Search Results (35)

Psoriasis and psoriatic arthritis (PsA) occasionally coexist with antinuclear antibody (ANA) positivity, cutaneous lupus erythematosus (CLE), or systemic lupus erythematosus (SLE), creating one of the most challenging therapeutic overlap scenarios in immunodermatology. Divergent immune pathways—IL-23/Th17-driven psoriatic inflammation versus type I interferon-mediated autoimmunity—generate unique vulnerabilities when systemic treatments are used. To synthesize treatment outcomes, lupus-related safety signals, and mechanistic insights across systemic therapies in patients with psoriasis or PsA who also exhibit ANA positivity, CLE, or SLE. A systematic review following PRISMA 2020 guidelines was conducted across PubMed/MEDLINE, Embase, the Cochrane Library, Scopus, and ClinicalTrials.gov from database inception through 31 October 2025. Thirty-three eligible reports (29 unique clinical studies; 1429 patients) were included and organized into six prespecified overlap subgroups. Mechanistic and translational studies—including ustekinumab and deucravacitinib SLE trial data and reports of IL-17 inhibitor-associated CLE—were reviewed separately to provide contextual interpretation. IL-23 inhibitors were consistently associated with a favorable cross-disease safety profile, with no clear signal for CLE worsening, SLE flares, or drug-induced autoimmunity. IL-17 inhibitors maintained strong psoriatic efficacy but were associated with an increased frequency of de novo or exacerbated CLE. TNF-α inhibitors showed the strongest association with ANA seroconversion, anti-dsDNA induction, drug-induced lupus, and lupus flares. Ustekinumab demonstrated a stable safety profile across lupus-spectrum disease despite variable efficacy in formal SLE trials. TYK2 inhibition provided dual modulation of IL-23 and type I interferon pathways and showed emerging utility in psoriasis or PsA coexisting with CLE or SLE. Apremilast, methotrexate, and mycophenolate mofetil remained reliable non-biologic systemic options. Phototherapy was associated with potential risk in ANA-positive or lupus-susceptible populations and therefore requires careful consideration. Interpretation is limited by the predominantly observational nature and heterogeneity of the available evidence. IL-23 inhibition and TYK2 inhibition appear to offer a balanced profile of efficacy and lupus-related safety in psoriatic disease complicated by lupus-spectrum autoimmunity. IL-17 inhibitors and TNF-α inhibitors may be associated with higher risk in CLE- or SLE-prone patients and therefore warrant particular caution. Personalized treatment strategies should integrate the relative dominance of psoriatic versus lupus disease, ANA/ENA profile, CLE subtype, and underlying mechanistic considerations. Prospective, biomarker-driven studies are needed to guide therapy in this increasingly recognized overlap population (PROSPERO registration: CRD420251241279). Full article

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder in which ocular involvement represents a clinically significant yet frequently underrecognized contributor to morbidity. Ocular manifestations in SLE may arise from disease activity itself, but also as adverse effects of long-term pharmacological therapy. With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways. These advances have improved systemic disease control and survival; however, their ophthalmological safety profiles remain only partially defined. This review synthesizes current evidence on ocular adverse events associated with both traditional and emerging SLE therapies. Established agents, particularly hydroxychloroquine and corticosteroids, are consistently linked to complications including retinopathy, posterior subcapsular cataracts, steroid-induced glaucoma, and central serous chorioretinopathy. In contrast, recently approved or investigational therapies—such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies—have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains. Although ocular complications appear infrequent in clinical trials, underdetection in real-world practice and insufficient long-term monitoring may underestimate their true incidence. These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient population. Full article

