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Rheumatology (Oxford, England) Jul 2022To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis.
OBJECTIVE
To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis.
METHODS
Patients with GCA, Takayasu's arteritis (TAK), PAN and the three forms of ANCA-associated vasculitis [AAV; granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA)] enrolled in a prospective, multicentre, longitudinal study were included.
RESULTS
The study included data on 2085 patients [63% female, 90% White] with a mean age of 54.6 years (s.d. 17.2). Diagnoses were GCA (20%), TAK (11%), PAN (5%), GPA (42%), microscopic polyangiitis (8%) and EGPA (14%). Hypothyroidism was present in 217 patients (10%) (83% female), with a mean age 59.8 years (s.d. 14.5). Age- and sex-adjusted risk of hypothyroidism was GCA, odds ratio (OR) 0.61 (95% CI 0.41, 0.90); TAK, OR 0.57 (95% CI 0.31, 1.03); PAN, OR 0.59 (95% CI 0.25, 1.38); GPA, OR 1.51 (95% CI 1.12, 2.05); microscopic polyangiitis, OR 1.81 (95% CI 1.18, 2.80) and EGPA, OR 0.82 (95% CI 0.52, 1.30). Among patients with AAV, age- and sex-adjusted risk of hypothyroidism was higher with positive MPO-ANCA [OR 1.89 (95% CI 1.39, 2.76)]. The clinical manifestations of vasculitis were similar in patients with and without hypothyroidism, except transient ischaemic attacks, which were more frequently observed in patients with GCA and hypothyroidism (12% vs 2%; P = 0.001).
CONCLUSIONS
Differences in the risk of hypothyroidism among vasculitides may be due to genetic susceptibilities or immune responses. This study confirms an association of hypothyroidism with MPO-ANCA.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Churg-Strauss Syndrome; Female; Granulomatosis with Polyangiitis; Humans; Hypothyroidism; Longitudinal Studies; Male; Microscopic Polyangiitis; Middle Aged; Prospective Studies
PubMed: 34730828
DOI: 10.1093/rheumatology/keab817 -
Innere Medizin (Heidelberg, Germany) Sep 2022Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rheumatic diseases characterized by small-to-medium vessel vasculitis. Three different...
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rheumatic diseases characterized by small-to-medium vessel vasculitis. Three different entities can be distinguished: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). While lung and renal involvement are typical manifestations of both GPA and MPA, EGPA usually shows paranasal sinus and lung involvement as well as a history of bronchial asthma. Furthermore, EGPA is frequently associated with cardiac disease and peripheral neuropathy. Cyclophosphamide or rituximab, combined with glucocorticoids, are used to induce remission of severe disease. Maintenance therapy options include rituximab as the first-line treatment, as well as methotrexate or azathioprine plus low-dose glucocorticoids.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Churg-Strauss Syndrome; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Rituximab
PubMed: 35925127
DOI: 10.1007/s00108-022-01386-w -
Journal of Thoracic Disease Sep 2018Systemic vasculitides frequently affect the pulmonary vasculature. As the signs and symptoms of pulmonary vasculitis are variable and nonspecific, diagnosis and... (Review)
Review
Systemic vasculitides frequently affect the pulmonary vasculature. As the signs and symptoms of pulmonary vasculitis are variable and nonspecific, diagnosis and treatment represent a real challenge. Vasculitides should be given consideration, as these diseases present severe manifestations of rapidly progressing pulmonary disease. Examining other organs usually affected by vasculitides (e.g., the skin and kidneys) and determining autoantibody levels are essential to a better management of the disease. A radiological study would also contribute to establishing a diagnosis. The lungs are commonly involved in small-vessel vasculitis, anti-glomerular basement membrane disease, and vasculitides associated with antineutrophil cytoplasmic antibodies. Associated life-threatening diffuse alveolar haemorrhages and irreversible damage to other organs-usually the kidneys-are severe complications that require early diagnosis. Vasculitides are rare diseases that affect multiple organs. An increasing number of treatments-including biological agent-based therapies-requiring cooperation between specialists and centers have become available in the recent years. In the same way, clinicians should be familiar with the complications associated with immunosuppressive therapies.
