Inflammation is a key pathophysiological process underlying a broad spectrum of chronic disorders, including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, neurodegenerative diseases, and metabolic syndrome, and is closely linked to oxidative stress, immune dysregulation, and sustained production of pro-inflammatory mediators. Curcumin, a bioactive polyphenol derived from Curcuma longa, has been extensively studied because of its pleiotropic anti-inflammatory mechanisms, however, its therapeutic translation is substantially limited by poor aqueous solubility, chemical instability, rapid metabolism, and low systemic bioavailability. In this context, lipid-based nanocarriers, notably liposomes, solid lipid nanoparticles, nanostructured lipid carriers, phytosomes, ethosomes, niosomes, nanoemulsions, self-nano-emulsifying drug delivery systems (SNEDDS), transfersomes, lipid nanocapsules, lipid micelles, spanlastic, and cubesomes, have emerged as promising formulation strategies to improve curcumin delivery. These platforms can enhance the solubility, stability, absorption, and pharmacokinetic performance of curcumin and, in selected cases, facilitate more efficient accumulation at inflamed sites. This review critically appraises recent advances in lipid-based nanocarrier systems for curcumin delivery in inflammatory diseases and addresses the principal formulation, translational, and clinical challenges that remain to be resolved.

Autoimmune manifestations occur in 25-75% of patients with Wiskott-Aldrich syndrome (WAS), commonly including autoimmune hemolytic anemia, skin vasculitis, IgA nephropathy, arthritis, and inflammatory bowel disease. Large vessel vasculopathy is rarely reported in WAS. We present a review of children with WAS and evidence of large vessel vasculopathy at our center, analyzing clinical, radiological, immunological, and genetic data. Among 80 patients diagnosed with WAS over two decades, four children (aged 10-18 years) developed large vessel vasculopathy. Two had classical WAS with bleeding, recurrent infections, and eczema since infancy, while two had milder phenotypes and presented for the first time during this illness. Clinical features included chest pain and heart failure, abdominal pain, upper limb claudication, and differential blood pressure. Imaging demonstrated aneurysmal dilatation of the aorta and its major branches. Epstein-Barr virus viremia was detected in three patients. All received intravenous immunoglobulin and immunosuppressive therapy; none could undergo hematopoietic stem cell transplantation (HSCT), and three patients died. Large vessel vasculopathy is a rare but life-threatening complication of WAS, underscoring the importance of early recognition and timely consideration of HSCT.

There has been progressive understanding in etiopathogenesis, clinical presentation, and effective treatment of anterior uveitis (AU) over the years. Sudden onset, symptomatic acute anterior uveitis (AAU) in a young adult, often male, classically arouses suspicion for human leukocyte antigen (HLA) B27-related uveitis. While the ocular presentation is frequently the earliest manifestation, its systemic counterparts within the spectrum, viz., spondyloarthropathies (SpA), including ankylosing spondylitis (AS), reactive arthritis (RA), psoriatic arthritis (PA), and inflammatory bowel disease-associated inflammation, pose greater diagnostic and therapeutic challenges for rheumatologists and internists. This places the ophthalmologist in a uniquely advantageous yet responsible position in initiating etiologic evaluation and facilitating early systemic recognition. Rapid advances in immunology and molecular medicine have significantly expanded the diagnostic and therapeutic landscape of HLA B27-related disease. Emerging insights implicating the gut microbiome, autoinflammatory mechanisms, and innate immune dysregulation have reshaped traditional concepts of pathogenesis. Concurrently, an improved understanding of cytokine networks and immune signaling pathways has led to the development of targeted biologic and synthetic disease-modifying therapies. Given the dynamic, multisystem nature of HLA B27-associated disease and its variable organ involvement, optimal management necessitates close multidisciplinary collaboration among ophthalmologists, rheumatologists, gastroenterologists, and internists. This article briefly explores the evolving concepts of the complex enigma of the HLA B27 molecule and the basis for recent trends in its understanding at the cellular, molecular, biochemical, and clinical levels.

The concept of difficult-to-treat (D2T)/difficult-to-manage (DTM) disease was first defined in rheumatoid arthritis (RA). Recent definitions for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) combine non-response to treatment including targeted and biologic treatment, inflammatory disease activity, and patient symptoms. This concept could apply to other chronic inflammatory diseases such as psoriasis (PsO) and inflammatory bowel disease (IBD). A consensus definition of D2T IBD is available but is yet to be fully articulated in PsO.

Boswellic acids (BAs), the major bioactive constituents of Boswellia serrata oleo-gum resin, exhibit well-documented anti-inflammatory and antioxidant activities, which correspond to their healing effects in arthritis, inflammatory bowel disease, asthma, metabolic syndrome, liver disorders, and certain cancers. However, their therapeutic potential is hindered by their poor aqueous solubility, low intestinal absorption, extensive metabolism, and overall low oral bioavailability. This review provides a comprehensive analysis of conventional Boswellia serrata products and advanced drug delivery systems designed to enhance the biological performance of BAs. We summarize recent developments in formulation strategies, including phytosomes, micelles, self-emulsifying drug delivery systems, solid lipid particles, polymeric nanoparticles, hydrogels, cyclodextrin complexes, metal-based nanocarriers, and hybrid delivery platforms. Available in vivo and cellular studies are critically evaluated, with a focus on disease-specific outcomes. Results indicate that emerging formulation technologies significantly increase the oral absorption, systemic exposure, and biological effectiveness of BAs. However, despite promising preclinical data, challenges remain regarding the standardization of Boswellia extracts, the stability of novel formulations, their safety, and limited clinical evaluation. By comparing the advantages and limitations of conventional preparations with modern drug delivery systems, this review outlines the most effective strategies to enhance the bioavailability of BAs and highlights future research directions for their translational development.