Background/Objectives: Cutaneous lupus erythematosus (CLE) is a complex autoimmune skin disease driven by genetic predisposition, environmental triggers, and immune dysregulation. Environmental factors such as ultraviolet radiation, smoking, and certain drugs can initiate disease onset by inducing keratinocyte apoptosis. The subsequent release of nucleic acids and danger-associated molecular patterns activates pattern recognition receptors (PRRs) on keratinocytes and immune cells, leading to the production of type I and type III interferons (IFNs) and pro-inflammatory cytokines. The objective of this review is to summarize recent advances in understanding the immunopathogenesis of CLE, with particular attention to emerging cellular players and their therapeutic implications. Methods: A narrative review of the recent literature was performed, including experimental, translational, and clinical studies investigating the cellular and molecular mechanisms underlying CLE and novel targeted treatments derived from these findings. Results: Although plasmacytoid dendritic cells (pDCs) have traditionally been considered the major producers of IFN-I, recent data indicate that pDCs in CLE are functionally impaired and are not the primary source. Other cells, such as keratinocytes have emerged as key producers of IFN-I, contributing to a prelesional, IFN-rich microenvironment. This promotes the recruitment and activation of dendritic cells and other inflammatory myeloid subsets, which are now recognized as central players in amplifying local inflammation. Concurrently, T cells infiltrate the skin, where cytotoxic CD8⁺ T cells attack keratinocytes and CD4⁺ T cells further propagate inflammation via cytokine production. B cells and plasma cells produce autoantibodies, forming immune complexes that perpetuate inflammation. Neutrophils release neutrophil extracellular traps (NETs), exposing autoantigens and further stimulating IFN pathways. Macrophages contribute by presenting autoantigens, producing pro-inflammatory mediators, and failing to effectively clear apoptotic cells and immune complexes. Conclusions: The dynamic interplay between the innate and adaptive immune systems sustains the chronic inflammatory state characteristic of CLE. Based on the pathogenetic novelties, new therapeutic agents targeting specific molecules have been developed, which may improve the treatment of this complex disease in the future. Full article

COVID-19 vaccination has played a pivotal role in mitigating the global health crisis and reducing morbidity and mortality associated with SARS-CoV-2 infection. While its public health benefits are unequivocal, the unprecedented scale of vaccination—reaching billions worldwide—has also enabled the detection of rare autoimmune events, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and Guillain–Barré syndrome. Although such events occur in only a small subset of individuals, often influenced by genetic, environmental, or dosage-related factors, they underscore the importance of understanding immune tolerance mechanisms in vaccination. This review synthesizes clinical observations and immunological findings from the COVID-19 vaccination era, highlighting key mechanisms such as molecular mimicry, adjuvant-induced inflammation, bystander activation, epitope spreading, and polyclonal B cell activation. We also consider how novel vaccine platforms, particularly mRNA-based technologies, may influence immune regulation and self-tolerance. Importantly, we discuss the therapeutic management of vaccine-associated autoimmunity, including the use of corticosteroids, intravenous immunoglobulin (IVIG), plasma exchange, disease-modifying anti-rheumatic drugs (DMARDs), and other immunosuppressive agents, many of which have led to favorable clinical outcomes. By integrating mechanistic insights with treatment strategies, this review emphasizes that the overall benefits of COVID-19 vaccination overwhelmingly outweigh the risks, while advocating for continued surveillance, mechanistic research, and risk stratification to inform safer and more targeted vaccination strategies in future pandemics. Full article

Ferroptosis, an iron-dependent programmed cell death driven by lipid peroxidation, plays a critical role in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. This review systematically explores the interaction between ferroptosis and the immune system, highlighting its dynamic regulation of immune cell function (e.g., Treg cell stability, neutrophil activity) and inflammatory microenvironments via signaling pathways including JAK/STAT and NF-κB. Ferroptosis suppresses inflammation in rheumatoid arthritis by eliminating pro-inflammatory synoviocytes but exacerbates tissue damage in systemic lupus erythematosus through neutrophil ferroptosis. While ferroptosis inhibitors (e.g., Fer-1) and inducers (e.g., IKE) show promise in preclinical models, clinical translation faces challenges such as disease-specific mechanistic heterogeneity, insufficient drug selectivity, and complex metabolic interactions. Future research should integrate multi-omics, organoid models, and AI-driven predictions to develop precision-targeted strategies, offering novel therapeutic paradigms for autoimmune diseases. Full article

Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren’s syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs. Full article

Background and Clinical Significance: Neuromyelitis optica (NMO) is a chronic demyelinating inflammatory disease of the central nervous system (CNS), mediated by autoantibodies against aquaporin-4 (AQ4) receptors. In the spectrum of NMO, other autoimmune diseases also coexist, though their association with systemic lupus erythematosus (SLE) is rare. Case Presentation: We present two cases of patients in their 70s who were diagnosed with NMO in the context of SLE. The first case concerns a 78-year-old woman with drug-induced SLE and thoracic myelitis who developed T4-level incomplete paraplegia over three weeks. The second case involves a 71-year-old woman with a history of SLE and myasthenia gravis, presenting with cervical myelitis with progressive worsening of walking and C4-level paraparesis over two months. In both cases, elevated serum anti-AQ4 titers were detected, establishing the diagnosis of NMO and differentiation from an atypical manifestation of SLE-related myelitis. High doses of intravenous corticosteroids with gradual tapering, along with cyclophosphamide, followed by rituximab, were administered in both patients. The first patient showed a poor response, while the second showed improvement. Conclusions: The coexistence of NMO with SLE is rare, but the occurrence of myelitis in patients with connective tissue diseases should raise the suspicion of NMO, especially in elderly women and several years after the diagnosis of SLE. Time to treatment is critical, as delays in treating NMO can result in cumulative and disabling damage. Full article

Background/Objectives: Mycophenolate mofetil (MMF) has emerged as a valuable immunosuppressive agent used in the management of oral mucocutaneous diseases, particularly in autoimmune and inflammatory conditions, such as pemphigus vulgaris (PV), oral lichen planus (OLP), mucous membrane pemphigoid (MMP), systemic lupus erythematosus (SLE), erythema multiforme (EM) and recurrent aphthous stomatitis (RAS). This review consolidates the current evidence regarding MMF’s efficacy, safety and clinical applications across these conditions. Methods: A comprehensive review of literature was performed, focusing on the mechanism of action, dosing strategies, therapeutic outcomes and adverse effects associated with MMF therapy in oral mucocutaneous diseases. The potential of therapeutic drug monitoring (TDM) in optimizing MMF therapy and minimizing adverse effects was also explored. Results: The review demonstrates that MMF is effective in inducing disease remission in up to 80% of patients with PV, with notable steroid-sparing effects. In OLP, MMF provided significant clinical improvement, especially in patients with severe and refractory forms of the disease. For MMP, MMF showed an 89% response rate, particularly when combined with corticosteroids, though gastrointestinal side effects were noted in some patients. In SLE, MMF was effective in managing both renal and non-renal manifestations, with favorable remission rates observed in patients receiving MMF therapy. For EM, MMF’s effectiveness was limited, with only a small number of patients responding to therapy. In RAS, there is limited evidence of MMF’s efficacy, with only partial improvement in severe cases reported. MMF is a promising immunomodulatory therapy for oral mucocutaneous diseases, particularly in reducing corticosteroid dependence and improving patient outcomes. However, the variability in the study designs, dosages and patient populations complicates the generalization of these findings. Conclusions: There is a pressing need for randomized controlled trials to validate MMF’s efficacy and long-term safety across all disease categories. The integration of therapeutic drug monitoring (TDM) shows potential for improving disease control and minimizing adverse effects, making it a key consideration for future research. 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

