ACR open rheumatology最新文献

A middle-aged woman presented with a granulomatous breast lesion in 2018. By 2021, antibiotic-resistant pneumonia led to the discovery of granulomatous inflammation in the lung and thyroid. Initially misdiagnosed as Erdheim-Chester disease (ECD), she was treated with interferon without success. Histopathology later ruled out ECD, suggesting an unspecified granulomatous disease, with granulomatosis with polyangiitis (GPA) initially excluded due to negative antineutrophil cytoplasmic antibodies (ANCAs) and foamy histiocytes. In 2023, repeated lung biopsy and PR3-ANCA positivity led to a revised diagnosis of mass-forming GPA. Rituximab therapy resulted in remission. This case highlights the diagnostic complexity of GPA with atypical histopathological features.

Objective: We aimed to assess whether the presence of radiographically confirmed calcinosis of the hands in patients with systemic sclerosis (SSc) is associated with increased osteoclastogenesis.

Methods: We recruited 20 patients with SSc (10 with calcinosis and 10 without calcinosis) and 10 age- and gender-matched healthy controls. Hand radiographs were scored using the validated Scleroderma Clinical Trials Consortium (SCTC) radiographic severity score for calcinosis. To evaluate osteoclastogenesis, peripheral blood mononuclear cells (PBMCs) were cultured with RANKL and macrophage colony-stimulating factor; osteoclasts were identified using tartrate-resistant acid phosphatase staining. Measures of bone resorption (RANKL, osteoprotegerin [OPG]) and ischemia or endothelial function (vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 [Ang-2]) were also evaluated.

Results: Patients with SSc were all women and Hispanic, and the majority (n = 12, 60%) had limited SSc skin type. Mean ± SD age was 55.2 ± 14.8 years; mean ± SD disease duration was 9.5 ± 6.5 years from first non-Raynaud phenomenon symptom. Patients with SSc with calcinosis had more digital ischemia than patients without calcinosis. Median SCTC score in patients with SSc with calcinosis was 11.1 (range 0.7-286). After 9 days in culture, PBMCs from patients with calcinosis originated a significantly higher number of osteoclasts (33.0 ± 20.3 cells/well) than patients without calcinosis (15.3 ± 6.9 cells/well) and healthy individuals (11.2 ± 2.6 cells/well) (P = 0.001). The severity of calcinosis was not correlated with the number of osteoclasts per well (r = 0.27, P = 0.5); however, it was correlated with RANKL (r = 0.82, P = 0.004), RANKL/OPG ratio (r = 0.86, P = 0.002), and Ang-2 levels (r = 0.86, P = 0.002).

Conclusion: Calcinosis in patients with SSc is associated with an increased propensity of peripheral blood cells to form osteoclasts. Targeted inhibition of osteoclastogenesis may provide a specific therapeutic option for patients with SSc-associated calcinosis.

Objective: This study aimed to report the safety of avacopan, an oral selective complement C5a receptor antagonist, using pooled data from clinical trials in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] or microscopic polyangiitis [MPA]).

Methods: Data were included from two phase 2 (CLEAR [NCT01363388] and CLASSIC [NCT02222155]) and one phase 3 (ADVOCATE [NCT02994927]) double-blind randomized controlled trials comparing the safety and efficacy of avacopan with active non-avacopan control regimens to induce remission in patients with GPA or MPA. In CLEAR and ADVOCATE, avacopan-treated patients received either no or lower doses of study-supplied prednisone than the control groups; in CLASSIC, all groups received the same dose of study-supplied prednisone. Assessments included rates of exposure-adjusted adverse events (AEs), serious AEs (SAEs), and AEs of special interest.

Results: Overall, 439 patients with GPA or MPA (avacopan: n = 239; non-avacopan: n = 200) were included. The exposure-adjusted rates of AEs, SAEs, white blood cell (WBC) count reductions, and infections were lower with avacopan versus control (between-group differences in rate per 100 patient-years -151.9 [95% confidence interval (CI) -218.6 to -85.3], -20.8 [95% CI -38.3 to -3.3], -11.6 [95% CI -22.2 to -1.2], and -24.3 [95% CI -48.5 to -0.1], respectively). SAEs associated with hepatic function abnormalities occurred in 4.4% of the avacopan group and 2.8% of the control group.

