Phenotypic characterization of patients with ANCA-associated vasculitis and diffuse alveolar hemorrhage: a data-driven analysis of a multicentre, retrospective, nationwide cohort.

BACKGROUND

Severe diffuse alveolar hemorrhage (DAH) is a potentially fatal complication of ANCA-associated vasculitides (AAV). This study aimed to identify distinct clinical phenotypes among patients to the ICU, and to examine their association with mortality.

METHODS

We conducted an ancillary analysis of the national multicenter retrospective PLEXHIA cohort, including 197 patients with severe AAV-related DAH, defined by respiratory symptoms with new infiltrates consistent with alveolar hemorrhage, along with oxygen saturation ≤85%, high-flow oxygen or mechanical ventilation requirement. Kohonen self-organizing maps were applied to predefined clinical variables at ICU admission, excluding treatment and outcomes. Clusters were interpreted and compared regarding organ involvement, severity, management, and mortality at 30 and 90 days.

RESULTS

Between 2012 and 2024, 197 patients (66 years old, 52% female) were included, revealing marked clinical heterogeneity. Three phenotypes emerged: The MPO pulmonary-renal (MPO-PR) cluster included patients with anti-MPO ANCA, renal involvement and high oxygen requirements. The mild-respiratory (Mild-R) cluster included predominantly female patients with less severe respiratory compromise and mild renal involvement. The PR3 multi-organ (PR3-MO) cluster involved younger patients with anti-PR3 ANCA, severe acute respiratory failure and multiorgan failure. Renal replacement therapy was most frequent in the MPO-PR group (73%), while invasive mechanical ventilation was most common in the MPO-PR and PR3-MO groups (71% and 68%). Thirty-day mortality differed significantly: 23% (MPO-PR), 4% (mild-R cluster), and 14% (PR3-MO cluster).

CONCLUSION

This large ICU cohort highlights three clinically relevant phenotypes of AAV-related DAH, which could inform the development of phenotype-driven immunosuppressive strategies.