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rheum.gpa.core.v1PRODUCTION
rheum.gpa.core.v1

Granulomatosis with polyangiitis (GPA)

rheumatologyacutechronicadult
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Necrotizing granulomatous small-vessel vasculitis spanning ENT + lung + pauci-immune crescentic GN; typically c-ANCA/anti-PR3. New diagnosis vs known-relapsing GPA both handled; pure renal-limited routes to neph engine, MPA/EGPA via §5.5.2 pivots

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AAV scope confirmed; GPA phenotype framed

Patient inputs (12)

HBV/HCV/TB/strongyloides screen pre-rituximab/cyclophosphamide; live-vaccine timing (2021 ACR/VF)

Cyclophosphamide gonadotoxicity — fertility preservation + GnRH-agonist protection; rituximab preferred if fertility priority (2021 ACR/VF)

Destructive upper-airway disease (sinusitis, septal perforation, saddle-nose, subglottic stenosis) is the GPA-defining axis vs MPA/EGPA (2022 ACR/EULAR)

PR3-ANCA vs MPO-ANCA — PR3 more relapsing, ENT-destructive, rituximab-responsive; MPO sways toward MPA-overlap phenotype (RAVE; KDIGO 2024)

Cr trend defines RPGN; dialysis dependence drives PEXIVAS PLEX consideration + drug dosing (KDIGO 2024)

Dysmorphic RBCs / RBC casts / proteinuria = pauci-immune necrotizing crescentic GN (KDIGO 2024)

Anemia (alveolar hemorrhage / GN), leukocytosis, eosinophilia (EGPA pivot); CYC/RTX cytopenia baseline

Disease-activity surrogate; CRP elevation prompts infection-vs-flare discrimination on immunosuppression

Nodules / cavities / ground-glass alveolar hemorrhage define lung involvement and severity (2021 ACR/VF)

Drives EUVAS severity grouping (limited vs systemic vs organ/life-threatening) and BVAS (2021 ACR/VF; KDIGO 2024)

Prior CYC cumulative dose (malignancy/bladder risk), prior RTX, glucocorticoid burden inform induction vs relapse strategy (2021 ACR/VF)

Subglottic / tracheobronchial stenosis is organ-threatening and may need urgent airway evaluation (2021 ACR/VF)

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Severity triggers (6)

6 need judgement
  • informationallife_threateningdiffuse_alveolar_hemorrhage
    Hemoptysis + hypoxia + diffuse alveolar infiltrates + falling Hb (DAH)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningrapidly_progressive_gn_dialysis_dependent
    Rising creatinine + RBC casts → pauci-immune crescentic GN; oliguric/dialysis-dependent AKI
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningsubglottic_airway_compromise
    Stridor / progressive dyspnea from subglottic or tracheobronchial stenosis
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcns_or_cardiac_vasculitis
    Cerebral vasculitis / pachymeningitis / seizure or myocarditis-pericarditis-coronary involvement
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremononeuritis_multiplex
    Acute foot/wrist drop or asymmetric sensorimotor deficit — vasculitic neuropathy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderaterelapse_pr3_anca_ent
    Rising PR3-ANCA with recurrent ENT/sinonasal disease on maintenance
    Trigger could not be auto-evaluated — needs clinician judgement.

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RED_FLAGSrequiredDrives severity classification
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Recommended regimen

GPA — severity triage → remission induction → adjunct prophylaxis → maintenance → relapse surveillance (2021 ACR/VF + KDIGO 2024 + PEXIVAS/ADVOCATE)
axis: gpa_severity_induction_maintenancestep 1 - Step 1 — Severity triage (EUVAS grouping)
Selected step "Step 1 — Severity triage (EUVAS grouping)" — New or relapsing GPA — classify limited/non-organ-threatening vs systemic vs organ/life-threatening (RPGN, DAH, airway, CNS, cardiac, mononeuritis)
  • tissue biopsy (renal / lung / ENT)
    first line
    diagnostic_procedure
    procedural
    triggers: diagnostic_confirmation_needed
    KDIGO 2024 — least-invasive accessible-site biopsy confirms pauci-immune necrotizing crescentic GN or necrotizing granulomatous inflammation; do not delay empiric induction in fulminant DAH/RPGN

outpatient playbook — drug actions (4)

