Eduovisual
Renal & Urinary
ANCA-associated vasculitis with renal involvement
— Granulomatosis with polyangiitis (GPA): typically PR3-ANCA (c-ANCA), upper + lower airway + kidney
— Microscopic polyangiitis (MPA): typically MPO-ANCA (p-ANCA), kidney + lung, no granulomas
— Eosinophilic granulomatosis with polyangiitis (EGPA): MPO-ANCA in ~40%, asthma + eosinophilia, renal disease less common
— Adult >50 with unexplained AKI + active urine sediment (dysmorphic RBCs, RBC casts, proteinuria <3 g/day)
— Constitutional symptoms (fever, weight loss, fatigue, myalgias) for weeks–months
— Sinusitis/epistaxis/saddle nose, hemoptysis, mononeuritis multiplex, palpable purpura, scleritis
— New cavitary lung lesions or diffuse alveolar hemorrhage
Board pearl: The classic Step 3 stem is an older adult with weeks of malaise + new AKI + hematuria + hemoptysis — think pulmonary-renal syndrome and order ANCA serologies before the kidney biopsy result returns. Empiric workup should not wait for tissue.
Step 3 management: In the ambulatory setting, an elderly patient with persistent sinusitis refractory to antibiotics, unexplained weight loss, and new microscopic hematuria warrants urgent outpatient nephrology and rheumatology referral plus same-day labs (CBC, BMP, UA with micro, ANCA, anti-GBM, C3/C4) — not a routine 6-week ENT follow-up. Delayed diagnosis is the single greatest driver of ESKD in AAV; the kidney that is dialysis-dependent at presentation rarely recovers.
— Constitutional: low-grade fever, night sweats, anorexia, 5–10% weight loss, arthralgias
— Frequently misattributed to occult malignancy, endocarditis, or "viral syndrome"
— Upper airway (GPA): chronic sinusitis unresponsive to antibiotics, bloody nasal discharge, nasal crusting, otitis media, hoarseness (subglottic stenosis), saddle-nose deformity
— Lower airway: cough, dyspnea, hemoptysis (ranges from blood-tinged sputum to massive DAH), pleuritic chest pain
— Renal: often asymptomatic until advanced — foamy urine, tea-colored urine, edema, oliguria are late
— Skin: palpable purpura on lower extremities, livedo, ulcers, splinter hemorrhages
— Neurologic: mononeuritis multiplex (foot drop + wrist drop), sensory neuropathy
— Ocular: scleritis, episcleritis, orbital pseudotumor (proptosis in GPA), retinal vasculitis
— GI: abdominal pain, melena (mesenteric vasculitis)
— Drug-induced ANCA vasculitis: hydralazine, propylthiouracil, methimazole, minocycline, levamisole-adulterated cocaine, allopurinol, TNF inhibitors
— These typically produce high-titer MPO-ANCA with anti-histone, anti-dsDNA antibodies
Key distinction: GPA vs MPA vs EGPA — GPA features granulomas + upper airway destruction; MPA lacks both granulomas and prominent ENT involvement; EGPA has asthma + eosinophilia + cardiac/peripheral nerve disease. All three can cause pauci-immune crescentic GN that looks identical on biopsy.
Board pearl: "Sinusitis + hemoptysis + hematuria" = GPA until proven otherwise. "Asthma + eosinophilia + foot drop" = EGPA. "Older adult + isolated RPGN + interstitial lung disease" = MPA (MPO-ANCA), often the most renal-predominant phenotype.
— Fever is common but usually low-grade; high spiking fevers should prompt evaluation for superimposed infection or endocarditis mimic
— Hypertension from acute glomerulonephritis (volume + renin-mediated)
— Tachypnea and hypoxemia suggest diffuse alveolar hemorrhage (DAH) — a medical emergency
— Nasal mucosal ulceration, septal perforation, saddle-nose deformity (collapse of nasal bridge from cartilage destruction)
— Serous otitis media, conductive hearing loss
— Scleritis (painful red eye, bluish hue), proptosis from retro-orbital granuloma
— Subglottic stenosis: inspiratory stridor, hoarseness
— Crackles (alveolar hemorrhage or fibrosis in MPA)
— Dullness if pulmonary infarct/consolidation
— Wheezing in EGPA
— Pericardial rub (pericarditis)
— EGPA: signs of heart failure from eosinophilic myocarditis — leading cause of EGPA mortality
Step 3 management: A patient with suspected AAV and SpO₂ <92%, hemoptysis, and falling hemoglobin has presumed DAH — admit to ICU, obtain stat CT chest, type and cross, and arrange emergent bronchoscopy with sequential BAL (progressively bloodier returns confirm DAH). Initiate pulse methylprednisolone empirically; do not wait for ANCA results.
Board pearl: Mononeuritis multiplex in a patient with constitutional symptoms is a vasculitis until proven otherwise — order ANCA, cryoglobulins, hepatitis B/C, and HIV; EMG/NCS shows asymmetric axonal neuropathy.
