BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and rela...BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and relapse manifestations have not been reported in myeloperoxidase(MPO)-AAV patients.CASE SUMMARY A 52-year-old woman was admitted to our hospital because of headache.Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria,serum creatinine of 243μmol/L,anti-MPO antibody titer of>400 RU/mL,and positive perinuclearantineutrophil cytoplasmic antibody.Renal biopsy showed pauci-immune crescentic glomerulonephritis.The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality.Therefore,MPO-AAV was diagnosed.Corticosteroids,plasmapheresis,and cyclophosphamide as induction therapy and mycophenolate mofetil(MMF)as maintenance therapy were administered.The patient’s headache disappeared;serum creatinine returned to normal;complete remission of microscopic hematuria and proteinuria was observed.Anti-MPO antibody titer reached normal limits after immunosuppressive treatment.Twenty-five months after stopping the immunosuppressive treatment,the patient relapsed with arthralgia,without neurological or renal involvement.The patient’s arthralgia improved after treatment with prednisone and MMF.CONCLUSION We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement.However,relapse presented with only arthralgia,which was completely different from the initial manifestations.This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission,when clinical manifestations at relapse are different from those at onset.Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.展开更多
Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis...Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.展开更多
Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease usually seen in middle-aged and older adults but which is rare in children and adolescents. We sought to determine...Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease usually seen in middle-aged and older adults but which is rare in children and adolescents. We sought to determine if there has been a change in the incidence of this disorder. Methods: Single-center, retrospective review. Results: Over the last 2 years, we have encountered a striking increase in the frequency of this disease in pediatric patients. All eight patients seen during this period had renal involvement and 5 patients rapidly progressed to end stage kidney disease. The prognosis was worse in younger patients, those with microscopic polyangiitis, and those with chronic kidney damage in the diagnostic renal biopsy. Conclusions: We report these observations to highlight this change in the epidemiology of ANCA-associated vasculitis and to promote earlier recognition and treatment of this severe form of glomerulonephritis.展开更多
Relapsing polychondritis(RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly ...Relapsing polychondritis(RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.展开更多
Diagnosis of anti-neutrophil cytoplasmic antibodies(ANCA)-associated vasculitis is usually not difficult in patient with systemic disease, including lung and kidneys involvement, and laboratory signs of inflammation. ...Diagnosis of anti-neutrophil cytoplasmic antibodies(ANCA)-associated vasculitis is usually not difficult in patient with systemic disease, including lung and kidneys involvement, and laboratory signs of inflammation. The presence of ANCA and the results of histological investigation confirm diagnosis of ANCAassociated vasculitis. Cyclophosphamide/azathioprine in combination with high dose steroids are used to induce and maintain remission of systemic vasculitis. The clinical trials also showed efficacy of rituximab that induces depletion of B-cells. Our understanding and management of ANCA-associated vasculitis improved significantly over the last decades but there is still a lot of debate over its classification, diagnostic criteria, assessment of activity and optimum treatment.展开更多
Antithyroid drugs are molecules known as thionamides that inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin. These extensively used drug...Antithyroid drugs are molecules known as thionamides that inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin. These extensively used drugs are associated with a variety of well-known side effects such as anti-neutrophil cytoplasmic antibody （ANCA）-positive vasculitis, granulocytopenia and aplastic anemia. Recently, an atypical hematological finding -- bone marrow plasmacytosis, related to the use of methimazole -- was reported twice in English literatures, but bone marrow plasmacytosis with the use of propylthiouracil （PTU） has hardly been reported so far. Herein we present a case of a patient with Graves＇ disease who was initially investigated for plasma cell dyscrasia but finally diagnosed as PTU-induced bone marrow plasmacytosis with granulocytopenia and ANCA-associated vasculitis.展开更多