PubMed: 30416807
DOI: 10.21037/jtd.2018.08.117 -
Medicine Jan 2011The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss syndrome [CSS]) is...
The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss syndrome [CSS]) is used to evaluate prognosis at diagnosis. In the current study we revisited the FFS, this time including Wegener granulomatosis (WG).We analyzed clinical, laboratory, and immunologic manifestations present at diagnosis of systemic necrotizing vasculitides for 1108 consecutive patients registered in the French Vasculitis Study Group database. All patients met the American College of Rheumatology and Chapel Hill nomenclature criteria. Univariable and multivariable analyses yielded the 2009 FFS for the 4 systemic necrotizing vasculitides.Overall mortality was 19.8% (219/1108); mortality for each of the SNV is listed in descending order: MPA (60/218, 27.5%), PAN (86/349, 24.6%), CSS (32/230, 13.9%), and WG (41/311, 13.2%) (p < 0.001). The following factors were significantly associated with higher 5-year mortality: age >65 years, cardiac symptoms, gastrointestinal involvement, and renal insufficiency (stabilized peak creatinine ≥150 μmol/L). All were disease-specific (p < 0.001); the presence of each was accorded +1 point. Ear, nose, and throat (ENT) symptoms, affecting patients with WG and CSS, were associated with a lower relative risk of death, and their absence was scored +1 point (p < 0.001). Only renal insufficiency was retained (not proteinuria or microscopic hematuria) as impinging on outcome. According to the 2009 FFS, 5-year mortality rates for scores of 0, 1, and ≥2 were 9%, 21% (p < 0.005), and 40% (p < 0.0001), respectively.The revised FFS for the 4 systemic necrotizing vasculitides now comprises 4 factors associated with poorer prognosis and 1 with better outcome. The retained items demonstrate that visceral involvement weighs heavily on outcome. The better WG prognosis for patients with ENT manifestations, even for patients with other visceral involvement, compared with the prognosis for those without ENT manifestations, probably reflects WG phenotype heterogeneity.
Topics: Biomarkers; Chi-Square Distribution; Churg-Strauss Syndrome; Female; France; Granulomatosis with Polyangiitis; Humans; Male; Microscopic Polyangiitis; Middle Aged; Polyarteritis Nodosa; Prognosis; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Survival Rate; Systemic Vasculitis
PubMed: 21200183
DOI: 10.1097/MD.0b013e318205a4c6 -
Rheumatic Diseases Clinics of North... Aug 2010In 1923, Friedrich Wohlwill described two patients with a "microscopic form of periarteritis nodosa," which was distinct from the classical form. This disease, now known... (Review)
Review
In 1923, Friedrich Wohlwill described two patients with a "microscopic form of periarteritis nodosa," which was distinct from the classical form. This disease, now known as microscopic polyangiitis (MPA), is a primary systemic vasculitis characterized by inflammation of the small-caliber blood vessels and the presence of circulating antineutrophil cytoplasmic antibodies. Typically, microscopic polyangiitis presents with glomerulonephritis and pulmonary capillaritis, although involvement of the skin, nerves, and gastrointestinal tract is not uncommon. Treatment of MPA generally requires use of a cytotoxic agent (such as cyclophosphamide) in addition to high-dose glucocorticoids. Recent research has focused on identifying alternate treatment strategies that minimize or eliminate exposure to cytotoxic agents. This article reviews the history, pathogenesis, clinical manifestations, and treatment of MPA.
Topics: Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Cyclophosphamide; Drug Administration Schedule; Humans; Immunosuppressive Agents; Microscopic Polyangiitis; Remission Induction
PubMed: 20688249
DOI: 10.1016/j.rdc.2010.04.003 -
Journal of Autoimmunity Dec 2022Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. The national incidence and prevalence of GPA/MPA and... (Observational Study)
Observational Study
BACKGROUND
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. The national incidence and prevalence of GPA/MPA and patient mortality remain unknown in France. A real-life study using retrospective data from the French National Health Data System was set up to describe the epidemiology and demographic characteristics of hospitalized GPA and MPA patients, overall and by disease.
