TAFRO syndrome is a rare systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever or inflammation, reticulin fibrosis or renal dysfunction, and organomegaly. Despite increasing recognition, its natural history, particularly the timeline of organ-specific recovery, remains poorly understood. We retrospectively analyzed seven patients, encompassing nine treatment courses, diagnosed with TAFRO syndrome at our institution. Time to recovery was assessed across four clinical domains—renal dysfunction, systemic inflammation, anasarca, and thrombocytopenia—using predefined objective criteria. The median time to recovery was 7.0 days for renal dysfunction, 21.0 days for systemic inflammation, 24.0 days for anasarca, and 46.0 days for thrombocytopenia. Recovery of thrombocytopenia and anasarca tended to be delayed compared with that of renal dysfunction and systemic inflammation, with thrombocytopenia showing the longest median time to recovery. These findings indicate substantial heterogeneity in organ-specific recovery trajectories in TAFRO syndrome, with hematologic and fluid-related manifestations resolving more slowly than inflammatory or renal abnormalities. Recognition of domain-specific recovery timelines may aid interpretation of treatment responses and support more balanced, individualized management strategies.

The clinical significance of serum lysozyme in sarcoidosis remains unclear. This study aimed to evaluate the clinical characteristics and kidney function of sarcoidosis patients with elevated serum lysozyme. We retrospectively analyzed 28 patients with sarcoidosis and measured levels of serum lysozyme. Clinical characteristics, laboratory data, and estimated glomerular filtration rate (eGFR) were evaluated. Median age was 57 years (interquartile range, 43–70 years), and 21% were men. High serum lysozyme levels were associated with a greater number of organ involvements (median 4 vs. 2, p = 0.022) and more frequent renal involvement (50 vs. 7%, p = 0.033). Serum lysozyme levels correlated inversely with eGFR (r = −0.814). Median serum lysozyme level was significantly higher in patients with renal sarcoidosis (RS) (30.2 μg/mL) than in non-RS patients (9.5 μg/mL, p = 0.003). Prominent intracytoplasmic lysozyme staining in proximal tubular epithelial cells was observed in the kidney of RS patients. Multiple regression analysis identified serum lysozyme as an independent risk factor for eGFR decline. Elevated serum lysozyme in sarcoidosis was associated with multiorgan involvements and renal impairment. Lysozyme may contribute to tubulointerstitial injury in RS, potentially through tubular reabsorption and cytotoxic effects. Further studies are warranted to clarify the role of lysozyme in the pathogenesis of RS.

We report a case of cold agglutinin disease (CAD) considered as other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) in a patient with rheumatoid arthritis (RA) and Sjögren’s disease. A 69-year-old woman developed hemolytic anemia and renal dysfunction after long-term methotrexate and infliximab therapy. Laboratory findings demonstrated monoclonal IgM-κ paraproteinemia and a high cold agglutinin titer, confirming CAD, while imaging studies and bone marrow evaluation revealed no evidence of overt malignancy. Renal biopsy revealed membranoproliferative glomerulonephritis–like lesions with C3-dominant deposition, consistent with C3 glomerulonephritis (C3GN). These findings suggest that both CAD and C3GN may represent manifestations of OIIA-LPD associated with long-term immunosuppressive therapy. Rituximab combined with glucocorticoids led to a prompt and marked improvement in anemia and renal lesions, resulting in sustained remission of both CAD and C3GN while maintaining RA remission. This case suggests the dual pathogenesis of B-cell dysregulation and complement activation and indicates that B-cell–targeted therapy may contribute to controlling both abnormalities. Accumulation of similar cases will be essential to refine disease classification and to optimize therapeutic strategies for immune-mediated overlap disorders.