Conclusion: In clinical trials of GPA or MPA, use of avacopan was associated with fewer AEs, SAEs, and WBC count reductions and fewer infections than non-avacopan treatment. Safety data support the use of avacopan in patients with GPA or MPA.

Objective: We aimed to analyze the RheuMetric physician 0 to 10 visual numeric subscale (VNS) estimates of inflammatory activity (DOCINF), organ damage (DOCDAM), and patient distress (DOCDIS) at initial and follow-up routine rheumatology visits for possible incremental information to clarify physician estimate of global assessment (DOCGL).

Methods: A retrospective cross-sectional study compared mean DOCGL, DOCINF, DOCDAM, and DOCDIS and the percentage contributed by inflammation, damage, and distress to DOCGL (total = 100%) at initial and follow-up visits in 563 unselected routine care patients, classified into four diagnosis categories: inflammatory (rheumatoid arthritis, systemic lupus erythematosus [SLE], spondylarthritis, vasculitis, and gout), primary osteoarthritis (OA), primary fibromyalgia (FM), and "other" diagnoses. Differences between initial and follow-up visits were estimated using t-tests.

Results: In all patients, mean DOCGL was 4.0/10, DOCINF 1.6/10, DOCDAM 2.9/10, and DOCDIS 2.4/10, indicating higher estimates for damage and distress than for inflammation, including in all inflammatory diagnoses other than SLE. Highest mean estimates were 2.2 for DOCINF in inflammatory diagnoses, 4.9 for DOCDAM in primary OA, 6.3 for DOCDIS in primary FM. However, DOCDAM was 2.8 (0.6 uniyts higher than DOCINF) in inflammatory diagnoses. RheuMetric estimates of inflammation were significantly higher at initial than at follow-up visits, and estimates of damage were significantly lower at initial than at follow-up visits in all patients and in those with inflammatory diagnoses. DOCGL did not differ significantly at initial versus follow-up visits.

Conclusion: DOCINF, DOCDAM, and DOCDIS add feasibly recorded, clinically relevant incremental information to DOCGL. Despite excellent contemporary control of inflammation, joint damage and patient distress remain important clinical problems in contemporary routine rheumatology care, documented by quantitative RheuMetric estimates.

Objective: Vasculitides are rare inflammatory disorders that sometimes can be difficult to diagnose due to their diverse presentations. This review examines the use of artificial intelligence (AI) to improve diagnosis and outcome prediction in vasculitis.

Methods: A systematic search of PubMed, Embase, Web of Science, Institute of Electrical and Electronics Engineers Xplore, and Scopus identified relevant studies from 2000 to 2024. AI applications were categorized by data type (clinical, imaging, textual) and by task (diagnosis or prediction). Studies were assessed for risk of bias using the Prediction Model Risk of Bias Assessment Tool and Quality Assessment of Diagnostic Accuracy Studies-2.

Results: A total of 46 studies were included. AI models achieved high diagnostic performance in Kawasaki disease, with sensitivities up to 92.5% and specificities up to 97.3%. Predictive models for complications, such as intravenous Ig resistance in Kawasaki disease, showed areas under the curves between 0.716 and 0.834. Other vasculitis types, especially those using imaging data, were less studied and often limited by small datasets.

Conclusion: The current literature shows that AI algorithms can enhance vasculitis diagnosis and prediction, with deep- and machine-learning models showing promise in Kawasaki disease. However, broader datasets, more external validation, and the integration of newer models like large language models are needed to advance their clinical applicability across different vasculitis types.

We report a case of a 34-year-old woman with systemic lupus erythematosus (SLE) who developed thrombocytopenia and was diagnosed with lupus-associated autoimmune myelofibrosis. She was treated with hydroxychloroquine, tofacitinib (5 mg twice daily), intravenous Ig, and prednisone (5 mg twice daily, tapered to 5 mg daily after one month). After 10 months of this regimen, her bone marrow showed complete resolution of myelofibrosis. This case highlights the effectiveness of tofacitinib in the treatment of autoimmune myelofibrosis associated with SLE.

Background: We evaluated changes in long-term glucocorticoid (GC) use and factors associated with persistent GC use in older adults with late-onset rheumatoid arthritis (LORA).

