Monica Rairikar Profile picture
Aug 30, 2022 21 tweets 13 min read Read on X
1/This July’s @aspneph pathology webinar was all about pediatric Antineutrophil Cytoplasmic Antibody (ANCA)- associated vasculitis (AAV). Let's kick off this pediatric AAV tweetorial✍️with a quick question #NephTwitter
🤔 What is the role of ANCA antibodies❓
2/
✅Diagnostic marker and Pathogenic in nature
▶️ Proteinase-3 (PR3) and Myeloperoxidase (MPO) antigens are sequestered in neutrophil primary granules
▶️ Antigen exposure triggers immune response leading to endothelial activation
linkinghub.elsevier.com/retrieve/pii/S…
3/
Mechanisms
📌Defective neutrophil apoptosis, leading to NETosis
📌Inefficient clearance of PR3/MPO
📌Antimicrobial antibodies cross reacting with PR3/MPO
📌Medication induced
4/
🔘 ANCA in vasculitis🧐first described in 1982 (PMID: 6297657)
🔘 PR3/MPO antigen specificity in 1988 and 1989 doi.org/10.1182/blood.…
🔘 ANCA have since been shown to have a role in pathogenesis, diagnosis and prognosis of AAV
doi.org/10.2215/CJN.19…
5/
Pediatric AAV is a rare,chronic,relapsing,systemic,immunologic small vessel vasculitis with granulomatous inflammation
📌 Incidence 1-6/1,000,000/yr in children
📌 Female preponderance
📌 Median age - 12-14 years, peak 2nd decade
doi.org/10.3389/fped.2…
6/
Classification of pediatric ANCA vasculitis
🔶 Granulomatosis with polyangiitis (GPA)
🔶 Microscopic polyangiitis (MPA)
🔶 Eosinophilic granulomatosis with polyangiitis (EGPA) associated with asthma & eosinophilia, seen in adults
🔶 Renal limited vasculitis
PMID: 23045170
7/
🔘 GPA and MPA most common AAV seen in children
🔘 Presence of PR3 🆚 MPO antibody determines clinico-pathologic course of disease
8/
🤔Another question for the think tank🧠‼️
What is the most common renal pathology in pediatric ANCA vasculitis❓
9/
✅ Crescentic Glomerulonephritis(GN)
▶️ Rapidly progressive GN (39%) with pauci immune crescentic necrotizing GN on light microscopy (50-60%) is the most common pathology in both pediatric GPA and MPA
▶️ Sclerotic lesions when present, carry the worst prognosis
10/
🔶 ANCA vasculitis is one of the most common causes of pulmonary-renal syndrome in children
🔶Other system involvement seen in 30-60% patients (doi.org/10.1093/ndt/gf…)
11/
📌ANCA vasculitis suspected in any patient with
🔶 Severe/rapidly worsening acute kidney injury (AKI), proteinuria, hematuria ➕
🔶 Signs/symptoms of small vessel vasculitis in other organs
📌 Prompt evaluation for primary vasculitis syndromes as recommended by #KDIGO
12/
📌 2021 #KDIGO guidelines recommend initiating treatment with clinical suspicion of kidney AAV and/or presence of ANCA in patients with a suspicion of RPGN, while awaiting kidney biopsy #dontwaitforbiopsy
13/
📌Randomized pediatric studies for treatment not available, data extrapolated from adult studies
🔶 Induction – Cyclophosphamide (CYC) v/s Rituximab (RTX) v/s Steroids
🔶 Plasma exchange (PLEX)
🔶 Maintenance – Steroids w/ additional immunosuppression
14/📌Induction
🔶RTX👌tolerated, preferable in children,🤏side effects, efficacy🟰CYC #RAVE #RITUXIVAS
🔶IV CYC pulses🤏cumulative dose, in severe disease/relapse #CYCLOPS
🔶🤏 dose noninferior to highdose steroids #PEXIVAS @NEJM
🔶Avacopan ​noninferior to steroids @landmark_neph
15/
PLEX
🔶 Aggressive disease only
🔶 Recent #PEXIVAS trial and a meta-analysis did not show long-term benefits in adults
🔶 However, pediatric RCTs needed - d/t earlier onset, prolonged course & prognosis
nejm.org/doi/full/10.10…
@NephroGuy @NEJM @bmj_latest @nephroseeker
16/
📌Maintenance
🔶 RTX is better than Azathioprine (AZA) (10.1056/NEJMoa1404231) (​​PMID: 28270229)
🔶 Low dose steroids or Avacopan
🔶 Duration is 18 - 24 months with first episode, 4 years for relapsing disease (10.1136/annrheumdis-2017-211123)
17/
📌Poor prognostic factors in pediatric ANCA
🔶 Severe renal impairment or need for dialysis – strongest predictor 🦾
🔶 Renal histology – sclerosis🔬
🔶 Severe neurological manifestation 🧠
🔶 Hypertension 🩺
doi.org/10.2215/CJN.19…
18/
📌Kidney transplant
🔶 Clinical resolution for at least 6 months irrespective of ANCA titers
🔶 Continue immunosuppression while on dialysis if other system involvement, awaiting transplant.
(doi.org/10.1016/j.kint…)
19/📌Take Home Points Pediatric AAV
🔰Rare disease, Rx extrapolated from adult RCTs
🔰Evaluate any RPGN for AAV, including drug induced
🔰PR3, MPO ANCA IgG+ANCA IFA
🔰Early aggressive Rx:RTX/CYC +steroids +rarely PLEX awaiting biopsy
🔰Maintenance 2-4 years - RTX/AZA + steroids
20/
For a case-based clinical discussion on #AAV with a pathologist @trumidor and an expert - login to @ASPNeph website,July 2022 webinar #Membereducation @yardleyjojo @menonshina @aspneph
Special thanks to #ASPNFOAM group @nefron1310 @swastithinks @RoshanPGeorgeMD @drM_Sudha

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Monica Rairikar

Monica Rairikar Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @MonicaVivek

Jun 10, 2023
#ASPNFOAM #tweetorialalert
Let's talk Goodpasture disease in children 🙅‍♂️#oldtimersname 🙈#misnomer ↗️refuted by the doc👨‍⚕️himself ‼️
Anti glomerular basement membrane (Anti GBM) disease with or without lung involvement #SPECTRUM #AntiGBM #NephTwitter #PedNeph @ASPNeph
#QUIZTIME
The following differentiates pediatric anti-GBM disease from adult disease except ❓
Answer ▶️ C
🎏Presents as RPGN in >80% of patients
🎏Pulmonary-renal syndrome
🎏Rare cause of childhood CKD
🎏Extremely rare cause of RPGN
🎏Similar incidence of RPGN in children as in adults
https://t.co/GEO9dyIemIdoi.org/10.1007/s00467…
Read 27 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us!

:(