What are the diagnostic criteria for Myeloperoxidase (MPO)-related conditions?

Diagnostic Criteria for MPO-ANCA-Associated Vasculitis

The diagnosis of MPO-ANCA-associated vasculitis requires histological confirmation of necrotizing vasculitis or pauci-immune glomerulonephritis on biopsy, combined with positive MPO-ANCA serology by ELISA and P-ANCA pattern on immunofluorescence, in the context of compatible clinical manifestations affecting multiple organ systems. 1, 2

Core Diagnostic Requirements

Serological Criteria

• High-quality antigen-specific ELISA for MPO-ANCA is the preferred screening method, with approximately 90% sensitivity in small-vessel vasculitis 2
• P-ANCA pattern on immunofluorescence should accompany positive MPO-ANCA ELISA for diagnostic confirmation 1
• Higher ANCA titers significantly increase the likelihood of true vasculitis (OR 14.16,95% CI 6.93-28.94), helping distinguish AAV from other conditions that can cause positive ANCA 3
• MPO-ANCA titers correlate with disease activity and decrease following effective therapy 4

Histopathological Criteria (Gold Standard)

• Biopsy showing necrotizing vasculitis, pauci-immune glomerulonephritis, or eosinophil-rich granulomatous inflammation establishes definitive diagnosis 1, 2
• Renal biopsy demonstrating necrotizing glomerulonephritis with few or no immune deposits is characteristic 5, 6
• Biopsy should be obtained in most cases, though treatment should not be delayed in rapidly deteriorating patients 1, 2

Clinical Criteria (When Biopsy Unavailable)

Patients without confirmatory biopsy may be diagnosed if they have:

• Positive MPO-ANCA/P-ANCA serology PLUS compatible clinical picture affecting multiple organ systems 1, 2
• Multiple affected organ systems significantly increase diagnostic probability (OR 7.67,95% CI 3.69-15.94) 3

Specific Clinical Manifestations Supporting Diagnosis

Renal Involvement

• Red cell casts or dysmorphic erythrocytes in urine 1
• Rapidly progressive glomerulonephritis 5
• Positive urine occult blood test 6

Pulmonary Involvement

• Fixed pulmonary infiltrates, nodules, or cavitations 1
• Diffuse alveolar hemorrhage 1
• Organizing pneumonia pattern on imaging (less common presentation) 6

Neurological Involvement

• Rapid-onset mononeuritis multiplex 1

Other Manifestations

• Episcleritis 1
• Purpura (more common in ANCA-positive patients) 1

Disease Classification Framework

MPO-ANCA vs PR3-ANCA Vasculitis

• MPO-ANCA-associated vasculitis predominantly affects small vessels without granulomatous inflammation (classified as Microscopic Polyangiitis) 2, 5
• MPO-ANCA-positive GPA represents a distinct subset with less severe renal involvement and higher female predominance compared to PR3-ANCA-positive GPA 7
• Up to 30% of MPA patients may be PR3-ANCA positive, so ANCA subtype alone should not determine classification 2

Required Duration and Exclusions

• History of chronic inflammatory disease lasting at least 4 weeks 1
• Exclusion of infections and malignancies that can mimic vasculitis is mandatory 1
• Alternative diagnoses to exclude include inflammatory bowel disease, other rheumatic diseases, infections, and malignancies 3

Critical Diagnostic Pitfalls to Avoid

• Do not delay treatment in ANCA-positive patients with compatible clinical presentation while awaiting biopsy, particularly in rapidly deteriorating patients 2
• Do not rely on classification criteria (ACR/CHCC) for primary diagnosis, as these are not suitable for initial diagnostic purposes 1
• Do not dismiss low-titer MPO-ANCA, though high titers are more specific for true vasculitis 3, 4
• Do not overlook MPO-ANCA positivity in patients with organizing pneumonia, as this can be a rare presentation requiring ANCA and occult hematuria testing 6
• Do not use ANCA subtype alone for disease classification, as clinical phenotype and histology must be integrated 2, 7

Diagnostic Algorithm Summary

1. Screen with antigen-specific MPO-ANCA ELISA in patients with compatible multi-system symptoms 2
2. Confirm with P-ANCA immunofluorescence pattern 1
3. Obtain tissue biopsy (kidney, lung, or other affected organ) showing necrotizing vasculitis or pauci-immune glomerulonephritis 1, 2
4. If biopsy unavailable or negative, diagnose based on high ANCA titer plus multiple affected organ systems with characteristic surrogate markers 1, 3
5. Exclude infections and malignancies before confirming diagnosis 1
6. Monitor ANCA titers to assess disease activity and treatment response 4