Background: In response to the SARS-CoV-2 pandemic, a massive vaccination campaign was launched. Nonetheless, concerns arose regarding some peculiar groups of patients, including those affected by Systemic Lupus Erythematosus (SLE), because of the immune-suppressive drugs routinely administered to patients and the risk of possible disease flares. Since the effects of the third booster vaccination in SLE have been poorly assessed, this study aims to evaluate the immunogenicity and safety of the third BNT162b2 vaccine dose, together with the effects of immunosuppressive drugs. Methods: A monocentric SLE cohort and a cohort of age- and sex-matched healthy controls (HCs) (all vaccinated with three homologous doses) were consecutively enrolled 6 months (T1) after their third vaccine shot. Vaccine immunogenicity was evaluated by analyzing humoral and cellular immune responses at T1 and 12 months (T2). Vaccine safety was evaluated by assessing adverse events related to vaccination (T0) and comparing disease activity among T0, T1, and T2. Effects of immunosuppressive drugs were assessed by stratifying patients according to therapy at vaccination: (1) receiving (IS) or (2) not receiving immunosuppressive drugs (Non-IS). Results: At T1, the humoral responses were comparable between SLE and HC subjects, while the cellular response was significantly higher in HC (p = 0.01). No differences were found at T2 between cohorts. Similarly, both at T1 and T2, the immune responses of IS and Non-IS groups were comparable. Moreover, lupus disease flares were limited and mostly mild, and no life-threatening adverse events were reported. Conclusions: The booster BNT162b2 vaccine is safe and induces an immune response, which is persistent and not affected by ongoing immunosuppressive drugs. Full article

Morbillivirus canis, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the Canidae family. In dogs (Canis lupus familiaris), common signs of infection include conjunctivitis, digital hyperkeratosis and neuropathologies. Even with vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes have been an interesting and promising area in new therapeutic drugs research in recent years. It is known that in the process of virus infection, the endoplasmic reticulum (ER) loses its homeostasis, inducing stress and the subsequent unfolded protein response or UPR in which three ER-trans-membrane proteins are implicated: PERK, IRE1 and ATF6. Moreover, in prolonged ER stress, the apoptosis is induced through the CHOP, as a final step of viral infection. Cell culture and molecular techniques such as RT-qPCR and RT-PCR were used in the present study. We demonstrate the activation in vitro of the three UPR pathways after infection with an attenuated strain of CDV. Also, the implication of a MAPK pathway through the p38 protein and the apoptotic CHOP was demonstrated to contribute to the process of infection. Even more, our study suggested that CDV replication occurs in a PERK-dependent manner. Full article

Systemic lupus erythematosus (SLE) and psoriasis (Ps) are two clinically distinct diseases with different pathogenesis. However, recent studies indicate some similarities in both clinical presentation and pathogenetic mechanisms. The coexistence of both entities is very uncommon and has not been fully elucidated. Thus, it remains a diagnostic and therapeutic challenge. In fact, drugs used in SLE can induce psoriatic lesions, whereas phototherapy effective in Ps is an important factor provoking skin lesions in patients with SLE. The aim of this work is to discuss in detail the common pathogenetic elements and the therapeutic options effective in both diseases. Full article

Psychotropic medications, commonly prescribed for psychiatric disorders, can have underappreciated dermatological side effects. This in-depth review explores the intricate relationship between psychotropic drugs and the skin, emphasizing the significance of recognizing and managing these side effects in clinical practice. It categorizes the dermatological side effects associated with different classes of psychotropic medications. These include antidepressants, antipsychotics, mood stabilizers, and anxiolytics. We delve into the spectrum of dermatological conditions, from mild issues like dry skin and acne to severe complications such as Stevens–Johnson syndrome and drug-induced lupus erythematosus. In conclusion, a comprehensive understanding of the dermatological side effects of psychotropic medications is essential for healthcare providers, enabling a holistic approach to patient care. This review is a valuable resource for clinicians, researchers, and educators, facilitating better-informed decision-making in the treatment of mental health disorders while prioritizing skin health and overall well-being. Full article

