Transcript Microscopic Polyangitis

Microscopic Polyangiitis
Saori Kobayashi
Doll’s Festival : Mar 3
ANCA-associated vasculitis






Involve small~middle vasculature
With or no immune deposits (Pauci-immune)
Wegener’s granulomatosis(WG)
Churg-Strauss syndrome
microscopic polyangitiis(MPA)
renal limited form of MPA/idiopathic crescentic
glomerulonephritis
MPA: clinical features
Most common cause of acute renal-pulmonary
syndrome
 Necrotizing glomerulonephritis(90%)
→crescent formation, red blood casts
 Pulmonary capillaritis(50%)
→Alveolar hemorrhage, hemoptysis
 Systemic symptoms: fever, weight loss
 (-) granulomatous inflammation
 (+)p-ANCA




Treatment of MPA
induction phase→remission phase
Corticosteroids+IV/oral Cyclophosphamide
90% of pts with MPA acquire remission within 12mo
NIH regimen:
oral CYC 2mg/kg/day (for>1y after remisssion)
+prednisolone (initial dose of 1mg/kg/day→taper)
 EuVas regimen
oral CYC (up to 12mo)+steroid
→substitute CYC with AZA after induction of remittion

Monitoring/reducing side-effects

Steroids: osteoporosis, gastritis, cataracts, DM….
monitor bone density, prophylaxis by Ca/ViD,
biphosphonate, PPI/H2 blocker
CYC: bladder toxicity, bone marrow suppression,
gonadal dysfunction
→ infection, infertility, cyctitis,
↑risk of bladder/hematological malignancies
monitor blood count , urinalysis, TMP/SMZ for PCP

CYC: IV vs oral
IV route is as effective as oral route at inducing
remission with
less infectious complications and leukopenia
higher risk of relapse


Pulsed IV (monthly 0.5 to 1.0 g/m² BSA until a
stable remission is induced ) reduce cumulative dose
and toxicity (study for efficacy is under trial)
Alternative medication in induction
therapy
Methotrexate
As effective as CYC, but higher rate of relapse
Should not be administered to pts with serum
Cr>2.0mg/dl

Plasma exchange( to remove ANCA)
Effective to pts with severe pulmonary hemorrhage,
severe renal disease/hemodialysis

Maintenance Therapy





12-18 mo after remission is induced
Longer maintenance therapy should be done to
those who have relapse
CYC should be switched to either MTX or AZA
as soon as a stable remission is attained
(generally within 3-6 mo)
MTX: higher relapse rate
not indicated for pts with renal insufficiency
AZA: higher relapse rate?
Alternative of maintenance therapy






Mycophenolate mofetil
Anti-TNF alpha agent (etanercept and
infliximab)
Rituximab
Anti-T-cell agent
IVIG
Plasmapheresis
Mycophenolate mofetil




Effective in lupus nephritis
does not appear to be as effective in ANCAassociated vasculitis
should not be employed as an agent for the
induction of remission
Limited data suggest this agent may have a role
in remission maintenance.
TNF-α in ANCA-associated vasculitis
ANCA-induced neutrophil activation is enhanced
by TNF-α
・upregulation of molecules involved in neutrophil
adhesion to endotherium
・release of oxygen radicals, toxic granules
 Plasma levels of TNF-α are increased in pts with
ANCA-associated GN
 TNF-α is responsible for the increased production
of proinflammatory cytokines

Anti-TNF-α agent
Etanercept (Enbrel)
fusion protein of p75 subunits of the TNF-αreceptor
 Infliximab (Remicade)
chimeric IgG1 mAb of TNF-α



Effective in RA, Crohn’s disease
It may be hypothesized that anti-TNF-α agent is
effective for ANCA-associated vasculitis
Human studies on TNF-α inhibition
Double-blind controlled trial among 181pts with
WG
 Standard regimen+etanercept/placebo
 No significant difference in remission rates,
flares, disease activities
 Higher incidence of cancer in etanercept group
→as for etanercept, this should not be used

Limitations to anti-TNF-α
Is anti-TNF-α really safe?





Infusion reaction
Infection
Carcinogenesis
Thromboembolic complications
Drug-induced lupus
Rituximab




anti-CD20(anti-B cell) antibody
Used for lymphoma, several autoimmune
diseases
Studies suggest that Rituximab is effective both
for induction and maintenance with rare adverse
events for pts who had not conventional therapy
The response was associated with elimination of
circulating B lymphocytes, and a decrease in
ANCA titers.
Conculusion




For MPA and other ANCA-associated vasculitis,
steroid combined with CYC is the standard.
CYC has problematic toxicity and some pts don’t
respond the regimen or have relapse
There are several alternative therapy but they are
not as effective as had been expected
Their true efficacy remain to be seen and larger,
randomized, controlled study is needed