Search Results (89)

Psoriasis vulgaris is a T-cell-mediated skin disease that may involve an autoimmune response against melanocytes. It develops through still unexplained pathomechanisms. Streptococcal tonsillopharyngitis is a major trigger of psoriasis onset and relapses. HLA-C*06:02 is the main psoriasis risk gene. Here we find that B cells isolated from streptococci-infected tonsils or peripheral blood of HLA-C*06:02⁺ psoriasis patients stimulate an HLA-C*06:02-restricted melanocyte-reactive Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8⁺ T cell clone in an IFN-γ-enhanced manner. Patients’ B cells furthermore induce proliferation of autologous blood CD8⁺ T cells. We identify several HLA-C*06:02-presented self-peptides in the immunopeptidomes we had isolated from four HLA-C*06:02 homozygous B-cell lines that stimulate the Vα3S1/Vβ13S1 TCR and differ from the melanocyte autoantigen recognized by this TCR. These data suggest that the proinflammatory environment of streptococcal tonsillopharyngitis may enable B cells to activate autoreactive CD8⁺ T cells that, owing to the polyspecificity of T-cell receptors, recognize several B-cell self-peptides presented by HLA-C*06:02 and subsequently cross-react against melanocytes in the skin, thereby triggering psoriasis. The capacity of B cells to stimulate a cross-reactive autoimmune response through HLA class I-presented B-cell peptides is a previously unknown mechanism in the induction of autoimmunity that could explain psoriasis onset and persistence. Full article

Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory arthritis associated with psoriasis, affecting joints, entheses, and the axial skeleton. While primary care providers and dermatologists frequently encounter psoriasis (PsO), early recognition of PsA remains critical to preventing irreversible joint damage. This paper is written to provide a comprehensive overview of PsA, beginning with a clinical case that highlights diagnostic and therapeutic challenges. In this review, the epidemiology of PsA will be discussed, emphasizing its prevalence and risk factors among patients with PsO. The discussion extends to the underlying pathogenesis, focusing on genetic predisposition, environmental triggers, and key cytokines, including TNF-α, IL-17, and IL-23, that have become targets for advanced therapeutics. The clinical features of PsA are explored in detail, including peripheral and axial arthritis, enthesitis, dactylitis, and extra-articular manifestations. Diagnostic approaches are discussed, with a focus on the Classification Criteria for Psoriatic Arthritis (CASPAR) and Moll & Wright criteria. Additionally, we examine screening tools designed to facilitate early detection in dermatology clinics. Diagnostic modalities, including imaging and serologic markers, are reviewed. Finally, we explore the evolving landscape of PsA treatment, spanning conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic agents (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). Given the increasing availability of cytokine-targeted therapies, an interdisciplinary approach between dermatologists and rheumatologists is essential for optimizing outcomes in PsA patients. Patients with PsA are cared for by rheumatologists, dermatologists, and primary care providers who help manage the comorbidities associated with PsA. By bridging primary care, dermatology, and rheumatology in the care of PsA, this paper aims to enhance understanding of PsA for facilitating early identification and timely intervention for improved patient care. Full article

The gut microbiota, a complex community of trillions of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining host health and regulating a wide range of physiological functions. Advances in molecular biology have greatly expanded our understanding of the dynamic interactions between the gut microbiome and the immune system. Disruption of this microbial community, known as dysbiosis, can compromise epithelial barrier integrity, trigger aberrant immune activation, and lead to the production of proinflammatory metabolites. These changes are increasingly recognized as contributing factors in the pathogenesis of chronic inflammatory diseases. Emerging research highlights the gut microbiota as a key modulator of immune homeostasis, influencing both local and systemic inflammatory processes during the initiation and progression of these diseases. Understanding the mechanisms underlying gut microbiota-immune interactions will offer new avenues for therapeutic interventions. This review focuses on six representative chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, asthma, and vasculitis, all of which are characterized by dysregulated immune responses and persistent inflammation. Our goal is to synthesize the recent research on the role of gut microbiome in the pathogenesis of the diseases listed above and provide insights into the development of microbiota-based therapies, particularly fecal microbiota transplant, dietary modifications, prebiotic and probiotic interventions, for their treatment. Full article

Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current data on IFN biology, their immunoregulatory and pathogenic mechanisms, and their contributions to distinct AD phenotypes. We conducted a comprehensive review of peer-reviewed literature on IFNs and autoimmune diseases, focusing on publications indexed in PubMed and Scopus. Studies on molecular pathways, immune cell interactions, disease-specific IFN signatures, and clinical correlations were included. Data were extracted and thematically organized by IFN type, signaling pathway, and disease context, with emphasis on rheumatic and systemic autoimmune disorders. Across systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathies, multiple sclerosis, type 1 diabetes, psoriasis, and inflammatory bowel diseases, IFNs were consistently associated with aberrant activation of pattern recognition receptors, sustained expression of interferon-stimulated genes (ISGs), and dysregulated T cell and B cell responses. Type I IFNs often preceded clinical onset, suggesting a triggering role, whereas type II and III IFNs modulated disease course and severity. Notably, IFNs exhibited dual immunostimulatory and immunosuppressive effects, contingent on tissue context, cytokine milieu, and disease stage. IFNs are central mediators in autoimmune pathogenesis, functioning as both initiators and amplifiers of chronic inflammation. Deciphering the context-dependent effects of IFN signaling may inform targeted therapeutic strategies and advance precision immunomodulation in autoimmune diseases. Full article

Psoriasis is a chronic inflammatory autoimmune skin disease characterized by erythematous plaques covered with silvery-white scales, often accompanied by systemic complications such as psoriatic arthritis and cardiovascular diseases. The disease and its systemic complications substantially impair quality of life, compromise socioeconomic status, and threaten patient safety. The occurrence and progression of this disease are related to the IL-23/IL-17 axis and involve the aberrant activation and interactions of multiple immune cells, along with genetic predispositions and environmental triggers. Although current therapeutic approaches, including topical agents, systemic medications, biologic agents targeting key cytokines, and Janus Kinase inhibitors, can control symptoms and delay disease progression, a complete cure has not been achieved. Furthermore, these strategies face challenges relating to the cost, safety, efficacy and precision of targeting. This review summarizes recent advances in mechanistic research, highlighting the interplay among microorganisms, innate and adaptive immunity in psoriasis. We also evaluate a range of emerging therapies, including biologics, small-molecule inhibitors, Chimeric antigen receptor T-cell cell therapy, RNA interference-based strategies, and alternative medicine. Specifically, we focus on their novel mechanisms, efficacy challenges, safety profiles, and targeting accuracy. Finally, we assess their potential in personalized treatment, aiming to achieve long-term remission, and propose the future prospects of precision medicine in psoriasis management. Full article

Background/Objectives: Psoriasis is an immune-mediated disease influenced by genetic predisposition, environmental triggers, and metabolic comorbidities. Biologic therapies have markedly improved disease control; however, variability in patient response remains insufficiently understood. The aim of the study is to evaluate whether CARD14 mutations and the season of treatment initiation influence the efficacy of biologic therapy in psoriasis. We also examined the potential interactions between CARD14 status, seasonality, drug class, and nutrition status on short-term clinical outcomes. Methods: This retrospective study included 72 patients receiving biologic therapy within the Polish NHF B.47 program. Clinical endpoints (PASI, BSA, DLQI) were assessed at baseline and after 1, 4, 7, and 10 months. CARD14 genotyping was performed using Sanger sequencing. Patients were stratified according to mutation status, season of therapy initiation (warm vs. cold), drug class, and BMI category. Statistical analyses included t-tests, chi-square, ANOVA, and MANOVA. Results: The CARD14 rs34367357 mutation was associated with earlier disease onset (15.6 vs. 22.7 years, p = 0.0134) and higher DLQI baseline (p = 0.0265) but did not significantly impact treatment response. Therapy initiated during the warm season (April–September) led to greater PASI improvement (p < 0.0001). Obesity was associated with reduced response (p = 0.02385). Drug class and interaction effects were not statistically significant. Conclusions: Our findings suggest that seasonal timing, nutritional status, and genetic background may modulate the efficacy of biologic therapies in psoriasis. Although not statistically conclusive, the potential interaction between CARD14 rs34367357 and seasonality warrants further investigation. Full article

A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article

Psoriasiform dermatitis refers to a spectrum of inflammatory skin disorders that resemble psoriasis both clinically and histologically. These conditions can occur idiopathically or as paradoxical reactions to biologic or targeted therapies, particularly in patients with atopic or autoimmune backgrounds. Histologic features often include acanthosis, parakeratosis, and lymphocytic infiltrates, but without the full molecular signature of classical psoriasis. This review provides an overview of psoriasiform dermatitis with a focus on its clinical presentation, differential diagnosis, and the immune pathways involved. Drug-induced forms, especially those triggered by anti-TNF agents, IL-4/IL-13 blockers, and JAK inhibitors, are highlighted due to their growing clinical relevance. We also summarize the main topical and systemic treatments, including corticosteroids, calcineurin inhibitors, PDE4 inhibitors, and JAK-STAT- or IL-23-targeted therapies. A better understanding of psoriasiform dermatitis is crucial to improve diagnosis and to guide treatment, especially in complex or refractory cases. Full article

