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.
Think
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
Remember
ENT involvement is uncommon in MPA (minus points) – unlike GPA.
Remember
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)
Remember
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
Side note
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.
References
- Watts R, et al. Rheumatology (Oxford). 2007;46(9):1356–1357.
- Robson J, et al. Ann Rheum Dis. 2022;81(3):315–320.
- Yates M, et al. Ann Rheum Dis. 2022;81(3):309–314.
- Chung SA, et al. Arthritis Rheumatol. 2021;73(8):1366–1383.
- Jennette JC, et al. Kidney Int. 2013;83(2):227–234.
Discussion