Crohn's disease (CD) in children with juvenile idiopathic arthritis (JIA) is frequently diagnosed late due to overlapping symptoms and non-specific biomarkers. We hypothesized that longitudinal cytokine profiling could identify a pre-symptomatic signature predictive of CD conversion in pediatric JIA patients. Ninety pediatric participants (JIA, CD, psoriatic arthritis, healthy controls) underwent serum cytokine profiling (IL-1α, IL-1β, IL-36α, IL-37, IL-6, IL-18, IL-27, IL-31) at baseline and 12 months. Statistical analysis used Mann-Whitney U tests for two-group comparisons, the Kruskal-Wallis test with Dunn's post hoc for multi-group comparisons, Fisher's Exact Test for categorical outcomes, and exploratory principal component analysis (PCA). Baseline screening identified a subgroup of JIA patients (N = 4) with significantly elevated IL-1α, IL-1β, and IL-36α. At 12 months, all four patients in this subgroup received a secondary CD diagnosis (4/4 converters vs. 0/21 non-converters; Fisher's Exact Test: p < 0.0001). The longitudinal analysis at conversion revealed a broader pro-inflammatory shift, with marked increases in IL-18 and IL-31, alongside elevated IL-37, suggesting a compensatory regulatory response. PCA confirmed that converters clustered distinctly from both stable JIA and established CD. A baseline IL-1 family signature may represent a preliminary predictive signature for CD onset in pediatric JIA. Although constrained by the small converter subgroup (N = 4), these data support cytokine profiling for earlier diagnosis in high-risk populations.

Background/Objectives: This study aimed to determine the incidence of herpes zoster (HZ) and risk factors associated with its occurrence in patients receiving Janus kinase inhibitors (JAKis) for immune-mediated inflammatory diseases (IMIDs), while evaluating preventive strategies and zoster vaccine uptake. Methods: We conducted a retrospective single-center cohort study including patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, atopic dermatitis and alopecia areata treated with upadacitinib, baricitinib or tofacitinib. The primary outcome was incident HZ during JAKi exposure. Incidence rates (IRs) were calculated per 100 person-years (PY) and Cox regression identified factors associated with HZ. Results: A total of 292 patients contributed 565.5 PY of JAKi exposure. During follow-up, 23 patients (7.9%) developed HZ, corresponding to an overall IR of 4.07/100 PY (95% CI 2.40-5.73). Incidence rates were numerically lower with upadacitinib and varied across disease groups; differences were not statistically significant. Diabetes mellitus (HR 3.05, 95% CI 1.28-7.29) and chronic kidney disease (HR 3.24, 95% CI 1.17-8.95) were independently associated with HZ. Herpes simplex infection requiring systemic antiviral therapy was more frequent among patients who developed HZ. Recombinant zoster vaccine (RZV) uptake was low (9.9%), but higher among patients evaluated in a dedicated infectious risk consultation. No HZ events were observed among RZV-vaccinated patients. Although six HZ events (26.1%) were severe, all cases resolved completely. Conclusions: HZ remains a relevant complication of JAKi therapy across IMIDs. Diabetes mellitus and chronic kidney disease may help identify higher-risk patients, while structured infectious risk assessment could improve vaccine uptake.

Oxidative stress is a key contributor to the pathogenesis of immune-mediated diseases through its effects on cellular metabolism, mitochondrial function, immune signaling pathways, and inflammatory tissue injury. Disruption of redox homeostasis promotes metabolic reprogramming and persistent activation of innate and adaptive immune responses, contributing to disease progression across multiple inflammatory and autoimmune disorders. Recent advances in high throughput molecular technologies have generated large scale multi-omics datasets that enable comprehensive investigation of redox-associated mechanisms at a systems level. Integration of these datasets with computational analytical approaches has facilitated the identification of multidimensional molecular signatures associated with disease development and progression. This systematic review evaluates studies applying computational frameworks to analyze redox-related molecular data in immune-mediated diseases including multiple sclerosis, systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, Sjögren's syndrome, and inflammatory bowel disease. Across the reviewed studies, oxidative stress associated with molecular signatures were consistently linked to immune activation, mitochondrial metabolism, and inflammatory signaling pathways. Computational analyses also identified regulatory genes involved in antioxidant defense and metabolic regulation, as well as pathways associated with regulated cell death. These findings highlight the translational potential of computational redox analysis for biomarker discovery, disease stratification, and development of targeted therapeutic strategies aimed at restoring redox balance and improving clinical management of immune-mediated diseases.