What are the diagnostic criteria for Microscopic Polyangiitis (MPA)?

Diagnostic Criteria for Microscopic Polyangiitis (MPA)

There are no validated diagnostic criteria for MPA; diagnosis requires a combination of clinical features (particularly rapidly progressive glomerulonephritis and pulmonary capillaritis), MPO-ANCA positivity (present in ~75% of cases), and histopathological evidence of necrotizing vasculitis with pauci-immune glomerulonephritis when feasible. 1

Core Diagnostic Elements

Clinical Manifestations Required

The diagnosis of MPA should be based on highly suggestive clinical features combined with objective evidence of vasculitis 1:

• Renal involvement is the hallmark feature, presenting as rapidly progressive glomerulonephritis with hematuria, proteinuria, and progressive renal insufficiency (creatinine >120 μmol/L in majority of patients) 1, 2
• Pulmonary capillaritis occurs frequently, with alveolar hemorrhage in 12-29% of patients, representing a major contributor to mortality 1, 2
• Systemic vasculitis symptoms including fever, weight loss, and malaise precede diagnosis in most patients 2

Laboratory Findings

• MPO-ANCA positivity is detected in approximately 75% of MPA patients using high-quality antigen-specific assays 1, 2
• A minority may have PR3-ANCA, and some patients are ANCA-negative 1
• Elevated inflammatory markers (ESR, CRP) reflect systemic inflammation 2
• Hepatitis B virus surface antigen is negative in almost all patients, distinguishing MPA from polyarteritis nodosa 2

Histopathological Confirmation

Biopsy is strongly recommended when feasible but not essential for diagnosis 1:

• Renal biopsy shows pauci-immune necrotizing and crescentic glomerulonephritis, which is the gold standard histopathological finding 1, 3
• Skin or lung biopsy may demonstrate necrotizing vasculitis of small vessels (capillaries, venules, arterioles) without immune deposits 1, 2
• Absence of granulomatous inflammation distinguishes MPA from granulomatosis with polyangiitis 1

Additional Clinical Features Supporting Diagnosis

Common Organ Involvement

• Cutaneous manifestations (44-58%): purpura, splinter hemorrhages, and necrotizing vasculitis of the skin 2, 3
• Musculoskeletal symptoms (65-72%): myalgias, arthralgias, and arthritis 2
• Peripheral neuropathy (14-36%): less frequent than in polyarteritis nodosa 2
• Gastrointestinal involvement (32-58%): abdominal pain and digestive tract bleeding 2
• ENT and ocular manifestations: more common than in polyarteritis nodosa 2
• Central nervous system involvement: rare but can include pachymeningitis and cerebral ischemic insults 3, 4

Key Diagnostic Distinctions

Differentiation from Other Vasculitides

MPA must be distinguished from polyarteritis nodosa and granulomatosis with polyangiitis 1, 2:

• Versus Polyarteritis Nodosa: MPA has predominant small vessel involvement, frequent glomerulonephritis and pulmonary involvement, MPO-ANCA positivity, and absence of microaneurysms on visceral angiography 2
• Versus Granulomatosis with Polyangiitis: MPA lacks granulomatous inflammation, has predominantly MPO-ANCA (not PR3-ANCA), and less upper respiratory tract involvement 1
• Versus Henoch-Schönlein Purpura: MPA has pauci-immune (not IgA-dominant) glomerulonephritis and MPO-ANCA positivity 5

Chapel Hill Consensus Conference Definition

The 2012 revised Chapel Hill Consensus Conference defines MPA as 1:

• Necrotizing vasculitis with few or no immune deposits
• Predominantly affecting small vessels (capillaries, venules, arterioles)
• Necrotizing arteritis of small and medium arteries may be present
• Necrotizing glomerulonephritis is very common
• Pulmonary capillaritis often occurs
• Granulomatous inflammation is absent

Critical Diagnostic Pitfalls

Classification criteria should never be used as diagnostic criteria - they were developed to distinguish between vasculitis types in research settings, not for clinical diagnosis 6:

• The 1990 ACR criteria and 2022 ACR-EULAR criteria have established sensitivity and specificity for classification but lack validation for diagnosis 6
• Diagnosis must rely on the combination of clinical presentation, ANCA testing, and histopathology when available 1

ANCA-negative MPA exists - approximately 25% of patients may be ANCA-negative, making histopathological confirmation particularly important in these cases 1, 2

Poor prognostic indicators include acute renal failure at presentation, central nervous system involvement, and high scores of fibro-cellular glomerular crescents on biopsy 3