METHODS
All adult patients (≥18 years of age) hospitalized for GPA (ICD-10 M31.3) or MPA (ICD-10 M31.7) between 01 and 01-2010 and 31-12-2017 and affiliated to the General health insurance Scheme (covering 76% of the French population) were included in this national retrospective observational study. Descriptive analyses, univariate and multivariable logistic models, Kaplan-Meier survival analysis, and Cox models were performed.
RESULTS
The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Distinction between GPA and MPA diagnosis could not be made for 303 patients (149 incident patients). In people aged over 20 years, the age-standardized incidence rates of GPA and MPA were 0.5 and 0.3/100,000 person-years, respectively and the age-standardized prevalence rates were 10 and 4/100,000 person-years, respectively. The standardized mortality ratios in GPA and MPA patients aged over 20 years were 2.0 and 2.7, respectively, and remained constant. Renal failure, pulmonary and urinary tract infections, as well as coronary disease were more frequent among MPA than GPA patients. One-year survival rates among GPA and MPA patients were 96% (95%CI 94%-97%) and 94% (92%-95%), respectively. Five-year survival rates among GPA and MPA patients were 81% (95% CI 79%-83%) and 72% (68%-75%), respectively. After adjusting for comorbidities, the risk of death was still higher in MPA (hazard ratio 1.26 [95%CI 1.06-1.50]) than in GPA patients.
CONCLUSIONS
Despite advances in the therapeutic management of patients, mortality rates are still high and stable over time, highlighting the need for improved management.
Topics: Humans; Adult; Infant; Child; Retrospective Studies; France
PubMed: 36108505
DOI: 10.1016/j.jaut.2022.102910 -
The Korean Journal of Internal Medicine May 2019Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in... (Review)
Review
Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.
Topics: B-Cell Activating Factor; Complement Inactivating Agents; Cyclophosphamide; Granulomatosis with Polyangiitis; Humans; Immunologic Factors; Interleukin-6; Microscopic Polyangiitis; Molecular Targeted Therapy; Rituximab
PubMed: 30613065
DOI: 10.3904/kjim.2018.366 -
Orphanet Journal of Rare Diseases Oct 2016The data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse the features at presentation, therapeutic approaches and the disease course of these rare diseases.
METHODS
Electronic searches of Medline and the Cochrane Central Register of Controlled trials database were conducted. We also checked the reference lists of the studies included and other systematic reviews, to identify additional reports. We included all cohorts, cross-sectional studies or registries reporting features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age <18 years). The pooled prevalence of clinical manifestations at presentation, ANCA and induction therapies for GPA and MPA was calculated.
RESULTS
We reviewed 570 full texts and identified 14 studies on GPA and 8 on MPA. Childhood-onset GPA and MPA occurred predominantly in female subjects during adolescence. For GPA, ear-nose-throat (ENT) disease (pooled prevalence 82 % [95 % CI 78-87]), constitutional symptoms (73 % [95 % CI 55-88]), renal (65 % [95 % CI 49-79]), and lower respiratory tract (61 % [95 % CI 48-74]) manifestations were the most frequently reported at presentation. Renal disease was a hallmark of MPA (94 % [95 % CI 89-97]). ANCA were detected in >90 % of children with GPA or MPA. Combined corticosteroids and cyclophosphamide was the most frequently used first remission-inducing treatment for GPA (76 % [95 % CI 69-82]) and MPA (62 % [95 % CI 20-96]). Relapses occurred more frequently in GPA (67-100 %) than in MPA (25-50 %). The leading causes of death were the disease itself, and infections.
CONCLUSIONS
Childhood-onset MPA and GPA remain severe diseases with frequent relapses and a high cumulative morbidity. Survival and disease-free survival need to be improved.
Topics: Adrenal Cortex Hormones; Cross-Sectional Studies; Cyclophosphamide; Disease Progression; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis
PubMed: 27770813
DOI: 10.1186/s13023-016-0523-y -
Annals of Medicine Dec 2023The association between pulmonary involvement and microscopic polyangiitis (MPA) has been increasingly recognized in recent years. Whether interstitial lung disease...
