RESUMEN

INTRODUCTION: Granulomatosis with polyangiitis (GPA), formerly termed Wegener's granulomatosis, is an autoimmune disease marked by necrotizing granulomatous inflammation and vasculitis affecting small-sized vessels. It commonly impacts the renal and respiratory systems. MATERIALS AND METHODS: This retrospective case series sampling conducted in a tertiary care hospital between May 2023 and April 2024 examined six newly diagnosed GPA patients who were proteinase 3 cytoplasmic-antinuclear cytoplasmic antibody (PR3 c-ANCA) positive and had concurrent respiratory infections. None of them had any prior immunosuppressive conditions. The age range was 18-47 years with a mean of 35.0 (standard deviation: 11.83). All the patients had pneumonia (N=6, 100%). Out of all, five had bacterial pneumonia (N=5, 83.3%) and one had tuberculous pneumonia (N=1, 16.7%). A high level of PR3 c-ANCA (>150 RU/mL) was noted in four patients (N=4, 66.7%). Common symptoms included dry cough (N=5, 83.3%), loss of weight and appetite (N=2, 33.3%), and fever (N=2, 33.3%). Three patients had otitis media and/or nasal polyposis (N=3, 50%). Two patients (N=2, 33.3%) with life-threatening organ dysfunction were given concurrent antibiotics and steroids; the antibiotics were later modified based on culture and sensitivity results. One of these patients received antituberculosis therapy as Mycobacterium tuberculosis (MTB) was detected after 27 days of incubation in mycobacterial growth indicator tube broth. The remaining four patients (N=4, 66.7%) received antibiotics initially for 5-7 days until clinical resolution of pneumonia. Ultimately, they all showed clinical and radiological resolution (N=6, 100%) within 3-6 months of treatment. RESULTS: The patients exhibited constitutional symptoms such as fever and weight loss; lower airway disease symptoms including dry cough and hemoptysis; nasal and ear disease symptoms like epistaxis, ear pain, and ear discharge; and a renal disease symptom, hematuria. Computed tomography of the thorax revealed bilateral consolidations, most of which were cavitating. Bronchoalveolar lavage cultures grew Escherichia coli, Burkholderia cepacia, Pseudomonas aeruginosa, Klebsiella pneumoniae, and MTB, whereas pus swab cultures from otitis media grew Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci. DISCUSSION: This study highlights the therapeutic challenges of GPA complicated by concurrent infections. Patients exhibited typical GPA signs, confirmed by PR3 c-ANCA levels. Concurrent infections require cautious antibiotic treatment before starting immunosuppressive therapy, except in life-threatening organ dysfunction. A unique case presented with both tuberculosis and GPA. Tailored treatment regimens combining antibiotics and immunosuppressives, including corticosteroids, methotrexate, and rituximab, resulted in clinical and radiological improvement in all the patients within 3-6 months. The addition of co-trimoxazole reduced the incidence of non-severe GPA relapses. CONCLUSION: Tailored treatment plans addressing both infectious and autoimmune aspects are essential for optimal care in GPA complicated by concurrent infections. This study highlights the need for a multidisciplinary approach involving pulmonologist, rheumatologist, microbiologist, and pathologist in the diagnosis and treatment of GPA, emphasizing the importance of individualized treatment plans tailored to the specific clinical scenario.

RESUMEN

The prognosis of anti-glomerular basement membrane (anti-GBM) nephritis, often accompanied by the presence of antineutrophil cytoplasmic antibodies (ANCA), is poor, and even with aggressive therapeutic approaches, kidney replacement therapy (KRT) is typically required. Here, we present a case of necrotizing crescentic glomerulonephritis in a patient double-seropositive for anti-GBM antibodies and ANCA who successfully achieved dialysis independence following aggressive treatment, including avacopan. The patient was a 77-year-old woman with rapidly progressive glomerulonephritis and double seropositivity for myeloperoxidase-ANCA and anti-GBM antibodies. A kidney biopsy revealed diffuse cellular crescents with necrosis and immunoglobin (Ig)G1 and IgG3 positivity on immunofluorescence staining, leading to a histological diagnosis of anti-glomerular basement membrane nephritis. Our treatment approach involved a novel combination of glucocorticoids, rituximab, low-dose cyclophosphamide, and plasma exchange complemented by avacopan. Temporary hemodialysis was required, and the patient successfully discontinued dialysis after 12 sessions despite a poor histological prognosis. This case underscores the significance of considering aggressive therapeutic strategies, including avacopan, for severe anti-GBM nephritis, even in the absence of lung involvement, to avert the need for KRT.