— CBC: normocytic anemia (chronic disease ± hemorrhage), leukocytosis, thrombocytosis; eosinophilia >1500/µL in EGPA
— BMP: elevated creatinine (AKI), hyperkalemia, metabolic acidosis
— LFTs, albumin: hypoalbuminemia from inflammation/proteinuria
— ESR, CRP: markedly elevated, useful for tracking activity
— CK: if myalgia, exclude myositis
— Dysmorphic RBCs, RBC casts (pathognomonic for GN), proteinuria typically <3 g/day (sub-nephrotic), pyuria possible
— Spot urine protein:creatinine ratio to quantify
— ANCA by IFA + antigen-specific ELISA: c-ANCA/PR3 vs p-ANCA/MPO
— Anti-GBM antibody (overlap syndrome occurs in ~10% of MPO-ANCA patients — worse prognosis)
— ANA, dsDNA, C3/C4 (exclude lupus; complements typically normal in AAV — pauci-immune)
— Cryoglobulins, hepatitis B/C, HIV (mimics)
— Anti-streptolysin O, blood cultures (post-infectious GN, endocarditis)
— RF, anti-CCP (RA-associated vasculitis)
— CXR: nodules, cavities (GPA), fleeting infiltrates, alveolar hemorrhage pattern
— High-resolution CT chest: nodules >1 cm with cavitation (GPA), ground-glass (DAH), interstitial fibrosis (MPA)
— CT sinuses: bony erosion, soft tissue mass in GPA
— Renal ultrasound: rule out obstruction, assess kidney size (normal/enlarged in acute GN)
Board pearl: Normal C3/C4 distinguishes pauci-immune AAV from lupus nephritis, post-infectious GN, MPGN, and cryoglobulinemic GN — all of which consume complement. This single lab dramatically narrows the differential.
Key distinction: ANCA can be negative in 10–20% of biopsy-proven AAV (especially limited GPA). Negative ANCA does not exclude diagnosis — pursue biopsy when clinical suspicion is high.
— Indications: AKI with active urine sediment, suspected RPGN, to confirm diagnosis before immunosuppression, to stage chronicity
— Light microscopy: focal segmental necrotizing GN with crescents (cellular, fibrocellular, fibrous)
— Immunofluorescence: pauci-immune (minimal/absent immunoglobulin and complement deposition) — the defining feature
— Electron microscopy: no electron-dense deposits
— Berden histopathologic classification predicts renal outcome:
— Focal (≥50% normal glomeruli) — best prognosis
— Crescentic (≥50% cellular crescents)
— Mixed
— Sclerotic (≥50% globally sclerotic) — worst prognosis, often dialysis-dependent
— Skin biopsy of purpuric lesion: leukocytoclastic vasculitis (non-specific)
— Nasal/sinus biopsy in GPA: granulomas + vasculitis + necrosis (the "GPA triad") — low yield (~20%)
— Lung biopsy: rarely needed; transbronchial often non-diagnostic, surgical wedge preferred if required
— Sural nerve biopsy if mononeuritis multiplex without other accessible tissue
— Confirms DAH (progressively bloodier returns, hemosiderin-laden macrophages)
— Rules out infection (especially before/during immunosuppression) — bacterial, fungal, PJP, mycobacterial cultures
CCS pearl: In a CCS case with suspected RPGN, the order set is: CBC, BMP, UA with microscopy, urine protein:creatinine, ANCA (PR3 + MPO), anti-GBM, ANA, C3, C4, hepatitis serologies, HIV, CXR, renal ultrasound — then advance the clock and consult nephrology for urgent renal biopsy within 24–48 hours. Initiating pulse steroids before biopsy is acceptable when biopsy delay is unavoidable and suspicion is high.
— Organ-threatening / severe disease: rising creatinine, alveolar hemorrhage, mononeuritis multiplex, gut ischemia, cardiac involvement — requires aggressive induction
— Non-organ-threatening / limited disease: sinonasal, skin, joint, mild eye involvement without renal/pulmonary compromise — can use less intensive induction
— Creatinine at presentation (strongest predictor of renal recovery)
— Percentage of normal glomeruli on biopsy (Berden class)
— Need for dialysis at diagnosis (~40% recover renal function if treated promptly)
— Induction (3–6 months): achieve remission
— Maintenance (≥18–24 months, often longer): prevent relapse
— Relapse management: re-induction
— Treat immediately once diagnosis is reasonably certain — delays cause irreversible nephron loss
— Co-manage with nephrology + rheumatology (and pulmonology if DAH, ENT if upper airway disease)
— Screen for and prevent infections before starting immunosuppression: TB (IGRA), hepatitis B/C, HIV, strongyloides (in at-risk populations), update vaccines (inactivated only once on immunosuppression)
— Five-Factor Score (FFS): age >65, cardiac involvement, GI involvement, renal insufficiency (Cr >1.7), absence of ENT symptoms — each point increases 5-year mortality
— Renal Risk Score (Brix): combines biopsy %normal glomeruli, %interstitial fibrosis, eGFR — predicts ESKD risk
Step 3 management: A 68-year-old with PR3-ANCA GPA, creatinine 3.2, hemoptysis, and 60% crescents on biopsy has severe organ-threatening disease. The correct induction regimen is pulse methylprednisolone 500–1000 mg IV daily × 3 days → oral prednisone taper PLUS rituximab OR cyclophosphamide. Outpatient azathioprine alone is wrong; observation is wrong; steroids alone are inadequate.