  1. 1. glucocorticoid (PEXIVAS-style reduced taper)
    Prednisone 0.5–1 mg/kg/d → rapid taper • PO • daily, taper
    trigger: Active limited GPA
    PEXIVAS — minimize cumulative steroid
  2. 2. rituximab OR methotrexate/MMF
    RTX 1 g ×2 (or 375 mg/m² ×4); MTX 15–25 mg weekly • IV/PO/SC • induction
    trigger: Non-organ-threatening
    2021 ACR/VF — RTX or MTX/MMF for limited disease
  3. 3. maintenance rituximab OR azathioprine/methotrexate
    RTX 500 mg q6 mo; AZA 2 mg/kg/d; MTX 15–25 mg weekly • IV/PO/SC • maintenance ≥18–48 mo
    trigger: Post-remission
    MAINRITSAN/RITAZAREM — RTX preferred maintenance
  4. 4. TMP-SMX + bone protection
    TMP-SMX SS daily; Ca/vitD ± bisphosphonate • PO • daily
    trigger: On immunosuppression / chronic steroid
    2021 ACR/VF — PJP + bone prophylaxis; TMP-SMX also reduces ENT relapse

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Refractory sinusitis / bloody nasal crusting / septal perforation / saddle-nose / new hearing loss; Hemoptysis / hypoxia + active urinary sediment (pulmonary-renal syndrome); Positive c-ANCA / anti-PR3 (or MPO) with multisystem disease.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Granulomatosis with polyangiitis (GPA)** (rheum.gpa.core.v1).
Phenotype framing: Within AAV: GPA vs MPA (no granuloma/ENT destruction, MPO/p-ANCA, less relapse) vs EGPA (asthma + eosinophilia, ANCA often negative). Non-AAV mimics: anti-GBM/Goodpasture, cryoglobulinemic vasculitis, IgA vasculitis, SLE, infective endocarditis, cocaine/levamisole-induced midline destruction, IgG4-RD, lymphomatoid granulomatosis, NTM/TB, malignancy
Scope: Necrotizing granulomatous small-vessel vasculitis spanning ENT + lung + pauci-immune crescentic GN; typically c-ANCA/anti-PR3. New diagnosis vs known-relapsing GPA both handled; pure renal-limited routes to neph engine, MPA/EGPA via §5.5.2 pivots

No severity triggers fired against current inputs.

Plan

Regimen axis: **GPA — severity triage → remission induction → adjunct prophylaxis → maintenance → relapse surveillance (2021 ACR/VF + KDIGO 2024 + PEXIVAS/ADVOCATE)** — step "Step 1 — Severity triage (EUVAS grouping)".
1. tissue biopsy (renal / lung / ENT) procedural (diagnostic_procedure, first line) — KDIGO 2024 — least-invasive accessible-site biopsy confirms pauci-immune necrotizing crescentic GN or necrotizing granulomatous inflammation; do not delay empiric induction in fulminant DAH/RPGN

Setting playbook (outpatient) — Induce/maintain remission in limited / non-organ-threatening GPA, surveil for relapse and treatment toxicity, manage accrued damage
2. glucocorticoid (PEXIVAS-style reduced taper) Prednisone 0.5–1 mg/kg/d → rapid taper PO daily, taper — Active limited GPA (PEXIVAS — minimize cumulative steroid)
3. rituximab OR methotrexate/MMF RTX 1 g ×2 (or 375 mg/m² ×4); MTX 15–25 mg weekly IV/PO/SC induction — Non-organ-threatening (2021 ACR/VF — RTX or MTX/MMF for limited disease)
4. maintenance rituximab OR azathioprine/methotrexate RTX 500 mg q6 mo; AZA 2 mg/kg/d; MTX 15–25 mg weekly IV/PO/SC maintenance ≥18–48 mo — Post-remission (MAINRITSAN/RITAZAREM — RTX preferred maintenance)
5. TMP-SMX + bone protection TMP-SMX SS daily; Ca/vitD ± bisphosphonate PO daily — On immunosuppression / chronic steroid (2021 ACR/VF — PJP + bone prophylaxis; TMP-SMX also reduces ENT relapse)

Non-pharmacologic actions:
- ANCA + clinical relapse surveillance (PR3/ENT phenotype higher relapse)
- Subglottic stenosis local therapy/dilation referral as needed
- Vaccination catch-up (non-live; timed pre-RTX)
- Cardiovascular + malignancy (CYC bladder) long-term risk modification
- Hearing/ENT rehabilitation for accrued damage

AVOID / contraindication checks:
- Cyclophosphamide gonadotoxicity — fertility counsel + GnRH agonist + gamete cryopreservation (2021 ACR/VF)
- Cyclophosphamide hemorrhagic cystitis — MESNA + hydration with each dose (2021 ACR/VF)
- Live vaccines contraindicated on active immunosuppression (2021 ACR/VF)
- Rituximab — screen/treat HBV and active infection before dosing (2021 ACR/VF)
- PJP prophylaxis with TMP SMX during RTX/CYC induction (2021 ACR/VF)
- Plasma exchange NOT routine — reserve for severe AKI/dialysis dependent GN, DAH, or anti GBM (PEXIVAS 2020)
- Methotrexate avoid if eGFR <60 or active alveolar hemorrhage (2021 ACR/VF)
- Azathioprine TPMT/NUDT15 testing before maintenance dosing (2021 ACR/VF)
- Avacopan hepatotoxicity — baseline + serial LFT monitoring (ADVOCATE 2021)

Monitoring

Regimen monitoring:
- creatinine + UA + UPCR weekly then biweekly during induction (KDIGO 2024)
- CBC at cyclophosphamide nadir 7–14 days + microscopic hematuria surveillance (2021 ACR/VF)
- CD19/CD20 B-cell count + IgG levels on rituximab (2021 ACR/VF)
- PR3/MPO-ANCA trend with clinical assessment for relapse anticipation (2021 ACR/VF)
- infection surveillance (PJP, HBV reactivation, neutropenia) on immunosuppression (2021 ACR/VF)
- serial LFT on avacopan (ADVOCATE 2021)
- serial spirometry/laryngoscopy for subglottic/tracheobronchial stenosis (2021 ACR/VF)
- cumulative cyclophosphamide dose tracking — long-term bladder/hematologic malignancy risk (2021 ACR/VF)

Setting (outpatient) monitoring:
- Creatinine + UA + CBC + ESR/CRP q1–3 months (2021 ACR/VF)
- PR3/MPO-ANCA trend with clinical correlation (2021 ACR/VF)
- B-cell + IgG on rituximab maintenance (2021 ACR/VF)
- Spirometry/laryngoscopy interval for airway disease (2021 ACR/VF)

Follow-up plan: Prolonged maintenance (RTX redosing schedule or AZA/MTX) ≥18–48 mo with relapse surveillance; manage accrued damage (VDI) — CKD, hearing loss, subglottic stenosis, nasal deformity; cardiovascular + venous-thromboembolism + infection + malignancy (CYC bladder) long-term risk; vaccination catch-up; bone health; fertility/pregnancy planning when stable
- Close-out criterion: long-term maintenance + damage-surveillance + relapse plan documented

Monitoring phase: Induction: CBC + creatinine + UA weekly→biweekly; CYC nadir CBC at 7–14 d + microscopic hematuria (bladder toxicity); RTX — CD19/CD20 B-cells + IgG, infusion reactions, HBV reactivation; ANCA + clinical surveillance (PR3 rise/ENT recurrence anticipates relapse); infection surveillance on immunosuppression; serial spirometry/laryngoscopy for airway disease

Disposition

Current setting: outpatient — Induce/maintain remission in limited / non-organ-threatening GPA, surveil for relapse and treatment toxicity, manage accrued damage

Disposition criteria:
- Continue outpatient unless organ/life-threatening relapse or serious treatment toxicity (2021 ACR/VF)

Escalation triggers (move to higher acuity):
- New organ-threatening feature (hemoptysis, rising Cr, stridor, foot drop) → urgent admission (2021 ACR/VF)
- Rising PR3-ANCA + ENT recurrence → intensify surveillance / consider re-induction (2021 ACR/VF)
- Severe infection on immunosuppression → hold ISD, ID evaluation (2021 ACR/VF)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Hemoptysis + hypoxia + diffuse alveolar infiltrates + falling Hb (DAH)
- [LIFE_THREATENING] Rising creatinine + RBC casts → pauci-immune crescentic GN; oliguric/dialysis-dependent AKI
- [LIFE_THREATENING] Stridor / progressive dyspnea from subglottic or tracheobronchial stenosis

Citations

- 2021 ACR/VF Vasculitis Guideline (ANCA-associated) + KDIGO 2024 ANCA GN + 2022 ACR/EULAR classification + PEXIVAS/ADVOCATE trials [PMID:34235894](https://pubmed.ncbi.nlm.nih.gov/34235894/)
- Cited evidence (PMID 35106964) [PMID:35106964](https://pubmed.ncbi.nlm.nih.gov/35106964/)
- Cited evidence (PMID 32053298) [PMID:32053298](https://pubmed.ncbi.nlm.nih.gov/32053298/)
- Cited evidence (PMID 33596356) [PMID:33596356](https://pubmed.ncbi.nlm.nih.gov/33596356/)
- Cited evidence (PMID 20647199) [PMID:20647199](https://pubmed.ncbi.nlm.nih.gov/20647199/)

Last reconciled with current guidelines: 2026-05-22.
References
  • 2021 ACR/VF Vasculitis Guideline (ANCA-associated) + KDIGO 2024 ANCA GN + 2022 ACR/EULAR classification + PEXIVAS/ADVOCATE trials — PMID:34235894
  • Cited evidence (PMID 35106964) — PMID:35106964
  • Cited evidence (PMID 32053298) — PMID:32053298
  • Cited evidence (PMID 33596356) — PMID:33596356
  • Cited evidence (PMID 20647199) — PMID:20647199