RESUMEN

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune disease that often involves the upper and lower respiratory tracts. In recent years, numerous studies have found a significant increase in the incidence of cancer among AAV patients, but the association between lung cancer and AAV remains inconclusive, with relatively low clinical attention. This review summarizes the current literature on the risk of lung cancer in patients with ANCA-associated vasculitis (AAV), detailing the potential mechanisms by which AAV may contribute to lung cancer, and further elucidates the inherent carcinogenic risks of immunosuppressants.There is a correlation between AAV and lung cancer, which is related to T cell senescence and damage, as well as the abnormal expression of cytokines such as IL-6 and IL-10. In AAV patients, the use of cyclophosphamide and azathioprine (AZA) alone has a clear carcinogenic risk, with frequent use of CYC potentially posing a high risk for lung cancer. Although TNF inhibitors (TNFi) combined with CYC have carcinogenic risks, there is insufficient evidence to link them directly to an increased risk of lung cancer. For patients at high risk for lung cancer, the judicious use of immunosuppressants, timely computed tomography (CT), and lung cancer screening can reduce the risk of lung cancer in AAV patients.

Asunto(s)

RESUMEN

Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease with multi-system involvement. It involves the upper respiratory tract, lungs and kidneys. A 36-year-old female patient presented to a tertiary care referral hospital in Central India in 2023 with complaints of low-grade fever, dry cough and loss of appetite initially followed by dyspnoea, purpuric skin lesions, right lower limb swelling with pain and redness. Her chest radiograph revealed right upper lobe cavitary lesion with consolidation in the right lower lobe. Mycobacterium tuberculosis was detected in sputum and broncho alveolar lavage via cartridge based nucleic acid amplification assay. Later, computed tomography pulmonary angiography revealed bilateral pulmonary artery thromboembolism. Furthermore, her cytoplasmic-antineutrophil cytoplasmic antibody test was positive, serum creatinine was rising, urine microscopy had red cell casts and lower limb venous doppler revealed deep venous thrombosis. Histopathological examination of the skin lesion revealed vasculitis. Based on these findings, the patient was diagnosed with GPA. The patient improved with pulse steroids, cyclophosphamide, anticoagulants and anti-tuberculous therapy.

Asunto(s)

RESUMEN

Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness.

Asunto(s)

RESUMEN

Drug-induced or associated vasculitis is a prevalent form of vasculitis that resembles primary idiopathic antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (AAV). Cocaine is a diffuse psychostimulant drug and levamisole is a synthetic compound used to cut cocaine. Their abuse may result in a spectrum of autoimmune manifestations which could be categorized into three overlapping clinical pictures: cocaine-induced midline destructive lesion (CIMDL), levamisole-adulterated cocaine (LAC) vasculopathy/vasculitis, and cocaine-induced vasculitis (CIV). The mechanisms by which cocaine use leads to disorders resembling AAV are not well understood. Cocaine can cause autoimmune manifestations ranging from localized nasal lesions to systemic diseases, with neutrophils playing a key role through NETosis and ANCA development, which exacerbates immune responses and tissue damage. Diagnosing and treating these conditions becomes challenging when cocaine and levamisole abuse is not suspected, due to the differences and overlaps in clinical, diagnostic, therapeutic, and prognostic aspects compared to primary idiopathic vasculitides.