Ustekinumab (UST), a biologic agent targeting interleukin-12 and interleukin-23, is widely used in the management of psoriasis and Crohn’s disease. Despite its efficacy, there have been instances of paradoxical psoriasis induction or exacerbation in some patients during UST therapy. This paper offers a comprehensive review of reported cases of UST-induced paradoxical psoriasis, including a case from our clinic. We focus on a 39-year-old female patient with a history of long-standing Crohn’s disease who developed a psoriasiform rash, as confirmed by biopsy, while undergoing UST treatment. The patient’s clinical journey, from initial diagnosis through the complexities of treatment adjustments due to various complications including drug-induced lupus and the subsequent onset of psoriatic manifestations, provides insight into the challenges encountered in the clinical management of such cases. This review emphasizes the necessity for clinicians to recognize the possibility of paradoxical psoriasis in patients receiving UST treatment and calls for further research to better understand this phenomenon and devise effective management strategies. Full article

UDP-Galactose: Glucosylceramide, β-1,4-Galactose transferase-V (β-1,4-GalT-V), is a member of a large glycosyltransferase family, primarily involved in the transfer of sugar residues from nucleotide sugars, such as galactose, glucose mannose, etc., to sugar constituents of glycosphingolipids and glycoproteins. For example, UDP-Galactose: Glucosylceramide, β-1,4-galactosyltransferase (β-1,4-GalT-V), transfers galactose to glucosylceramide to generate Lactosylceramide (LacCer), a bioactive “lipid second messenger” that can activate nicotinamide adenine dinucleotide phosphate(NADPH) oxidase (NOX-1) to produce superoxide’s (O₂⁻) to activate several signaling pathways critical in regulating multiple phenotypes implicated in health and diseases. LacCer can also activate cytosolic phospholipase A-2 to produce eicosanoids and prostaglandins to induce inflammatory pathways. However, the lack of regulation of β-1,4-GalT-V contributes to critical phenotypes central to cancer and cardiovascular diseases, e.g., cell proliferation, migration, angiogenesis, phagocytosis, and apoptosis. Additionally, inflammation that accompanies β-1,4-GalT-V dysregulation accelerates the initiation and progression of cancer, cardiovascular diseases, as well as inflammation-centric diseases, like lupus erythematosus, chronic obstructive pulmonary disease (COPD), and inflammatory bowel diseases. An exciting development in this field of research arrived due to the recognition that the activation of β-1,4-GalT-V is a “pivotal” point of convergence for multiple signaling pathways initiated by physiologically relevant molecules, e.g., growth factors, oxidized-low density lipoprotein(ox- LDL), pro-inflammatory molecules, oxidative and sheer stress, diet, and cigarette smoking. Thus, dysregulation of these pathways may well contribute to cancer, heart disease, skin diseases, and several inflammation-centric diseases in experimental animal models of human diseases and in humans. These observations have been described under post-transcriptional modifications of β-1,4- GalT-V. On the other hand, we also point to the important role of β-1-4 GalT-V-mediated glycosylation in altering the formation of glycosylated precursor forms of proteins and their activation, e.g., β-1 integrin, wingless-related integration site (Wnt)/–β catenin, Frizzled-1, and Notch1. Such alterations in glycosylation may influence cell differentiation, angiogenesis, diminished basement membrane architecture, tissue remodeling, infiltrative growth, and metastasis in human colorectal cancers and breast cancer stem cells. We also discuss Online Mendelian Inheritance in Man (OMIM), which is a comprehensive database of human genes and genetic disorders used to provide information on the genetic basis of inherited diseases and traits and information about the molecular pathways and biological processes that underlie human physiology. We describe cancer genes interacting with the β-1,4-GalT-V gene and homologs generated by OMIM. In sum, we propose that β-1,4-GalT-V gene/protein serves as a “gateway” regulating several signal transduction pathways in oxidative stress and inflammation leading to cancer and other diseases, thus rationalizing further studies to better understand the genetic regulation and interaction of β-1,4-GalT-V with other genes. Novel therapies will hinge on biochemical analysis and characterization of β-1,4-GalT-V in patient-derived materials and animal models. And using β-1,4-GalT-V as a “bonafide drug target” to mitigate these diseases. Full article