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Kidney International Reports Oct 2023Diagnosis and management of microscopic polyangiitis (MPA) have evolved considerably over the past decades, but it is unknown whether clinical and histological...
INTRODUCTION
Diagnosis and management of microscopic polyangiitis (MPA) have evolved considerably over the past decades, but it is unknown whether clinical and histological presentation and patient and renal outcomes have changed accordingly.
METHODS
We compared clinical and histopathological characteristic at diagnosis, risk of death, end-stage kidney disease (ESKD), and relapse rate in patients diagnosed with MPA between 1980 and 2022, after grouping them in 2 periods (p): p1980-2001 and p2002-2022. We compared the mortality rate between the 2 periods using Kaplan-Meier estimator and Cox-regression, and competing risks of ESKD and death using the Aalen-Johansen estimator, Fine-Gray multiple regression, and multistate models.
RESULTS
Out of 187 patients, 77 were in p1980-2001 and 110 in p2002 to 2022. Patients in p2002 to 2022 were older (66.2 ± 14.0 SD vs. 57.7 ± 15.8; < 0.001), had a better kidney function (estimated glomerular filtration rate [eGFR] 25.9 ± 24.8 vs. 21.5 ± 28.2 ml/min per 1.73 m; = 0.011) and a lower prevalence of the Berden sclerotic class (5.9 vs. 20.9%; = 0.011). Despite a similar crude and adjusted patient survival, the risk of ESKD decreased during p2002 to 2022 (subdistribution hazard ratio [HR] 0.30, 95% confidence interval [CI]: 0.16-0.57; < 0.001). The results remained significant after accounting for death after ESKD and after adjusting for potential confounders (HR 0.33 [95% CI: 0.18-0.63; < 0.001]). The risk of relapse was numerically higher during p2002 to 2022 (subdistribution-HR 1.64 [95% CI: 0.95-2.83; = 0.075]).
CONCLUSION
MPA kidney involvement has become less severe over the past decades, leading to a reduced risk of ESKD and a higher relapse rate, despite a comparable risk of death.
PubMed: 37850011
DOI: 10.1016/j.ekir.2023.07.008 -
International Journal of Molecular... Nov 2022This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and...
This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA ( = 37) and other non-inflammatory neurological diseases (ONDs; = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.
Topics: Humans; Microscopic Polyangiitis; Tissue Inhibitor of Metalloproteinase-1; Peripheral Nervous System Diseases; Biomarkers; C-Reactive Protein
PubMed: 36362162
DOI: 10.3390/ijms232113374 -
Arthritis Research & Therapy Dec 2023To classify the different clinical phenotypes and compare the distinct prognoses of microscopic polyangiitis (MPA).
BACKGROUND
To classify the different clinical phenotypes and compare the distinct prognoses of microscopic polyangiitis (MPA).
METHODS
A retrospective analysis of 436 patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) from 2015 to 2022 was conducted in our center, of which 90 patients were diagnosed with MPA and underwent renal biopsy.
RESULTS
Among the 90 MPA patients, 63% were female, and the median age at onset was 63 years (25th-75th percentile: 58-68). The median follow-up time was 26 months (25th-75th percentile: 10-53). We identified four subtypes: renal impairment type (cluster 1, 39%), pure type (cluster 2, 22%), systemic inflammation type (cluster 3, 26%), and rapid progress type (cluster 4, 13%). Cluster 1, characterized by renal dysfunction at onset (80%), demonstrated poor prognoses with only 26% achieved complete remission (CR), 11% dying, and 19% developing renal failure. In contrast, patients in cluster 2, exclusively female, most had only kidney involvement showed the best prognoses with 55% achieving CR and none experiencing death or renal failure within 10 years. Cluster 3 mostly consisted of males; high fever and C-reactive protein levels were the primary characteristics. These cases exhibited moderate prognoses with 53% achieving CR, 9% dying, and 4% developing renal failure. Finally, patients in cluster 4, which was characterized by rapidly progressive glomerulonephritis, had the worst prognoses, with none achieving CR, 8% dying, and 75% developing renal failure despite aggressive treatment.