RESUMEN

INTRODUCTION: Complement was long thought not to be involved in ANCA vasculitis pathogenesis until studies in murine models demonstrated its central role. The current theory is ANCA-activated neutrophils degranulate and release factors that activate complement, which, in turn, recruits more neutrophils and causes an inflammatory amplification loop that results in the vascular inflammation characteristic of disease. Targeting this amplification loop through complement inhibition has proven to be effective in ANCA vasculitis treatment. AREAS COVERED: A PubMed search was conducted using key terms 'ANCA vasculitis' AND 'complement system.' We review findings from experimental mouse models, in vitro studies, and human ANCA vasculitis that support a role for complement activation in disease pathogenesis. We also summarize results from pivotal clinical studies demonstrating the safety and efficacy of complement inhibition in ANCA vasculitis treatment. EXPERT OPINION: While complement activation is undoubtedly involved in ANCA vasculitis pathogenesis, less clear is whether measuring complement activation markers can reliably assess disease activity, predict those who will benefit from complement-targeting therapy, or identify patients in stable remission and able to stop therapy. Better understanding the clinical implications of complement activation will shed more light on the utility of complement inhibition and facilitate precision medicine in ANCA vasculitis.

RESUMEN

Background: The remission rate of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients who received standard induction therapy is far from satisfactory. Improving the remission rate of MPO-AAV patients is essential. Hydroxychloroquine (HCQ), one of the classic antimalarial drugs, has been widely used in various autoimmune rheumatic diseases. This retrospective observational cohort study is aimed to evaluate the efficacy and safety of HCQ during induction treatment for MPO-AAV. Methods: The medical records of patients diagnosed with MPO-AAV at Xiangya Hospital, Central South University from January 2021 to September 2023 were collected. They were assigned to the HCQ group or control group according to whether they used HCQ. The patients included were screened by propensity score matching. To evaluate whether MPO-AAV patients benefited from HCQ, we compared the prognosis of the two groups. The adverse effects of HCQ during follow-up were recorded. Results: The composition ratio of complete remission, response and treatment resistance between HCQ group and control group were different statistically (P = .021). There was no significant difference between the two groups in 1-year renal survival (P = .789). The HCQ group had better 1-year patient survival than the control group (P = .049). No serious adverse effects were documented in the HCQ group. Conclusions: HCQ together with standard induction treatment may improve the remission rate of MPO-AAV patients, and HCQ had good safety in our study.

RESUMEN

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) microscopic polyangiitis is a rare but life-threatening small vessel vasculitis in childhood that affects multiple systems. Emerging clinical evidence suggests a possible association between SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) as well as the futuredevelopment of autoimmune diseases. A 14-year-old boy with a diagnosis of MIS-C two years prior to presentation was admitted to our hospital due to edema and left lower limb joint pain along with concomitant upper surface petechia. The patient had a positive higher SARS-CoV-2 IgG than MIS-C diagnosis titers and MPO-ANCA-positive antibody titers. Kidney biopsy favored a pauci-immune crescentic glomerulonephritis. Restrictive lung disease with concomitant diffusion abnormalities was also observed. Pancreatitis and gastrointestinal wall edema were additional clinical manifestations. SARS-CoV-2 breakthrough infection and MIS-C could contribute to the onset of autoimmune vasculitis through various immunological mechanisms. Further research is still needed to elucidate the role of SARS-CoV-2 in the pathophysiology of newly diagnosed autoimmune vasculitis.

RESUMEN

This systematic review evaluates the efficacy of rituximab in inducing and maintaining remission in patients with granulomatosis with polyangiitis (GPA). We conducted a comprehensive search across multiple databases, identifying 81 studies, of which 11 met our inclusion criteria after rigorous screening and assessment for relevance and quality. Our analysis shows that rituximab, compared to traditional treatments such as cyclophosphamide and azathioprine, significantly improves remission rates and reduces relapse frequency in GPA patients. Notably, rituximab's benefits extend across various patient demographics, including pediatric groups, and are evident in different dosing regimens, highlighting its versatility and potential as a first-line therapy. The review also underscores the importance of personalized medicine approaches in managing GPA, as rituximab's effectiveness was particularly pronounced in patients with relapsing disease forms. Future research should focus on long-term outcomes, optimal dosing strategies, and the economic implications of widespread rituximab use in clinical practice. Our findings advocate for the integration of rituximab into standard treatment protocols for GPA, offering new hope for patients afflicted with this challenging autoimmune disorder.

