Profiles of cytokines in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: This study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV. Methods: Cytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity. Results: We identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse. Conclusion: A group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

Exposome: Epigenetics and autoimmune diseases.

Systemic autoimmune diseases are complex conditions characterized by an immune system dysregulation and an aberrant activation against self-antigens, leading to tissue and organ damage. Even though genetic predisposition plays a role, it cannot fully explain the onset of these diseases, highlighting the significant impact of non-heritable influences such as environment, hormones and infections. The exposome represents all those factors, ranging from chemical pollutants and dietary components to psychological stressors and infectious agents. Epigenetics, which studies changes in gene expression without altering the DNA sequence, is a crucial link between exposome and the development of autoimmune diseases. Key epigenetic mechanisms include DNA methylation, histone modifications, and non-coding RNAs. These epigenetic modifications could provide a potential piece of the puzzle in understanding systemic autoimmune diseases and their connection with the exposome. In this work we have collected the most important and recent evidence in epigenetic changes linked to systemic autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myopathies, ANCA-associated vasculitis, and rheumatoid arthritis), emphasizing the roles these changes may play in disease pathogenesis, their potential as diagnostic biomarkers and their prospective in the development of targeted therapies.

Update on targeted treatments for ANCA-associated vasculitis.

Targeted therapy has revolutionized the management of ANCA-associated vasculitis (AAV) over the last fifteen years. Rituximab, an approved induction and maintenance agent for severe AAV, is no less effective than cyclophosphamide as induction therapy and particularly useful in relapsing or refractory disease, or in women. In patients with relapsing AAV, granulomatosis with polyangiitis or PR3-ANCA, it is more effective than cyclophosphamide. Rituximab maintenance is superior to the conventional immunosuppressive drugs that it replaces. Low-dose preemptive rituximab infusions are recommended every six months for 18 months, followed by re-evaluation to decide whether 4 additional biannual infusions should be administered, balancing the probability of relapse and the risk of serious infections on rituximab. A growing body of experimental and clinical data shows that C5a pathway inhibition is a promising therapeutic option for AAV, which could reduce glucocorticoids needs. Avacopan is a first approved oral C5A receptor antagonist, used when there is a high risk that glucocorticoids will cause serious adverse events. In eosinophilic granulomatosis with polyangiitis, the importance of IL-5 for eosinophil activation and survival led to evaluation and approval of mepolizumab, a humanized monoclonal antibody directed against IL-5. Mepolizumab showed a steroid-sparing effect. Its effectiveness in active vasculitis remains uncertain and is currently being evaluated. Benralizumab targeting the IL-5 receptor was recently shown to be noninferior to mepolizumab. Rituximab has had disappointing results in non-severe active vasculitis and is being evaluated as maintenance therapy. Plasma exchange is not indicated as first-line treatment but remains recommended when creatinine levels exceed 300 µmol/L.

Kidney involvement in myelodysplastic syndromes.

Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

The Coexistence of Microscopic Polyangiitis and Rheumatoid Arthritis: A Case Report.

