chronic kidney disease (CKD). For the population-based study, we analyzed the National Health and Nutrition Examination Survey (NHANES) data from five cycles (2003–2006 and 2009–2014) on psoriasis and renal functions. Subgroup analyses were conducted among different categories of participants. Meanwhile, a bidirectional two-sample Mendelian randomization (TSMR) study in European populations was also performed using summary-level genetic datasets. Causal effects were derived by conducting an inverse-variance weighted (MR-IVW) method. A series of pleiotropy-robust MR methods was employed to validate the robustness. Multivariable MR (MVMR) was conducted to complement the result when five competing risk factors were considered. A total of 20,244 participants were enrolled in the cross-sectional study, where 2.6% of them had psoriasis. In the fully adjusted model, participants with psoriasis had significantly lower eGFR (p = 0.025) compared with the healthy group. Individuals who are nonoverweight are more likely to be affected by psoriasis, leading to an elevation of BUN (Pint = 0.018). In the same line, TSMR showed a negative association between psoriasis and eGFR (p = 0.016), and sensitive analysis also consolidated the finding. No causality was identified between psoriasis and other renal functions, as well as the inverse causality (p > 0.05). The MVMR method further provided quite consistent results when adjusting five confounders (p = 0.042). We detected a significant negative effect of psoriasis on eGFR, with marginal association between BUN, UACR, and CKD. The adverse of psoriasis on the renal should merit further attention in clinical cares. [ABSTRACT FROM AUTHOR]

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of HDAC4_rs4852054*A were more susceptible (OR = 1.79, p = 0.0038), whereas those with GSE1_rs13339618*A (OR = 0.57, p = 0.0011) and homozygotes for PHF21A_rs4756055*A (OR = 0.39, p = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4+ T lymphocytes, using RNAseq. In these cells, we found a higher expression of KAT2B, PHF20, and ZEB2 and lower expression of KAT14 and JAD1 in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF. [ABSTRACT FROM AUTHOR]

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections. [ABSTRACT FROM AUTHOR]

Background and Objectives: Desquamative gingivitis (DG) is a clinical term indicating "peeling gums" and is associated with different oral manifestations. In this study, we aimed to assess the association between DG and autoimmune blistering mucocutaneous diseases (ABMD) with oral manifestations. Materials and Methods: A retrospective study including 88 patients diagnosed between 1998 and 2019 with ABMD (intraepithelial and subepithelial autoimmune blistering diseases) was performed at the Oral Medicine Department, Faculty of Dentistry, "Carol Davila" University of Medicine and Pharmacy in Bucharest. For each patient, the sociodemographic and anamnestic data, as well as clinical features of oral lesions (location), histological evaluation, and direct immunofluorescence data were collected. Results: Most of the patients involved in the study were female (78.4%). In total, 34 patients (38.63%) were diagnosed with subepithelial autoimmune diseases (SAD) and 54 (61.36%) had intraepithelial autoimmune diseases (IAD). Differences in the anatomic distribution of oral involvement were found between SAD and IAD. The presence of DG was significantly more common in patients with SAD compared to those with a diagnosis of IAD. Conclusions: Specific anatomical locations of the oral lesions are significantly associated with different subtypes of ABMD, with gingiva and hard palate mucosa being more involved in SAD and the soft palate and buccal mucosa in IAD. Desquamative gingivitis is a clinical sign that raises diagnostic challenges for several conditions in oral medicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sleep disorder is a disease that can be categorized as both an emotional and physical problem. It imposes several difficulties and problems, such as distress during the day, sleep-wake disorders, anxiety, and several other problems. Hence, the main objective of this research was to utilize the strong capabilities of machine learning in the prediction of sleep disorders. In specific, this research aimed to meet three main objectives. These objectives were to identify the best regression model, the best classification model, and the best learning strategy that highly suited sleep disorder datasets. Considering two related datasets and several evaluation metrics that were related to the tasks of regression and classification, the results revealed the superiority of the MultilayerPerceptron, SMOreg, and KStar regression models compared with the other twenty three regression models. Furthermore, IBK, RandomForest, and RandomizableFilteredClassifier showed superior performance compared with other classification models that belonged to several learning strategies. Finally, the Function learning strategy showed the best predictive performance among the six considered strategies in both datasets and with respect to the most evaluation metrics. [ABSTRACT FROM AUTHOR]

The multicenter, retrospective cohort study was aimed at examining adverse events in biologic-treated patients with moderate-to-severe psoriasis by using a real-world database. Thus, we analyzed exposure-adjusted incidence rates for new-onset inflammatory bowel disease (IBD), oral and gastrointestinal candidiasis, pulmonary tuberculosis, herpes zoster, and major cardiovascular events (MACEs) in biologic-treated patients with moderate-to-severe psoriasis. Overall, 2085 patients were found to have been exposed to tumor necrosis factor (TNF)-α, interleukin (IL)-12/23, IL-17, and IL-23 inhibitors (n = 463, 540, 635, and 447, respectively). No patient developed new-onset IBD. The incidence rates of oral and gastrointestinal candidiasis were comparable between patients treated with IL-23 and IL-17 inhibitors (5.6 and 5.3 per 1000 PY, respectively). None treated with IL-17 or IL-23 inhibitors reported pulmonary tuberculosis. The incidence rate of herpes zoster was the highest in patients treated with TNF-α inhibitors (17.0 per 1000 PY), followed by IL-17, IL-23, and IL-12/23 inhibitors (13.3, 7.8, and 2.7 per 1000 PY, respectively). MACEs were not reported in patients treated with IL-17 inhibitors but were reported in those treated with TNF-α, IL-23, and IL-12/23 inhibitors (incidence: 5.6, 3.8, and 1.8 per 1000 PY, respectively). The study indicated favorable safety profiles of biologics in Korean patients with moderate-to-severe psoriasis. [ABSTRACT FROM AUTHOR]