Vasculitis Patients Research Articles

#2684 Free light chains levels in ANCA associated vasculitis: a new potential inflammatory biomarker

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disease characterized by an immune-mediated process where inflammation plays a central role. The widely available serum biomarkers of inflammation are not always able to detect ongoing disease activity in ANCA-associated vasculitis (AAV) patients. Free light chains (FLCs) expression levels have been proposed as new promising biomarker in some immune-mediated and inflammatory diseases. The aim of this study is to evaluate the expression levels of FLCs in patients affected by AAV and investigate the potential effect of rituximab treatment on FLCs levels. Method We conducted a retrospective multicenter study enrolling AAV patients in complete remission of AAV (defined as BVAS/GPA = 0); those with clinical suspicion of underlying hematologic malignancy were excluded. We analyzed κ and λ FLCs serum concentrations and evaluated their correlation with biomarkers of immune system activation, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin (Ig) levels, serum C3 and C4 complement and albumin levels (which has a negative correlation with acute inflammatory phase). We assessed impact of rituximab (RTX) therapy within the last 6 months on the same laboratory parameters. Results A total of 137 patients with AAV were recruited, who were gender balanced, had an average age of 68 years and an estimated glomerular filtration rate of 68 (43-89) mL/min/1.73 m2. Fifty-one patients received rituximab treatment (RTX group), while 86 patients were on other immunosuppressive maintenance therapies (non-RTX group). In comparison to non-RTX group, patients treated with RTX experienced higher complement C3 levels, lower ESR levels and lower FLCs κ (p = 0.063) and λ (p = 0.013) levels. The differences between RTX and non-RTX groups in terms of FLCs were even more prominent after correction to total Ig concentration (p = 0.004 for κ /Ig and p = 0.003 for λ /Ig, respectively). Both, serum free κ and λ levels were found to correlate significantly with ESR (R = 0.55 and p < 0.001 for κ; R = 0.53 and p < 0.001 for λ) and albumin (R = ‒0.38 and p < 0.001 for κ; R = ‒0.33 and p < 0.001 for λ). Additionally, serum free κ levels showed an inverse association with C3 (R = ‒0.18 and p = 0.041). Conclusion In subjects with AAV, FLC levels were found to be associated with markers of inflammation and complement activation; hence FLCs levels may represent a promising biomarker for detection of subclinical inflammation in AAV patients on maintenance therapy. Rituximab therapy showed a potential to reduce the levels of markers of subclinical inflammation, including FLCs.

#1828 Venous thromboembolic events in ANCA associated vasculitis patients—data from Croatian referral center

Abstract Background and Aims Our aim was to investigate the prevalence of venous thromboembolic events (VTE) in a cohort of patients with ANCA-associated vasculitis (AAV) and define factors associated with the frequency of VTE considering there is data on high incidence of VTE in AAV patients. In these cohorts VTE occurred mostly early in the course of disease. Method This study included 114 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Patients were classified according to clinical: granulomatosis with poliangitis (GPA), microscopic polingitis (MPA) and eosinophilic granulomatosis with poliangitis (EGPA) and serological phenotype: MPO-ANCA positive, PR3-ANCA positive, MPO- and PR3-ANCA positive and ANCA-negative. Ordinal variables were analysed using logistical regression test. Statistical analysis was done in MedCalc Statistical Software version 18.11.6 (MedCalc Software Bvba, Ostend, Belgium). Results In the cohort there were 64 (56%) females, mean age was 58 (IQR 16-84) with mean follow up time 46.9 months (IQR 1-127). Clinically there were 84 (73%) patients with MPA, 26 (22%) with GPA and 4 (5%) with EGPA. Serologically there were 20% PR3-ANCA, 54% MPO-ANCA, 8% MPO- and PR-3 ANCA positive patients and 18% ANCA-negative patients. Mean serum creatinine levels (SCr) was 380.9 μmol/l (IQR 65-1402). Mean BVAS (Brimingham vasculitis score) at the time of diagnosis of AAV was 17 (IQR 5-50) and at the time of VTE 0, 9 (0-22). Mean body weight was 71kg (IQR 48-110) and mean CRP was 84 mg/ml (IQR 0, 3-256). During the follow up 7 (6.14%) of the patients had VTE, with 4 having VTE in first month after the diagnosis and other two at month 14 and 19. Logistic regression showed the connection of weight (P = 0.0052) and CRP (0.0138) with VTE with odds ratio of 1,0829 for CRP (1.003-1.027) and 1.0150 for weight (1.0284-1.1736) respectively. There was no statistical significance for clinical or serological phenotype being associated with VTE nor for other clinical or laboratory parameters. Conclusion In our cohort patients with AAV were at risk of VTE, particularly within the first year following onset of disease. In this cohort the frequency of VTE did not depend of clinical or serological AAV phenotype, age or gender. Only CRP and body weight were associated significantly with VTE occurrence. Despite VTE rates in AAV patients, routine anticoagulation is not recommended in AAV patients, given the potential risk of bleeding complications. Prospective studies are needed to assess VTE risk stratification in AAV patients and to evaluate the both benefits and potential risks ratio of prophylactic anticoagulation in AAV patients.

