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Herein, we present the first case of chronic Campylobacter fetus infection-related glomerulonephritis (IRGN) in a 69-year-old man with a permanent cardiac pacemaker. The patient had a prior episode of fever and glomerulonephritis of undetermined etiology, and at that time, low-dose steroid therapy resulted in improved urinary findings and kidney function. This time the patient again developed deterioration of kidney function with microhematuria, proteinuria, high serum C-reactive protein levels, and positive titers of anti-double-stranded DNA antibody and proteinase 3 anti-neutrophil cytoplasmic antibody (ANCA). A kidney biopsy revealed endocapillary and mesangial hypercellularity, interstitial infiltration of neutrophils, and positive staining for C3 and IgM in the mesangium and glomerular capillary walls. Notably, histological staining for nephritis-associated plasmin receptor (NAPlr)/plasmin activity was also positive. Similar laboratory and pathological findings in the first and second kidney biopsies and repeated detection of C. fetus in blood cultures led to the diagnosis of IRGN associated with persistent pacemaker-related infection. The nephritis improved following antibiotic therapy targeting C. fetus. C. fetus can cause sustained bacteremia and prolonged infection of indwelling devices, and can be a causative organism for recurrent IRGN. Clinicians must distinguish IRGN from autoimmune diseases such as lupus nephritis and ANCA-associated vasculitis.
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Doenças Autoimunes , Infecções por Campylobacter , Campylobacter fetus , Glomerulonefrite , Humanos , Masculino , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/complicações , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/microbiologia , Glomerulonefrite/diagnóstico , Glomerulonefrite/microbiologia , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Idoso , Campylobacter fetus/isolamento & purificação , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Doenças Autoimunes/diagnóstico , Rim/patologia , Doença Crônica , Biópsia , Anticorpos Anticitoplasma de Neutrófilos/sangueRESUMO
Background and Clinical Significance: Isolated mediastinal lymphadenopathy is an exceptionally rare and diagnostically challenging initial manifestation of microscopic polyangiitis (MPA), often mimicking malignancy or infection. This case highlights the pivotal role of an innovative minimally invasive technique in achieving a definitive diagnosis. To the best of our knowledge, this is the first reported case of MPA diagnosed via EBUS-TMC. Case Presentation: A 55-year-old male livestock farmer from a rural area with a history of recurrent pneumonia presented with four weeks of persistent fever, significant weight loss (7 kg), myalgia, and asthenia. Physical examination revealed fever and cachexia. Notable findings included leukocytosis (17,000/µL), normocytic anemia, thrombocytosis (672,000/µL), highly elevated inflammatory markers (CRP 145 mg/L, ESR 120 mm/h), and strongly positive MPO-ANCA (>134 U/mL). Serological testing was significant for IgG antibodies against Coxiella burnetii (Phase I 1:64, Phase II 1:256). PET-CT imaging demonstrated hypermetabolic bilateral hilar and mediastinal lymphadenopathy. Diagnostic challenges included overlapping serological findings suggestive of past Coxiella burnetii exposure. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) of a subcarinal lymph node was performed, providing a high-quality sample that revealed neutrophilic small-vessel vasculitis with fibrinoid necrosis, definitive for MPA. Immunosuppressive therapy with high-dose corticosteroids and rituximab (1000 mg on days 1 and 15) was initiated, leading to the complete resolution of all constitutional symptoms. Conclusions: This case illustrates that EBUS-TMC is a safe and highly effective diagnostic tool for obtaining critical histological evidence in systemic vasculitides with atypical presentations. This technique should be considered in the diagnostic algorithm for unexplained mediastinal lymphadenopathy to avoid more invasive surgical procedures.
