GN AAV Flashcards
What is ANCA?
Anti Neutrophil Cytoplasmic Antibody
~ autoantibodies againts cytoplasmic antigens in neutrophils granules + monocytes lysosomes
- specifically againts MPO / PR3
- igG (in active stage)
What is AAV?
**A group of disorder characterized by:
- destruction of small & medium sized blood vessels
- presence if circulating ANCA
**
Int Chapel Hill Concensus Conf 2012
- calssified vasculitis according to vessels size
Male predominance
Higher in 60-70 y/o
White asian
Clinical dz of AAV
- GPA: granulomatous with polyangitis / Wegener
- MPA: microscopic polyangitis
- EGPA: Eusinophilic GPA / Churg strauss dz
What is major target antigen in AAV?
- PR3: Proteinase 3
- MPO: myeloperoxidase
Higher relapse rate
**PR3 **ANCA
Higher mortality rate
MPO ANCA
why?
poor response to IS
» GS / Int fibrosis
Chapel Hill concensus classification
Small vessel vasculitis (svv)
- AAV
- Immune mediated SVV
- anti GBM
- ig A Nephropathy
- anti-C1q
- cyoglobulinaemia
Chapel Hill Consensus
Medium vessels vasculitis
- PAN
- Kawasaki dz
Chapel Hills Consensus
Large vessels vasculitis
Variable vessels
Large
1. Takayasu arteritis
2. Giant cells arteritis GCA
Variable
1. Behcet dz
2. Cogan syndrome
ANCA testing
Screening-
indirect immunoflourecence assay (IIF)
- granules disaolved post ethanol fixation
- MPO attached to perinuclear membrane – perinuclear pattern (pANCA)
-** PR3— cytoplasmic pattern (cANCA)
**
Confirmation
**Antigen specific immunoassays ** *
*2017 concensus: initial testing
ANCA & dz associations
- PR3 ANCA - GPA (75%)
- MPO ANCA - MPA (60%)
- renal limted ANCA (80%) - Atypical ANCA (+ve IIF / -ve assays): nonvasculitic (IBD / malignancy)
- chronic infection (IE / HIV / hep C) - either ways
- both: drug induced vasculitis
*
What is ANCA -ve pauci immune vasculitis
- similar clinical presention
- ANCA testing negative
- 10% of population
- similar response to therapy
- — renal limited dz
- —less severe systemic dz
- natural inhibitor: ceruloplasmin (MPO), alpha1-antitrypsin
Pathogenesis of AAV
activation of alternative pathways:
high serum / urinary C5a
low C3
What is pathalogic hall mark of ANCA related GN?
- necrotizing and / or crescenteric GN
- without significant immune complex deposition on IF / EM
HPE
no immune complex deposit /pauci immune
a. small igG / C3
necrotizing crescenteric GN
a. necrotic area / sclerosis
b. crescent
less common
a. necrotizing extraglomerular vasculitis
b. medullary angiitis with prominent neutrophils
EGPA
+ prominent eusinophil inflammation surrounding necrotizing vasculitis or interlobar-sized and larger vessels
features of GPA / MPA / EGPA
GPA
1. constituinal symptoms
2. chronic sinusitis
3. arthalgia
4. leukocytolastic skin rash
5. AKI
6. Rbx: necrotizing crescenteric GN + pauci immune
7. serology: PR3 +ve
MPA
1. as above
2. no granulomatous manifestations
3. MPO ANCA +ve
EGPA = GPA
1. + eusinophilia
2. asthma
3. 50% MPO ANCA +ve
4. 20% renal involvement (in +ve ANCA only)
Renal manifestation in AAV
- RPGN
- subnephrotic range ptnuria
- nephritic: hematuria + HPT
- Rbx findings as mentioned
- prognosis
2.prognostic factor - marker to predict relapse ?
1.prognosis poor
- prognostic factor
a.age
b. MPO- ANCA
c. low egfr at presentation
d. RBx findings: if +immune complex (50%) > ptnuria > crescent / low % normal gloms / higher degree tubular atrophy
e. freq relapse - marker predict relapse
a. ANCA level
b. urine CD 163
c. serum / urine CD25
d. PR3 - more relapse
*not a guide for tx
Systemic involvement of AAV
- constituinal symptoms
- Lungs: nodules / cavitation (GPA) alveolar h/rage / fibrosis (MPA)
- Upper respi: rhinitis / sinusitis / otitis media / septal perforation / nasal collapse (GPA)
- eye / ENT: hearing loss / scleritis / uveitis / strawberry gum / palate perforation
- skin: leucocytoclastic vasculitis / cutaneous nodular (GPA)
- CNS: peripheral neuropathy / mononeuritis multiplex
- GI: mesenteric vasculitis
- heart: myocarditis / heart block
- thrombosis
Dual +ve ANVA + anti GBM
anti GBM +ve: 10-40% +ve ANCA (MPO)
ANCA: 5-14% +ve anti GBM
severe presentation
higher morbidity / mortality
treatment course
a. induction 3/6 month
b. maintenance 1-2 years
Induction agent
- steroids
- IV MTP 500-1g x 3/7
- then oral pred 1mg/kg/day till 2-4 weeks – taper - Cyclophosphomide
- Rituximab
- MMF
- non life threatening
Trials in steroid induction
MEPEX
PEXIVAS
*** MEPEX: **
- PLEX 7x vs high dose steroid 1g/day x 3d
-PLEX better renal recovery NOT death
* PEXIVAS trial
- PLEX vs no PLEX
- high dose vs low dose steroid
- + Cyclo / ritux
- no difference in death / ESKD in PLEX /non PLEX group & high / low dose steroid
- low dose steroid: less infection
Trials in Cyclo induction
CYCLOPS trial
*** CYCLOPS trial **
- oral Cyclo (2mg/kg/day) vs IV Cyclo (15mg/kg in every 2 week) x 3-6/12
- no difference in remission rate
- oral: higher cumulative dose
- IV: lower leucopenia
Trials in Ritux induction
RAVE
RITUXVAS
**1. RAVE trial **
- new & relapse AAV
- Cyclo 2mg/kg/day - Aza x 12/52 vs Ritux 375mg/m2 x 4 doses + [pred 1mg/kg/day – 40mg/d 4/52 – 0mg at week 20)
- achieved remission at 6/12 (ritux)- esc PR3
- but not superior to Cyclo
- ritux group req less stroid for
2.RITUXVAS trial
Definition of
a. disease activity
b. remission
c. relapse
d. treatment resistant
- remission:
- no GN / vasculitis
- stable egfr
- no hematuria / ptnuria - relapse
- sx of active dz after PR / CR
- Major: life / organ threatening
- minor - tx resistant
- persistent sx while receiving tx equal to initial IS therapy
KDIGO GN 2021