#1155 Outcomes after kidney transplantation in anti-glomerular basement membrane disease

Abstract Background and Aims Anti-glomerular basement membrane antibody disease-associated glomerulonephritis (anti-GBM-GN) can lead to end-stage kidney disease (ESKD), requiring replacement therapy with dialysis or kidney transplant (KT). Few studies evaluated the outcome of these patients after KT. Our aim was to describe, in comparison with a control group, the occurrence of the following events: delayed graft function recovery, graft survival, relapse, acute rejection, overall survival; and to study the risk factors associated with these events. Method This was a retrospective, multicenter (6 French centers), observational study including patients who received a KT between 2005 and 2023 for ESKD secondary to anti-GBM-GN. Each vasculitis case receiving a KT was matched with 2 controls, matched on gender, center, recipient age (±5 years) and transplant period (±1 year). Event-free survival and the associated risk factors were analyzed. Results 126 patients were included, including 42 with anti-GBM-GN and 84 control patients. The median post-KT follow-up for vasculitis patients was 95 months. There was no difference in the occurrence of DGF between the groups (24 vs 18%, p = 0.5). There was no difference in graft survival when comparing both groups (78% vs 82% at 10 years, p = 0.48) (Fig. 1A). Only one patient experienced a relapse after KT (being anti-GBM negative at the time of transplantation). There was no difference in the incidence of acute rejection between the groups (p = 0.82). There was no difference in overall survival when comparing both groups (83% vs 89% at 10 years, p = 0.76) (Fig. 1B). Conclusion Kidney transplantation is an interesting option for patients with anti-GBM-GN: outcomes are similar to those of a matched population with similar occurrence of acute rejection, graft loss or death. Moreover, relapse rate is low. Comparison with a matched anti-GBM-GN population remaining on dialysis would be of interest to go further.

Carotid intima-media thickness correlated with age and pulse wave velocity in ANCA-associated vasculitis patients

Objective: Cardiovascular diseases are the main causes of mortality in the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. Carotid intima-media thickness (CIMT) measurement and pulse wave velocity (PWV) were performed to determine atherosclerosis and arterial stiffness as cardiovascular risk markers. Patients and Methods: The data of 31 patients with AAV were compared with 21 healthy controls. Demographic and laboratory findings were recorded. Results: Seventeen patients (54.8%) were male. Mean age was 52.6±11.5 years. CIMT was higher in the patient group [0.74 (0.65 – 0.84) vs 0.63 (0.57-0.74) mm; p=0.048]. PWV [7.9 (6.7-9.3) vs 7.8 (6.8-8.5) m/s; p=0.295] and augmentation index (AI) [22.5 (11.0-30.0) vs. 23 (9.5-30.5) mm/Hg, p=0.801] were similar in both groups. CIMT was correlated with age (r: 0.538, p

