Search Results (3,365)

Background/Objectives: Rheumatoid neutrophilic dermatosis (RND) is a rare extra-articular manifestation of rheumatoid arthritis (RA) with variable clinical presentations. Although typically non-blistering, a rare bullous or vesiculobullous subtype has been described, mainly in patients with seropositive and active RA, and may mimic autoimmune blistering diseases. The objective of this review was to systematically summarize the clinical, histopathological, immunopathological, and therapeutic features of vesiculobullous rheumatoid neutrophilic dermatosis. Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines utilizing the PubMed, MEDLINE, and Google Scholar databases, which were searched through December 2025. Case reports and case series describing vesiculobullous or bullous RND with extractable patient-level data were included. Non-English articles were translated. Demographic, clinical, histopathological, immunopathological, microbiological, and therapeutic data were extracted and analyzed using Statistica 12.0 software. Results: Results were synthesized descriptively due to clinical heterogeneity and limited sample size. Thirty reported cases were identified, of which 28 non-duplicate cases were included. The mean patient age was 60.8 ± 14.9 years, with a female predominance (male-to-female ratio, 1:2.5). Most patients were of Asian descent (67.9%). Bullous or vesicular lesions most frequently involved the lower legs (64.3%), palms and soles (41.7%), and thighs (35.7%). Rheumatoid factor data were available in 67.9% of patients, all indicating high RA activity. Histopathological examination was reported in 71.4% of cases and most commonly demonstrated a predominantly neutrophilic infiltrate, often dense and extending throughout the dermis, with subepidermal blister formation being the most frequent pattern. Direct immunofluorescence, serological testing for autoimmune bullous diseases, and microbiological investigations were predominantly negative. Dapsone and systemic corticosteroids, alone or combined with RA-specific therapies, were the most commonly used treatments. Conclusions: This review represents the most comprehensive synthesis to date focused exclusively on the bullous/vesiculobullous subtype of RND, highlighting key diagnostic features such as neutrophil-predominant histopathology, negative direct immunofluorescence, and favorable response to dapsone. Full article

The gut microbiota is one of the key elements responsible for maintaining the body’s homeostasis. Its diverse composition affects, among others, the digestive and immune systems and also the circulatory system. Imbalances within the microbial community, referred to as dysbiosis, may lead to increased intestinal barrier permeability, chronic inflammation, and abnormal immune responses, which can be associated with the development of numerous diseases. Gut dysbiosis results in disturbances in the production of short-chain fatty acids, which exert anti-inflammatory effects, regulate blood pressure, and inhibit cardiac fibrosis. At the same time, it promotes the increased synthesis of trimethylamine N-oxide, a metabolite linked to inflammation, endothelial dysfunction, a higher risk of thrombosis, and the occurrence of arrhythmias. Additionally, small intestinal bacterial overgrowth (SIBO) may increase inflammation and contribute to metabolic and cardiovascular diseases (CVDs). The gut microbiota also influences the immune system through the production of neurotransmitters and modulation of T-cell activity, which may play a role in the development of autoimmune diseases. Reduced microbial diversity and an increased abundance of pathogenic bacteria are observed in individuals with hypertension and CVD, underscoring the importance of the microbiota as both a preventive and therapeutic factor. These findings highlight the crucial role of the gut microbiota in maintaining cardiovascular health and emphasize the need for further research into its modulation in the treatment of chronic diseases. Full article

Kidney aging is receiving growing attention in middle- to high-income societies due to increasing longevity in general population. Chronic Kidney Disease (CKD) has been widely accepted as a major non-communicable human disease affecting over 10% of the adult population in industrialized countries. CKD is mainly caused by metabolic and cardiovascular disorders such as diabetes mellitus and hypertension, disproportionally affecting older people, whereas natural kidney aging is driven by age-dependent systemic and renal low-grade inflammation. Interleukin-6 (IL-6) is the key cytokine mediating age-related inflammation. At the same time, IL-6 has been implicated in the pathophysiology of cardiovascular and renal disorders as a major pro-inflammatory cytokine. Thereby, IL-6 is placed at the intersection between natural and pathophysiological kidney aging, and the latter accelerates systemic aging and substantially limits life quality and expectancy. Growing clinical availability of IL-6 inhibitors for treatment of autoimmune and autoinflammatory disorders demands clarification of potential renal consequences as well. Available data suggests that IL-6 inhibition may be renoprotective in some kidney disorders, but the setting of kidney aging has received only minor attention. The present review focuses on the known effects of IL-6 associated with natural or pathophysiological renal aging. Full article