Board pearl: Plasma exchange (PLEX) is no longer routine for AAV after PEXIVAS; reserve for anti-GBM/AAV overlap, severe DAH, or possibly Cr >5.7/dialysis-dependent with careful weighing of infection risk.
— Pulse methylprednisolone 500–1000 mg IV daily × 3 days for severe disease (RPGN, DAH, neuro involvement)
— Followed by oral prednisone, with PEXIVAS-validated reduced-dose taper (starts ~50–60 mg/day, tapers to 5 mg/day by month 5–6) — equally effective and fewer serious infections than standard taper
— Continue low-dose prednisone (~5 mg) through induction; many taper off by 6–12 months
— 375 mg/m² IV weekly × 4 doses, or 1000 mg IV × 2 doses (days 0, 14)
— Preferred for: relapsing disease, PR3-ANCA, young patients (fertility preservation), women of reproductive age
— Pre-medicate with acetaminophen, diphenhydramine, methylprednisolone to reduce infusion reactions
— Screen for hepatitis B (risk of reactivation) — give prophylactic entecavir if HBcAb+
— IV pulse: 15 mg/kg (max 1.2 g) every 2–3 weeks × 3–6 doses (lower cumulative dose, less toxicity than oral)
— Oral: 2 mg/kg/day × 3–6 months (rarely used now)
— Adjust dose for renal function and age (≥60: reduce 25%; ≥70: reduce 50%)
— Mesna to reduce hemorrhagic cystitis risk; aggressive hydration
— Cumulative dose >25 g raises bladder cancer/MDS risk
— Added to rituximab or cyclophosphamide; allows rapid steroid taper
— Approved as adjunct in severe AAV; reduces glucocorticoid toxicity
Board pearl: Rituximab is non-inferior to cyclophosphamide for induction (RAVE trial) and superior for relapsing disease. Choose rituximab when fertility preservation, prior cyclophosphamide exposure, or PR3-ANCA relapse risk is a concern.
Key distinction: Maintenance therapy uses rituximab 500 mg IV every 6 months (MAINRITSAN — superior to azathioprine) for ≥18–24 months; alternatives are azathioprine 2 mg/kg/day or methotrexate 20–25 mg/week (non-renal disease only).
— Strong indication: anti-GBM/ANCA overlap syndrome — treat as Goodpasture (daily PLEX × 14 days or until anti-GBM negative)
— Consider: severe DAH with hypoxemic respiratory failure, Cr >5.7 mg/dL or dialysis-dependent at presentation (controversial — PEXIVAS showed no reduction in death/ESKD but possibly reduced ESKD in highest-risk subgroup)
— Typical regimen: 7 sessions over 14 days, 60 mL/kg per session, replace with albumin (or FFP if active bleeding/recent biopsy)
— Risks: catheter complications, hypocalcemia, coagulopathy, infection, hypotension
— Indications: refractory hyperkalemia, volume overload, uremia, severe acidosis
— Initiate early in oliguric AKI; continue immunosuppression even if dialysis-dependent — ~40% recover renal function within 3–6 months
— If no recovery by 3–6 months, transition to chronic hemodialysis or peritoneal dialysis
— Wait ≥12 months in sustained clinical remission (most centers require ANCA negative or stable low titer is acceptable)
— Outcomes comparable to other causes of ESKD
— Recurrence in allograft ~10–20%
— Subglottic stenosis: intralesional steroid injection + serial dilation; tracheostomy if severe
— Sinonasal disease: nasal saline irrigation, topical steroids; avoid unnecessary surgery during active disease
CCS pearl: A dialysis-dependent AAV patient at presentation should still receive full induction immunosuppression — withholding therapy because "the kidneys are gone" is a common Step 3 trap. Renal recovery off dialysis occurs in a meaningful minority, and untreated extra-renal disease (lung, nerve) progresses.
Step 3 management: For combined anti-GBM + ANCA positivity (more common with MPO-ANCA, older patients), treat as the more aggressive Goodpasture protocol: PLEX + cyclophosphamide (or rituximab) + steroids. Anti-GBM titers should fall to undetectable; ANCA-related relapse risk persists long-term.