Cardiovascular disease and antineutrophil cytoplasmic antibodies-associated vasculitis: A systematic review

ABSTRACT Recent evidence suggests that cardiovascular disease and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are interconnected. This investigation aims to examine the epidemiology, potential risk, and cardiovascular events among AAV sufferers to shed light on the intricate relationship between these seemingly unrelated conditions. A systematic review following PRISMA criteria encompassed 18 relevant studies with a pooled sample size of 21,291 ANCA-associated vasculitis patients. Studies were retrieved from PubMed, Embase, and Cochrane Library. Inclusion criteria focused on longitudinal studies reporting cardiovascular events in AAV patients. Data extraction and synthesis were performed, focusing on prevalence, types of cardiovascular events, comparison with control groups, and identification of risk factors and independent predictors. The study found that patients with ANCA-associated vasculitis had a mean age of 57.5 years, with 47% being male. The mean follow-up duration was 4.77 years. Overall, 1350 cardiovascular events were reported across the studies, yielding a pooled prevalence of 6.3%. Major adverse cardiovascular events, ischemic heart disease, stroke, venous thromboembolism, and acute coronary syndromes were the specific events. Comparison with control groups demonstrated a higher cardiovascular risk in AAV patients. Age, systolic blood pressure, estimated glomerular filtration rate, and the Birmingham Vasculitis Activity Score were independent predictors. In conclusion, ANCA-associated vasculitis patients have elevated cardiovascular risk and a variety of manifestations. AAV-specific variables,such as inflammation and disease activity, and conventional risk factors, play a role in cardiovascular complications. The study challenges conventional assessment timelines by highlighting the importance of early and proactive cardiovascular risk management.

The Contribution of Vessel Wall Magnetic Resonance Imaging to the Diagnosis of Primary and Secondary Central Nervous System Vasculitis.

To describe high-resolution brain vessel wall MRI (VW-MRI) patterns and morphological brain findings in central nervous system (CNS) vasculitis patients. Fourteen patients with confirmed CNS Vasculitis from two tertiary centers underwent VW-MRI using a 3T scanner. The images were reviewed by two neuroradiologists to assess vessel wall enhancement characteristics and locations. Fourteen patients were included (six females; average age 48 ± 19 years). Diagnoses included primary CNS vasculitis (PCNSV) in six patients and secondary CNS vasculitis (SCNSV) in eight, half of which were infection-related. Thirteen patients showed vessel wall enhancement, which was intense in eleven patients (84.6%) and concentric in twelve (92.3%), affecting the anterior circulation in nine patients (69.2%), posterior in two patients (15.4%), and both circulations in two patients (15.4%). The enhancement patterns were similar across different CNS vasculitis types. DWI changes corresponded with areas of vessel wall enhancement in 77% of patients. Conclusions: CNS vasculitis is often associated with intense, concentric vessel wall enhancement in VW-MRI, especially in the anterior circulation. The consistent presence of DWI alterations in affected territories suggests a possible link to microembolization or hypoperfusion. These imaging findings complement parenchymal brain MRI and MRA/DSA data, potentially increasing the possibility of a clinical diagnosis of CNS vasculitis.

P184 Geographical variations in delivery of intravenous treatments for ANCA-associated vasculitis

