Accurate, early diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is essential, albeit challenging, for timely intervention according to AAV management guidelines.

Historically, the classification criteria for AAV have included 3 items: the 1990 American College of Rheumatology (ACR) criteria, which outline classification criteria for granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA); the 2007 European Medicines Agency (EMA) algorithm for the classification of AAV and polyarteritis nodosa; and the 2012 International Chapel Hill Consensus Conference (CHCC) definitions, which represent the revised nomenclature of vasculitides.

Recently, in 2022, the ACR, together with the European Alliance of Associations for Rheumatology (EULAR), have proposed new classification criteria for AAV—the 2022 ACR/EULAR criteria. These are based on the Diagnostic and Classification Criteria in Vasculitis (DCVAS) data sets for GPA, microscopic polyangiitis (MPA), and EGPA.

To apply the 2022 ACR/EULAR criteria for patients suspected to have AAV, it is essential to fulfill 2 mandatory requirements: a confirmed diagnosis of small- or medium-vessel vasculitis, and other medical conditions resembling vasculitis have been excluded.

Read more about AAV etiology 

These new criteria differ from previous ones in 2 key aspects: they encompass clinical, laboratory, radiological, and histological categories, and they assign differently weighted points to each item and provide cutoff values for the total score to classify GPA, MPA, and EGPA.

Concordance Rates Between New and Previous Criteria

To compare the 2022 ACR/EULAR criteria with previous criteria, Pyo and colleagues applied the new criteria for GPA, MPA, and EGPA to patients who were classified based on the previous criteria for these conditions. According to their analysis, the highest concordance rates between the new and previous criteria were observed in patients with MPA (96.6%), followed by EGPA (86.3%) and GPA (73.8%).

In the article published in Yonsei Medical Journal, Pyo and colleagues also discussed factors contributing to this discordance and suggested improvements for current classification. In the following sections, we highlight their main conclusions.

Patients previously diagnosed with GPA

Factors contributing to the discordance between 2022 ACR/EULAR criteria and previous criteria included:

  • Underestimation of the item related to granuloma, granulomatous inflammation, or giant cells on biopsy, which is a characteristic histological feature of GPA;
  • Underestimation of the item concerning cartilaginous involvement, which is another typical clinical feature of GPA among the AAV subtypes; and
  • Overestimation of the item of proteinase 3 (PR3)-ANCA (or C-ANCA) positivity.

“According to the 2022 ACR/EULAR criteria, if ANCA is not detected even when a patient with clear evidence of necrotizing vasculitis in small vessels together with granuloma on biopsy is suspected of GPA, it may be impossible to classify this patient as having GPA unlike the 2007 EMA algorithm or the 2012 CHCC definitions,” Pyo and colleagues explained.

Experts’ suggestions:

  • Cautious consideration for the revision of assigned points to the items concerning granuloma, granulomatous inflammation, or giant cells on biopsy, as well as cartilaginous involvement.
  • Encouraging biopsy in cases where GPA is strongly suspected, even in the absence of PR3-ANCA (or C-ANCA).
  • Further discussion of the weighted points assigned to the items of myeloperoxidase (MPO)-ANCA (or P-ANCA) and PR3-ANCA (or C-ANCA) positivity.

Patients previously diagnosed with MPA

Factors contributing to the discordance between 2022 ACR/EULAR criteria and previous criteria included:

  • The specific histological findings of major organs related to MPA, excluding pauci-immune glomerulonephritis, did not significantly contribute to the classification of MPA, including ANCA-associated glomerulonephritis or renal-limited vasculitis;
  • Overestimation of the item of MPO-ANCA (or P-ANCA) positivity; and
  • Controversial issue regarding the item pertaining to fibrosis or interstitial lung disease (ILD) observed on chest imaging, which may lead to confusion in real-world clinical practice due to the diverse causes of such conditions.

Experts’ suggestions:

  • Adding a new item of histological features of MPA based on the 2012 CHCC definitions.
  • Downgrading the points assigned to the items of MPO-ANCA (or P-ANCA) positivity due to the presence of various antigenic epitopes of MPO-ANCA (or P-ANCA) and the potential for false positivity of P-ANCA.
  • Evaluation of other causes of lung lesions.
  • Increasing attention to the accurate classification of MPA, particularly in cases where there are no clinical indications suggesting MPA apart from MPO-ANCA (or P-ANCA) positivity.

Read about AAV differential diagnosis

Patients previously diagnosed with EGPA

Factors contributing to the discordance between 2022 ACR/EULAR criteria and previous criteria included:

  • Missing items of nonfixed pulmonary infiltration and paranasal sinusitis for EGPA classification, which are recognized as typical radiological and clinical manifestations of the allergic stage of EGPA;
  • Overestimation of the item of PR3-ANCA (or C-ANCA) positivity; and
  • Overestimation of hematuria.

Experts’ suggestions:

  • Adding a new item concerning nonfixed pulmonary infiltrates.
  • Downgrading points for PR3-ANCA (or C-ANCA) positivity.
  • Reconsidering the hematuria item.

Final Considerations

In an editorial published in Rheumatology, Kronbichler and colleagues raised intriguing questions: is there a genuine necessity to categorize patients into distinct clinical phenotypes? Wouldn’t it be more pragmatic to classify patients with AAV based on their ANCA serotype?

As they discussed, current treatment strategies for GPA and MPA are interchangeable and determined by the severity of the disease and the specific organs affected. Moreover, emerging evidence from recent research has shown that various aspects of the disease course, such as relapse rate, therapy duration, mortality, cardiovascular complications, and more, along with genetic and experimental markers, exhibit a stronger correlation with ANCA status rather than the clinical phenotype.

Therefore, in future revisions of the classification criteria, it may be advisable to place greater emphasis on prognostic factors, such as ANCA status and other biomarkers, rather than solely relying on the clinical phenotype.

While such revisions remain hypothetical, Pyo and colleagues gave a general suggestion for improvement of current AAV classification criteria. “To increase the diagnostic accuracy and reduce the discordance rate among the new and previous criteria for AAV, we suggest that the 2007 EMA algorithm and the 2012 CHCC definitions should be considered together with the 2022 ACR/EULAR criteria when applying the classification criteria for AAV to patients suspected of AAV,” they said.

Reference

Pyo JY, Lee LE, Park Y-B, Lee S-W. Comparison of the 2022 ACR/EULAR classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis with previous criteria. Yonsei Med J. 2023;64(1):11-17. doi:10.3349/ymj.2022.0435

Kronbichler A, Bond M, Dejaco C. Classification criteria for ANCA-associated vasculitis: one size does not fit all! Rheumatology. 2023;62(3):993-995. doi:10.1093/rheumatology/keac423