BHLHE40 is a transcription factor regulating proinflammatory cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD4+ T cells. Although implicated in autoimmune inflammation, its regulation by interleukin (IL)-1 signaling in human CD4+ T cells remains unclear. Peripheral blood (PB) from healthy controls (HCs) and patients with giant cell arteritis (GCA) was analyzed using flow cytometry to assess BHLHE40 expression across helper T cells. Immunohistochemistry was performed on the aortas of IL-1 receptor antagonist knockout (IL-1Rn KO) mice and temporal artery biopsies from GCA patients. We also analyzed public microarray datasets and CD4+ T cells stimulated with anti-CD3/CD28 and IL-1β. We identified BHLHE40 expression in T cells in the IL-1Rn KO mice and GCA-inflamed arteries. BHLHE40 expression was higher in helper T subsets than in naïve CD4+ T cells. Co-stimulation with IL-1β and anti-CD3/CD28 induced stronger BHLHE40 expression than CD3/CD28 alone. Microarray data showed increased expression of BHLHE40 in CD4+ T cells from the PB of GCA patients. IL-1 signaling enhances BHLHE40 expression during CD4+ T cell activation. Its sustained expression in inflamed tissues suggests a disease-relevant pathway linking IL-1 signaling to pathogenic T cell responses in GCA.

Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) and anti­phospholipid syndrome (APS) represent complex clinical challenges due to their diverse presentations and multifactorial pathogenesis. Neuropsychiatric SLE (NPSLE) affects approximately 30–40% of SLE patients, with symptoms ranging from cognitive dysfunction to severe conditions such as stroke, seizures, and psychosis. In APS, cerebrovascular events, including ischemic stroke and transient ischemic attacks, occur in ∼20% of patients, alongside non-thrombotic manifestations like migraine and chorea. The underlying mechanisms involve immune-mediated neuronal injury, vascular thrombosis, and neuroinflammation. In NPSLE, autoantibodies, inflammatory cytokines, and complement activation drive neuronal damage, while APS is primarily characterized by antiphospholipid antibody-mediated thrombosis, with additional direct neuronal effects. Advanced neuroimaging, including diffusion tensor imaging, functional MRI, and positron emission tomography, reveals subtle structural and functional brain alterations. Emerging biomarkers, such as neurofilament light chain and glial fibrillary acidic protein, show promise for detecting neural and glial injury. This review synthesizes current insights into the pathophysiology, diagnostic approaches to neuropsychiatric manifestations in SLE and APS, emphasizing the need for integrated clinical, imaging, and laboratory evaluations to improve diagnostic precision and patient outcomes.

To investigate the potential association between COVID-19 vaccination and Vogt-Koyanagi-Harada (VKH) syndrome, offering novel insights for the diagnosis and management of vaccine-related ocular disorders. A case report combined with a literature review was conducted. A 19-year-old male developing VKH after receiving the second dose of an inactivated COVID-19 vaccine was analyzed. Clinical features, treatment outcomes (glucocorticoid therapy with 2-year follow-up), and literature-based comparisons were evaluated. PubMed-indexed cases of vaccine-associated VKH were systematically reviewed, and causality was assessed using the Naranjo Adverse Drug Reaction Probability Scale. The patient presented with bilateral blurred vision 14 days post-vaccination, diagnosed as VKH with retinal neuroepithelial detachment via fluorescein angiography (FFA) and optical coherence tomography (OCT). Oral prednisone (starting at 60 mg/day, tapered gradually)restored visual acuity to near-normal levels (OD: 20/40, OS: 20/33), consistent with the patient’s reported baseline vision. Within 8 weeks, with no recurrence during follow-up. Literature analysis revealed vaccine-associated VKH symptoms typically emerged at a median of 8 days post-vaccination, aligning with the WHO’s 40-day adverse event monitoring window. A Naranjo score of 4 indicated a probable vaccine-triggered immune response. COVID-19 vaccines may induce VKH via immune dysregulation mechanisms, particularly in genetically predisposed individuals. Although causality remains unconfirmed, clinicians should maintain vigilance for acute bilateral uveitis post-vaccination. Glucocorticoid therapy demonstrates efficacy in symptom resolution and relapse prevention. Enhanced active surveillance and mechanistic studies on vaccine-related ocular adverse events are warranted.