RESUMEN

Granulomatosis with polyangiitis (GPA) is a form of ANCA-associated vasculitis characterized by necrotizing vasculitis affecting small blood vessels. The clinical presentation varies based on organ involvement, commonly affecting the upper and lower respiratory tracts and kidneys. Typical GPA presents as recurrent sinus infection, otitis media, dyspnea, chest pain, and glomerulonephritis, which can present as hematuria, proteinuria, and elevated serum creatinine. ANCA tests positive in the majority of cases. Treatment strategies involve induction of remission and maintenance therapy. We report a case of a 48-year-old female presenting with a hypertensive emergency, a rarely reported manifestation of GPA. She initially presented with severe headache and cough, with systolic blood pressure exceeding 220 mmHg, necessitating hospital admission. The initial workup revealed elevated serum creatinine and CT chest findings suggestive of multi-lobar pneumonia, for which she received antibiotic treatment. Despite aggressive antihypertensive therapy, her blood pressure remained refractory, and she developed hematuria and anemia, requiring a blood transfusion. Further evaluation revealed a history of joint pain, recurrent sinus infections, and a pruritic skin rash, prompting suspicion of vasculitis. Further work-up included elevated erythrocyte sedimentation rate (ESR), normal IgE, absence of eosinophilia, and positive PR3 antibodies and c-ANCA. Prompted by clinical suspicion, treatment with steroids was initiated, and a kidney biopsy confirmed acute necrotizing pauci-immune glomerulonephritis consistent with GPA. Subsequently, rituximab therapy was initiated, resulting in significant improvement in her clinical symptoms and blood pressure, and the patient was successfully discharged home. This case highlights a rare presentation of GPA as a hypertensive emergency, possibly linked to renal involvement in the form of glomerulonephritis. Pulmonary manifestations mimicking infections posed diagnostic challenges. Cutaneous findings potentially associated with increased joint and renal involvement underscore the clinical complexity of GPA. The unusual presentation of hypertensive emergency in young patients underscores the need for heightened awareness of this potential manifestation in GPA. Early recognition and aggressive immunosuppressive therapy are crucial to mitigate irreversible renal damage in such atypical presentations.

RESUMEN

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a spectrum of autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have shown that avacopan and mepolizumab are promising therapeutics for partial or complete replacement of glucocorticoids (GC), with sustained remission while completely weaning off GC. Avacopan inhibits C5aR in the complement pathway, preventing neutrophil migration, while mepolizumab targets IL-5R, reducing eosinophil activity. Additionally, complement inhibition has not only contributed to the recovery of renal function and alleviation of physical symptoms but has also enhanced patients' overall quality of life and mental well-being. This systematic review explores the pathogenesis of AAV, traditional treatments, and the potential of emerging complement and interleukin antagonist therapies such as avacopan and mepolizumab in revolutionizing AAV management.

RESUMEN

To explore the expression patterns and potential roles of mRNAs in exosomes from patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV). Plasma exosomes were isolated from MPO-AAV patients and healthy controls (HCs) to screen for differential mRNA expression via exosomal mRNA sequencing. The differentially expressed mRNAs in exosomes from the 2 groups were comparatively explored by bioinformatics analysis. The six most differentially expressed mRNAs were selected and validated in larger groups of MPO-AAV patients and HCs by real-time quantitative polymerase chain reaction (RT‒qPCR). The relationships between these selected mRNAs and patient characteristics were statistically analyzed. Compared with HCs, a total of 1077 mRNAs in exosomes from MPO-AAV patients were found to be significantly upregulated, including DEPDC1B and TPST1, while NSUN4 and AK4 were significantly downregulated. Statistical analysis did not reveal any correlation between the six selected mRNAs and clinical indicators, including disease activity. GO enrichment analysis revealed that these differentially expressed genes participate in various enzyme activities, protein synthesis, etc. KEGG pathway analysis revealed that metabolic pathways, cell adhesion molecules, epithelial signaling, and mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched in the exosomal mRNAs. There were significant differences in the expression of exosomal mRNAs between MPO-AAV patients and HCs, which may be related to the occurrence and development of MPO-AAV. These findings provide clues for further investigations of MPO-AAV pathogenesis and the identification of new potential therapeutic targets.