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BACKGROUND/OBJECTIVE: The DANGER (Death in ANCA Glomerulonephritis-Estimating the Risk) score was developed to assess mortality risk in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to validate score in a cohort of Latin American patients. METHODS: This cohort study included patients with AAV evaluated between 2000 and 2022. The DANGER score was calculated, and its performance evaluated using the c-statistic and time-dependent area under the receiver operating characteristic curve. Multivariable Cox regression analysis was performed to identify variables that could enhance the score's predictive accuracy. RESULTS: We included 154 patients, 104 (68%) female, with a median age of 52 years (interquartile range [IQR], 38-61 years) and creatinine of 2.5 mg/dL (IQR, 1.7-2.5 mg/dL). Over a median follow-up of 74 months (IQR, 32-126 months), 24 patients died, with mortality rates of 6.5%, 8.6%, and 11.9% at 1, 2, and 5 years, respectively. The leading cause of death was infection. Mortality rates at 1 and 3 years in the low-, intermediate-, and high-risk categories were 1.0% and 3.1%, 14.0% and 16.8%, and 40.0% and 70.0%, respectively. The overall c-statistic for the DANGER model was 0.81 (95% confidence interval [CI], 0.73-0.90), with areas under the receiver operating characteristic curve of 0.81 (95% CI, 0.70-0.91), 0.78 (95% CI, 0.67-0.89), and 0.80 (95% CI, 0.70-0.90) at 1, 3, and 5 years, respectively. A revised model incorporating age, creatinine, C-reactive protein, and pulmonary involvement had a c-statistic of 0.86 (95% CI, 0.79-0.94). CONCLUSIONS: The DANGER score has good predictive accuracy for mortality in AAV patients with kidney involvement. In younger patients, the score may be modified to include variables such as C-reactive protein and severe pulmonary involvement to enhance its performance.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Adulto , Prognóstico , América Latina/epidemiologia , Curva ROC , Creatinina/sangue , Índice de Gravidade de Doença , Glomerulonefrite/mortalidade , Valor Preditivo dos TestesRESUMO
BACKGROUND/OBJECTIVE: Relapses occur in 14% to 44% of patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV). The French Vasculitis Study Group Relapse Score (FRS) was recently proposed to predict relapse risk. This study aimed to identify relapse-associated factors and evaluate the FRS performance in a Mexican cohort. PATIENTS AND METHODS: We performed a medical records review study including patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who were followed for ≥12 months at a Mexican tertiary care center. Demographic, clinical, laboratory, and treatment data were analyzed using descriptive statistics, survival analysis, and ROC curves. RESULTS: Among 147 patients (110 GPA, 37 MPA), the median age at diagnosis was 49 years (IQR: 36 to 59). Over a median follow-up of 93 months (IQR: 48 to 152), 90 patients (61%) relapsed. Cumulative relapse rates at 12, 24, 36, 48, and 60 months were 13.6%, 32.3%, 40.3%, 47.5%, and 58.0%, respectively. FRS scores of 1, 2, and 3 corresponded to median relapse-free survivals of 85, 68, and 33 months, with 5-year relapse risks of 40.5%, 48.4%, and 68.3%, respectively. Discrimination was significant (log-rank p < 0.0004). The C-statistic for FRS alone was 0.648 (95% CI: 0.586-0.710); for model 1 (adding cluster 4), 0.666 (95% CI: 0.605-0.728); and for model 2 (adding cluster 4 and rituximab as maintenance), 0.700 (95% CI: 0.643-0.757). An age cutoff of ≤50 years showed better accuracy (AUC: 0.67, p = 0.0006) for relapse prediction. CONCLUSIONS: In this cohort, relapses were frequent. Incorporating clinical clusters and rituximab therapy to the FRS may enhance its predictive performance.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Poliangiite Microscópica , Humanos , Feminino , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Recidiva , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Adulto , Estudos Retrospectivos , Rituximab/uso terapêutico , Imunossupressores/uso terapêutico , Índice de Gravidade de Doença , Prognóstico , Fatores de Risco , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/tratamento farmacológicoRESUMO
