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PULMONARY-RENALSYNDROMES by Nick Mark MD & Mithu Maheswaranathan MD ONE @nickmmark
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PRESENTATION: WORKUP & DIAGNOSIS @MithuRheum version →
· Pulmonary Renal Syndromes (PRS) are life-threatening Labs:
PULMONARY FINDINGS:
diseases with pulmonary hemorrhage (DAH) & renal failure • BMP (quantify renal injury), Coags (r/o coagulopathy) · AAV or Goodpasture’s cause pulmonary capillaritis leading
(glomerulonephritis). Although pulmonary and renal • CBC w differential (check eosinophil count for EGPA) to diffuse alveolar hemorrhage (DAH)
involvement is the defining feature, PRS can affect many organs: • Auto-antibodies: ANCA antibody, Anti-GBM antibody · Diffuse ground glass or consolidative opacities with sparing
acute respiratory failure glomerulonephritis: • Urine: UA, Urine protein to creatinine (UPC) ratio or the lung periphery is typically seen on chest CT.
or diffuse alveolar acute kidney injury (AKI), • Cardiac: consider BNP, troponin if concern for EGPA · BAL reveals increasing blood return in serial lavages and
hemorrhage (DAH) proteinuria, hematuria • ESR and CRP (non-specific, ESR usually low in anti-GBM) >20% hemosiderin laden macrophages (diagnostic of DAH)
Other tests: Lavage #1 Lavage #2 Lavage #3
inflammatory ENT: sinus, nasal, hearing loss, • CT chest to evaluate pulmonary involvement BAL of airways
eye disease saddle nose deformity • Bronchoscopy: confirm DAH, r/o infection and alveoli
scleritis, uveitis, • Echocardiogram for EGPA (↓ LVEF, pericardial effusion)
episcleritis pulmonary hemorrhage (DAH),
• PFTs (outpatient; increased DLCO after recent DAH)
asthma in EGPA, tracheal Initial
(subglottic stenosis) in GPA, • EMG/NCS for mononeuritis multiplex/neuropathy lavages
cardiac pulmonary nodules, asthma (EGPA) Diagnosis of PRS: biopsy (gold standard) or serologies + clear
(in EGPA) symptoms (not-optimal but may be necessary)
glomerulonephritis (AKI,
digital ischemia proteinuria, hematuria)
AUTO-ANTIBODIES:
• MPA ⇢ usually p-ANCA • Goodpasture’s ⇢ anti-GBM
cutaneous • GPA ⇢ usually c-ANCA •
neuropathy, mononeuritis Subsequent lavages reach more distal airways & alveoli
palpable purpura • EGPA ⇢ ANCA in 40-50%
multiplex ANCA Associated Vasculitis (AAV) · Surgical lung biopsy (not always required) may reveal:
2/2 vasculitis, Anti
ulcers, nodules BM · linear IgG staining along BM (anti-GBM)
MPA GPA EGPA
Pulmonary & · granular immune complex deposition (SLE & rheum dx)
DIFFERENTIAL DIAGNOSIS: Renal failure P-ANCA · pauci immune (no Ig, immune complex) with neutrophil
65% 15% 45% 20%
C-ANCA (MPO) infiltration of vessels (GPA) or eosinophils (EGPA).
· Cytoplasmic
·“Chocolate Chip C-ANCA OTHER FINDINGS:
Cookie” like 15% 85% 5% 10% Skin lesions: palpable purpura, petechiae, ulcerations, &
Antibody Other Drug induced (PR3)
Other
mediated autoimmune vasculitis occasionally nodules. Nasal or sinus mucosa often involved
X-ANCA Perinuclear pattern (but not MPO)
· Infx organisms that Seen with medications:
in EGPA. Biopsy of skin or nasal mucosa can reveal
· SLE · PTU (elastase,
· APS · methimazole cause lung/renal failure: cathepsin, Levamisole/cocaine, hydralazine vasculitis, such as leukocytoclastic vasculitis of skin
lysozyme, ANCA also seen in many diseases: APPROACH: Initial tx focused on remission-induction
· cryoglobulinemia · hydralazine Leptospirosis, Hantavirus, P-ANCA
TB, CMV, Legionella
· Perinuclear others) SLE, RA, PSC, PBC, AIH, IBD (UC > CD)
· systemic sclerosis · minocycline ·“Popcorn” like Later tx focused on maintenance.

PATHOLOGY
· HSP & IgA vasculitis · others - Post infections (e.g RENAL FINDINGS:
post-strep GN) Linear BM Pauci-immune
U/A: microscopic or gross hematuria, RBC deposition crescentic GN
· Sepsis (e.g. PNA & AKI)
casts, low grade proteinuria
Path: rapidly progressive (crescentic)

SEROLOGY
Autoimmune ANCA vasculitis Anti-basement membrane glomerulonephritis (fibrinoid necrosis, ANCA (-) ANCA (+) ANCA (+)
(AAV) (Goodpasture) hypercellular glomeruli, & cellular crescents) GBM (+) GBM (+) GBM (-)
· GPA (granulomatous with polyangiitis) IF staining patterns in crescentic GN:

v1.0 (2021-06-04) CC BY-SA 3.0

ANTI-GBM DISEASE OVERLAP SYNDROME ANCA VASCULITIS
· EGPA (eosinophilic granulomatosis w polyangiitis) LINEAR PATTERN GRANULAR PATTERN PAUCI IMMUNE
· MPA (microscopic polyangiitis) IG G C3
Pulse dose steroids
Plasmapheresis (PLEX)

INITIAL TX
PATHOPHYSIOLOGY: Rituximab and/or
· AAV: ANCA activates primed neutrophils ⇢ vessel endothelial Cyclophosphamide
cyclophosphamide
damage & inflammation; Granulomatous inflammation (cell- Pulse dose steroids
+/- PLEX
mediated immunity) in some forms of AAV (GPA, EGPA)
· GBM: Auto-antibodies against ⍺3 chain of type IV collagen,
MAINT TX

Linear IgG staining on Complement deposits Absence of IF staining;

Renal transplant Maintenance
distrupting the basement membrane integrity in lungs and kidney. basement membranes in clusters; seen in seen in AAV (MPA, GPA,
· Environmental risk factors: silica exposure (AAV), smoking (GBM) seen in anti-GBM dx SLE, post-strep GN, and EGPA) evaluation therapy