What is Microscopic Polyangiitis (MPA)?

Microscopic Polyangiitis (MPA): Definition and Clinical Features

Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that primarily affects small vessels without granulomatous inflammation, characterized by pauci-immune glomerulonephritis and pulmonary capillaritis, and is associated predominantly with myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA).

Disease Classification and Epidemiology

MPA belongs to the ANCA-associated vasculitides (AAV) group, along with:

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

The prevalence of MPA ranges from 0 to 66 cases per million in European countries and approximately 86 cases per million in Japan 1. MPA typically affects patients around 50 years of age, with males being more frequently affected than females 2.

Pathophysiology

MPA is characterized by:

• Necrotizing vasculitis affecting small vessels (capillaries, venules, arterioles)
• Possible involvement of small and medium arteries
• Absence of granulomatous inflammation (key distinguishing feature from GPA)
• Association with ANCA, predominantly MPO-ANCA (in approximately 75% of cases)
• Pauci-immune pattern (few or no immune deposits) on immunofluorescence microscopy

Clinical Manifestations

Major Organ Involvement

1. Renal Involvement (most common and significant):

   • Rapidly progressive glomerulonephritis
   • Pauci-immune necrotizing and crescentic glomerulonephritis on histopathology
   • Renal impairment at presentation in most patients

2. Pulmonary Involvement:

   • Pulmonary capillaritis
   • Alveolar hemorrhage (12-29% of patients)
   • Interstitial lung disease mimicking idiopathic pulmonary fibrosis

3. Other Systems:

   • Musculoskeletal: myalgias, arthralgias, arthritis (65-72%)
   • Cutaneous: purpura, splinter hemorrhages (44-58%)
   • Gastrointestinal: abdominal pain (32-58%), digestive tract bleeding (29%)
   • Neurological: peripheral neuropathy (14-36%)
   • Ocular manifestations
   • Ear, nose, and throat lesions

Diagnostic Approach

1. Laboratory Tests:

   • ANCA testing (positive in ~75% of patients, predominantly MPO-ANCA)
   • Elevated inflammatory markers (ESR, CRP)
   • Renal function tests (elevated creatinine)
   • Urinalysis (hematuria, proteinuria)
   • Negative hepatitis B virus surface antigen (differentiating from polyarteritis nodosa)

2. Histopathology:

   • Renal biopsy: pauci-immune necrotizing and crescentic glomerulonephritis
   • Lung biopsy: capillaritis
   • Biopsy of affected tissues (e.g., skin, nerve, nasal mucosa)

3. Imaging:

   • Chest radiography and CT for pulmonary involvement
   • Visceral angiography (microaneurysms rarely seen, unlike in polyarteritis nodosa)

Treatment

According to the 2021 American College of Rheumatology/Vasculitis Foundation guidelines 1:

1. Remission Induction:

   • Rituximab (375 mg/m² once weekly for 4 weeks) plus glucocorticoids is recommended for severe disease
   • Cyclophosphamide plus glucocorticoids is an alternative option

2. Maintenance Therapy:

   • Rituximab for maintenance in severe disease
   • Azathioprine as an alternative option

3. Adjunctive Therapies:

   • Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis or pulmonary hemorrhage 1
   • Reduced-dose glucocorticoid regimens may decrease the risk of serious infections 1

Prognosis and Monitoring

Without treatment, MPA has a poor prognosis with rapid deterioration of renal function. With appropriate immunosuppressive therapy, outcomes have significantly improved. However, relapses are common, necessitating long-term monitoring.

Regular monitoring should include 1:

• Assessment of disease activity using validated clinical tools
• Monitoring of organ-specific manifestations, particularly renal function and pulmonary status
• Surveillance for treatment-related complications (infections, malignancy, osteoporosis)

Differential Diagnosis

• Granulomatosis with polyangiitis (GPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA)
• Polyarteritis nodosa
• Goodpasture's syndrome
• Systemic lupus erythematosus
• Cryoglobulinemic vasculitis
• IgA vasculitis (Henoch-Schönlein purpura)

MPA can be distinguished from GPA by the absence of granulomatous inflammation and from EGPA by the absence of asthma and eosinophilia.