CONCLUSIONS
MPA is classified into four subtypes with distinct clinical manifestations and prognoses.
Topics: Male; Humans; Female; Middle Aged; Microscopic Polyangiitis; Retrospective Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Prognosis; Antibodies, Antineutrophil Cytoplasmic; Kidney; Phenotype; Renal Insufficiency; Biopsy; Granulomatosis with Polyangiitis
PubMed: 38062524
DOI: 10.1186/s13075-023-03218-0 -
Skin Therapy Letter May 2020Small-vessel vasculitides (SVV) are a group of disorders that occur due to primarily systemic inflammation or as sequelae of an infection, malignancy, or other rheumatic... (Review)
Review
Small-vessel vasculitides (SVV) are a group of disorders that occur due to primarily systemic inflammation or as sequelae of an infection, malignancy, or other rheumatic disease. Arising in any organ including the skin, the clinical features of SVV encompass a variety of manifestations. A comprehensive diagnostic assessment should be performed as management protocols widely differ. Although rare, physicians should be familiar with the common types of SVV to ensure prompt management and prevention of severe, life-threatening end-organ damage. Given the variable manifestations and associated etiologies of SVV, the following review aims to discuss the pathogenesis of more prevalent SVVs, highlight distinguishing features to aid in patient evaluation and diagnosis, and examine evidence-based management options for treatment and care.
Topics: Blood Vessels; Humans; Systemic Vasculitis
PubMed: 32510891
DOI: No ID Found -
European Journal of Rheumatology Sep 2016Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's... (Review)
Review
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine-chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received.
PubMed: 27733943
DOI: 10.5152/eurjrheum.2015.0043 -
Frontiers in Immunology 2021Endogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated...
BACKGROUND
Endogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV.
METHODS
We enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction before and after the initiation of immunosuppressive therapy. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure of eosinophil extracellular traps (EETs) and neutrophil extracellular traps (NETs) and stability against DNase were assessed . Platelet adhesion of EETs were also assessed.
RESULTS
Serum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. The structure of EETs showed bolder net-like chromatin threads and EETs showed greater stability against DNase than NETs. EETs provided a scaffold for platelet adhesion.
CONCLUSION
cfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs in small-vessel thrombi might contribute to higher concentration of cfDNA and the occurrence of immunothrombosis in EGPA.
Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Blood Platelets; Cell-Free Nucleic Acids; Diagnosis, Differential; Disease Susceptibility; Eosinophils; Extracellular Traps; Female; Fibrin Fibrinogen Degradation Products; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Kidney Function Tests; Leukocyte Count; Liquid Biopsy; Male; Microscopic Polyangiitis; Middle Aged; Platelet Aggregation; Thromboinflammation
PubMed: 35095884
DOI: 10.3389/fimmu.2021.801897 -
Clinical and Experimental Rheumatology Apr 2023Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV),...
Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.
OBJECTIVES
Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features.
METHODS
We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%).
RESULTS
NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex.
CONCLUSIONS
Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.
Topics: Humans; Microscopic Polyangiitis; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Rheumatology; Cross-Sectional Studies; Lung Diseases, Interstitial; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myeloblastin; Demography; Peroxidase
PubMed: 36200955
DOI: 10.55563/clinexprheumatol/xu4hmh -
Journal of Rheumatic Diseases Jan 2022This study retrospectively reviewed the process of classifying antineutrophil cytoplasmic antibody (ANCA)-negative granulomatosis with polyangiitis (GPA) and microscopic...
OBJECTIVE
This study retrospectively reviewed the process of classifying antineutrophil cytoplasmic antibody (ANCA)-negative granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in a cohort of patients with ANCA-associated vasculitis (AAV), and investigated the association between recurrent idiopathic cutaneous leukocytoclastic angiitis and ANCA-negative MPA.