— Higher infection-related mortality from immunosuppression than from disease itself
— Lower cyclophosphamide dose (15% reduction at age 60–70; 25% at >70) and shorter induction duration
— Rituximab generally better tolerated — preferred in many elderly patients
— Use PEXIVAS reduced-dose steroid taper — substantially fewer infections
— Aggressive PJP prophylaxis (TMP-SMX); screen for and treat latent TB before therapy
— Bone protection: DEXA, bisphosphonate, calcium/vitamin D
— Cumulative cardiovascular risk from chronic inflammation — manage BP, lipids, diabetes aggressively
— Cyclophosphamide dose adjustment: reduce by 20–30% for eGFR <30; further reduce in elderly
— Rituximab: no renal dose adjustment needed — advantage in CKD
— MMF: no renal dose adjustment; may be used in maintenance
— TMP-SMX prophylaxis: monitor potassium and creatinine; alternatives are dapsone (check G6PD), atovaquone, inhaled pentamidine
— Avoid NSAIDs entirely
— Azathioprine: check TPMT activity before initiation (TPMT-deficient patients develop life-threatening myelosuppression); avoid with concurrent allopurinol/febuxostat (xanthine oxidase inhibition increases active metabolites)
— Methotrexate: contraindicated in significant liver disease, avoid alcohol
— Cyclophosphamide: hepatotoxicity rare but possible
— Rituximab + live vaccines: contraindicated
— Cyclophosphamide + allopurinol: increased marrow toxicity
— Azathioprine + allopurinol/febuxostat: profound myelosuppression — reduce azathioprine 75% or avoid combination
Board pearl: A 75-year-old with new MPA and Cr 3.5 should receive rituximab + reduced-dose prednisone (PEXIVAS taper) + PJP prophylaxis + osteoporosis prophylaxis — not full-dose cyclophosphamide + high-dose prednisone, which carries unacceptable infection mortality in this demographic.
Key distinction: In elderly AAV, infection is the leading cause of death in the first year, not vasculitis itself — calibrate immunosuppression intensity accordingly and monitor closely for opportunistic infections.
— Best outcomes when conceived in sustained remission ≥6–12 months off teratogenic agents
— Pre-conception counseling is essential; involve maternal-fetal medicine + rheumatology + nephrology
— Contraindicated in pregnancy: cyclophosphamide (teratogenic, gonadotoxic), methotrexate, mycophenolate, leflunomide
— Compatible with pregnancy: azathioprine (≤2 mg/kg/day), low-dose prednisone, hydroxychloroquine, rituximab (preferably stopped before conception; if needed, can be given but causes neonatal B-cell depletion)
— Active disease during pregnancy: prednisone ± azathioprine; rituximab in second trimester if severe
— Increased risk of preeclampsia, preterm birth, IUGR, fetal loss — aspirin 81 mg from 12 weeks
— Cyclophosphamide causes premature ovarian insufficiency and azoospermia (dose- and age-dependent)
— Offer GnRH agonist (leuprolide) co-treatment in premenopausal women to reduce ovarian toxicity
— Sperm/oocyte cryopreservation before cyclophosphamide initiation
— Rituximab does not impair fertility — strong rationale for choosing rituximab in young patients
— Rare; GPA most common pediatric AAV
— Subglottic stenosis more common than adults
— Treatment principles similar to adults with weight-based dosing
— Long-term growth, fertility, vaccination, and psychosocial considerations
— Compatible: prednisone (<20 mg/day; otherwise time feeds 4 hours after dose), azathioprine, hydroxychloroquine
— Avoid: cyclophosphamide, methotrexate, mycophenolate
— Rituximab: limited data; generally considered compatible (large molecule, minimal oral absorption)
Step 3 management: A 28-year-old woman with newly diagnosed PR3-ANCA GPA and RPGN who desires future fertility should receive rituximab-based induction (not cyclophosphamide) plus PEXIVAS steroid taper. If cyclophosphamide is unavoidable, add leuprolide for ovarian protection and refer for oocyte cryopreservation.
Board pearl: Pregnancy planning in AAV centers on timing conception during stable remission and switching to pregnancy-compatible immunosuppression (azathioprine ± low-dose prednisone) ≥3 months pre-conception.
— End-stage kidney disease: 20–25% at 5 years despite treatment
— Diffuse alveolar hemorrhage: mortality 25–50% in severe cases
— Pulmonary fibrosis: especially MPO-ANCA/MPA, progressive even without active vasculitis
— Subglottic/tracheal stenosis (GPA): may require repeated dilations
— Permanent neurologic deficits: mononeuritis multiplex often only partially recovers
— Hearing loss, saddle-nose deformity, vision loss from orbital granuloma
— Cardiac involvement (EGPA): cardiomyopathy, arrhythmias, pericarditis — leading cause of EGPA death
— Venous thromboembolism: AAV carries ~7× increased VTE risk (active inflammation, immobility) — maintain low threshold for evaluation
— Infection (the dominant cause of death in first year): bacterial pneumonia, PJP, CMV, fungal, reactivation TB/HBV, late hypogammaglobulinemia from rituximab
— Glucocorticoid toxicity: weight gain, hyperglycemia, hypertension, osteoporosis, osteonecrosis (especially femoral head), cataracts, glaucoma, mood disturbance, adrenal suppression
— Cyclophosphamide: hemorrhagic cystitis, infertility, bladder cancer (lifetime ~5%), myelodysplastic syndrome/AML, leukopenia
— Rituximab: hypogammaglobulinemia (check IgG levels — supplement with IVIG if recurrent infections), late-onset neutropenia, PML (rare), infusion reactions
— Azathioprine: myelosuppression (especially with TPMT deficiency), hepatotoxicity, pancreatitis, increased skin cancer/lymphoma risk
— Accelerated cardiovascular disease from chronic inflammation
— Increased malignancy risk: bladder (cyclophosphamide), skin (immunosuppression), lymphoma
— Relapse: 50% at 5 years (higher in PR3-ANCA, GPA, persistent ANCA positivity, nasal carriage of S. aureus)
Board pearl: S. aureus nasal carriage in GPA is associated with relapse — nasal mupirocin and/or TMP-SMX (which also serves as PJP prophylaxis) reduces upper-airway relapse in GPA.
