Down syndrome (DS) increases risk for autoimmune conditions, including coeliac disease (CeD). Here, we report five adults with DS and biopsy-proven CeD who developed enteritis and symptomatic small bowel stricturing, a clustering not previously described in this population. All five patients had confirmed DS and CeD, and despite apparent adherence to a gluten-free diet, all developed small bowel strictures requiring endoscopic intervention, most commonly at the duodenal D1/D2 junction. Stricture histology demonstrated active CeD with varying degrees of inflammation and fibrosis. Three patients had elevated faecal calprotectin without consistent colonic pathology, suggesting enteritis as an important inflammatory driver. Two patients responded well to open capsule budesonide with symptom resolution and histological improvement. One patient showed no sustained benefit from multiple immunosuppressive agents, including corticosteroids, azathioprine, and infliximab, requiring repeated endoscopic dilatations. Differential diagnoses, including Crohn's disease, tuberculosis, nonsteroidal anti-inflammatory drug (NSAID) enteropathy, refractory CeD, and cryptogenic multifocal ulcerating stenosing enteritis were excluded based on clinical history, imaging, and histological findings. No granulomas or aberrant T-cell populations were identified. We propose this clustering may reflect a shared pathogenic mechanism linked to the interferonopathy of DS. Trisomy 21 causes overexpression of interferon receptors, creating heightened interferon signalling. Combined with CeD-triggered interferon production from gluten exposure, this may drive amplified immune activation, chronic enteritis, and fibrotic stricture formation. This hypothesis warrants further investigation through transcriptomic and immunohistochemical studies. Clinicians should consider this clustering in DS patients with CeD who present with persistent gastrointestinal symptoms. Given the underlying biology, JAK inhibitors may represent a promising therapeutic option for this phenotype and merit future study.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can involve the ocular surface and deeper ocular tissues, leading to a spectrum of ophthalmic manifestations ranging from dry eye disease to vision-threatening inflammation, such as scleritis and peripheral ulcerative keratitis (PUK). This paper presents the results of a narrative review conducted using PubMed and Google Scholar from database inception to March 2026. Eligible publications describing clinical features and management of RA-associated ocular disease were synthesized, and no unpublished data were included. According to the literature, dry eye disease (DED) is the most frequent ocular manifestation of RA, and it is primarily managed with lubrication and topical anti-inflammatory therapies, including cyclosporine and lifitegrast. Additional options for refractory disease include neurostimulation and evaporation-targeted therapy. Scleritis and PUK are less common but represent severe inflammatory complications that generally require systemic immunosuppression. Conventional management includes systemic corticosteroids and steroid-sparing agents such as methotrexate (MTX), azathioprine (AZA), cyclophosphamide (CYC), and mycophenolate mofetil (MMF) in aggressive cases. Escalation to biologic disease-modifying antirheumatic drugs (bDMARDs), specifically tumor necrosis factor-alpha (TNF-α) inhibitors and rituximab (RTX), is supported for refractory scleritis and corneal melt, although evidence is largely observational. Among anti-TNF agents, monoclonal antibodies, such as infliximab and adalimumab, appear more effective than etanercept for ocular inflammation. Rituximab is preferred for vasculitis-associated or refractory disease, and Janus Kinase (JAK) inhibitors represent an emerging option requiring careful safety monitoring. Evidence for DED therapies includes randomized controlled trials (RCTs), whereas data for RA-associated scleritis and PUK are largely derived from registries, case series, and case reports. Prospective studies with standardized ocular outcomes are needed to refine treatment algorithms and compare the effectiveness of biologic versus targeted synthetic agents.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently identified autoimmune disorder of the central nervous system. It commonly manifests as meningitis, encephalitis, myelitis, or optic neuritis. However, presentations resembling stroke are exceedingly rare. Here, we report a case of autoimmune GFAP astrocytopathy initially misdiagnosed as acute ischemic stroke. The correct diagnosis was later established through the detection of GFAP antibodies in both the patient's serum and cerebrospinal fluid (CSF) using a cell-based assay (CBA). The patient initially responded to corticosteroid therapy; however, a relapse occurred during the tapering phase. After one year of treatment with oral prednisone and azathioprine, the patient achieved remission, with a subsequent negative result for GFAP antibodies. At the three-year follow-up, no recurrence was observed.

Biological agents are the cornerstone of first-line treatment for inflammatory bowel disease. However, approximately 33% of patients either fail to respond initially or experience diminished efficacy over time. The use of combination therapies, such as pairing biological agents with immunomodulators or small-molecule drugs, has proven effective in enhancing efficacy and mitigating resistance. For instance, the combination of infliximab and azathioprine elevated corticosteroid-free clinical remission and mucosal healing rates in patients with ulcerative colitis to 39.7 and 62.8%, respectively; triple therapy with vedolizumab, adalimumab, and methotrexate raised the week 10 clinical remission rate in patients with Crohn's disease to 61.8%; and combining guselkumab with golimumab increased the response rate in patients with ulcerative colitis to 83%. Despite these successes, challenges remain in optimizing dosing regimens and managing systemic toxicities. Nanocarriers offer a solution by encapsulating one or more drugs within a single system, facilitating targeted delivery, simplifying treatment protocols, and minimizing toxicity. Research indicates that advanced delivery systems, including poly(lactic-co-glycolic acid) nanoparticles, mulberry leaf liposomes, and sodium alginate hydrogels, can enhance anti-inflammatory effects, promote mucosal healing, and modulate the gut microbiota, providing effective colitis treatment. This review examines combination dosing strategies for inflammatory bowel disease, nanodelivery methods, and novel approaches to advance the clinical application of nanodelivery technology in combination therapies.

IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multiple organs. Although glucocorticoids remain the cornerstone of therapy, high relapse rates and treatment-related toxicity have prompted the development of steroid-sparing strategies and targeted therapies. This review summarizes current evidence on pharmacological and non-pharmacological management of IgG4-RD and proposes a practical treatment approach based on available data and clinical experience.

Background/Objectives: Growing evidence suggests that disruption of circadian rhythms contributes to the pathogenesis of inflammation and inflammatory bowel disease; however, clinical data linking circadian gene variants to ulcerative colitis remain limited. In this study, we aimed to investigate associations between key circadian rhythm gene polymorphisms and clinical and treatment-related characteristics in ulcerative colitis. Methods: A total of 107 patients with ulcerative colitis and 80 healthy controls were included in this single-center cross-sectional study. The BMAL1 rs7950226, CLOCK rs1801260, and CRY1 rs2287161 polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype and allele frequency distributions were compared between patients and controls, and associations with clinical characteristics were evaluated within the ulcerative colitis cohort. Results: Genotype distributions of BMAL1 rs7950226 and CLOCK rs1801260 were similar between patients with ulcerative colitis and healthy controls; however, the G allele of BMAL1 was more frequent in patients (p = 0.028). Within the ulcerative colitis cohort, CLOCK rs1801260 genotypes were significantly associated with inflammatory and treatment-related characteristics, with the CC genotype linked to higher C-reactive protein levels (p = 0.021) and the TT genotype associated with increased azathioprine use (p = 0.006). Conclusions: These findings suggest a potential association between circadian rhythm gene variants and clinical features of ulcerative colitis, particularly in relation to inflammatory activity and treatment requirements, and provide preliminary clinical insight that warrants further investigation in larger and longitudinal studies.