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a frequently relapsing systemic autoimmune disorder characterized by inflammation and destruction of small- to medium-sized blood vessels resulting in potentially life-threatening organ damage. Of the three AAV subtypes, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are the most common. The aims of treatment are to rapidly control active disease with induction therapy [typically rituximab (RTX) (the new standard-of-care) or cyclophosphamide alongside glucocorticoids (GC) and avacopan], followed by less aggressive maintenance strategies to reduce the risk of relapse. International and national guidelines for the treatment of GPA/MPA are generally aligned, with all guidelines highlighting a need to reduce treatment-related adverse events through rapid GC tapering and the use of GC-sparing avacopan treatment. Guidelines will continue to evolve as ongoing studies provide new insights into alternative (GC-sparing) treatment options and optimal RTX-based treatment regimens.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Rituximab/uso terapêutico , Glucocorticoides/uso terapêutico , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Poliangiite Microscópica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Granulomatose com Poliangiite/tratamento farmacológico , Efeitos Psicossociais da Doença , Quimioterapia CombinadaRESUMO
INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes severe multisystemic organ damage. The main phenotypes, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), share similarities but differ in clinical presentation and outcome. To uncover their molecular differences, we performed transcriptomic profiling of kidney tissue, then focused on type I interferon (IFN-I) pathway activation in kidney and blood and its clinical implications. METHODS: We analyzed two independent cohorts (Maine-Anjou and RENVAS registries) totaling 193 patients with AAV and glomerulonephritis. NanoString nCounter transcriptomic profiling, and serum inflammatory molecules quantification were conducted. Comparative analyses of MPA vs. GPA (and MPO-AAV vs. PR3-AAV) were validated using independent public datasets (including kidney spatial transcriptomic datasets, European cDNA Renal Biobank and blood from the RAVE trial). RESULTS: The kidney IFN-I signature found in AAV-GN is upregulated in MPA/MPO-AAV compared to GPA/PR3-AAV and controls. Quantitative PCR, MxA immunohistochemistry, and analysis of external datasets confirmed these findings. This IFN-I signature, close to the one found in lupus nephritis, is linked to the extent of pDC infiltration. Kidney IFN-I activation correlated with increased kidney fibrosis, independently of kidney function. High kidney IFN-I signatures were linked to lower kidney survival, independently of kidney function and pathological scores. MPA kidneys also exhibited higher mast cell and T-cell infiltration. Systemic analyses showed elevated IFNα and interferon related inflammatory molecules in all patients with AAV, but a stronger IFN-I gene signature was found in immune cells from MPA. CONCLUSIONS: Our study identifies an IFN-I signature in AAV, especially in MPA/MPO-AAV, underscoring its potential role in disease heterogeneity and kidney pathology. IFN-I emerges as a potential prognostic biomarker and therapeutic target in AAV, particularly for MPA. Further studies are needed to clarify its mechanisms and explore IFN-I modulation in clinical trials.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Granulomatose com Poliangiite , Interferon Tipo I , Rim , Poliangiite Microscópica , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Interferon Tipo I/sangue , Masculino , Feminino , Rim/patologia , Rim/imunologia , Prognóstico , Pessoa de Meia-Idade , Fenótipo , Perfilamento da Expressão Gênica , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite/genética , Glomerulonefrite/patologia , Glomerulonefrite/sangue , Glomerulonefrite/diagnóstico , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/sangue , Idoso , Transcriptoma , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/genética , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/patologia , Adulto , Regulação para Cima , Células Dendríticas/imunologiaRESUMO
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease characterized by autoantibodies against neutrophil cytoplasmic antigens such as myeloperoxidase (MPO) and proteinase 3 (PR3). AAV affects small blood vessels, leading to systemic inflammation and multiorgan damage. Recent advances in multi-omics analyses, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, have significantly improved our understanding of AAV complex pathophysiology. Genome-wide association studies (GWASs) have revealed robust genetic associations, especially within the human leukocyte antigen (HLA) region. Epigenomic analyses have elucidated regulatory mechanisms that affect autoantigen gene expression and disease activity. Transcriptomic approaches, particularly single-cell RNA sequencing (scRNA-seq), have identified distinct gene expression profiles and cellular interactions, which have been further enriched by the recent application of spatial transcriptomics of diseased tissues. Proteomic and metabolomic approaches have been used to identify potential biomarkers. This review discusses recent advances in multi-omics research aimed at developing personalized diagnostic and therapeutic strategies based on the molecular and genetic profiles of AAV.