Group A β-hemolytic Streptococcus (GAS) is a Gram-positive, coccoid-shaped bacterium that tends to grow in chains; it is a non-spore-forming, facultatively anaerobic, catalase-negative, aerobic bacterium. It is known to cause a wide range of infections in children, ranging from mild upper respiratory tract infections, such as pharyngitis, to severe invasive disease. GAS also notably triggers post-infectious immune sequelae, including acute poststreptococcal glomerulonephritis (APSGN), acute rheumatic fever (ARF), and rheumatic heart disease (RHD), which are major health burdens, especially in low-income countries. In this review, we will present the general characteristics of GAS, highlighting its structural and microbiological features. We will also discuss its pathogenetic mechanisms, especially molecular mimicry, and its ability to cause autoimmune responses. Finally, we will elucidate some of the autoimmune sequelae that mark GAS infections, such as ARF, RHD, APSGN, and guttate psoriasis. Understanding GAS as a model pathogen for infection-induced autoimmunity provides insight into host–pathogen interactions and supports the development of targeted interventions. Emphasis on early diagnosis and antibiotic treatment is essential to reduce the burden of autoimmune complications Full article

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation, impaired epidermal barrier function, and immune dysregulation. The Th17/IL-23 axis plays a central role in its pathogenesis, promoting the production of key pro-inflammatory cytokines such as IL-17, IL-23, and TNF-α, which sustain chronic inflammation and epidermal remodeling. Emerging evidence suggests that SARS-CoV-2 may trigger new-onset or exacerbate existing psoriasis, likely through viral protein-induced activation of toll-like receptors (TLR2 and TLR4). This leads to NF-κB activation, cytokine release, and enhanced Th17 responses, disrupting immune homeostasis. Erythrodermic psoriasis (EP), a rare and severe variant, presents with generalized erythema and desquamation, often accompanied by systemic complications, including infection, electrolyte imbalance, and hemodynamic instability. In a murine model of SARS-CoV-2 infection, we found notable cutaneous changes: dermal collagen deposition, hair follicle destruction, and subcutaneous adipose loss. Parallel findings were seen in a rare clinical case (only the third reported case) of EP in a patient with refractory psoriasis, who developed erythroderma after off-label initiation of dupilumab therapy. The patient’s histopathology closely mirrored the changes seen in the SARS-CoV-2 model. Histological evaluations also reveal similarities between psoriasis flare-ups following dupilumab treatment and cutaneous manifestations of COVID-19, suggesting a shared inflammatory pathway, potentially mediated by heightened type 1 and type 17 responses. This overlap raises the possibility of a latent connection between SARS-CoV-2 infection and increased psoriasis severity. Since the introduction of COVID-19 vaccines, sporadic cases of EP have been reported post-vaccination. Although rare, these events imply that vaccine-induced immune modulation may influence psoriasis activity. Our findings highlight a convergence of inflammatory mediators—including IL-1, IL-6, IL-17, TNF-α, TLRs, and NF-κB—across three triggers: SARS-CoV-2, vaccination, and dupilumab. Further mechanistic studies are essential to clarify these relationships and guide management in complex psoriasis cases. Full article

(1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using wild-type, keratin 14-specific IL-33 transgenic, IL-18 transgenic, caspase-1 transgenic, and caspase-1 transgenic mice with IL-17AF deletion, reflecting diverse aspects of human skin inflammation. IL-36α was administered subcutaneously in five doses on alternate days across the five strains to examine cellular infiltration patterns and cytokine expression levels. (3) Results: The skin phenotype was exacerbated, accompanied by worsening edema and skin thickness in all mouse groups upon IL-36α administration. An increase in infiltrating cells was observed among innate immune cells, while lymphocyte counts, including T cells and innate lymphoid cells, did not rise. Additionally, anti-inflammatory cytokines were induced simultaneously with inflammatory cytokines and downstream cytokines of IL-36α as well. Infiltrating lymphocytes in the skin displayed a distinct Type 2 cytokine-dominant profile for innate lymphoid cells and a Type 3 cytokine-dominant profile for T helper cells and γδ T cells, contrasting with the Type 1-dominant cell profile in draining lymph nodes. Type 1, Type 2, and Type 3 cytokine dominance patterns were not affected by the administration of IL-36α. (4) Conclusions: IL-36α triggers inflammatory responses in atopic dermatitis by activating innate immunity. The infiltrating lymphocytes in the skin have different cytokine production profiles between innate lymphoid cells and T cells, as well as different patterns of cytokine production in their draining lymph nodes. Full article

