Microscopic Polyangiitis Armando Hasudungan

Overview

Microscopic polyangiitis (MPA) is a small-vessel necrotizing vasculitis, commonly associated with myeloperoxidase-ANCA (MPO-ANCA) positivity. It typically presents with glomerulonephritis and pulmonary capillaritis, but does not involve granulomatous inflammation, distinguishing it from GPA.Incidence: ~3–24 cases per million annually; more common in middle-aged adults and slightly more frequent in males. ¹

Definition

MPO-ANCA (Myeloperoxidase-ANCA): An autoantibody typically associated with MPA, targeting myeloperoxidase in neutrophils and contributing to vessel inflammation.
Pauci-immune glomerulonephritis: A type of rapidly progressive kidney inflammation seen in MPA with little or no immune complex deposition on biopsy.
Pulmonary capillaritis: Inflammation of lung capillaries leading to alveolar hemorrhage, a serious respiratory complication of MPA.
Necrotizing vasculitis: Destructive inflammation of small to medium-sized blood vessels without granulomas, characteristic of MPA.

Aetiology and Risk Factors

Aetiology

Unknown
ANCA (especially MPO-ANCA) plays a central pathogenic role.

Risk Factors

Genetic predisposition
Medication induced ANCA vasculitis
Infections (e.g. Staphylococcus aureus)

Pathophysiology

Trigger (e.g. drug/infection) activates neutrophils.
ANCA binds to neutrophil antigens (mainly MPO).
Activated neutrophils adhere to endothelium and release lytic enzymes and ROS.
Result: vessel wall necrosis (leukocytoclastic vasculitis), inflammation, and thrombosis.
No granulomas formed (key differentiator from GPA).

MPA affects small vessels, including capillaries, venules, and arterioles. Involvement often includes:

Renal system: glomerular capillaries → rapidly progressive glomerulonephritis.
Pulmonary system: alveolar capillaries → alveolar hemorrhage.

Pulmonary-renal syndrome in a patient with MPO-ANCA strongly suggests MPA. However GPA and Anti-GBM also involve pulmonary-renal syndrome (typically with other autoantibodies).

Clinical Manifestations

Constitutional: Fever, malaise, weight loss, fatigue
Pulmonary (85%): Cough, haemoptysis, pleuritic chest pain
Renal (80%): Microscopic haematuria, proteinuria, rising creatinine → rapidly progressive GN
Neurological: Mononeuritis multiplex (e.g., foot drop)
Vasculitic orchitis
Palpable purpura (Leukocytoclasic vasculitis)
Polyarthralgia

Skin: Palpable purpura, ulcers

ENT involvement is uncommon in MPA (minus points) – unlike GPA.

Pulmonary haemorrhage is most common with MPA>GPA>EGPA.

Diagnosis

Classification Criteria (2022 ACR/EULAR)

Entry Requirement: A diagnosis of small- or medium-vessel vasculitis has been made (biopsy), and other mimicking conditions have been excluded.
Variables	GPA	MPA	EGPA
Clinical criteria
Nasal passage involvement	+3	−3	—
Cartilaginous involvement	+2	—	—
Conductive or sensorineural hearing loss	+1	—	—
Obstructive airway disease	—	—	+3
Nasal polyp	—	—	+3
Mononeuritis multiplex	—	—	+1
Laboratory criteria
PR3-ANCA (or C-ANCA) positivity	+5	−1	−3
MPO-ANCA (or P-ANCA) positivity	−1	+6	—
Serum eosinophil ≥1000/µL	−4	−4	+5
Hematuria	—	—	−1
Histological criteria
Granuloma, granulomatous inflammation, or giant cells	+2	—	—
Pauci-immune glomerulonephritis	+1	+3	—
Extravascular eosinophilic-predominant inflammation	—	—	+2
Radiological criteria
Pulmonary nodules, mass, or cavitation on chest imaging	+2	—	—
Fibrosis or ILD on chest imaging	—	+3	—
Nasal/paranasal sinusitis or mastoiditis on imaging	+1	—	+1
Total Score Cut-off for Classification	≥5	≥5	≥6

Investigations

MPO-ANCA+
Raised CRP/ESR
Elevated creatinine and reduced eGFR
Urinalysis: hematuria, red cell casts, proteinuria
Imaging: CXR/CT chest for pulmonary hemorrhage or ILD
Biopsy: kidney (pauci-immune GN), skin (leukocytoclastic vasculitis)

Classification

MPA is classified under ANCA-associated vasculitides alongside:

Granulomatosis with polyangiitis (GPA)
Eosinophilic granulomatosis with polyangiitis (EGPA)

Treatment

Induction (Severe/Relapse)

Glucocorticoids (IV methylprednisolone then tapering oral pred)
Immunosuppressants:
- Rituximab (preferred for relapse) or Cyclophosphamide
Avacopan (C5a inhibitor)

Induction (Non-severe)

Glucocorticoids + Methotrexate or Mycophenolate mofetil

Maintenance

Rituximab (first-line) or Azathioprine, Methotrexate

Supportive

TMP-SMX prophylaxis (for PCP)
Vaccination (influenza, pneumococcal, shingles if on JAK inhibitor)
Bone protection (DEXA, calcium, vit D)

Relapse rates are lower in MPA vs GPA.

Complications and Prognosis

Complications

ESRD from glomerulonephritis
Pulmonary hemorrhage
Infections from immunosuppression
ILD
Increased risk of VTE during active disease
Treatment side effects: infertility, cytopenias, malignancy (CYC)

Prognosis

5-year survival ~75–90% with modern therapy
Poor prognostic factors:
- Dialysis dependence at presentation
- ILD
- Alveolar hemorrhage
- Advanced age, cardiac involvement

Pulmonary hemorrhage occurs in ~12 % of patients with MPA but is associated with high mortality (~10–25 %); importantly, up to half may have silent hemorrhage without hemoptysis.