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Genômica , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/metabolismo , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Poliangiite Microscópica/genética , Poliangiite Microscópica/metabolismo , Poliangiite Microscópica/diagnóstico , Proteômica/métodos , Genômica/métodos , Metabolômica/métodos , Estudo de Associação Genômica Ampla , Epigenômica , Transcriptoma , Biomarcadores , MultiômicaRESUMO
Orbital pseudotumor is uncommon in children and may rarely herald antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We report a 4yearold girl who presented with progressive bilateral proptosis due to extraconal-intraconal inflammatory masses. Histopathology showed small and mediumvessel changes with features suggestive of vasculitis, and serology was MPOpANCA-positive. Taken together with the clinical-radiologic pattern and exclusion of neoplasm, infection, and histiocytosis, the findings supported a diagnosis of granulomatosis con poliangeítis (GPA) with orbitalpredominant disease. The child improved with highdose corticosteroids and cyclophosphamide. This case underscores that an orbital pseudotumor-although rare-can be the sentinel manifestation of systemic vasculitis in pediatrics; early biopsy, targeted ANCA testing, and multidisciplinary management are critical to preserve vision and guide therapy.
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This report describes a case of biopsy-confirmed EGPA in which early initiation of mepolizumab, guided by biomarker surveillance, resulted in steroid-free MPO-ANCA seroconversion. These findings suggest a potential steroid-sparing strategy for ANCA-positive EGPA.
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BACKGROUD: Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease characterized by necrotizing small-vessel vasculitis, commonly involving the head and neck region, facial palsy is an uncommon head and neck presentation of GPA, and bilateral facial palsy is exceedingly rare. OBJECTIVE: We present the case of a patient who presented with bilateral acute facial paralysis with final diagnosis of GPA to raise awareness of this rare presentation of GPA. METHODS: retrospective chart review. CASE PRESENTATION: We present a case of a 52-year-old female, who presented with right-sided facial paralysis started 6 weeks earlier and left sided facial nerve paralysis started 5 days before presentation. In addition, patient suffered from severe bilateral mixed hearing loss and otorrhea. Physical exam revealed polypoid tissue occluding the ear canal and purulent otorrhea. Computed tomography showed completely opacified mastoids bilaterally without bony erosion, and without evidence of cholesteatoma on magnetic resonance imaging. No evidence of nasal, respiratory, or renal involvement was detected. Extensive lab work was within normal limits, besides elevated C-reactive protein and positive serine-proteinase 3 (PR3). Patient underwent left mastoidectomy with facial nerve decompression. The left middle ear space and mastoid were filled with dense granulation tissue. The facial nerve was decompressed and found to be intact to nerve stimulation. Pathology report was positive to PR3, confirming the diagnosis of GPA. She was started on rituximab and prednisone, and 6 weeks after surgery, the patient had improved otalgia, as well as significant improvement in left FN function to HB II, with right FN function at HBV. CONCLUSION: In the existing literature, there are 14 cases of bilateral facial palsy as a presentation of GPA, however, this presentation is the first in the existing literature without evidence of systemic involvement. This highlights that the absence of other systemic involvement and negative initial autoimmune workup does not exclude GPA as the etiology of facial palsy. Continued re-evaluation of systemic involvement and biopsies of middle ear contents is crucial in diagnosis.
