The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis

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.

Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

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.

Severe Pulmonary Embolism,Thrombosis of Lower Extremity,Unexpected Mild Renal Disorder in MPO-ANCA Associated Vasculitis:A Case Report

Myeloperoxidase antineutrophil cytoplasmic antibody(MPO-ANCA)associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome,especially prominent acute renal failure.A 65-year-old woman was admitted with progressive dyspnoea for six months and fever,sputum with blood,pain of the lower extremities and intermittent claudication for two days,indicating multiple organ involvement(respiratory system,blood vessels).The renal involvement was relatively mild,presenting with microscopic haematuria.The chest computed tomography demonstrated multiple pulmonary embolisms.Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis.Exclusion of other diseases that can cause multiple organ damage and thrombosis,the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis.The patient’s physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.

Renal Amyloidosis Secondary to ANCA-Associated Vasculitis:A Case Report

Renal amyloidosis secondary to anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis is extremely rare.Here,we reported a 77-year-old woman with ANCA-associated vasculitis.Renal biopsy with Masson trichrome staining showed pauci-immune crescentic glomerulonephritis,and electron microscopy showed amyloid deposition in the mesangial area.Immunofluorescence revealed kappa light chain and lambda light chain negative.Bone marrow biopsy revealed no clonal plasma cell.Finally,she was diagnosed as ANCA-associated vasculitis with secondary renal amyloid A amyloidosis.

Oral cyclophosphamide-induced posterior reversible encephalopathy syndrome in a patient with ANCA-associated vasculitis:A case report

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.

Propylthiouracil induced anti-neutrophil cytoplasmic antibody-associated vasculitis with bone marrow plasmacytosis and granulocytopenia

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.

Olfactory dysfunction in antineutrophil cytoplasmic antibodyassociated vasculitides: A review of the literature

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.

耳鼻受累首发的肉芽肿性血管炎1例

1临床资料患者,女,57岁,既往体健,因“右耳不适1个月”于2022-01-03收治入院。1个月前患者因右耳耳闷伴轻度听力下降反复就诊于当地医院,考虑分泌性中耳炎,经口服抗生素、激素等药物保守治疗后未能完全缓解,收治于我科。专科查体:右耳耳道湿润可见淡黄色脓液,稍黏稠,量稍多,鼓膜充血肿胀,标志欠清,鼓室可见积液(图1A)。

Eosinophilic granulomatosis with polyangiitis,asthma as the first symptom,and subsequent Loeffler endocarditis:A case report

BACKGROUND Eosinophilic granulomatosis with polyangiitis(EGPA),formerly known as Churg-Strauss syndrome,is a rare form of anti-neutrophil cytoplasmic antibodyassociated vasculitis characterized by asthma,vasculitis,and eosinophilia.CASE SUMMARY We report an atypical case of EGPA in a 20-year-old female patient.Unlike previously reported cases of EGPA,this patient’s initial symptom was asthma associated with a respiratory infection.This was followed by Loeffler endocarditis and cardiac insufficiency.She received treatment with methylprednisolone sodium succinate,low molecular weight heparin,recombinant human brain natriuretic peptide,furosemide,cefoperazone sodium/sulbactam sodium,and acyclovir.Despite prophylactic anticoagulation,she developed a large right ventricular thrombus.EGPA diagnosis was confirmed based on ancillary test results and specialty consultations.Subsequent treatment included mycophenolate mofetil.Her overall condition improved significantly after treatment,as evidenced by decreased peripheral blood eosinophils and cardiac markers.She was discharged after 17 d.Her most recent follow-up showed normal peripheral blood eosinophil levels,restored cardiac function,and a reduced cardiac mural thrombus size.CONCLUSION This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

Epidemiology of Biopsy Proven Glomerular Disorders and Effect of Severe Cyclone on Its Incidence in Central Queensland Region of Australia

Aim: The objectives of this study are to determine the epidemiology of biopsy-proven glomerular disease (GD) in Central Queensland and the effect of a severe cyclone on its incidence and clinical phenotype. Background: Central Queensland (CQ) has a relatively high incidence of kidney disease. Since its biopsy service commenced in 2005, there have been no data on biopsy-proven GD. It has been suggested that GD incidence changes around times of natural disasters. In February 2015, the CQ region was affected by a category 5 Cyclone Marcia. This provides an opportunity to explore possible environmental triggers of GD. Methods: This was a single-centre retrospective observational study on biopsy-proven kidney disease in CQ. All kidney biopsies performed between January 2005 and December 2019 were included. Patients with biopsy-proven GD during 3 years before and after Cyclone Marcia (from 2012 to 2018) were analysed. Results: 170 native kidney biopsies occurred during the 15 years. The number of annual biopsies steadily increased from 7 to 16. The most common biopsy-proven kidney disease was IgA Nephropathy (27%) followed by diabetic nephropathy (20%). GD comprised 64% of biopsies. Unlike other GD, the incidence of ANCA-associated vasculitis (AAV) significantly increased after cyclone (one pre- and eight post-cyclone, P value = 0.039). The majority of AAV cases occurred in the first year after the cyclone. Conclusion: Kidney biopsies in CQ provide important epidemiological data on biopsy-proven kidney disease. Cyclones have a possible effect on the incidence and clinical phenotype of ANCA associated vasculitis.

Neutrophil Extracellular Traps in Autoimmune Diseases

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.