Inflammation is strongly related to the development of multiple chronic diseases, such as cardiovascular and autoimmune diseases, and is considered a crucial target for new therapeutic approaches, since it significantly impacts public health, contributes to high mortality rates, and decreases the quality of life. Conventional anti-inflammatory approaches are commonly used, but they present multiple limitations, such as undesirable side effects and low target-specificity. Medicinal plants and their bioactive phytochemical compounds have been studied in recent years and are considered promising alternatives to classical therapies. They are widely recognized for their capacity to modulate inflammatory pathways, regulate inflammatory responses, and consequently reduce inflammation and related symptoms. Although they are considered a good therapeutic alternative, their application in the human body is limited by certain characteristics, such as low solubility, which leads to rapid metabolism and excretion by the organism, significantly reducing bioavailability; for these reasons, the use of medicinal plants remains a biopharmaceutical challenge. Nanotechnology represents a promising tool in this context, since it can improve several characteristics of these compounds. By incorporating plant-derived compounds in nanosystems, considerable advantages, including sustained release, protection from degradation, an increase in the specificity to target tissues, and consequent reduction in toxicity, can be achieved. Thus, nanosystems promote more favorable therapeutic outcomes. This work aims to compile scientific evidence supporting the use of medicinal plants and their bioactive phytochemical compounds, incorporated in nanosystems, in inflammatory disorders. This review enlarges knowledge by integrating both in vitro and in vivo studies involving multiple medicinal plants and bioactive phytochemical compounds, describing their mechanisms of action and the nanosystems employed for drug delivery. In the future, the need for deeper mechanistic studies, the development of targeted and stimuli-responsive systems, and advancement toward clinically translatable, sustainable, and cost-effective plant-based nanotherapies is required. Full article

Juvenile scleroderma (JS), comprising localized (JLSd) and systemic (JSSc) forms, is a rare autoimmune disorder. This study investigated associations of polymorphisms in extracellular matrix (MMP1, MMP9) and vascular homeostasis (NOS3) genes with JS risk and immunological phenotypes. A case–control study involved 215JS patients (194 JLSd, 21 JSSc) and 72 controls. SNPs (MMP1 rs1799750, MMP9 rs3918242, NOS3 rs1799983) were genotyped using real-time PCR followed by minisequencing and mass spectrometric analysis of reaction products. Associations with disease risk, subtypes, and immunological markers were analyzed statistically. The MMP9 (rs3918242) CT genotype was significantly associated with JLSd (OR = 2.23, 95% CI: 1.14–4.37, p = 0.022), showing a trend in linear facial forms. The NOS3 (rs1799983) GG genotype demonstrated a trend toward association with JSSc (OR = 2.61, 95% CI: 0.92–7.37, p = 0.065). No significant associations were found for rs1799750 MMP1 and risk of disease development. The MMP9 risk genotype did not correlate with scleroderma-specific autoantibodies, while the NOS3 GG genotype was associated with lower serum levels of anti-collagen IV antibodies (p = 0.039). Genetic associations differ for JS subtypes: MMP9 with JLSd and NOS3 with JSSc. Children with CT polymorphism MMP9 (rs3918242) and with NOS3 (rs1799983) GG genotype were found to be genetically predisposed for the development of JS. Full article

Sjögren’s syndrome is a chronic autoimmune disease marked by lymphocytic infiltration of the exocrine glands and the development of sicca symptoms, yet some patients also develop extraglandular involvement. Imaging has become relevant for describing these systemic features and supporting clinical assessment. This review discusses the roles of ultrasonography, elastography, computed tomography, and magnetic resonance imaging in evaluating multisystem disease associated with Sjögren’s syndrome. Ultrasonography and elastography help assess muscular involvement by showing changes in echogenicity and stiffness that reflect inflammation and later tissue remodeling. In joints, ultrasound can detect synovitis, tenosynovitis, and early erosive changes, including abnormalities not yet evident on examination. Pulmonary disease, most often with interstitial lung involvement, is best evaluated with high-resolution computed tomography, which remains the most reliable imaging modality for distinguishing interstitial patterns. Magnetic resonance imaging is valuable in assessing neurological complications. It can reveal ischemic and demyelinating lesions, neuromyelitis optica spectrum features, or pseudotumoral appearances. Imaging is also essential for detecting lymphoproliferative complications, for which ultrasound and magnetic resonance imaging can reveal characteristic structural and diffusion-weighted imaging findings. When combined with clinical and laboratory information, these imaging methods improve early recognition of systemic involvement and support accurate monitoring of disease progression in Sjögren’s syndrome. Full article