Abstract Background/Aims Timely access to intravenous immunosuppressant therapy is essential to effectively manage systemic vasculitis; however, significant variations in care and outcomes exists across centres. We systematically evaluated access to treatment for ANCA-associated vasculitis across the UK and Ireland. Methods This multi-method study included: a survey of 87 UK and Ireland Vasculitis Society sites and 11 Scottish Health Boards between Nov 2020 and June 2021; interviews with staff and patients with systemic vasculitis. Survey data was analysed descriptively. Interviews were audio or video recorded and analysed thematically. Results 59 responses from 51 Trusts/Health Boards across Scotland (n = 11), England (n = 33), Wales (n = 2), and Ireland (n = 5) included equal numbers of rheumatology and nephrology vasculitis services across diverse healthcare settings. 67 healthcare professionals across six case studies in Scotland (n = 3) and England (n = 3) and 32 patients with systemic vasculitis were interviewed. Services faced significant challenges in prescribing and delivering high-cost drugs to manage systemic vasculitis: balancing accountability versus bureaucracy, and tensions between different specialties looking after vasculitis patients when implementing access to high-cost drugs via multi-disciplinary networks. There was significant variation in how services delivered intravenous treatments: 10%(5/51) used inpatient beds; 35% (18/51) accessed another specialty unit or shared a daycase facility; 65% (33/51) used their own specialty daycase unit. Average wait time for urgent IV treatment was 2.67 days (range 1-10 days). 18% of services had waiting times >7 days, and of those 67% accessed intravenous treatments via another daycase facility. Specific challenges in accessing daycase facilities included availability of slots and staff, particularly in shared units, due to competition with other services and limited awareness of the importance of timely treatment for systemic vasculitis. This could impact on timing and treatment decisions e.g., prolonged steroid prescriptions. Staff training, competencies and governance to deliver cytotoxic drugs was problematic, particularly for smaller services, and 70% of services said national training modules would be helpful. Oncology units could provide workarounds but daycase nurses with vasculitis knowledge were a valuable source of advice and support for patients attending for treatments, identifying medical issues and arranging assessment if required. Conclusion There is significant variation in access to intravenous treatment for systemic vasculitis. Healthcare organisations should ensure timely access to urgent intravenous treatment for systemic vasculitis within 7 days and appropriately trained staff. National training modules for non-cancer chemotherapy could facilitate equitable access to training. Where treatment is delivered via other units, greater awareness of systemic vasculitis would help provision of information and support for patients. Disclosure W. James: None. A. Nicoll: None. L. Locock: None. L. Harper: None. M. Little: None. N. Basu: None. R.J. Hollick: None.

Development and organization of Tabriz University of Medical Sciences Vasculitis Registry: TUOMS-VR

This manuscript describes the establishment and initial results of a patient-driven registry in Tabriz, Iran to collect demographic, clinical, and paraclinical data, treatment and outcomes of patients with vasculitis. The Tabriz University of Medical Sciences Vasculitis Registry (TUOMS-VR), a patient-driven, prospective and web-based disease registry system, is conducted at the Connective Tissue Diseases Research Center, TUOMS located in Tabriz, Iran. The primary objective of this registry is to comprehensively document prospective data of patients diagnosed with systemic or single-organ vasculitis according to the Chapel Hill Consensus Conference nomenclature and definitions. To date, the registry has successfully enrolled 743 patients. The gender distribution within this existing cohort is balanced, with 50.5% male and 49.5% female participants. The most frequently diagnosed condition was Behcet’s disease, representing 56.5% of cases. Polymyalgia rheumatica also emerged as a notable diagnosis, accounting for 13.7% of cases. By providing a comprehensive and prospective documentation of vasculitis cases, the TUOMS-VR aims to enhance vasculitis patients care and outcomes.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA

Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients’ clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the “dominant” phenotype in idiopathic double-positive AAV.

Risk factors for serious infections and infection-related mortality in patients with microscopic polyangiitis: Multicentre REVEAL cohort study.

Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

Suitability of reduced dose glucocorticoids therapy regimen for antibody-associated vasculitis patients with TB: a retrospective study.

Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.

Pneumocystis jirovecii Pneumonia Prophylaxis in Patients with ANCA Vasculitis on Rituximab Maintenance Therapy.