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Paralisia Facial , Granulomatose com Poliangiite , Humanos , Feminino , Pessoa de Meia-Idade , Paralisia Facial/etiologia , Paralisia Facial/diagnóstico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Tomografia Computadorizada por Raios X , Descompressão Cirúrgica/métodos , Doença Aguda , Processo Mastoide/cirurgia , Processo Mastoide/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diagnóstico DiferencialRESUMO
ANCA-associated vasculitis (AAV) is a group of chronic multisystem inflammatory disorders affecting multiple organs throughout the body. Despite advances in AAV therapies, patients with AAV continue to experience higher rates of mortality than the general population. AAV outcomes can be improved by providing patients with rapid access to multidisciplinary medical teams and early treatment with glucocorticoid- (GC-) based therapy. However, GCs are associated with a high risk of toxicity. The phase 3 ADVOCATE trial demonstrates that blocking the alternative complement pathways using avacopan alongside immunosuppression enables patients with AAV to reduce their GC exposure without compromising efficacy or safety outcomes. ADVOCATE subgroup analyses show benefits for avacopan in patients with a wide range of AAV-related manifestations, disease stages and ages, with the greatest benefits in patients with kidney impairment, lung manifestations and AAV relapse.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Imunossupressores/uso terapêutico , Compostos de Anilina , Ácidos NipecóticosRESUMO
OBJECTIVE: This study aims to assess the incidence and factors linked to venous thromboembolic events (VTE) in a large national cohort of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) from the Turkish Vasculitis Study Group (TR-VaS). METHOD: This retrospective analysis included patients with granulomatosis with polyangiitis, microscopic polyangiitis, renal-limited vasculitis, and eosinophilic granulomatosis with polyangiitis. VTE that occurred within 3 months before the diagnosis of AAV or during the follow-up period was classified as AAV-associated VTE (AAV-VTE). Demographic, clinical, and disease-related features, along with the presence of well-known VTE risk factors, were compared between AAV patients with and without VTE. Multivariate analyses were performed to identify independent risk factors linked to the development of AAV-VTE. RESULTS: A total of 559 patients were included, and VTE was detected in 43 (7.7%). In univariate analysis, baseline body mass index (BMI) (HR: 1.13, 95% CI: 1.02-1.25, p = 0.01), erythrocyte sedimentation rate (HR: 1.01, 95% CI: 1.00-1.02, p = 0.04), BVAS score (HR: 1.05, 95% CI: 1.01-1.09, p = 0.01), renal involvement (HR: 2.01, CI: 0.96-4.20, p = 0.06), the presence of immobilization (HR: 11.4, 95% CI: 5.64-23.37, p < 0.001), and trauma (HR: 28.84, 95% CI: 3.5-215.7, p < 0.001) were identified as risk factors for VTE-AAV. In multivariate analysis, baseline BMI (HR: 1.14, CI: 1.02-1.26, p = 0.002) was the only independent risk factor for the development of VTE. CONCLUSION: Our findings suggest that physicians caring for AAV patients should be cautious about the risk of VTE in patients with an elevated BMI and active disease, along with other recognized risk factors for VTE.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Índice de Massa Corporal , Obesidade , Tromboembolia Venosa , Humanos , Masculino , Feminino , Estudos Retrospectivos , Fatores de Risco , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/diagnóstico , Pessoa de Meia-Idade , Turquia/epidemiologia , Incidência , Análise Multivariada , Fatores de Tempo , Idoso , Adulto , Medição de Risco , Obesidade/diagnóstico , Obesidade/epidemiologia , Modelos de Riscos ProporcionaisRESUMO
Systemic vasculitides can affect any type of blood vessel and can present with various signs and symptoms depending on the site and type of affected blood vessels. The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can affect small- to medium-sized vessels. It can involve various organs and present with varying clinical and pathological features. Although rare, it can affect the blood vessels of the toes, leading to distal ischemia and gangrene. A 74-year-old woman with multiple comorbidities presented with symptoms of chronic nasal congestion, joint pain, and neuropathy, prompting autoimmune evaluation. Due to positive antinuclear antibody and perinuclear ANCA titer, initial treatment with low-dose prednisone and methotrexate was introduced. However, later during the course, she developed bilateral toe necrosis despite being on treatment. The workup for neurological and cardiovascular causes for the toe necrosis was negative. The patient ultimately required bilateral metatarsal amputation. Post-surgery, she was treated with rituximab and prednisone, which resulted in improvement in vasculitis. This case highlights the importance of recognizing rare presentations of AAV to enable timely intervention and prevent severe complications.
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Autoimmune anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) and glomerulonephritis is characterized by the presence of autoantibodies (so-called ANCA), which, by binding to the body's own antigens, lead to damaged blood vessels (vasculitis) and subsequently to organ damage, particularly of the kidneys. The primary endogenous antigens are the enzymes proteinase 3 (PR3) and myeloperoxidase (MPO) expressed by neutrophil granulocytes and monocytes. In addition to the autoantibodies, both T-cellular response to those autoantigens and monocyte/macrophage-mediated processes play a decisive role. Since conventional therapy is based on the widespread suppression of the immune system, susceptibility to infections or the development of cancer are possible side effects. Furthermore, not all patients respond to conventional therapy or, despite responding at first, suffer multiple relapses. Therefore, there is a need for alternative treatment strategies and one promising option is the use of CD19-targeting chimeric antigen receptor (CAR)-T cells.