Asunto(s)

RESUMEN

Introduction: Apheresis allows the fast removal of autoantibodies in anti-glomerular basement membrane (anti-GBM) disease, and in severe antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. The CINEVAS study tested whether immunoadsorption (IA) allowed a faster removal of ANCA and/or anti-GBM antibodies than plasma exchanges (PEx). Methods: CINEVAS was a prospective multicenter study comparing IA to PEx in consecutive patients with ANCA and/or anti-GBM vasculitides. The primary objective was the reduction rate in autoantibody titers between the beginning of the first and the end of the seventh apheresis session. Secondary objectives were number of sessions needed to obtain desired reduction rates; reduction rates of total Ig levels; tolerance of sessions; and patients' outcome. Results: The results of 38 patients (16 treated with IA and 22 with PEx), and 43 autoantibodies, were analyzed. There was no difference in the reduction rates in autoantibody titers between IA and PEx over 7 sessions (respectively 98% vs. 96%, P = 0.39). The numbers of sessions needed to obtain undetectable autoantibodies, or 50%, 75%, or 90% reductions, did not differ between techniques. Greater reduction rates of autoantibodies were observed when plasma was separated by filtration compared to centrifugation, with IA and PEx. IA allowed a greater reduction in total IgG levels, and better preservation of total IgA and IgM levels than PEx. PEx sessions required higher volumes of plasma, IA sessions higher volumes of citrate; IA sessions were longer. Conclusions: IA and PEx were comparable in ANCA or anti-GBM removal kinetics, despite a faster reduction in total IgG with IA.

RESUMEN

We discuss the case of a 60-year-old male who presented with ankle pain, a necrotic rash, and progressive weakness in both lower limbs and the right upper limb. An infectious workup of the skin lesions came back negative. Additionally, his kidney function tests indicated an acute kidney injury. This prompted investigations for vasculitis etiologies, which revealed a positive cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA). His neurological deficits were also investigated, and imaging suggested embolic infarcts. Cardiac imaging showed valve vegetations and blood culture showed a lack of growth suggestive of a noninfective nature of these lesions. Based on all these findings, a kidney biopsy was obtained and demonstrated pauci-immune segmental vasculitis consistent with ANCA-associated glomerulonephritis. As such, the patient showed improvement with heavy pulse steroid and immunomodulator therapy. Although skin, heart, and CNS involvement have been previously reported with ANCA-associated vasculitis, it is rare, especially together, and can prove a diagnostic challenge. Therefore, it is important to consider vasculitis etiology in patients presenting similarly. In addition, this case highlights the overlapping clinical picture between infective endocarditis and vasculitis with valvular involvement, making differentiation between the two challenging.

RESUMEN

BACKGROUND: ANCA-associated vasculitis (AAV), and nephrotic syndrome encompassing diseases including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSG), membranous nephropathy (MN), remain a challenge due to their varied immunological characteristics. Recent therapeutic advancements have highlighted the importance of understanding these diseases' immunological landscapes. METHODS: This study analyzed transcriptomics data from renal glomerular tissues of patients with AAV, FSG, MCD, MN, and normal controls. Utilizing an immune-related gene set of 883 genes, methods including Gene Set Variation Analysis (GSVA), LASSO regression, and Weighted Correlation Network Analysis (WGCNA) were used. Predictions of immune cell compositions were made through CIBERSORT, TIMER, MCPcounter, and quanTIseq algorithms. RESULTS: The study revealed distinct immunogenetic pathways enriched in each disease: hematopoietic cell lineage in ANCA, linoleic acid metabolism in FSG, PPAR signaling in MCD, and drug metabolism in MN. Classifiers based on immune gene expression showed high accuracy (AUC: ANCA 0.812, FSG 0.99, MCD 1, MN 0.888). Co-expression modules and PPI networks highlighted unique pathways for each disease. Predictions of immune cell composition showed elevated macrophages in FSG and MN, with Treg levels elevated across all four diseases compared to normal controls and highest in FSG. Correlation analyses demonstrated significant associations between classifier scores and immune cell types. CONCLUSION: This study offers accurate classifiers for AAV, FSG, MCD, and MN, and reveals distinct immunological pathways. These findings advance personalized treatments and highlight potential therapeutic targets in AAV and nephrotic syndrome. Further research should validate these results for clinical applications.