Key distinction: Once on rituximab maintenance, late-onset hypogammaglobulinemia (IgG <400) with recurrent infections is an indication for IVIG replacement, not necessarily discontinuation of rituximab if disease control depends on it.
— Diffuse alveolar hemorrhage with hypoxemia (SpO₂ <92% on supplemental O₂) or hemoptysis with hemodynamic instability
— Respiratory failure requiring mechanical ventilation
— Hemodialysis-requiring AKI with hyperkalemia or volume overload requiring urgent intervention
— Hemodynamic instability (sepsis, cardiogenic shock from EGPA myocarditis)
— Severe neurologic involvement (CNS vasculitis, cranial nerve palsies)
— Need for emergent plasmapheresis
— Nephrology: any suspected RPGN — for biopsy planning, dialysis access, immunosuppression input
— Rheumatology: confirmation of diagnosis, immunosuppression selection, longitudinal management
— Pulmonology: pulmonary hemorrhage, ILD, bronchoscopy
— ENT: subglottic stenosis (airway emergency), severe sinonasal disease, biopsy
— Ophthalmology: scleritis, orbital pseudotumor, vision loss
— Cardiology: EGPA with troponin elevation or new heart failure
— Neurology: mononeuritis multiplex, suspected CNS vasculitis
— Infectious disease: complex prophylaxis, suspected opportunistic infection
— Inpatient: any organ-threatening manifestation, AKI with active sediment, new diagnosis requiring biopsy + IV induction, infection workup
— Outpatient: stable limited disease (skin, joints, mild sinonasal) with normal renal function, established follow-up, no acute change
— Suspected RPGN → biopsy within 24–48 hours, do not delay immunosuppression for biopsy if delay >72 hours
— Suspected DAH → empiric pulse steroids before BAL results
— Anti-GBM positive → start PLEX same day
CCS pearl: In a CCS case, ordering "rheumatology consult" and "nephrology consult" early — with concurrent labs, imaging, and admission to monitored bed — scores higher than serial single-discipline workup. AAV is a multidisciplinary disease.
Step 3 management: Transfer to a tertiary center if your facility lacks (1) nephrology with renal biopsy capability, (2) plasmapheresis services, (3) ICU-level care, or (4) rheumatology — these patients deteriorate rapidly and care fragmentation worsens outcomes.
— Linear IgG on IF (vs pauci-immune in AAV), anti-GBM antibody positive
— Younger bimodal distribution, often abrupt onset
— Treatment: PLEX + cyclophosphamide + steroids
— Overlap with AAV in ~10% (especially MPO) — check both antibodies
— IgA vasculitis (Henoch-Schönlein): palpable purpura, arthralgia, abdominal pain, IgA nephropathy on biopsy with mesangial IgA deposits; usually children but adult cases occur with renal predominance
— Cryoglobulinemic vasculitis: hepatitis C–associated, low C4, palpable purpura, MPGN pattern, cryoglobulins positive
— Hypocomplementemic urticarial vasculitis: urticaria >24h, low C1q antibodies
— ANA, anti-dsDNA, anti-Sm positive; low C3 and C4
— IF: "full house" (IgG, IgA, IgM, C3, C1q)
— Class III/IV crescentic LN can mimic RPGN clinically — biopsy distinguishes
— Recent streptococcal/staphylococcal infection, ASO/anti-DNase B, low C3 (normal C4 usually)
— Subepithelial humps on EM
— Polyarteritis nodosa (PAN): hepatitis B–associated, microaneurysms on angiography, does NOT cause glomerulonephritis (causes renal artery vasculitis, renovascular hypertension, infarcts) — important distinction
— GCA, Takayasu: do not typically cause GN
Key distinction: PAN does not cause glomerulonephritis — if a vasculitis stem includes RBC casts, dysmorphic hematuria, or biopsy showing GN, eliminate PAN. PAN causes renal infarcts and hypertension via medium-vessel involvement.