Although an increased risk of Pneumocystis jirovecii pneumonia (PJP) has been reported in adults receiving rituximab for induction therapy, current evidence is lacking on the utility of PJP prophylaxis in ANCA-associated vasculitis (AAV) patients on maintenance rituximab therapy. The purpose of this study was to compare the incidence of PJP pneumonia and the outcomes of AAV patients with and without PJP prophylaxis. We performed an observational, single-center, retrospective study examining patients with AAV in clinical remission and on rituximab maintenance therapy. We divided the patients into two groups: those with and without PJP prophylaxis. We explored factors associated with PJP prophylaxis use. We additionally looked at several outcomes, including PJP infections, infections requiring hospitalizations, end-stage kidney disease (ESKD), and death. Data were analyzed using T test, Fisher's exact test, univariate, and multivariate logistic regression as appropriate. A total of 129 patients with mean follow-up time of 7.2 (5.4) years were included: 44% received PJP prophylaxis and 56% of patients did not. There were no PJP infections in the entire cohort. Lung involvement was associated with increased odds of prescribing PJP prophylaxis (OR: 4.09 [95% CI: 1.8-9.82]). PJP prophylaxis did not decrease infection rates requiring hospitalizations, ESKD, or death. Glucocorticoid use, however, was associated with increased rates of infections requiring hospitalizations (OR: 5.54 [95% CI: 2.01-15.4]) and death (OR: 4.67 [95% CI: 1.36-15.71]) even after adjustment for age, gender, and use of PJP prophylaxis. Regardless of the use of PJP prophylaxis during the maintenance phase of AAV management, PJP pneumonia was not observed. AAV patients with lung involvement were more likely to be on PJP prophylaxis.

Von Willebrand factor: a possible biomarker for disease activity in vasculitis

Objective Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature. Method Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment. Results Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active. Conclusion vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Mononeuritis multiplex following immune checkpoint inhibitors in malignant pleural mesothelioma

IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplex—all with mesothelioma—identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015–October 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86 years; range 72–88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event.

Analysis of Thyroid Function in ANCA-Associated Vasculitis Patients with Renal Injury.

Previous studies indicated common thyroid dysfunction in various kidney diseases. This study aimed to investigate the thyroid function in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal injury. Briefly, 174 patients diagnosed as having AAV with renal injury and without previous thyroid disease history were included in the retrospective and prospective study. The clinical parameters were collected and compared between different groups. Of the patients included, 24 exhibited normal thyroid function, while 150 had thyroid dysfunction, including 55 (36.67%) with hypothyroidism. Those AAV patients with thyroid dysfunction showed different clinical parameters from those with normal thyroid function. The patients were followed up for a median of 68.6 (64.3; 72.8) months. Those with thyroid dysfunction were more prone to progressing to dialysis dependence compared to the group with normal thyroid function. Logistic regression analysis showed advanced age and decreased albumin as independent risk factors for thyroid dysfunction in patients with AAV. Survival analysis and multivariate Cox regression analysis showed that thyroid dysfunction was a risk factor for AAV patients with renal injury to progress to the endpoint of dialysis dependence. Thyroid dysfunction, predominantly hypothyroidism, was commonly complicated in AAV patients with renal injury. AAV patients with thyroid dysfunction were presented with different clinical parameters and more prone to progressing to dialysis dependence compared to those with normal thyroid function.

Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD20 therapy.

Patients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients. We performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidic-based immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30). Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7-38.8) nM vs. 4.6 (2.3-44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximab-treated patients [median (range) KD: 1.05 (0.45-1.84) nM vs. 20.25 (13.2-38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination. Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.

Trends in health care of patients with vasculitides, including giant cell arteritis, Takayasu arteritis, ANCA-associated vasculitis and Behçet’s disease: cross-sectional data of the German National Database 2007–2021