Methods: Using 20% Medicare data from 2008 to 2017, we identified adults ≥66 years with a new diagnosis of LORA, disease-modifying antirheumatic drug (DMARD) use or at least two rheumatologist visits, and at least 12 months of follow-up data. Older adults were categorized as DMARD-exposed or DMARD-unexposed based on treatment during the 12 months after LORA diagnosis (index date). For each quarter after the index date, long-term GC use was defined as having oral GC prescriptions for at least 30 days with a dose >5 mg/day prednisone equivalent. We compared long-term GC use between quarter (Q)1 and Q4 and performed stratified mixed-effects logistic regression for factors associated with persistent GC use, defined as long-term GC use in Q2 to Q4.

Results: The cohort included 15,425 individuals with two-thirds (62.5%) being DMARD-exposed. Between Q1 and Q4, the proportion of older adults on long-term GC declined from 44.1 to 24.9% (∆19.2%) among the DMARD-exposed and from 25.8 to 17.9% (∆7.9%) among the DMARD-unexposed. One year after the index date, 13.5% of the DMARD-exposed and 9.8% of the DMARD-unexposed were persistent GC users. In stratified mixed-effects logistic models, persistent GC use was associated with low-income subsidy status among the DMARD-exposed and with greater comorbidity burden among DMARD-unexposed.

Conclusion: Long-term GC use declined more among DMARD-exposed than DMARD-unexposed patients. One in seven DMARD-exposed and one in ten DMARD-unexposed have persistent GC use which is associated with financial barriers and multimorbidity that may limit the use of steroid-sparing DMARDs.

Objective: The aim of this report is to raise awareness of a rare inborn error of immunity (IEI) that can predispose to inflammatory disease and infection risk by describing a patient case.

Methods: We reviewed clinical findings, laboratory and pathology evaluations, and genetic results.

Results: A 13-year-old female patient with a history of prematurity and spastic diplegic cerebral palsy underwent planned orthopedic procedures to correct chronic gait abnormalities. Her postoperative course was complicated by fevers associated with respiratory failure and wound dehiscence at the surgical sites. A chest computed tomography scan revealed bilateral consolidative pneumonia with parapneumonic effusions. Infectious and clinical immune evaluations were unremarkable. She had resolution of fevers and respiratory failure with broad-spectrum antibiotics; however, her wounds became progressively ulcerative and necrotic. A skin biopsy demonstrated skin ulceration with acute neutrophilic inflammation. She was started on glucocorticoids and infliximab infusions with prompt improvement in wound healing. Subsequently, a clinical genetic panel revealed a heterozygous variant in OTULIN c.787C>T, p.Arg263Trp, located at the same amino acid previously reported in OTULIN haploinsufficiency. OTULIN haploinsufficiency is a rare IEI that predisposes to life-threatening necrosis of the skin and lungs, often in response to Staphylococcus aureus infection.

Conclusion: OTULIN haploinsufficiency predisposes to increased susceptibility to infections and tissue-specific necrosis often triggered by infection. Recognition of this rare IEI is important because patients with OTULIN haploinsufficiency may require combined antibiotic and immunomodulatory therapy.

Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are heterogeneous disorders. The aim of this study was to identify and characterize subgroups of patients based on sex, ANCA, age at diagnosis, and organ involvement.

Methods: In total, 1,167 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively recruited to the study. Data including cumulative involvement of 10 different organ systems, end-stage kidney disease (ESKD), sex, proteinase (PR) 3-ANCA, myeloperoxidase (MPO)-ANCA, age at diagnosis, disease duration, and relapse were obtained from medical records. Clinical variables were analyzed for associations with sex, age at diagnosis, and relapse using logistic regression analysis. Thirteen clinical variables were included in hierarchical cluster analyses using the Ward method.

Results: In patients with GPA, PR3-ANCA, renal and pulmonary involvement, and ESKD were significantly associated with male sex, whereas MPO-ANCA was associated with female sex. Patients with GPA who were younger than 32 years of age at diagnosis were significantly more often females and had more ear-nose-throat involvement than patients older than 32 years. In patients with MPA, female patients were significantly younger at diagnosis than male patients. Relapse was significantly associated with young age at diagnosis and pulmonary involvement in GPA and with musculoskeletal involvement in MPA. Hierarchical cluster analyses identified five and seven patient clusters among individuals with GPA and MPA, respectively. PR3-/MPO-ANCA defined the largest clusters, whereas heart, gastrointestinal, and central nervous system involvement were hallmarks for three clusters for both patients with GPA and MPA.

Conclusion: Sex, age at diagnosis, and specific organ involvements define clinically relevant subgroups among patients with ANCA-associated vasculitides.