ANCA and Anti GBM antibody disease Flashcards
what are the pulmonary renal syndrome and what are the 2 subtypes
development of diffuse alveolar hemorrhage and glomerulonephritis
- ANCA-associated vasculitis
- Anti-GBM disease (goodpasture disease)
what is a cardiorenal syndrome?
Development of renal failure in setting of acute or chronic heart failure
-there are 5 types
what is a hepatorenal syndrome?
Development of renal failure in the setting of cirrhosis (portal hypertension)
-type 1 and 2
what are the three ANCA-Associated small vessel vasculitis
Microscopic polyangitis
Granulomatosis with polyangiitis
Eosinophillic granulamatosis with polyangiitis
what are immune complex small vessel vasculitis
Cryoglobulinemic vasculitis
IgA vasculitis (henoch-schonlen)
Hypocomplementemic urticarial vasculitis
what does ANCA stand for and what are the two types
Antineutrophil cytoplasmic antibodies
- PR3 causes C-ANCA
- MPO causes P-ANCA
characteristics of Granuomatosis with polyangitis?
necrotizing vasculitis with necrotizing granulomas affecting respiratory tract (upper or lower) with no asthma symptoms or eosiophilla
associated with PR3-ANCA (c-ANCA)
characteristics of Microscopic polyangiitis?
Nectorizing vasculitis without granulomas r asthma symptoms or eosinophilia
associated with MPO-antibody
Characteristics of Eosinophilic granulomatosis with polyangiitis
necrotizing vasculitis with necrotizing granulomas affecting respiratory tract (upper and lower) with asthma symptoms and eosinophila
typically associated with MPO antibody
PR3-ANCA vs MPO-ANCA which one has higher relapse rates, which has higher mortality rates?
PR3-ANCA disease has a higher relapse rate
MPO-ANCA disease has a higher mortality rate
Epidemiology of ANCA associated Vasculitis
AAV more common in men and Caucasians and asians than African americans
GPA more common in North America and australia
MPA more common in southern Europe and asia
Major clinical manifestations of ANCA associated vasculitis
Constitutional symptoms:
-fever, malaise, anorexia, weight loss, myalgias, and migratory arthralgias
ENT manifestations
Pulmonary cough, dyspnea and hemoptysis
Skin: palpable purpura
Renal: hematuria, proteinuria, and renal failure
Neurologic:
-Mononeuritis multiplex
what vasculitis is ENT symptoms more common
GPA: Granuomatosis with polyangitis
what is palpable purpura suggestive of
what is non-palapable purpura suggestive of
Palpable purpura: raised non blanching erythematous lesion suggestive of vasculitis
Non-palpable purpura is a non blanching erythematous lesion usually from simple hemorrhage in skin suggestive of thrombocytopenia
what do you need for a definitive diagnosis of ANCA associated vasculitis
Definitive diagnosis requires a biopsy
ANCA testing
Anti GBM antibody testing
what is the Treatment for ANCA associated vasculitis
Induction therapy:
High dose glucocorticoids + rituximab
High dose glucocorticoids + cyclophosphamide
Maintenance therapy:
- 1st line azathioprine or mycophenolate or rituximab
- 2nd line Methotrexate
what must you test for to determine dosing of azathioprine in ANCA associated vasculitis
Thiopurine methyltransferase testing because this effects the dosage of azathioprine initially
what are the main complications of ANCA associated Vasculitis
Lungs:
- Hemoptysis from diffuse alveolar hemorrhage
- respiratory failure
Kidneys:
- Pauci-immune glomerulonephritis (can be rapidly progressive GN, RPGN)
- Renal failure
what is the epidemiology of anti-GBM disease and what is special about its distribution
Anti-GBM disease is a small vessel vasculitis in which antibodies are directed against the glomerular basement membrane (GBM) and alveolar basement membrane (ABM)
more common in caucasians
Bimodal distribution
- 2nd decade of life (more likely to be male and both renal and pulmonary involvement)
- 6th decade of life (more likely female and usually only renal involvement)
what can Anti-GBM disease be associate with as well?
ANCA associated vasculitis (usually MPO)
what is anti GBM antibodies directed at?
Type 4 collagen in Mature GBM specifically A3 chains
what mutation is found in alport syndrome
Type 4 collage specifically mutation in the a5 chain
what is the pathogenesis of Anti-GBM disease
Not fully understood
- genetic predisposition
- environmental trigger or infection may expose A3 chain to the immune system
- antibodies are directed primarily at the NC1 portion of the a3 chain
what are the classic clinical presentation for the anti-GBM disease
Most patients present with systemic signs and symptoms
- fever, malaise, weight loss, and arthralgias but just for a few weeks
- symptoms longer then suggest patient has both anti-GBM disease and ANCA positivity
Rapidly progressive GN (RPGN)
Nephritic syndrome
Diffuse alveolar hemorrhage
-dyspnea, cough, hemoptysis, pulmonary infiltrates on CXR
what is the diagnosis of anti-GBM disease?
should be suspected in any patient with RPGN and nephritic syndrome, especially if there is concurrent pulmonary hemorrhage
Testing:
- anti-GBM antibody
- ANCA testing
- Renal biopsy
- crescentic glomerulonephritis with liner IgG staining along the GBM
- chest x-ray, CT chest , and/or bronchoscopy with BAL
what is the pathologic diagnosis of Anti-GBM?
demonstration by immunofluorescence of diffuse linear IgG staining along the GBMs in the setting of crescentic glomerulonephritis
Treatment of Anti-GBM disease
Plasmapheresis + high dose glucocorticoids + cyclophosphamide
rituximab used in refactory disease
blood layers in plasmapharesis
- Plasma
- Platelets
- Buffy Coat
- Packed RBCs