The aim of this study is to present the current care situation of patients with giant cell arteritis (GCA), Takayasu arteritis (TAK), ANCA-associated vasculitis (AAV) and Behçet’s disease (BD). Trends over the last 15 years will reflect improvements and remaining deficits in the management of vasculitides. Consecutive cross-sectional data from patients with vasculitides from the German National Database (NDB) of the Collaborative Arthritis Centres between 2007 and 2021 were included. Medication, physician- and patient-reported outcomes on disease activity and disease burden, inpatient stays and occupational participation are compared for different vasculitis entities and over time. Employment rates were compared to German population rates. Between 502 and 854 vasculitis patients were annually documented. GCA and AAV were the most common vasculitides. Median disease duration ranged from 2 to 16 years. Over the years, glucocorticoids decreased in proportion and dose, most markedly in GCA and TAK, while biologic therapies increased up to 27%. Physicians rated disease activity as low for the vast majority of patients, while patients-reported moderate outcomes in many dimensions. PROs remained largely unchanged. The proportion of employed patients (< 65 years) increased from 47 to 57%. In recent years, biologics are increasingly used in patients with vasculitides, while glucocorticoids decreased significantly. PRO’s have not improved. Work participation increased but remains lower than that in the German population.

Pits of Fire: Post Scleral Graft Vasculitis in Patients With Optic Disc Pit Maculopathy.

Occlusive vasculitis is a rare complication following an uneventful surgery. In this article, we report two cases of optic disc pit maculopathy that underwent scleral graft and developed vasculitis following uneventful surgery. Both patients underwent autologous scleral graft for optic disc pit maculopathy through 25-gauge pars plana vitrectomy. Scleral graft was harvested from patient's same eye and plugged in the optic disc pit. After a postoperative period of approximately 3 months, both patients developed features of occlusive vasculitis with vitreous base contraction. Uveitic workup did not reveal other causes of vasculitis. Both patients were treated with topical and systemic steroids and responded well until the last follow-up. [Ophthalmic Surg Lasers Imaging Retina 2024;55:172-175.].

Ocular fundus changes and association with systemic conditions in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and systems. Ocular involvement is estimated to manifest in one-third of individuals with SLE, of which lupus retinopathy and choroidopathy represent the severe subtype accompanied by vision impairment. Advancements in multimodal ophthalmic imaging have allowed ophthalmologists to reveal subclinical microvascular and structural changes in fundus of patients with SLE without ocular manifestations. Both ocular manifestations and subclinical fundus damage have been shown to correlate with SLE disease activity and, in some patients, even precede other systemic injuries as the first presentation of SLE. Moreover, ocular fundus might serve as a window into the state of systemic vasculitis in patients with SLE. Given the similarities of the anatomy, physiological and pathological processes shared among ocular fundus, and other vital organ damage in SLE, such as kidney and brain, it is assumed that ocular fundus involvement has implications in the diagnosis and evaluation of other systemic impairments. Therefore, evaluating the fundus characteristics of patients with SLE not only contributes to the early diagnosis and intervention of potential vision damage, but also holds considerate significance for the evaluation of SLE vasculitis state and prediction of other systemic injuries.

Correlation between antiphospholipid antibodies and renal involvement in children with Henoch-Schönlein purpura: A cross-sectional study.

Renal involvement is the most damaging long-term complication of Immunoglobulin-A (IgA) vasculitis. In the lack of a definite predictive biomarker for renal involvement, antiphospholipid antibodies (aPL) have been proposed in recent years. In this prospective cohort of 48 pediatric patients who were admitted with IgA vasculitis from September 2015 to June 2017, two serum samples were taken 12 weeks apart to detect Anti-Phospholipid antibodies. All patients were followed-up for renal involvement for six months. Renal involvement occurred in 14 out of 48 patients with IgA vasculitis (29.16%). APLs were positive in nine out of 14 patients with IgA vasculitis and renal involvement (64.28%), in contrast to only six out of 34 patients with IgA vasculitis without renal involvement (17.64%). The presence of aPL antibodies was statistically associated with renal involvement (P=0.002). Although, the relationship between both sex (P=0.025) and age (P=0.046) with aPL positivity was statistically significant, performing a modified logistic regression test, the odds ratio was significant between the groups with and without renal involvement only in term of age and aPL positivity). The presence of aPL antibodies was statistically associated with renal involvement. We found a significant relationship between the age and aPL positivity. Hence, we need multicenter, more extensive cohort studies to reach a better and more accurate conclusion on the relationship between serum aPLs and renal involvement in IgA vasculitis patients.