Microscopic polyangiitis (MPA) is a rare autoimmune disease characterized by the inflammation and necrosis of small vessels, primarily affecting kidneys and lungs. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) due to the presence of ANCA. MPA can manifest as diffuse alveolar hemorrhage (DAH) and rapidly progressive glomerulonephritis. In contrast, rheumatoid arthritis (RA) is an inflammatory disease that mainly targets the synovial joints. The coexistence of these two conditions presents significant diagnostic challenges, highlighting the need for further research and understanding. We report a case of a 58-year-old male with a past medical history of RA, chronic bronchitis, tobacco use, and recent Legionella pneumonia who presented with acute dyspnea. The patient was intubated for acute hypoxemic respiratory failure. Laboratory workup revealed anemia, hyponatremia, and acute kidney injury. Urinalysis showed hematuria and proteinuria. A CT scan of the chest exhibited bilateral extensive patchy infiltrates. He was transfused with one packed red blood cell (PRBC) unit. Hemoglobin decreased below 6 g/dL after transfusion. A bronchoscopy revealed erythema throughout the tracheobronchial tree, and blood on bronchial alveolar lavage suggested DAH. High-dose steroids were started. Subsequent laboratory results were positive for rheumatoid factor (RF), perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), and antinuclear antibody (ANA). The kidney biopsy demonstrated focal crescentic necrotizing glomerulonephritis pauci-immune type, confirming MPA. RA pathogenesis involves immune dysregulation and activation of various cells, leading to the release of cytokines. Antibodies such as RF and anti-cyclic citrullinated peptide (anti-CCP) can be detected up to 10 years before the clinical manifestation of RA. Recent studies have revealed a predominance of MPA in AAV while coexisting with RA. The underlying mechanism of its occurrence remains unclear. Our patient had recurrent respiratory symptoms and renal dysfunction before hospitalization. MPA-RA overlap syndrome is potentially treatable and clinicians should maintain a high index of suspicion when encountering patients with preexisting RA. Timely initiation of immunosuppressive therapy at early stages is essential to prevent renal and pulmonary complications. ANCA serology should be assessed in these cases.

Early skeletal muscle manifestations in polyarteritis nodosa and ANCA-associated vasculitis.

Skeletal muscle involvement is common in patients with small- and medium-sized vasculitis, particularly polyarteritis nodosa (PAN) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Despite being not included in the standard classification criteria for PAN and AAV, skeletal muscle involvement is an important clinical indicator, particularly when vasculitic myopathy is the only pathological evidence in the absence of other organ involvement. Herein, we comprehensively reviewed and compared the clinical features of 71 and 135 patients with PAN and AAV, respectively, with skeletal muscle involvement at the time of disease onset. Most patients with PAN and AAV exhibited skeletal muscle involvement, often characterized by myalgia and occasional muscular weakness, predominantly in the lower extremities. Myalgia and weakness were observed more frequently in the distal lower extremities in patients with PAN than in those with AAV. In contrast, skeletal muscle involvement tended to exhibit a more dispersed distribution across all four extremities in those with AAV. Muscle magnetic resonance imaging T2-weighted and short-tau inversion recovery sequences can effectively identify hyperintense areas attributed to hypervascularity of affected muscle tissues and serve as a sensitive and useful modality for visually determining the suitable biopsy site. >90% of patients with PAN and AAV demonstrated perivascular inflammation in their affected muscle tissues, whereas fibrinoid necrosis of the vessel walls was reported in two-thirds of patients. Serum creatine kinase (CK) levels were within the normal range in approximately 80% of patients presenting with skeletal muscle involvement in PAN and AAV. Furthermore, muscle fiber damage was milder in patients with skeletal muscle involvement in PAN and AAV than those with idiopathic inflammatory myositis. Meanwhile, serum CK levels were elevated in 65-85% of patients with PAN and AAV who had myofiber necrosis and degeneration in the affected muscles. Most patients with PAN and AAV showed improvement in skeletal muscle involvement following glucocorticoids (GCs) administration; however, relapse was observed in some patients during the tapering of GCs. In summary, skeletal muscle involvement is a potential indicator for establishing PAN and AAV diagnoses during the early phases of the disease.

Effectiveness and safety of rituximab in severely relapsed antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective analysis of a Japanese multicentre cohort from the J-CANVAS.

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47-3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97-9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV.

Relapses and serious adverse events during rituximab maintenance therapy in ANCA-associated vasculitis: a multicentre retrospective study.