BACKGROUND
The association between pulmonary involvement and microscopic polyangiitis (MPA) has been increasingly recognized in recent years. Whether interstitial lung disease (ILD) and bronchiectasis (BE) are disease manifestations of MPA, preexisting comorbidities or important complications remains unclear. The purpose of this study was to determine the clinical characteristics and prognosis of MPA with pulmonary involvement to further guide clinical management.
METHODS
The data for 97 patients with a definitive diagnosis of MPA were retrospectively reviewed. The MPA diagnosis was based on the 2012 revised Chapel Hill Consensus Conference (CHCC) criteria. The baseline clinical information and laboratory parameters were collected and analysed at each patient's initial diagnosis.
RESULTS
Forty-seven out of the 97 (48.5%) patients who were diagnosed with MPA presented with pulmonary involvement, including 37 patients with ILD, 12 patients with BE and two patients with diffuse alveolar haemorrhage (DAH). ILD and BE antedated MPA in 56.76% and 75.00% of the patients, respectively. Compared with that in the MPA-BE group, the serum LDH level (222.86 ± 68.19 vs. 171.58 ± 31.43, = .016) in the MPA-ILD group was significantly higher. In the multivariate Cox analysis, elevated serum creatinine (HR 4.08, confidence interval (CI) 1.38-12.05, = .011) was an independent risk factor for shorter survival in MPA patients with pulmonary involvement, and treatment with glucocorticoid pulse cyclophosphamide therapy (HR 0.095, 95% CI 0.019-0.47, = .004) was independently associated with prolonged survival. Among the patients in the MPA-ILD group, acute exacerbations of ILD (HR 4.55 CI 1.16-17.86, = .029) and elevated serum creatinine (HR 4.95, CI 1.39-17.54, = .014) were independently associated with a poor prognosis, and treatment with glucocorticoids (HR 0.057, 95% CI 0.012-0.28, < .001) was independently associated with significant prolongation of survival.
CONCLUSIONS
Patients with MPA have a high prevalence of pulmonary involvement, and ILD is the most common subtype of MPA. ILD and BE can be considered preexisting comorbidities of MPA. Elevated serum creatinine was associated with shorter survival. However, remission induction regimens with glucocorticoids and/or immunosuppressants may improve this outcome.
Topics: Humans; Microscopic Polyangiitis; Retrospective Studies; Clinical Relevance; Glucocorticoids; Creatinine; Lung Diseases, Interstitial; Prognosis; Probability; Bronchiectasis
PubMed: 37126372
DOI: 10.1080/07853890.2023.2204449 -
Frontiers in Pediatrics 2021The aim of this study was to explore the clinical features, pathological characteristics, and the prognosis of children with microscopic polyangiitis (MPA). Ten...
The aim of this study was to explore the clinical features, pathological characteristics, and the prognosis of children with microscopic polyangiitis (MPA). Ten children with MPA that were hospitalized in our hospital were included in this study. The children's pre-diagnosis status, clinical manifestations, renal pathology, treatment, and prognosis data were analyzed retrospectively. All 10 cases included female patients with a median age of 8.9 years old at the time of diagnosis. MPO-ANCA antibody was positive in all cases, combined with a positive anti-GBM antibody in two cases. Nine cases had primary AAV and one had antithyroid drug (ATD)-associated MPA (secondary to methimazole). Renal involvement was found in all 10 patients, lung impairment was present in eight cases, and anemia was present in nine patients. Renal biopsies were performed in all 10 patients. Segmental focal or global glomerular necrosis was observed in 70% of the patients (7/10). The treatment mainly included steroid use combined with Cyclophosphamide and Mycophenolate. The follow-up s of the patients revealed normal renal function in eight patients and progression to end-stage renal disease (ESRD) in two patients. Female predisposition and positive MPO-ANCA antibody were prominent in children with MPA. The patients' kidneys and lungs were the most frequently involved organs. Corticosteroid combined with immunosuppressive therapy was recommended for the treatment of MPA. Early diagnosis, prompt aggressive treatment, and regular follow-ups are also very important factors associated with a good prognosis.
PubMed: 33937151
DOI: 10.3389/fped.2021.645785