METHODS
The medical records of 242 patients with AAV were retrospectively reviewed Of 49 patients with ANCA-negative AAV, 24 patients with ANCA-negative eosinophilic GPA (EGPA) were excluded, because ANCA positivity or negativity is not critical in classifying EGPA Ultimately, 25 patients with ANCA-negative GPA and MPA were analysed in this study The classification of GPA and MPA were based on the 2007 European Medicines Agency algorithm for AAV.
RESULTS
The median age of patients with ANCA-negative GPA and MPA was 540 years and 24% were male Of the 25 patients without ANCA, 8 patients were classified as GPA and 17 as MPA Eight patients with ANCA-negative GPA were easily confirmed as definitive GPA Fourteen of the 17 patients ANCA-negative MPA were classified as MPA based on histological features suggestive of AAV without granuloma formation and the absence of surrogate markers for GPA Meanwhile, three of the patients that were ANCA-negative exhibited only recurrent idiopathic cutaneous leukocytoclastic angiitis without other major organs affected and thus were classified as possible MPA Within one year, they were classified as definitive MPA based on ANCA positivity and/or renal histology.
CONCLUSION
Recurrent idiopathic cutaneous leukocytoclastic angiitis may be associated with ANCA-negative MPA in patients who exhibit cutaneous necrotising vasculitis.
PubMed: 37476704
DOI: 10.4078/jrd.2022.29.1.40 -
Journal of Thoracic Disease Sep 2020In the era of Precision Medicine, diagnostic imaging plays a key role in initial diagnosis and treatment response assessment in thoracic manifestation of various... (Review)
Review
In the era of Precision Medicine, diagnostic imaging plays a key role in initial diagnosis and treatment response assessment in thoracic manifestation of various rheumatic disorders; resulting in increased dependency on imaging for treatment planning. Chest radiographs serve as a good initial screening tool for assessment of emergent and urgent thoracic conditions, e.g., pneumothorax, pulmonary edema, consolidation and pleural effusions. Cross-sectional imaging techniques, e.g., computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) are most commonly utilized to evaluate more detailed pulmonary and mediastinal manifestations of rheumatic conditions. Magnetic resonance imaging (MRI) and ultrasound are most commonly used in cardiovascular, neural and musculoskeletal structures. This review article aims to highly key common thoracic imaging findings of rheumatic disorders, highlighting imaging test of choice for the particular disorder.
PubMed: 33145088
DOI: 10.21037/jtd.2020.04.16 -
Journal of Thoracic Disease Feb 2017Major pulmonary manifestations associated with microscopic polyangiitis (MPA) include diffuse alveolar hemorrhage (DAH) and interstitial pneumonia (IP).We previously...
BACKGROUND
Major pulmonary manifestations associated with microscopic polyangiitis (MPA) include diffuse alveolar hemorrhage (DAH) and interstitial pneumonia (IP).We previously showed bronchiectasis (BE) was one of the pulmonary complications of MPA. However, clinical features of BE patients with MPA are not fully understood. We investigated the characteristics and prognosis of BE patients with MPA.
METHODS
Forty-five MPA patients were retrospectively studied. The patients were divided into two groups: patients with BE and those without BE.
RESULTS
Thirty-one of 45 patients (69%) had pulmonary involvement including IP (23/45, 51%), BE (7/45, 16%), and DAH (5/45, 11%). There were no differences between the patients with BE versus those without with regard to clinical characteristics and initial treatments. However, the prognosis for patients with BE was better than those without BE during the first year after diagnosis, but it was worse between 1 and 5 years, which was statistically significant. Two BE patients died between 1 and 5 years as a result of pneumonia.
CONCLUSIONS
BE as a complication of MPA might be related to lower mortality in the acute phase and higher mortality in the chronic phase compared to other pulmonary manifestations. More attention to pulmonary infection is needed for patients with BE during the chronic phase.
PubMed: 28275478
DOI: 10.21037/jtd.2017.02.15