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Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis affecting medium and small arteries, with heterogeneous clinical manifestations ranging from constitutional symptoms to life-threatening organ ischemia. We present the case of a 36-year-old male patient with PAN manifesting as severe abdominal pain and bilateral upper limb ischemia, highlighting the diagnostic and therapeutic challenges of this condition. Initial evaluation revealed elevated inflammatory markers and characteristic arterial stenosis with aneurysmal dilation on Doppler ultrasound, supporting a PAN diagnosis with negative antineutrophil cytoplasmic antibody (ANCA) serology. Treatment with high-dose glucocorticoids induced remission, underscoring the efficacy of immunosuppression in managing this disease. This case illustrates the importance of considering PAN in patients with unexplained ischemic symptoms, particularly in the absence of ANCA positivity. While glucocorticoids remain first-line therapy, emerging evidence supports the use of biologic agents in refractory cases. The discussion explores the evolving treatment paradigms, including the role of cyclophosphamide, tumor necrosis factor (TNF) inhibitors, and rituximab, while emphasizing the need for risk-stratified management. Given PAN's variable presentation and potential for severe complications, early recognition and tailored immunosuppressive therapy are crucial for optimizing outcomes.
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BACKGROUND: Tularemia is a zoonotic disease that is rarely diagnosed in Europe. Its clinical presentation is highly variable, requiring consideration of a broad differential diagnosis. METHODS: We present a case report of a pulmonary tularemia with antineutrophil-cytoplasmic-antibody-negative pauci-immune crescentic glomerulonephritis causing acute kidney injury, and a systematic review of the literature. CASE REPORT: We report the case of a 73-year-old white man who presented with pneumonia, sepsis and acute kidney injury due to a pauci-immune crescentic glomerulonephritis with negativity for antineutrophil cytoplasmic antibodies. Initial management with dialysis, empirical antibiotics, and immunosuppression was adjusted after identification of Francisella tularensis, and targeted antibiotic therapy was administered successfully. At 4 years of follow-up, no recurrence was observed. LITERATURE REVIEW: Our review of the literature identified only a few case reports of tularemia complicated by acute kidney injury. None documented biopsy-proven pauci-immune crescentic glomerulonephritis. CONCLUSION: Pulmonary tularemia complicated by acute kidney injury is an uncommon clinical constellation. Biopsy-proven pauci-immune crescentic glomerulonephritis with antineutrophil-cytoplasmic-antibody-negativity in this setting appears to be very rare. Careful differential diagnosis, early recognition of tularemia, and timely initiation of effective antibiotic therapy are critical to achieving favorable outcomes.
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Introduction: Novel molecular tools have the potential to improve current clinical and histology-based risk classification systems for various medical renal diseases including glomerulonephritis (GN). We aimed to assess the utility of gene expression for improving biopsy-based risk prediction in patients with GN with and without crescent formation. Methods: This retrospective case-control study used NanoString nCounter to measure the expression of 54 previously described inflammation, nephron injury, endothelium, and crescent-related genes in 335 archival, formalin-fixed paraffin-embedded native kidney biopsies, including a 288-biopsy discovery cohort representing a broad spectrum of crescentic GN subtypes, and an independent 47-biopsy validation cohort focused on ANCA-associated crescentic GN. Clinical, histologic, and gene expression data were compared. Results: Discovery cohort analysis demonstrated increased expression of 13 genes in crescentic GN cases that developed end-stage renal disease (ESRD) versus those that did not (false discovery rate <0.05). Within the 75-biopsy subset of ANCA-associated crescentic GN cases in the discovery cohort, this 13-gene set was found to be independently predictive of ESRD in multivariate Cox proportional hazards regression analysis (p = 0.015), with significant differentiation of high and low risk patients in the Kaplan-Meier renal survival analysis (log-rank test, p = 0.002). However, validation cohort analysis did not demonstrate significant improvement in risk stratification with the 13-gene set when compared with established clinicopathologic models. Conclusion: These results suggest that biopsy-based gene expression may provide the opportunity for improved risk stratification in crescentic GN; however, the genes evaluated in this study appear to have limited added clinical utility over existing risk scores.