OBJECTIVES: There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission-maintenance agent in microscopic-polyangiitis (ΜPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well serious-adverse-events (SAEs) in MPA/GPA patients during RTX-maintenance. METHODS: Retrospective cohort of newly-diagnosed/relapsing GPA/MPA patients who received RTX-maintenance (≥1 RTX-cycle, ≥6 months follow-up) following complete-remission (Birmingham-Vasculitis-Activity-Score-version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious-infections, COVID-19-associated hospitalizations, deaths, cardiovascular-events, malignancies and hypogammaglobulinemia. Incidence-rates (IR) and relapse-free survival through Kaplan-Meier plots were estimated. Cox-regression was conducted to investigate factors associated with the time-to-relapse. RESULTS: 101 patients were included; 48% females, 69% GPA, 53% newly diagnosed, median age: 63 years. During follow-up (294.5 patient-years, median: 3 RTX-cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted-Hazard-Ratio/aHR: 0.20; 95% CI: 0.06-0.74, p= 0.016), prior induction with RTX plus cyclophosphamide (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001-0.43, p= 0.012) and shorter time-interval until complete-remission (aHR = 1.07; 95% CI: 1.01-1.14, p= 0.023) were associated with decreased relapse-risk. We recorded 17 serious-infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular-events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years). CONCLUSION: In this real-world study, relapses during RTX-maintenance occurred in approximately in 1 out of 4 patients. Kidney involvement, induction with RTX plus cyclophosphamide and earlier achievement of complete-remission were associated with lower relapse-risk. Serious-infections rate was consistent with previous reports, whereas an increased rate of COVID19-associated hospitalizations was observed.

Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis.

OBJECTIVES: Current guidelines provide limited evidence for cardiovascular screening in ANCA-associated vasculitis (AAV). This study aimed to investigate the prevalence of electrocardiogram (ECG) abnormalities and associations between no, minor or major ECG abnormalities with cardiovascular mortality in AAV patients compared with matched controls. METHOD: Using a risk-set matched cohort design, patients diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis with digital ECGs were identified from Danish registers from 2000-2021. Patients were matched 1:3 to controls without AAV on age, sex, and year of ECG measurement. Associated hazards of cardiovascular mortality according to ECG abnormalities were assessed in Cox regression models adjusted for age, sex, and comorbidities, with subsequent computation of 5-year risk of cardiovascular mortality standardized to the age- and sex-distribution of the sample. RESULTS: A total of 1431 AAV patients were included (median age: 69 years, 52.3% male). Median follow-up was 4.8 years. AAV was associated with higher prevalence of left ventricular hypertrophy (17.5% vs 12.5%), ST-T deviations (10.1% vs 7.1%), atrial fibrillation (9.6% vs 7.5%), and QTc prolongation (5.9% vs 3.6%). Only AAV patients with major ECG abnormalities demonstrated significantly elevated risk of cardiovascular mortality [HR 1.99 (1.49-2.65)] compared with controls. This corresponded to a 5-year risk of cardiovascular mortality of 19.14% (16-22%) vs 9.41% (8-11%). CONCLUSION: Patients with AAV demonstrated a higher prevalence of major ECG abnormalities than controls. Notably, major ECG abnormalities were associated with a significantly increased risk of cardiovascular mortality. These results advocate for the inclusion of ECG assessment into routine clinical care for AAV patients.

A Curious Case of Weakness: Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Presenting With Muscle Weakness.