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are characterized by destruction of small vessels, granulomatous inflammation of the respiratory tract and necrotizing glomerulonephritis. This revie...Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are characterized by destruction of small vessels, granulomatous inflammation of the respiratory tract and necrotizing glomerulonephritis. This review describes the clinical diagnosis and therapy as well as the patho-physiology of ANCA-associated vasculitides with a specific focus on the interplay of ANCAs with activated neutrophils and the deleterious pathophysiological consequences of neutrophil-endothelium interaction.展开更多
Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease,...Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.展开更多
Background： Primary anti-neutrophil cytoplasmic antibody-associated vasculitis （AAV） is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with ...Background： Primary anti-neutrophil cytoplasmic antibody-associated vasculitis （AAV） is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center. Methods： Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute ofNephrology, Sichuan Provincial People＇s Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality. Results： Of the 123 patients, 46 （37.4%） died by the end of 2 years after diagnosis, with 41 （33.3%） patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score （BVAS）, the incidence of pulmonary hemorrhage and digestive system （DS） involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 （C3） were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS （hazard ratio [HR] = 1.058, 95% confidence interval [CI]： 1.002-1. I17; P = 0.042）, pulmonary hemorrhage （MR = 1.970, 95% CI： 1.033-3.757; P = 0.04）, DS involvement （HR = 2.911,95% （7：1.212-6.911 ： P = 0.017）4 and serum creatinine 〉400 μmol/L （MR = 2.910, 95% CI： 1.271-6.664, P = 0.012） were independent predictors of death in patients with AAV-related renal injury. Conclusions： Patients with AAV-related renal injury have high early mortality. Those with high BVAS （particularly with pulmonary or DS involvement） and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.展开更多
目的嗜酸性肉芽肿性多血管炎(eosinophilic granulomatosis with polyangiitis,EGPA)中以血管炎为主要特征和以嗜酸性粒细胞浸润为主要特征的两种亚型分类标准尚未明确,本研究探讨EGPA两种亚型的准确、简明分类方式。方法回顾性收集2000...目的嗜酸性肉芽肿性多血管炎(eosinophilic granulomatosis with polyangiitis,EGPA)中以血管炎为主要特征和以嗜酸性粒细胞浸润为主要特征的两种亚型分类标准尚未明确,本研究探讨EGPA两种亚型的准确、简明分类方式。方法回顾性收集2000年1月—2023年11月北京协和医院呼吸内科、全科医学科、风湿免疫科等多科确诊的EGPA患者临床资料,将患者根据单纯抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibodies,ANCA)、ANCA与组织病理活检结果相结合以及MIRRA标准三种分类方法分为不同的阳性组和阴性组,分析患者的临床特征。结果共纳入245例患者。根据ANCA结果分类时,阳性组51例,阴性组194例,相较于阴性组,阳性组患者的年龄(60.9比55.4)、NEUT%(59.12比51.87)、PLT(312.94比264.64)、ESR(55.40比27.62)、CRP(46.51比23.57)均较高,上述指标均达显著统计学意义;阳性组肾脏系统(47.1%比25.8%)和神经系统(72.5%比58.2%)的受累比例也显著高于阴性组。根据ANCA结果和组织病理活检结果分类时,阳性组88例,阴性组157例,两组间的分析结果与第一种分类方法一致。根据MIRRA标准分类时,MIRRA标准组患者161例,MIRRA非标准组患者84例,MIRRA标准组的NEUT%(55.39比49.58)显著高于MIRRA非标准组,而LY%(18.57比21.30)和HGB(128.80比136.36)显著低于MIRRA非标准组。结论根据ANCA结果可将EGPA患者分为血管炎亚型和嗜酸性粒细胞浸润亚型;尽管ANCA联合组织病理活检结果也可明确区分血管炎亚型与嗜酸性粒细胞浸润亚型,但由于病理活检存在风险,需根据患者的具体情况进行个体化评估;而MIRRA标准不能准确区分两类亚型。展开更多
文摘BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and relapse manifestations have not been reported in myeloperoxidase(MPO)-AAV patients.CASE SUMMARY A 52-year-old woman was admitted to our hospital because of headache.Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria,serum creatinine of 243μmol/L,anti-MPO antibody titer of>400 RU/mL,and positive perinuclearantineutrophil cytoplasmic antibody.Renal biopsy showed pauci-immune crescentic glomerulonephritis.The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality.Therefore,MPO-AAV was diagnosed.Corticosteroids,plasmapheresis,and cyclophosphamide as induction therapy and mycophenolate mofetil(MMF)as maintenance therapy were administered.The patient’s headache disappeared;serum creatinine returned to normal;complete remission of microscopic hematuria and proteinuria was observed.Anti-MPO antibody titer reached normal limits after immunosuppressive treatment.Twenty-five months after stopping the immunosuppressive treatment,the patient relapsed with arthralgia,without neurological or renal involvement.The patient’s arthralgia improved after treatment with prednisone and MMF.CONCLUSION We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement.However,relapse presented with only arthralgia,which was completely different from the initial manifestations.This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission,when clinical manifestations at relapse are different from those at onset.Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.