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

Background: Chronic urticaria (CU) is a complex skin condition, frequently challenging both patients and clinicians and requiring wise individualized management. While allergy, autoimmunity, and depression are recognized comorbidities, evidence linking CU and malignancy remains underexplored. Screening for malignancy is not a routine standard of care for CU patients. Methods: A literature review was conducted to explore the potential risk or associations, including immune mechanisms, between CU and malignancy, based on searches in the PubMed and Google Scholar databases. Results: Scientific evidence on the malignancy risk in CU and its causal relationship is limited to a few population-based studies and case reports. A higher incidence of hematologic malignancy in CU patients has been reported in several publications, but the overall risk of malignancy in the CU population remains controversial. Antihistamine resistance, ultra-low IgE, and older age at the time of CU diagnosis may be related to a higher risk of malignancy, especially shortly after CU diagnosis. Immunological pathways linking CU and cancer are not clear. Immune system dysregulation, including alterations in immune checkpoints, is a feature of both cancer and CU. Such dysregulation may promote immunotolerance, abnormal immune responses, and mast cell activation through novel autoantigens and autoantibodies involved in the tumor microenvironment. Conclusions: There is growing, although limited, evidence suggesting a possible link between CU and malignancy, especially hematologic cancers. Large multicenter cohort studies are warranted to determine whether CU may act as a clinical harbinger of malignancy and to identify patient subsets that may benefit from targeted cancer screening. Full article

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an immune-mediated neurological disorder driven by dysregulated neuroimmune interactions, yet the molecular architecture linking tumor-associated immune activation, peripheral immunity, and neuronal dysfunction remains insufficiently understood. In this study, we established an integrative computational framework that combines multi-tissue transcriptomic profiling, weighted gene co-expression network analysis, immune deconvolution, and machine learning-based feature prioritization to systematically characterize the regulatory landscape of the disease. Joint analysis of three independent GEO datasets spanning ovarian teratoma tissue and peripheral blood transcriptomes identified 2001 consistently dysregulated mRNAs, defining a shared tumor–immune–neural transcriptional axis. Across multiple feature selection algorithms, ACVR2B and MX1 were reproducibly prioritized as immune-associated candidate genes and were consistently downregulated in anti-NMDAR encephalitis samples, showing negative correlations with neutrophil infiltration. Reconstruction of an integrated mRNA-miRNA-lncRNA regulatory network further highlighted a putative core axis (ENSG00000262580–hsa-miR-22-3p–ACVR2B), proposed as a hypothesis-generating regulatory module linking non-coding RNA regulation to immune-neuronal signaling. Pathway and immune profiling analyses demonstrated convergence of canonical immune signaling pathways, including JAK-STAT and PI3K-Akt, with neuronal communication modules, accompanied by enhanced innate immune signatures. Although limited by reliance on public datasets and small sample size, these findings delineate a systems-level neuroimmune regulatory program in anti-NMDAR encephalitis and provide a scalable, network-based multi-omics framework for investigating immune-mediated neurological and autoimmune disorders and for guiding future experimental validation. Full article