Disease manifestations of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a small vessel vasculitis with multisystemic effects, include respiratory, renal, nervous, gastrointestinal, and skin implications. Muscle weakness and inflammatory myopathy are rare manifestations of AAV. We report the case of a 77-year-old female with a medical history of hypothyroidism and osteoarthritis who presented with a two-month history of worsening muscle weakness (mainly proximal). She endorsed dysphagia, a 40-lb unintentional weight loss, and persistent sinusitis with middle ear effusions, requiring bilateral tympanostomy. The physical examination was notable for 2/5 muscle strength in her hip flexors and extensors, with 4/5 strength in other extremities. Lower extremity MRI showed diffuse intramuscular edema between fat planes and intramuscular septal regions. Erythrocyte sedimentation rate (70 mm/hr), C-reactive protein (141 mg/L), creatine kinase (690 U/L), and anti-myeloperoxidase (MPO) antibodies (>999 AU/mL) were elevated. A thigh biopsy revealed fibrinoid necrosis of small intramuscular arteries, confluent circumferential granulomatous vessel wall inflammation, and associated mild chronic inflammation, including occasional eosinophils and a few plasma cells. She was diagnosed with MPO-positive AAV. The patient was started on high-dose steroids (prednisone), with a taper on a disease-modifying agent, azathioprine, with significant improvement in symptoms over the next four months and complete resolution at 16-month follow-up. This patient's clinical presentation of predominant lower extremity weakness due to inflammatory myositis is an unusual manifestation of AAV. Clinicians should keep a broad differential diagnosis and consider the possibility of AAV, especially in cases of muscle weakness presenting as inflammatory myositis, in the absence of other clinical manifestations of systemic vasculitis or specific myositis serologies.

Granulomatosis With Polyangiitis as an Etiology of Silent Sinus Syndrome: A Case Report.

Silent sinus syndrome (SSS) is a rare condition characterized by the collapse of the maxillary sinus and the sinking of the eye socket (enophthalmos). Only around 100 cases of SSS have been reported so far. The underlying cause of this condition is the chronic obstruction of the osteomeatal complex, which leads to sinus contraction. In this case, we present a novel finding linking SSS with granulomatosis with polyangiitis (GPA). The patient described is a 39-year-old male who was diagnosed with SSS after a prolonged period of sinus pressure, headaches, epistaxis, and generalized congestion. Additionally, the patient reported a significant autoimmune history, including a previous occurrence of ANCA-mediated glomerulonephritis. Surgical intervention revealed the presence of significant granulation tissue, while histopathological examination identified areas of necrosis, vasculitis, and multinucleated giant cells consistent with GPA. This finding was further supported by the detection of positive blood c-ANCA. This case is particularly noteworthy as it is the first reported instance of GPA causing SSS. It serves as an excellent example to illustrate the underlying pathophysiology of SSS.

Genetics of vasculitis.

Systemic vasculitis encompasses a wide range of conditions characterized by varying degrees of inflammation in blood vessels. Although the etiology of vasculitis remains unclear, accumulated data suggest that it is triggered in genetically predisposed individuals by the concurrence of certain environmental factors. The importance of the genetic component has been consistently supported by evidence of familial aggregation, differential prevalence by ethnicity, and multiple genetic associations with disease susceptibility and severity reported in recent years. The strongest association signals in most vasculitides correspond to genetic variants within the HLA region, suggesting an important role of the immune system in its pathophysiology. However, each type of vasculitis has distinct defining HLA association markers, likely due to disease-specific differences in antigenic drivers. Furthermore, other genetic polymorphisms located outside the HLA region play an important role in susceptibility to different vasculitides. More recent research has assessed the shared genetic susceptibility evident across different vasculitides. Future studies should focus on the identification of genetic markers that can serve as reliable biomarkers for early diagnosis, prognosis, and treatment response in systemic vasculitis.

Identification of an ANCA-Associated Vasculitis Cohort Using Deep Learning and Electronic Health Records.

