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
Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell fun...Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.展开更多
BACKGROUND Posterior reversible encephalopathy syndrome(PRES)manifests many neurological symptoms with typical features on neuroimaging studies and has various risk factors.Cyclophosphamide is one of the therapeutic a...BACKGROUND Posterior reversible encephalopathy syndrome(PRES)manifests many neurological symptoms with typical features on neuroimaging studies and has various risk factors.Cyclophosphamide is one of the therapeutic agents for antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.Cyclophosphamide as the sole cause of PRES has been reported in only a few cases.Herein,we report a unique case of early-onset oral cyclophosphamide-induced PRES in a patient with ANCA-associated vasculitis.CASE SUMMARY A 73-year-old man was transferred to our hospital for sepsis due to acute cholangitis.He had already received hemodialysis for two weeks due to septic acute kidney injury.His azotemia was not improved after sepsis resolved and perinuclear-ANCA was positive.Kidney biopsy showed crescentic glomerulonephritis.Alveolar hemorrhage was observed on bronchoscopy.He was initially treated with intravenous methylprednisolone and plasma exchange for one week.And then,two days after adding oral cyclophosphamide,the patient developed generalized tonic-clonic seizures.We diagnosed PRES by Brain magnetic resonance imaging(MRI)and electroencephalography.Seizures were controlled with fosphenytoin 750 mg.Cyclophosphamide was suspected to be the cause of PRES and withdrawal.His mentality was recovered after seven days and brain MRI showed normal state after two weeks.CONCLUSION The present case shows the possibility of PRES induction due to short-term use of oral cyclophosphamide therapy.Physicians should carefully monitor neurologic symptoms after oral cyclophosphamide administration in elderly patients with underlying diseases like sepsis,renal failure and ANCA-associated vasculitis.展开更多
INTRODUCTIONIn 2004, NETosis was first reported as an important step to kill bacteria by neutrophils. During the process ofN ETosis, neutrophil extracellular traps （NETs） that contain large web-like structures of de...INTRODUCTIONIn 2004, NETosis was first reported as an important step to kill bacteria by neutrophils. During the process ofN ETosis, neutrophil extracellular traps （NETs） that contain large web-like structures of decondensed chromatin decorated with histones and intracellular components, including neutrophil elastase （NE）, myeloperoxidase （MPO）, high mobility group protein B I （HMGBI）, and proteinase 3 （PR3）, are extruded into the extracellular space, The structures of NETs enable the neutrophil to potently catch and kill pathogens at the site of inflammation. Furthermore, increasing studies have identified the presence of NETs in autoimmune diseases. NETs deliver multiple autoantigens to host immtme system that induce autoimmune responses and directly release damage-associated molecular patterns to amplify inflammatory responses. Therefore, NETs are commonly described to play a crucial role in the pathogenesis and development of autoimmune diseases in recent years.展开更多
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Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.
文摘BACKGROUND Posterior reversible encephalopathy syndrome(PRES)manifests many neurological symptoms with typical features on neuroimaging studies and has various risk factors.Cyclophosphamide is one of the therapeutic agents for antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.Cyclophosphamide as the sole cause of PRES has been reported in only a few cases.Herein,we report a unique case of early-onset oral cyclophosphamide-induced PRES in a patient with ANCA-associated vasculitis.CASE SUMMARY A 73-year-old man was transferred to our hospital for sepsis due to acute cholangitis.He had already received hemodialysis for two weeks due to septic acute kidney injury.His azotemia was not improved after sepsis resolved and perinuclear-ANCA was positive.Kidney biopsy showed crescentic glomerulonephritis.Alveolar hemorrhage was observed on bronchoscopy.He was initially treated with intravenous methylprednisolone and plasma exchange for one week.And then,two days after adding oral cyclophosphamide,the patient developed generalized tonic-clonic seizures.We diagnosed PRES by Brain magnetic resonance imaging(MRI)and electroencephalography.Seizures were controlled with fosphenytoin 750 mg.Cyclophosphamide was suspected to be the cause of PRES and withdrawal.His mentality was recovered after seven days and brain MRI showed normal state after two weeks.CONCLUSION The present case shows the possibility of PRES induction due to short-term use of oral cyclophosphamide therapy.Physicians should carefully monitor neurologic symptoms after oral cyclophosphamide administration in elderly patients with underlying diseases like sepsis,renal failure and ANCA-associated vasculitis.
文摘INTRODUCTIONIn 2004, NETosis was first reported as an important step to kill bacteria by neutrophils. During the process ofN ETosis, neutrophil extracellular traps （NETs） that contain large web-like structures of decondensed chromatin decorated with histones and intracellular components, including neutrophil elastase （NE）, myeloperoxidase （MPO）, high mobility group protein B I （HMGBI）, and proteinase 3 （PR3）, are extruded into the extracellular space, The structures of NETs enable the neutrophil to potently catch and kill pathogens at the site of inflammation. Furthermore, increasing studies have identified the presence of NETs in autoimmune diseases. NETs deliver multiple autoantigens to host immtme system that induce autoimmune responses and directly release damage-associated molecular patterns to amplify inflammatory responses. Therefore, NETs are commonly described to play a crucial role in the pathogenesis and development of autoimmune diseases in recent years.
