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❓
🤔 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…
✅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
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…
🔘 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…
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
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
🔘 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❓
🤔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
✅ 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…)
🔶 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
📌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
📌 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
📌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
🔶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
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)
📌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…
📌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…)
📌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
🔰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
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
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