RESUMEN

Microscopic polyangiitis (MPA) is a form of necrotizing vasculitis affecting the small vessels. Our study is the first study with the objective of describing the difference in clinical presentation of MPA and response to treatment at 6 months based on the age of disease onset. All patients seen at a tertiary vasculitis clinic between 2015 and 2023 with a diagnosis of MPA were included. Patients were divided into an elderly group (age > = 65 years) and a younger group (age < 65). Comparative analysis was conducted to characterize differences amongst the elderly and younger patients, including differences in organ involvement and clinical presentation, Birmingham Vasculitis Activity Score (BVAS) scores, Vasculitis Damage Index( VDI) scores, and response to treatment at 6 months. Thirty-one patients were included in our study. Younger MPA patients (n = 18) with mean age at diagnosis of 53.17 years were compared with older MPA patients(n = 13) with mean age at diagnosis of 76.08 years. The younger patients had statistically significant higher BVAS scores (p = 0.009), along with higher incidence of renal (p = 0.028), pulmonary (p = 0.0069), and cutaneous (p = 0.026) manifestations at disease onset. Furthermore, amongst the younger population, there was noted statistically significant clinical improvement at 6 months following treatment induction, particularly in the domains of general symptoms (p = 0.011), MSK (p = 0.019), cutaneous (p = 0.011), and pulmonary symptoms (p = 0.04). In contrast, the elderly population presented with a predominant of non-specific constitutional symptoms, with statistically significant improvement in the domain of non-specific general symptoms at 6 months (p = 0.00008). All MPA patients responded well to treatment, with statistically significant improvement amongst younger patients (p = 0.0032), but no statistically significant improvement amongst elderly patients (p = 0.67). Our study findings concluded that MPA's clinical presentation differed by age group. Younger patients had more aggressive vasculitis disease presentation with better response to treatments, whereas, elderly patients had less severe disease presentation with predominant of general symptoms at disease onset. Key Points • MPA clinical presentation differed by age at disease onset. Younger patients presented with more aggressive and classic vasculitis-like presentations, with multi-system organ involvement and statistically significant higher incidence of renal, pulmonary, and cutaneous manifestations. In contrast, elderly patients had a predominant of constitutional and non-specific symptoms with often delayed diagnosis. • All MPA patients responded well to treatment. Amongst the younger population, there was statistically significant improvement in BVAS scores after treatment induction at 6 months; however, there was no statistically significant improvement of BVAS scores in the elderly population. • Future studies are required to further understand the difference in the clinical presentation of MPA based on the age at disease onset, and the implication on disease diagnosis and management.

RESUMEN

Objectives: Rituximab is used for remission induction and the prevention of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the incidence of safety events and compared time to first serious adverse event (SAE) between a rituximab cohort and a cohort treated with non-rituximab therapies in a real-life setting. Methods: Rituximab surveillance study in vasculitis was a retrospective observational study of patients with AAV who received rituximab (MabThera) or other treatments between 2003 and 2017 at a specialist vasculitis clinic. The primary endpoint was time to first SAE. Results: 392 patients were enrolled: 247 in the rituximab and 145 in the control cohorts with a total follow up of 2217 person-years (mean study duration 5.7 years). Mean age was 61 years, 77% had granulomatosis with polyangiitis (GPA). There were differences in baseline characteristics (disease duration and prior immunosuppressive use) between groups. 134/247 patients (54%) in the rituximab and 58/145 (40%) of controls experienced at least one SAE. Time to first SAE was shorter in the rituximab group (hazard ratio (HR) 1.55, 95% CI 1.07-2.26, P = 0.022). Predictors of first SAE were higher vasculitis damage index and the presence of chronic pulmonary or kidney disease. The risk of serious infection was higher in the rituximab group (relative risk (RR) 2.12, 95% CI 1.31-3.43). Conclusion: Over 40% of patients with AAV experienced at least one SAE. Although shorter time to first SAE and higher risk of infection were observed in the rituximab group, baseline imbalances necessitate a careful interpretation of these results.

RESUMEN

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.