Psoriasis, a chronic inflammatory skin disorder, is driven by dysregulated immune responses and keratinocyte dysfunction. Here, we explore the therapeutic potential of Astilbin (AST), a flavonoid with potent anti-inflammatory properties, in modulating ferroptosis and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in IL-17-stimulated HaCaT keratinocytes. Our psoriatic cell model recapitulated key pathological features, including hyperproliferation, membrane integrity loss, mitochondrial dysfunction, and heightened oxidative stress, alongside elevated proinflammatory cytokine levels. Ferroptosis-related biomarkers were significantly altered, with increased malondialdehyde (MDA) accumulation, reduced glutathione (GSH) levels, iron overload (Fe²⁺), and enhanced lipid peroxidation (detected via C11-BODIPY). Mechanistically, mitochondrial damage triggered cytoplasmic leakage of mitochondrial DNA (mtDNA), activating the cGAS-STING pathway, as evidenced by upregulated pathway-associated protein expression. AST intervention effectively mitigated these pathological changes by suppressing ferroptosis and modulating cGAS-STING signaling. These findings reveal a dual-pathway regulatory mechanism, positioning AST as a promising therapeutic candidate for psoriasis. By elucidating the interplay between ferroptosis and the cGAS-STING pathway, this study provides new insights into psoriatic inflammation and offers a rationale for targeting these pathways in therapeutic strategies. Full article

Bullous pemphigoid (BP) is a rare autoimmune disease, primarily affecting elderly individuals, that significantly impacts the patient’s quality of life. In contrast, psoriasis vulgaris (PV) is a common, chronic, immune-mediated skin condition recognized as a systemic T-cell-mediated disorder. We aim to present the case of a patient suffering from a dermatologic association of BP and PV, which unveiled hepatitis C viral infection as a potential trigger and led to complex therapeutic challenges. A literature review is also included, exploring previous cases of overlapping BP and PV, along with a discussion of the unique pathogenic mechanisms and an analysis of the available therapeutic options. The patient, a 53-year-old male with a seven-year history of PV, presented with tense bullae overlying the psoriatic papules and plaques, with a generalized distribution. The presence of hepatitis C infection was considered a potential trigger for the concurrent presentation of BP and PV. Recent GWASs have demonstrated a potential causal relationship between PV and the subsequent development of BP, suggesting shared genetic susceptibility and immune pathways. However, the exact mechanisms driving this transition remain incompletely understood. Our case is particularly relevant as it exemplifies how environmental triggers—such as chronic hepatitis C infection—together with chronic cutaneous inflammation may act as cofactors in this process, possibly through the ‘epitope spreading’ phenomenon. This case underlines the importance of identifying triggering factors in patients with overlapping autoimmune diseases and reinforces the need for future research to further elucidate the pathogenic link between genotype and phenotype, in order to improve personalized therapeutic strategies. Full article

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released into the extracellular space by almost all known cell types. They facilitate communication between cells by transferring bioactive molecules, which impact both physiological processes and the development of diseases. EVs play a crucial role in the pathogenesis of various diseases by participating in multiple pathological processes. They contribute to disease progression by triggering cytokine release, modulating immune cell activity, and inducing inflammatory and immune responses. Beyond their pathological implications, EVs also offer significant therapeutic potential. Both natural and engineered EVs show great potential in the fields of targeted therapy, drug delivery, and immune modulation in dermatological applications. The development of EV-based treatments is showing promise in advancing patient outcomes, particularly in chronic inflammatory and immune-mediated skin conditions. This review comprehensively examined the biogenesis, classification, and functional roles of EVs, including advanced methods for their isolation and characterization. Furthermore, we summarized recent studies highlighting the involvement of EVs in four major inflammatory skin diseases: psoriasis, atopic dermatitis, systemic lupus erythematosus, and wound healing. Full article

Introduction: About one in four people show an immunological reaction to an infection with Mycobacterium tuberculosis, which can remain latent or lead to active forms of the disease. Psoriasis is a chronic, immune-mediated skin disease that can be associated with numerous comorbidities. Biologic therapies have revolutionized psoriasis treatment but carry the risk of reactivating latent tuberculosis infection. However, the link between tuberculosis as a triggering factor for the onset of psoriasis remains unknown. Clinical Case: We present the case of a patient initially diagnosed with secondary pulmonary tuberculosis, who, two months after the diagnosis, showed a remarkable clinical evolution by developing lesions consistent with vulgar psoriasis, necessitating a multidisciplinary treatment approach. Discussions: This unique case highlights the shared immune mechanism of these diseases, particularly involving TNF-α, IL-17, and CD4+ T cells. Conclusions: The coexistence of these conditions raises critical questions about the interplay between infectious and autoimmune diseases and the impact of genetic susceptibility. Full article