Board pearl: Pauci-immune crescentic GN with negative ANCA (10–20% of cases) is sometimes called "ANCA-negative renal-limited vasculitis" — treat as AAV; outcomes similar.
— Infective endocarditis: fever, constitutional symptoms, glomerulonephritis (immune complex), can be ANCA-positive (often PR3); blood cultures, echocardiogram mandatory before steroids
— Hepatitis B/C: PAN (HBV), cryoglobulinemic vasculitis (HCV) — serologies
— HIV: can cause vasculitis-like syndromes, immune complex GN
— Tuberculosis, syphilis, fungi: granulomatous mimics
— Lymphoma, leukemia: paraneoplastic vasculitis, intravascular lymphoma
— Renal cell carcinoma: rare paraneoplastic vasculitis
— Lung cavities in older smokers — always exclude malignancy before assuming GPA
— Hydralazine, propylthiouracil, methimazole, minocycline, levamisole-cocaine, TNF inhibitors, allopurinol
— Often high-titer MPO-ANCA, anti-histone+, anti-dsDNA+
— Management: stop offending agent; immunosuppression for severe organ involvement
— HUS, TTP, atypical HUS, scleroderma renal crisis, malignant hypertension
— Schistocytes, low platelets, MAHA — distinguishing labs (ADAMTS13, complement panel)
— Post-catheterization, eosinophilia, livedo, AKI, blue toes — biopsy shows cholesterol clefts
— Granulomas + multisystem, but ACE elevation, hilar lymphadenopathy, hypercalcemia
— Tumefactive lesions, elevated IgG4, storiform fibrosis on biopsy
— Mimics GPA sinonasal disease; positive PR3 or atypical ANCA; urine toxicology
Step 3 management: Always obtain blood cultures and echocardiogram before immunosuppressing a presumed AAV patient with fever and GN — endocarditis with septic emboli can mimic AAV exactly, and immunosuppression in undiagnosed endocarditis is catastrophic.
Board pearl: In a stem with chronic cocaine use + sinonasal destruction + PR3-ANCA, the diagnosis may be cocaine/levamisole-induced vasculitis, not GPA — cessation is the primary intervention; immunosuppression only for severe systemic disease.
— Rituximab 500 mg IV every 6 months — preferred (MAINRITSAN, MAINRITSAN 2, RITAZAREM trials show superiority to azathioprine for relapse prevention)
— Alternatives: azathioprine 2 mg/kg/day or methotrexate 20–25 mg/week (non-renal disease only, requires preserved renal function)
— Mycophenolate mofetil: second-line; some evidence in maintenance
— Continue low-dose prednisone (5 mg) in many patients; some advocate stopping by 6–12 months per PEXIVAS
— TMP-SMX SS daily (or DS three times weekly) for PJP — continue throughout induction and ≥6 months after rituximab/until CD4 recovery
— Antiviral prophylaxis if HBcAb+ on rituximab: entecavir or tenofovir
— Influenza vaccine annually, pneumococcal (PCV20 or PCV15+PPSV23), shingles (Shingrix — recombinant, safe on immunosuppression), COVID-19 — administer before rituximab when possible (response blunted for ≥6 months after rituximab)
— Calcium 1000–1200 mg/day, vitamin D 800–2000 IU/day
— Bisphosphonate for patients on ≥7.5 mg prednisone for ≥3 months or with low DEXA
— Baseline DEXA, repeat every 1–2 years
— Statin per ASCVD risk (chronic inflammation accelerates atherosclerosis)
— BP target <130/80 (ACE inhibitor or ARB preferred for proteinuria, renoprotection)
— Smoking cessation
— Aspirin if established ASCVD
— Annual skin exam (immunosuppression)
— Bladder cancer surveillance with urinalysis ± cystoscopy in patients with cumulative cyclophosphamide exposure (especially >25 g) — lifelong
— Age-appropriate screening (mammography, colonoscopy, cervical)
— Recognize relapse symptoms; report promptly
— Avoid live vaccines while on immunosuppression
— S. aureus decolonization in GPA with mupirocin if recurrent nasal carriage
Step 3 management: At discharge from AAV induction admission, the medication list typically includes prednisone (tapering schedule written explicitly), rituximab (planned q6mo) or oral immunosuppressant, TMP-SMX, calcium/vitamin D, bisphosphonate, PPI, ACE inhibitor, statin — plus written instructions on warning signs (hemoptysis, hematuria, dyspnea, fever).
Board pearl: Vaccinate BEFORE rituximab when possible — B-cell depletion blunts vaccine response for 6+ months. The window between diagnosis and first rituximab dose is precious for catch-up immunization.