Background: Differentiating hypophysitis from non-functioning pituitary macroadenomas (NFPMA) remains a clinical and radiological challenge. Both entities present as sellar masses with overlapping features but require distinct therapeutic approaches. Accurate preoperative identification is necessary to avoid unnecessary surgery in inflammatory forms. This review aims to compare the clinical, endocrine, and imaging characteristics of hypophysitis and NFPMA, incorporating recent findings and evaluating the performance of three diagnostic scoring systems currently in use. Methods: A comprehensive narrative literature review was conducted using original articles, clinical series, radiological studies, and systematic reviews retrieved from international databases. The analysis focused on demographic characteristics, clinical presentation, hormonal profiles, magnetic resonance imaging (MRI) features, and the comparative evaluation of the three published diagnostic scoring systems designed to differentiate hypophysitis from NFPMA. Results: Hypophysitis predominantly affects women, particularly during late pregnancy or the postpartum period, and is frequently associated with autoimmune diseases. Corticotropic deficiency and central diabetes insipidus (CDI) are disproportionately frequent in hypophysitis, whereas somatotropic deficiency is more characteristic of NFPMA. Radiologically, hypophysitis typically appears as a smaller, symmetric, and homogeneous mass with intense, uniform contrast enhancement, associated with pituitary stalk thickening and loss of the posterior pituitary bright spot. In contrast, NFPMA generally present as larger, asymmetric, and heterogeneous lesions, frequently invading the cavernous sinus and compressing the optic chiasm. Analysis of the three diagnostic scores indicates that combining clinical, hormonal, and imaging data improves accuracy compared to relying on single features. The most recent score includes hormonal markers, which significantly enhance sensitivity and specificity, emphasizing the importance of integrated assessment. Conclusions: No single clinical, hormonal, or imaging feature is pathognomonic. However, integrating clinical context, endocrine profile, imaging characteristics, and validated diagnostic scores significantly enhances preoperative diagnostic accuracy. The systematic use of composite scores may help optimize therapeutic decision-making and reduce unnecessary surgical interventions in patients with hypophysitis. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with rising prevalence in the Middle East. Real-world comparative data on disease-modifying therapies from this region remain limited. This retrospective study compared the clinical outcomes and tolerability of fingolimod and interferon beta-1a (IFN-β1a) among patients with relapsing–remitting multiple sclerosis treated at a large public referral hospital in Jordan. Materials and Methods: All eligible RRMS patients received fingolimod or IFN-β1a at a single tertiary hospital. The annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) scores, and adverse effect frequencies were analyzed using descriptive and inferential statistics. A full-cohort inclusion approach was applied instead of sample-size calculation, as all available cases at Al-Basheer Hospital (Amman, Jordan) were included. Results: Fingolimod-treated patients showed a significantly higher ARR than those on IFN-β1a (0.51 vs. 0.26, p = 0.016), an association likely influenced by treatment sequencing and baseline disease activity. EDSS distributions were similar between treatment groups, with most patients demonstrating mild disability (EDSS ≤ 3.5). IFN-β1a was linked to injection site reactions, while fingolimod was better tolerated. Conclusions: The higher observed relapse rate among fingolimod-treated patients possibly reflects treatment sequencing and underlying disease severity rather than pharmacologic efficacy, as fingolimod was commonly prescribed as an escalation therapy. These findings highlight the importance of individualized treatment selection and underscore the need for prospective studies incorporating standardized baseline disease activity measures to better inform multiple sclerosis care in Jordan and the wider Middle Eastern region. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple and heterogeneous clinical manifestations (e.g., skin lesions, kidney damage, neuropsychiatric dysfunction), that primarily affects women and whose etiology remains unclear. Various therapies that regulate and reduce the immune system activity are in use or are being developed; however, many of them have serious side effects. Therefore, new approaches are needed to maximize remission periods and reduce associated side effects. In this review, we summarize the currently recommended therapeutic strategies. Furthermore, we hypothesize that the combined use of drugs targeting various dysregulated cellular processes in SLE (i.e., cytokine production, neutrophil extracellular traps (NETs), phagocytosis) might have therapeutic potential, at least in some disease phenotypes. Preliminary data show that Toll-like receptors 7/8 (TLR 7/8) inhibition (e.g., Enpatoran) may reduce interferon-α (IFN-α) production by monocytes and NET formation by neutrophils. Our hypothesis is that future therapies combining compounds that modulate the three cellular processes might result in a better disease management as current therapies. Full article

Systemic sclerosis (SSc) is a rare multisystemic autoimmune disease associated with progressive fibrosis, vasculopathy, and immune dysregulation. Despite advances in its management, the disease remains associated with substantial morbidity and mortality, with limited therapeutic options. This systematic review aimed to identify phytocompounds and medicinal plants that had demonstrated efficacy in SSc. A comprehensive literature search was performed in PubMed and ScienceDirect, yielding 7797 records, of which 32 studies met the inclusion criteria. A second search was performed using the SwissTargetPrediction tool to identify new putative molecular targets for these phytocompounds, whose relevance for SSc pathogenesis was verified by a third search in PubMed and ScienceDirect databases. Our search found 24 phytocompouds (e.g., halofunginone, crocetin, and tanshinone IIA) and 5 plant extracts (e.g., caper bush and ciplukan) reported to modulate key pathogenic processes in SSc. These phytochemicals were mainly associated with effects on endothelial to mesenchymal transition, oxidative stress, inflammation, and profibrotic signaling pathways, particularly TGF-β/Smad. The SwissTargetPrediction tool indicated 93 new potential molecular targets of the selected phytochemicals, among which only 41 showed relevance to SSc pathogenesis. In conclusion, available evidence is scarce but promising. Further studies, especially human investigations, are required to clarify clinical efficacy, safety, and potential interactions with drugs used in SSc. Full article

Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization—driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding—deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome–immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases. Full article

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond oncology, CAR-T cell therapy has also shown promise in autoimmune diseases, where early clinical studies suggest that B cell-directed CAR-T cells can induce sustained remission in conditions such as systemic lupus erythematosus. This review highlights advances in CAR-T cell engineering, including DNA- and mRNA-based platforms for ex vivo and in vivo programming, and discusses emerging strategies to enhance CAR-T cell trafficking, persistence, and resistance to TME. Full article