Aicardi–Goutières syndrome (AGS) and Singleton–Merten syndrome (SMS) are associated with heterozygous gain-of-function mutations in the interferon induced with helicase C domain 1 (IFIH1) gene. Recent reports describe patients exhibiting overlapping clinical features of AGS and SMS, along with marked type I interferon (IFN) overproduction. However, the clinical characteristics and optimal treatment strategies remain unclear. Herein, we present a patient with overlapping clinical features of AGS and SMS who was initially misdiagnosed with juvenile idiopathic arthritis. Surgical soft tissue release of the hip and knee joints improved joint deformities and spastic paraparesis. Baricitinib effectively treated refractory chilblains and skin ulcers while reducing IFN-stimulated gene overexpression in peripheral blood. These findings indicate that baricitinib may be a safe and effective treatment for AGS–SMS overlap, and surgical intervention may be a viable option for refractory joint deformities with spastic paraparesis.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition of unknown etiology characterized by lymphocytic infiltration, fibrosis, and infiltration of IgG4-positive plasma cells. It affects various organs, including the pancreas and salivary glands. Immunological abnormalities are suspected to play a role in its pathogenesis, and there is an epidemiological link to allergic conditions and type 2 inflammation. This study focused on the expression of thymus and activation-regulated chemokine (TARC)/CCL17, which is involved in the migration of T helper 2 and/or regulatory T cells, in salivary gland tissues of patients with IgG4-RD. We analyzed 60 salivary gland biopsy samples obtained from patients at Sapporo Medical University Hospital between 2015 and 2020. Immunohistochemical analysis revealed TARC/CCL17 positivity in 87.2% of histologically confirmed IgG4-RD cases and negativity in 84.6% of histologically unconfirmed but clinically suspected IgG4-RD cases. There was a significant correlation between histologically confirmed IgG4-RD and TARC/CCL17 expression, suggesting its potential diagnostic utility and possible involvement in the pathogenesis of IgG4-RD.

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of immune-mediated arthritis, which comprises rheumatoid arthritis and spondyloarthritis. This review outlines the key findings and advancements in scRNA-seq studies focused on the pathogenesis of autoimmune arthritis and its clinical application. In rheumatoid arthritis, scRNA-seq has elucidated the heterogeneity among synovial fibroblasts and immune cell subsets in inflammatory sites, offering insights into disease mechanisms and the differences in treatment responses. Various studies have identified distinct synovial fibroblast subpopulations, such as THY1 + inflammatory and THY1 - destructive fibroblasts. Furthermore, scRNA-seq has revealed diverse T cell profiles in the synovium, including peripheral helper T cells and clonally expanded CD8+ T cells, shedding light on potential therapeutic targets and predictive markers of treatment response. Similarly, in spondyloarthritis, particularly psoriatic arthritis and ankylosing spondylitis, scRNA-seq studies have identified distinct cellular profiles associated with disease pathology. Challenges such as cost and sample size limitations persist, but collaborative efforts and utilization of public databases hold promise for overcoming these obstacles. Overall, scRNA-seq emerges as a powerful tool for dissecting cellular heterogeneity and driving precision medicine in immune-mediated arthritis.

Elevated liver enzymes are commonly observed among adult-onset Still’s disease (AOSD), but severe acute liver failure is extremely rare. Although severe acute liver failure associated with AOSD poses a life-threatening condition, the appropriate treatment is unclear. Some case reports have demonstrated the efficacy of high-dose prednisolone (PSL) and cyclosporin A (CyA), although the adverse effects of CyA led certain patients to cease its use. Therefore, an alternative treatment option is crucial, and thus far, there have been no reports of tocilizumab (TCZ) being used for this severe phenotype. Here, we report the first case of successful treatment using TCZ as maintenance therapy for severe ALF associated with AOSD. Following initial treatment with high-dose PSL and CyA, our case was switched to TCZ due to CyA-related side effects including alopecia and tremors. Our case highlights TCZ as a potential option for maintenance therapy of this severe condition.