— First 3 months: every 2–4 weeks (active induction, drug titration, infection surveillance)
— Months 3–12: every 1–2 months
— Year 1–2: every 2–3 months
— Beyond year 2 in stable remission: every 3–6 months — but lifelong follow-up
— Symptom review (constitutional, ENT, pulmonary, renal, neurologic, skin) — Birmingham Vasculitis Activity Score (BVAS) used in research
— Blood pressure, weight
— CBC with differential (immunosuppression toxicity, eosinophilia in EGPA)
— BMP, urinalysis with microscopy, urine protein:creatinine — monitor for renal relapse (microscopic hematuria + proteinuria = early relapse)
— ESR, CRP
— ANCA titer: trend over time — rising titer increases relapse risk but does not mandate treatment in isolation
— Liver function (azathioprine, methotrexate)
— CD19+ B-cell count in rituximab patients — guides re-dosing timing
— Quantitative immunoglobulins (IgG, IgA, IgM) annually on rituximab — surveil for hypogammaglobulinemia
— DEXA every 1–2 years on chronic steroids
— Urinalysis for hematuria (bladder cancer screening after cyclophosphamide)
— Skin examination
— Vaccinations
— Lipids, A1c
— Annual PFTs and chest imaging if known ILD
— High-resolution CT if new respiratory symptoms
— Sick-day rules: hold immunosuppressants during serious infection (with prescriber input); stress-dose steroids if on chronic prednisone undergoing surgery/severe illness
— Fever protocol: temperature >100.4°F → contact rheumatology/PCP same day, low threshold for evaluation
— Relapse warning signs: new hemoptysis, sinusitis, hematuria, foot drop, purpura, weight loss
— Adherence: missed rituximab dose increases relapse risk
CCS pearl: Schedule labs 1 week before each follow-up visit so results are available for decision-making — and document the next rituximab infusion date at discharge. Care gaps drive relapse.
Board pearl: Microscopic hematuria + proteinuria in an AAV patient in clinical remission is renal relapse until proven otherwise — repeat ANCA, consider biopsy, do not wait for elevated creatinine to act.
— Document discussion of fertility risks (especially cyclophosphamide) and offer fertility preservation referral — failure to offer is a recognized malpractice exposure
— Long-term malignancy risk (bladder, MDS/AML, skin) — must be disclosed
— Infection risk including opportunistic infections — informed consent should include realistic mortality discussion in elderly
— In dialysis-dependent elderly patients with severe comorbidity, discuss whether aggressive induction immunosuppression aligns with patient values — some patients elect supportive dialysis without immunosuppression
— Advance directives, healthcare proxy, code status — revisit at each major decision point
— Hospital-to-outpatient handoff: explicit communication of taper schedule, next rituximab date, PJP prophylaxis, lab follow-up plan — medication reconciliation errors at discharge are a leading cause of relapse and toxicity
— Subspecialty-to-PCP handoff: PCP must know to avoid live vaccines, manage steroid stress dosing, recognize infection warning signs
— Avoid abrupt steroid discontinuation — taper schedules must be written explicitly, not "follow up with rheum"
— Medication errors: cyclophosphamide and methotrexate are high-alert drugs — verify dosing intervals (methotrexate is weekly, not daily — daily dosing is fatal)
— TPMT testing before azathioprine — failure to test is a sentinel safety issue
— Vaccine errors: avoid MMR, varicella, yellow fever, intranasal flu, and live shingles (Zostavax — now off market) while on immunosuppression
— Latent TB identified on pre-immunosuppression IGRA: treat per CDC; report to health department if active TB
— Reportable infections: hepatitis B/C reactivation, active TB
— Rituximab and avacopan are expensive — prior authorization and patient assistance programs may be needed; document medical necessity carefully
Step 3 management: A patient with AAV on chronic prednisone scheduled for elective surgery requires stress-dose hydrocortisone (50–100 mg IV at induction, then taper) — communicate this to the surgical team in writing pre-operatively. Failure to provide perioperative stress dosing in adrenally suppressed patients is a preventable cause of intra-operative hypotension and is a Step 3 patient safety favorite.
Board pearl: Always verify methotrexate is dosed weekly, not daily — daily dosing causes fatal pancytopenia and mucositis and is a classic ambulatory prescribing error.
— PR3-ANCA (c-ANCA) → GPA, higher relapse rate
— MPO-ANCA (p-ANCA) → MPA, EGPA; more renal-predominant, more ILD
— Both PR3 and MPO → suspect drug-induced
— Atypical p-ANCA (anti-lactoferrin, anti-elastase) → IBD, autoimmune hepatitis, cocaine-levamisole
— Saddle-nose deformity → GPA
— Subglottic stenosis → GPA
— Late-onset asthma + eosinophilia + cardiomyopathy → EGPA
— Pauci-immune crescentic GN → AAV (until proven otherwise)
— Normal complements + RPGN → AAV (vs lupus, post-infectious, MPGN — all low complement)
— Mononeuritis multiplex → vasculitis (AAV, PAN, cryoglobulinemia)
— DAH + AKI → pulmonary-renal syndrome (AAV, anti-GBM, lupus)
— RAVE: rituximab non-inferior to cyclophosphamide for induction
— RITUXVAS: rituximab + cyclophosphamide vs cyclophosphamide alone — comparable
— MAINRITSAN/MAINRITSAN 2: rituximab superior to azathioprine for maintenance
— RITAZAREM: rituximab > azathioprine for relapsing disease maintenance
— PEXIVAS: reduced-dose steroids non-inferior; PLEX did not reduce death/ESKD
— ADVOCATE: avacopan + rituximab/cyclophosphamide enables steroid sparing
— Hydralazine, i = thIonamides (PTU, methimazole), Minocycline, Propylthiouracil, Allopurinol, Levamisole-adulterated cocaine, anti-TNF (iLfliximab)
Board pearl: Memorize the "PR3 = GPA, MPO = MPA, eosinophilia = EGPA" triad, then layer organ-specific findings on top — this single framework solves the majority of AAV stems.
— "A 64-year-old man with 6 weeks of fatigue presents with hemoptysis and Cr 3.4. UA: 50 RBC, RBC casts. CXR: bilateral patchy infiltrates."
— Answer pathway: send ANCA + anti-GBM + complements → renal biopsy → induction with steroids + rituximab; BAL if DAH suspected
— "A 58-year-old woman with 4 months of bloody nasal discharge and crusting, now with new microscopic hematuria. Saddle-nose deformity on exam."
— Answer: GPA; check PR3-ANCA, urine microscopy, CT sinuses, biopsy
— "A 50-year-old with long-standing asthma develops weight loss, peripheral eosinophilia 8000/µL, and right foot drop."
— Answer: EGPA; check MPO-ANCA, EMG, echocardiogram, troponin (cardiac involvement risk)
— "A 72-year-old on hydralazine for HTN develops arthralgias, palpable purpura, hematuria. High-titer MPO-ANCA, anti-histone+."
— Answer: stop hydralazine; immunosuppress only if severe organ involvement
— Pauci-immune IF → AAV
— Linear IgG → anti-GBM
— "Full house" or granular → lupus
— Granular subepithelial humps → post-infectious
— Young woman desiring fertility → rituximab (not cyclophosphamide)
— Severe DAH + dialysis-dependent → steroids + rituximab/cyclophosphamide; consider PLEX
— Anti-GBM + ANCA overlap → add PLEX
— Patient on azathioprine maintenance relapses → switch to rituximab maintenance
— Patient on chronic prednisone undergoing elective procedure → stress-dose hydrocortisone
— Check IgG level → hypogammaglobulinemia → IVIG replacement
— Fever + GN + ANCA-positive but with murmur, embolic phenomena → echocardiogram and blood cultures before immunosuppression
Step 3 management: Recognize that the "best next step" in most AAV stems is either (1) the appropriate diagnostic test (ANCA, biopsy, BAL), (2) the correct induction regimen tailored to severity and patient factors, or (3) the infection-prevention adjunct (PJP prophylaxis, vaccination, TB screening) — the distractors usually omit one of these three.
ANCA-associated vasculitis with renal involvement is a pauci-immune necrotizing small-vessel vasculitis (GPA/MPA/EGPA) presenting as rapidly progressive glomerulonephritis — diagnosed by ANCA serology plus renal biopsy showing crescentic pauci-immune GN, treated with prompt induction (glucocorticoids + rituximab or cyclophosphamide, with avacopan as a steroid-sparing adjunct) followed by years of rituximab maintenance, supported by infection prophylaxis, vaccination, and lifelong relapse surveillance.
— Older adult with constitutional symptoms + AKI + active urine sediment (RBC casts) → send PR3/MPO-ANCA, anti-GBM, complements (normal in AAV); pursue renal biopsy showing pauci-immune crescentic GN
— Always exclude endocarditis, drug-induced AAV (hydralazine, PTU, levamisole-cocaine), and anti-GBM overlap before committing to a treatment plan
— Induction: pulse methylprednisolone → reduced-dose PEXIVAS prednisone taper + rituximab (preferred, especially for relapsing, PR3+, fertility concerns) or cyclophosphamide; add avacopan to spare steroids; PLEX reserved for anti-GBM overlap and selected severe cases
— Maintenance: rituximab 500 mg IV every 6 months for ≥18–24 months (superior to azathioprine)
— TMP-SMX for PJP prophylaxis, vaccinate before rituximab when possible, calcium/vitamin D + bisphosphonate for steroid bone protection, S. aureus decolonization in GPA, lifelong bladder cancer surveillance after cyclophosphamide
— Perioperative stress-dose steroids; methotrexate is weekly, not daily — a high-alert prescribing pitfall
— Outcomes depend on how quickly induction begins; renal recovery off dialysis occurs in ~40% even when dialysis-dependent at presentation; relapse rate ~50% at 5 years (higher in PR3-ANCA/GPA); infection — not vasculitis — is the leading cause of death in the first year, so calibrate immunosuppression to age, organ severity, and comorbidity
Board pearl: "Pauci-immune crescentic GN with normal complements" = AAV until proven otherwise — the single highest-yield Step 3 trigger phrase for this diagnosis.