STEPTRACKERCARDIOVASCULAR | PATHOLOGY + IMMUNOLOGY | HIGH-YIELD REVIEW

Small-Vessel Vasculitis — ANCA

Granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis — pauci-immune, lung and kidney.

FOCUS ON
Sort the three by two questions: granulomas? and eosinophils/asthma? GPA = upper airway + lung + kidney, c-ANCA (PR3). MPA = lung + kidney, no granulomas, p-ANCA (MPO). EGPA = asthma + eosinophilia + neuropathy. All give pauci-immune crescentic GN. Contrast with anti-GBM disease.
FEATURE
GPA (WEGENER)
MICROSCOPIC POLYANGIITIS
EGPA (CHURG-STRAUSS)
ANCA
c-ANCA (anti-PR3)
p-ANCA (anti-MPO)
p-ANCA (MPO) in ~40%
Granulomas
Necrotizing granulomas
None
Granulomas with eosinophils
Upper airway
Chronic sinusitis, otitis, nasal ulcers, saddle nose, septal perforation
Absent
Allergic rhinitis, nasal polyps
Lungs
Nodules, cavities, hemoptysis
Pulmonary capillaritis → alveolar hemorrhage
Asthma, migratory infiltrates
Kidney
Pauci-immune crescentic GN
Pauci-immune crescentic GN
Less common, milder
Other
Eye (scleritis), skin purpura
Skin purpura, neuropathy
Eosinophilia, ↑ IgE, mononeuritis multiplex, heart (eosinophilic myocarditis — major cause of death)
Treatment
Steroids + rituximab or cyclophosphamide
Same
Steroids; mepolizumab (anti-IL-5)

Mechanism — ANCA turn neutrophils on vessels

Infection / cytokinesPrime neutrophils
→
PR3 / MPO on surface
→
ANCA bindNeutrophil fires
→
Degranulation + ROSNecrotizing vasculitis
→
Pauci-immuneLittle Ig on IF

Drug-induced p-ANCA vasculitis: hydralazine, propylthiouracil, levamisole-cut cocaine.

Pulmonary-renal syndromes

DISEASE
SEROLOGY
KIDNEY IF
GPA
c-ANCA (PR3)
Pauci-immune
MPA
p-ANCA (MPO)
Pauci-immune
EGPA
p-ANCA ± eosinophilia
Pauci-immune
Goodpasture
Anti-GBM (α3 type IV collagen)
Linear IgG
SLE
ANA, dsDNA, ↓ C3/C4
Granular ("full house")

How it's tested

COMMON CONFUSIONHemoptysis + hematuria has several causes. Immunofluorescence decides: pauci-immune (ANCA), linear (anti-GBM), or granular (immune complex).
THE TRAPA saddle-nose deformity with septal perforation can come from GPA or from cocaine use. Levamisole-cut cocaine can even induce ANCA vasculitis.
YOUR APPROACHSmall-vessel vasculitis + lung/kidney → ANCA type → granulomas? asthma/eosinophils? → name it.

If you see… think…

Chronic sinusitis + hemoptysis + hematuria, c-ANCA → GPA
Saddle nose and septal perforation → GPA (or cocaine)
Cavitating lung nodules + RBC casts → GPA
Alveolar hemorrhage + RPGN, p-ANCA, no granulomas → MPA
Adult-onset asthma + eosinophilia + foot drop → EGPA
Hemoptysis + linear IgG along the GBM → Goodpasture (not ANCA)
Crescents with almost no immunofluorescence → pauci-immune (ANCA)
New p-ANCA vasculitis on hydralazine or PTU → drug-induced
Leading cause of death in EGPA → cardiac involvement