Renal/Urology · PANCE / PANRE

Granulomatosis with Polyangiitis (Wegener) and ANCA-Associated Vasculitides

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Pauci-immune small-vessel vasculitis (GPA, MPA, EGPA) presenting with RPGN and multisystem disease.

Also known as: GPA, Wegener granulomatosis, MPA, microscopic polyangiitis, EGPA, Churg-Strauss, ANCA-associated vasculitis, AAV, pauci-immune GN

Overview

A group of small-vessel vasculitides characterized by necrotizing inflammation of small to medium vessels with few or no immune deposits on biopsy (pauci-immune). Three syndromes per the 2012 Chapel Hill nomenclature: granulomatosis with polyangiitis (GPA, formerly Wegener), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss). Most patients have ANCA against either proteinase 3 (PR3-ANCA, c-ANCA) or myeloperoxidase (MPO-ANCA, p-ANCA).

Epidemiology

Incidence ~20 per million per year combined. GPA more common in Northern Europe and North America; MPA more common in Southern Europe and Asia. Peak age 65-75; slight male predominance. EGPA is rarer (~1-3 per million) and associated with asthma and eosinophilia.

Try two board-style Granulomatosis with Polyangiitis (Wegener) and ANCA-Associated Vasculitides questions

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

Question 1RenalMedium
A 62-year-old man reports 8 weeks of fatigue, low-grade fevers, and a 12-lb weight loss. He has had persistent bloody nasal crusting, recurrent sinusitis, and a new "collapse" of the bridge of his nose. Over the past week he developed cough with streaky hemoptysis. Vitals: temperature 38.1°C, blood pressure 134/82 mm Hg. Labs show creatinine 2.9 mg/dL (was 1.0 mg/dL three months ago), and urinalysis reveals dysmorphic red blood cells with red blood cell casts. Chest CT shows bilateral cavitary pulmonary nodules. C3 and C4 are normal, and PR3-ANCA (c-ANCA) is positive. Which of the following is the most likely diagnosis?
  • AGranulomatosis with polyangiitis
  • BPolyarteritis nodosa
  • CAnti-glomerular basement membrane disease
  • DMicroscopic polyangiitis
Reveal answer & full explanation
Correct answer: A — Granulomatosis with polyangiitis
  • AGranulomatosis with polyangiitis✓
  • BPolyarteritis nodosa
  • CAnti-glomerular basement membrane disease
  • DMicroscopic polyangiitis

Why Granulomatosis with polyangiitis is correct

  • The triad of upper-airway granulomatous disease (chronic sinusitis, bloody nasal crusting, saddle-nose deformity), lower-airway cavitary nodules with hemoptysis, and rapidly progressive glomerulonephritis (rising creatinine, dysmorphic RBCs, RBC casts) is the hallmark of GPA.
  • GPA is a pauci-immune small-vessel vasculitis, so complement (C3/C4) is characteristically normal, helping exclude immune-complex disease.
  • PR3-ANCA (c-ANCA) is the typical serology for GPA and strongly supports the diagnosis in this clinical context.

Why the others are wrong

  • Microscopic polyangiitis is also a pauci-immune RPGN with possible alveolar hemorrhage, but it is MPO-ANCA (p-ANCA) predominant and lacks the granulomatous upper-airway features (saddle-nose, destructive sinusitis) and cavitary nodules seen here.
  • Anti-glomerular basement membrane disease causes a pulmonary-renal syndrome but is defined by linear IgG on immunofluorescence and circulating anti-GBM antibody; it does not produce chronic destructive sinonasal disease or PR3-ANCA-driven cavitary nodules.
  • Polyarteritis nodosa is a medium-vessel vasculitis that spares glomeruli (no glomerulonephritis, RBC casts, or lung cavities) and is ANCA-negative, classically showing renal microaneurysms and a hepatitis B association.
Question 2RenalMedium
A 68-year-old man has 2 months of fatigue, chronic sinusitis with bloody nasal crusting, and a 4-kg weight loss, followed this week by dark urine. Blood pressure is 138/84 mm Hg. Serum creatinine has risen from 1.0 to 3.2 mg/dL. Urinalysis shows 3+ blood with dysmorphic red cells and red-cell casts. Chest CT reveals two cavitary nodules. Which of the following findings would best support a diagnosis of granulomatosis with polyangiitis?
  • ALow serum C4 with positive cryoglobulins and HCV
  • BLow serum C3 and C4 with positive anti-dsDNA
  • CLinear IgG along the glomerular basement membrane
  • DNormal serum C3 and C4 with positive PR3-ANCA
Reveal answer & full explanation
Correct answer: D — Normal serum C3 and C4 with positive PR3-ANCA
  • ALow serum C4 with positive cryoglobulins and HCV
  • BLow serum C3 and C4 with positive anti-dsDNA
  • CLinear IgG along the glomerular basement membrane
  • DNormal serum C3 and C4 with positive PR3-ANCA✓

Why Normal serum C3 and C4 with positive PR3-ANCA is correct

  • GPA is a pauci-immune small-vessel vasculitis with few or no immune deposits, so complement is consumed minimally and serum C3/C4 are characteristically normal, distinguishing it from immune-complex glomerulonephritides.
  • PR3-ANCA (c-ANCA) is the dominant serology in GPA; combined with the classic triad of upper airway disease, cavitary pulmonary nodules, and a rapidly progressive nephritic picture (rising creatinine, dysmorphic RBCs, RBC casts), it strongly supports GPA.
  • Per ACR/EULAR 2022 classification, ANCA specificity plus normal complement and pauci-immune necrotizing crescentic GN on biopsy define the disease.

Why the others are wrong

  • Low serum C4 with positive cryoglobulins and HCV points to cryoglobulinemic vasculitis, an immune-complex process with low complement, not the normal-complement pauci-immune pattern of GPA.
  • Linear IgG along the glomerular basement membrane is the hallmark of anti-GBM (Goodpasture) disease; GPA shows pauci-immune staining, not linear IgG. About 30% of anti-GBM patients are also ANCA-positive, but linear IgG itself favors anti-GBM.
  • Low serum C3 and C4 with positive anti-dsDNA indicates lupus nephritis, an immune-complex GN with full-house staining and hypocomplementemia, which does not fit the pauci-immune, normal-complement GPA picture.
🔒 Free preview limit reached

Keep reading — start your free trial

You've read your 2 free diagnosis previews. Create your free account to unlock the full Granulomatosis with Polyangiitis (Wegener) and ANCA-Associated Vasculitides outline — plus all 514 diagnoses, 6,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.

Start your 7-day free trial → Sign in
Free to start · No credit card · Cancel anytime

Risk factors

  • Age >50
  • Genetic: HLA-DPB1*0401 (GPA), HLA-DQ (MPA)
  • Silica exposure, farming dust
  • Drugs: hydralazine, propylthiouracil, minocycline, levamisole-adulterated cocaine
  • Chronic nasal carriage of Staphylococcus aureus (GPA)
  • Pre-existing asthma and eosinophilia (EGPA)

Pathophysiology

Loss of tolerance to neutrophil cytoplasmic antigens (PR3 or MPO) generates pathogenic ANCA. ANCA binds primed neutrophils, causing degranulation, reactive oxygen species, and release of neutrophil extracellular traps (NETs) that damage endothelium. The end result is necrotizing inflammation of arterioles, capillaries, and venules. GPA additionally features granulomatous inflammation of the upper and lower respiratory tract; EGPA features eosinophilic tissue infiltration and asthma.

Clinical presentation

Symptoms

  • Constitutional: weeks-to-months of fever, weight loss, fatigue, arthralgia, myalgia
  • GPA upper airway: sinusitis, epistaxis, nasal crusting, saddle-nose deformity, subglottic stenosis, otitis media, hearing loss
  • GPA/MPA lower airway: cough, hemoptysis, pulmonary infiltrates or cavitary nodules, alveolar hemorrhage
  • EGPA: asthma (often poorly controlled), allergic rhinitis, eosinophilic pneumonia
  • Renal: hematuria, proteinuria, rapidly rising creatinine — features of RPGN
  • Skin: palpable purpura, ulcers, livedo
  • Nervous system: mononeuritis multiplex (especially EGPA), CNS involvement (rare)
  • Eye: scleritis, episcleritis, retro-orbital pseudotumor (GPA)

Signs / physical exam

  • Saddle-nose deformity, septal perforation (GPA)
  • Purpura, nailfold infarcts
  • Diffuse pulmonary crackles, sometimes hemoptysis
  • Foot drop or wrist drop (mononeuritis multiplex)
  • Hypertension less common than in other GN syndromes

Classic findings

Triad of upper airway disease + pulmonary cavitary nodules + necrotizing crescentic GN suggests GPA. Asthma + peripheral eosinophilia + pulmonary infiltrates + mononeuritis multiplex suggests EGPA.

Differential diagnosis

  • Anti-GBM disease — Linear IgG on IF, anti-GBM antibody, often pulmonary hemorrhage; may coexist with ANCA
  • Lupus nephritis — Full-house IF, positive ANA/anti-dsDNA, low complement
  • IgA vasculitis (Henoch-Schönlein) — Palpable purpura, abdominal pain, mesangial IgA on biopsy
  • Polyarteritis nodosa — Medium-vessel vasculitis without GN; aneurysms on angiography; associated with HBV
  • Cryoglobulinemic vasculitis — Palpable purpura, low C4, positive cryoglobulins; often HCV-associated
  • Endocarditis with immune-complex GN — Fever, murmur, low complement, positive blood cultures; echocardiogram diagnostic
  • Drug-induced AAV — Hydralazine, propylthiouracil, minocycline, levamisole-cocaine — high-titer MPO-ANCA and often anti-elastase

Diagnostic workup

Diagnostic criteria

ACR/EULAR 2022 classification criteria distinguish GPA, MPA, and EGPA using weighted clinical, laboratory, and biopsy features. Histologic confirmation: kidney biopsy showing pauci-immune necrotizing crescentic GN; lung or upper airway biopsy showing necrotizing granulomas with vasculitis (GPA) or eosinophilic vasculitis with granulomas (EGPA).

Labs

  • ANCA — PR3-ANCA (c-ANCA, GPA predominant) and MPO-ANCA (p-ANCA, MPA and EGPA predominant); ELISA preferred over IF
  • CBC (anemia of inflammation; marked eosinophilia in EGPA), CMP, ESR/CRP (markedly elevated)
  • UA with microscopy (dysmorphic RBCs, RBC casts), UPCR or 24-hour protein
  • Complement C3/C4 (typically normal — distinguishes from immune-complex GN)
  • Anti-GBM antibody (always check — ~30% of anti-GBM patients are dual-positive)
  • Hepatitis B, hepatitis C, HIV, blood cultures (exclude endocarditis), cryoglobulins
  • IgG, IgA, IgE (elevated IgE in EGPA), tryptase
  • TB screening before immunosuppression

Imaging

  • Chest CT — cavitary nodules (GPA), ground-glass opacities (alveolar hemorrhage in MPA), migratory infiltrates (EGPA)
  • Sinus CT for GPA upper airway disease
  • Echocardiogram if cardiac involvement (EGPA myocarditis, endocarditis exclusion)

Diagnostic algorithm

FeatureGPA (Wegener)MPAEGPA (Churg-Strauss)
Predominant ANCAPR3 (c-ANCA) ~75%MPO (p-ANCA) ~60%MPO (p-ANCA) ~40%
Upper airwayYes — sinusitis, saddle nose, subglottic stenosisRareAllergic rhinitis, nasal polyps
Asthma / eosinophiliaNoNoYes (defining)
Granulomas on biopsyYesNoYes (eosinophilic)
Renal involvementCommon (RPGN)Most common (RPGN)Less common
CardiacUncommonUncommonCommon — leading cause of death
Treatment cornerstoneSteroids + rituximab or CYC; avacopanSame as GPASteroids + mepolizumab; CYC/RTX for severe
Comparative features of the three ANCA-associated vasculitides.

Treatment

First-line

  • Severe organ-threatening disease (RPGN, alveolar hemorrhage, mononeuritis multiplex) — induction with corticosteroids + cyclophosphamide OR rituximab
  • IV methylprednisolone pulse (500-1000 mg × 3 days) followed by oral prednisone 1 mg/kg/day taper
  • Rituximab 375 mg/m² weekly × 4 OR 1000 mg × 2 (preferred for relapsing disease, PR3-ANCA, and younger patients)
  • Cyclophosphamide IV pulse 15 mg/kg q2-3 weeks × 3-6 doses (alternative to rituximab)
  • Plasmapheresis — selective use after PEXIVAS trial (consider in severe pulmonary hemorrhage or creatinine >5.7 mg/dL; routine use not recommended)
  • Avacopan (C5a receptor antagonist) — adjunct that reduces steroid exposure (ADVOCATE trial)
  • Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole during immunosuppression

Non-severe disease (mild renal, sinus, joint, skin involvement)

  • Methotrexate or mycophenolate mofetil + corticosteroids for induction
  • Maintenance with the same agent or rituximab

Severe disease — maintenance after induction remission

  • Rituximab every 6 months for ≥4 years (preferred per MAINRITSAN, RITAZAREM trials)
  • Azathioprine 2 mg/kg/day or methotrexate 20-25 mg weekly are alternatives
  • Taper prednisone to ≤5 mg/day by 6 months; consider full discontinuation with avacopan
  • Continue maintenance for at least 24-48 months

EGPA

  • Mepolizumab (anti-IL-5) is approved for EGPA — particularly effective for asthma and eosinophilic features
  • Cyclophosphamide or rituximab for severe organ involvement (cardiac, renal, neuro)
  • High-dose corticosteroids for induction

Second-line / adjunct

  • Intravenous immunoglobulin (IVIG) for refractory disease
  • Belimumab as adjunct (limited data)
  • Kidney transplantation for ESKD — generally safe once disease quiescent for >12 months

Complications

  • ESKD (~25% within 5 years of severe renal involvement)
  • Subglottic stenosis (GPA) requiring tracheal dilation
  • Pulmonary fibrosis, recurrent infections
  • Cardiac (EGPA): cardiomyopathy, pericarditis — leading cause of EGPA mortality
  • Mononeuritis multiplex with persistent neurologic deficits
  • Cyclophosphamide-related: gonadal toxicity, hemorrhagic cystitis, bladder cancer, secondary malignancies
  • Opportunistic infections from chronic immunosuppression

PANCE pearls

  • PR3-ANCA → think GPA (Wegener); MPO-ANCA → think MPA or EGPA; both can overlap.
  • Saddle-nose deformity, subglottic stenosis, and cavitary lung nodules are GPA hallmarks.
  • Asthma + eosinophilia + mononeuritis multiplex = think EGPA.
  • Rituximab is non-inferior to cyclophosphamide for induction (RAVE, RITUXVAS) and preferred for relapsing, PR3-ANCA, or fertility-concern patients.
  • Avacopan permits dramatic steroid reduction without losing efficacy (ADVOCATE trial).
  • Drug-induced AAV (hydralazine, PTU, levamisole-cocaine) usually resolves with drug withdrawal — search for it.

References

  • Chapel Hill 2012 — Jennette JC et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (Arthritis Rheum 2013;65:1-11)
  • KDIGO 2021 — KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases (Kidney Int 2021;100:S1-S276)
  • ACR/EULAR 2022 — ACR/EULAR 2022 Classification Criteria for ANCA-Associated Vasculitis (Arthritis Rheumatol 2022)
  • PEXIVAS — Walsh M et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis (NEJM 2020;382:622-631)
  • ADVOCATE — Jayne DRW et al. Avacopan for the treatment of ANCA-associated vasculitis (NEJM 2021;384:599-609)
  • RAVE — Stone JH et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis (NEJM 2010;363:221-232)

Practice Renal/Urology questions on FirstPassPA

Turn this outline into retention. 6,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.

Answer the 2 free questions above → Get today's free question →

Related Renal/Urology diagnoses

Acute Kidney Injury (AKI)Chronic Kidney Disease (CKD)End-Stage Renal Disease and DialysisNephrotic SyndromeNephritic SyndromeIgA NephropathyAcute Tubular Necrosis (ATN)Acute Interstitial Nephritis (AIN)Post-Streptococcal Glomerulonephritis (PSGN)Autosomal Dominant Polycystic Kidney Disease (ADPKD)Urolithiasis (Kidney Stones)Acute Cystitis (Uncomplicated UTI)Acute PyelonephritisRenal Cell Carcinoma (RCC)

Differentials & related conditions

Goodpasture Syndrome (Anti-GBM Disease)Lupus NephritisIgA Vasculitis (Henoch-Schönlein Purpura)

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.