文摘Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.
文摘Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease usually seen in middle-aged and older adults but which is rare in children and adolescents. We sought to determine if there has been a change in the incidence of this disorder. Methods: Single-center, retrospective review. Results: Over the last 2 years, we have encountered a striking increase in the frequency of this disease in pediatric patients. All eight patients seen during this period had renal involvement and 5 patients rapidly progressed to end stage kidney disease. The prognosis was worse in younger patients, those with microscopic polyangiitis, and those with chronic kidney damage in the diagnostic renal biopsy. Conclusions: We report these observations to highlight this change in the epidemiology of ANCA-associated vasculitis and to promote earlier recognition and treatment of this severe form of glomerulonephritis.
基金Supported by Department of Nephrology,University of Debrecen,Clinical Centre,Debrecen,HungaryThe project implemented through the New Hungary Development Planco-financed by the European Union and the European Social Fund,No.TáMOP4.2.2.A-11/1/KONV-2012-0045
文摘Relapsing polychondritis(RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.
文摘Diagnosis of anti-neutrophil cytoplasmic antibodies(ANCA)-associated vasculitis is usually not difficult in patient with systemic disease, including lung and kidneys involvement, and laboratory signs of inflammation. The presence of ANCA and the results of histological investigation confirm diagnosis of ANCAassociated vasculitis. Cyclophosphamide/azathioprine in combination with high dose steroids are used to induce and maintain remission of systemic vasculitis. The clinical trials also showed efficacy of rituximab that induces depletion of B-cells. Our understanding and management of ANCA-associated vasculitis improved significantly over the last decades but there is still a lot of debate over its classification, diagnostic criteria, assessment of activity and optimum treatment.
文摘Antithyroid drugs are molecules known as thionamides that inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin. These extensively used drugs are associated with a variety of well-known side effects such as anti-neutrophil cytoplasmic antibody （ANCA）-positive vasculitis, granulocytopenia and aplastic anemia. Recently, an atypical hematological finding -- bone marrow plasmacytosis, related to the use of methimazole -- was reported twice in English literatures, but bone marrow plasmacytosis with the use of propylthiouracil （PTU） has hardly been reported so far. Herein we present a case of a patient with Graves＇ disease who was initially investigated for plasma cell dyscrasia but finally diagnosed as PTU-induced bone marrow plasmacytosis with granulocytopenia and ANCA-associated vasculitis.
文摘Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are characterized by destruction of small vessels, granulomatous inflammation of the respiratory tract and necrotizing glomerulonephritis. This review describes the clinical diagnosis and therapy as well as the patho-physiology of ANCA-associated vasculitides with a specific focus on the interplay of ANCAs with activated neutrophils and the deleterious pathophysiological consequences of neutrophil-endothelium interaction.
文摘Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.
文摘Background： Primary anti-neutrophil cytoplasmic antibody-associated vasculitis （AAV） is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center. Methods： Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute ofNephrology, Sichuan Provincial People＇s Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality. Results： Of the 123 patients, 46 （37.4%） died by the end of 2 years after diagnosis, with 41 （33.3%） patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score （BVAS）, the incidence of pulmonary hemorrhage and digestive system （DS） involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 （C3） were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS （hazard ratio [HR] = 1.058, 95% confidence interval [CI]： 1.002-1. I17; P = 0.042）, pulmonary hemorrhage （MR = 1.970, 95% CI： 1.033-3.757; P = 0.04）, DS involvement （HR = 2.911,95% （7：1.212-6.911 ： P = 0.017）4 and serum creatinine 〉400 μmol/L （MR = 2.910, 95% CI： 1.271-6.664, P = 0.012） were independent predictors of death in patients with AAV-related renal injury. Conclusions： Patients with AAV-related renal injury have high early mortality. Those with high BVAS （particularly with pulmonary or DS involvement） and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.