Background: ANCA-associated vasculitis (AAV) is a rare but serious disease. Traditional case-identification methods using claims data can be time-intensive and may miss important subgroups. We hypothesized that a deep learning model analyzing electronic health records (EHR) can more accurately identify AAV cases. Methods: We examined the Mass General Brigham (MGB) repository of clinical documentation from 12/1/1979 to 5/11/2021, using expert-curated keywords and ICD codes to identify a large cohort of potential AAV cases. Three labeled datasets (I, II, III) were created, each containing note sections. We trained and evaluated a range of machine learning and deep learning algorithms for note-level classification, using metrics like positive predictive value (PPV), sensitivity, F-score, area under the receiver operating characteristic curve (AUROC), and area under the precision and recall curve (AUPRC). The deep learning model was further evaluated for its ability to classify AAV cases at the patient-level, compared with rule-based algorithms in 2,000 randomly chosen samples. Results: Datasets I, II, and III comprised 6,000, 3,008, and 7,500 note sections, respectively. Deep learning achieved the highest AUROC in all three datasets, with scores of 0.983, 0.991, and 0.991. The deep learning approach also had among the highest PPVs across the three datasets (0.941, 0.954, and 0.800, respectively). In a test cohort of 2,000 cases, the deep learning model achieved a PPV of 0.262 and an estimated sensitivity of 0.975. Compared to the best rule-based algorithm, the deep learning model identified six additional AAV cases, representing 13% of the total. Conclusion: The deep learning model effectively classifies clinical note sections for AAV diagnosis. Its application to EHR notes can potentially uncover additional cases missed by traditional rule-based methods.

Application of Diffusion Kurtosis Imaging and Blood Oxygen Level-Dependent Magnetic Resonance Imaging in Kidney Injury Associated with ANCA-Associated Vasculitis.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) has been applied to assess the microstructure of the kidney. However, it is not clear whether fMRI could be used in the field of kidney injury in patients with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: This study included 20 patients with AAV. Diffusion kurtosis imaging (DKI) and blood oxygen level-dependent (BOLD) scanning of the kidneys were performed in AAV patients and healthy controls. The mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) parameters of DKI, the R2* parameter of BOLD, and clinical data were further analyzed. RESULTS: In AAV patients, the cortex exhibited lower MD but higher R2* values compared to the healthy controls. Medullary MK values were elevated in AAV patients. Renal medullary MK values showed a positive correlation with serum creatinine levels and negative correlations with hemoglobin levels and estimated glomerular filtration rate. To assess renal injury in AAV patients, AUC values for MK, MD, FA, and R2* in the cortex were 0.66, 0.67, 0.57, and 0.55, respectively, and those in the medulla were 0.81, 0.77, 0.61, and 0.53, respectively. CONCLUSIONS: Significant differences in DKI and BOLD MRI parameters were observed between AAV patients with kidney injuries and the healthy controls. The medullary MK value in DKI may be a noninvasive marker for assessing the severity of kidney injury in AAV patients.

Trimethoprim sulfamethoxazole prophylaxis and serious infections in granulomatosis with polyangiitis treated with rituximab.

OBJECTIVE: To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA). METHODS: This retrospective cohort study included adults with GPA (2011-2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, PJP, and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment, or Dec 31, 2020. RESULTS: Among 919 rituximab-treated individuals (53% female), mean age was 52.1 years (SD 16) and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (IQR 138, 979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 [95% CI 5.0-7.4] per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted HR 0.5; 95% CI 0.3-0.9). The aHR for outpatient infections was 0.8 (95% CI 0.6-1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI 0.03-1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI 0.9-1.9). CONCLUSIONS: TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.

Angiography Revealing a Possible Paraneoplastic Vasculitis: A Case Report.

Various conditions under the umbrella term of vasculitis have been well documented in the literature. These have been classified into small, medium, and large vessel vasculitis. In addition, vasculitis has been categorized into radiation-induced, systemic, and paraneoplastic. Of these, paraneoplastic vasculitis accounts for 2-5% of all cases of vasculitides and is less well documented. We present a case of a female patient with a history of breast cancer presenting with an upper gastrointestinal tract (GI) bleed, which subsequently revealed an underlying diagnosis of systemic vasculitis, possibly paraneoplastic. This case highlights the importance of imaging for revealing underlying vasculitis as an etiology of GI bleed.

Ocular manifestations in ANCA-associated vasculitis: a comprehensive analysis from Chinese medical centers.

INTRODUCTION: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. METHODS: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. RESULTS: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. CONCLUSION: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes.