Microscopic Polyangiitis

ANCA-associated small-vessel vasculitis characterised by necrotising vasculitis without granulomata, predominantly affecting the kidneys and lungs. Strongly associated with p-ANCA/MPO antibodies. Distinguished from GPA by the absence of granulomatous inflammation and upper airway involvement.

Key Facts

MPA is characterised by pauci-immune crescentic GN and pulmonary haemorrhage WITHOUT granulomata or upper airway involvement p-ANCA (anti-MPO): positive in ~70%; c-ANCA (anti-PR3) in ~20% Renal involvement is the most common organ manifestation (>80%); MPA is the most common cause of pulmonary-renal syndrome after GPA No upper airway involvement (unlike GPA); no asthma (unlike EGPA) Treatment: same as GPA – rituximab or cyclophosphamide induction; rituximab or azathioprine maintenance Lower relapse rate than GPA (MPO-ANCA associated with fewer relapses than PR3-ANCA) Higher mortality than GPA: more severe renal disease at presentation Skin: palpable purpura; nervous system: mononeuritis multiplex

Overview

Key Facts

MPA is often considered the 'renal-dominant' ANCA vasculitis. It presents with severe renal disease and/or pulmonary haemorrhage.

Epidemiology

  • Incidence: ~5-10 per million/year
  • Peak age: 60-70; M=F or slight male predominance
  • More common in Japanese populations

Pathophysiology

  • Anti-MPO antibodies activate neutrophils → necrotising small-vessel vasculitis
  • NO granuloma formation (distinguishing feature from GPA and EGPA)
  • Pauci-immune GN: minimal immunoglobulin deposition on biopsy
  • Pulmonary capillaritis → diffuse alveolar haemorrhage

Clinical Presentation

Renal (>80%)

  • Rapidly progressive GN: rising creatinine, haematuria, proteinuria
  • May present as RPGN
  • Often the predominant organ involved

Pulmonary

  • Diffuse alveolar haemorrhage: haemoptysis, dyspnoea, ground-glass on CT
  • Pulmonary-renal syndrome
  • ILD (rarely fibrotic)

Other

  • Constitutional: fever, weight loss, malaise
  • Skin: palpable purpura, livedo reticularis
  • Nervous system: mononeuritis multiplex (30%)
  • GI: mesenteric vasculitis
  • Eyes: scleritis (less common than GPA)

Red Flags

  • Pulmonary haemorrhage → life-threatening; consider plasma exchange
  • Rapidly rising creatinine → urgent renal biopsy and treatment

Differential Diagnosis

DiagnosisKey FeaturesInvestigation
GPAUpper airway involvement, granulomata, PR3-ANCAANCA, biopsy
Anti-GBM diseaseLinear IgG, anti-GBM positiveAnti-GBM, biopsy
SLEANA/dsDNA positive, low complementImmunology
IgA vasculitisPurpura, IgA depositsBiopsy
Polyarteritis nodosaMedium vessels, aneurysms, no GNAngiography

Diagnosis / Investigation

Bloods

  • p-ANCA (anti-MPO): positive in ~70%
  • c-ANCA (anti-PR3): positive in ~20%
  • U&Es: often significantly impaired
  • Urinalysis: haematuria, red cell casts
  • CRP/ESR: elevated
  • Anti-GBM: exclude dual positivity

Imaging

  • CT chest: ground-glass (haemorrhage)
  • Renal USS: normal-sized kidneys

Biopsy

  • Renal biopsy: focal segmental necrotising GN with crescents; pauci-immune (no/minimal Ig on IF)
  • No granulomata (distinguishes from GPA)

Management

Induction

  • Rituximab 375mg/m² × 4 or IV cyclophosphamide + prednisolone 1mg/kg tapering
  • Plasma exchange: consider if severe renal disease (creatinine >500) or pulmonary haemorrhage

Maintenance

  • Rituximab 500mg every 6 months (MAINRITSAN) or azathioprine for ≥24 months

Supportive

  • PCP prophylaxis (co-trimoxazole)
  • Bone protection
  • BP control with ACEi/ARB

Referral

  • All MPA → nephrology + rheumatology
  • Pulmonary haemorrhage → ICU

Prognosis

  • 5-year survival: 70-75% (slightly lower than GPA)
  • Relapse rate: 20-30% (lower than GPA; MPO < PR3 for relapse)
  • Renal prognosis: depends on creatinine at presentation; dialysis-dependent at presentation = 30% recover renal function
  • Leading cause of death: infections (immunosuppression), renal failure
  • More severe renal disease at presentation compared to GPA

Other Relevant Information

MPA vs GPA

FeatureMPAGPA
ANCAp-ANCA/MPO (70%)c-ANCA/PR3 (90%)
Upper airwayNoYes (sinusitis, saddle nose)
GranulomataNoYes
Renal+++ (predominant)++
PulmonaryDAHCavitating nodules, DAH
Relapse rateLowerHigher