Background Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are necrotizing small-vessel vasculitides in conjunction with autoantibodies to neutrophil constituents. Diffuse alveolar hemorrhage (DAH) and renal involvement are the most serious manifestations, and higher five factor score (FFS) has been associated with higher mortality rate. Although the introduction of cyclophosphamide and corticosteroids has changed the natural history of disease from an almost fatal condition to a relapsing and remitting one with greatly increased survival, patients with AAV still have a 9-fold increased risk of death in the first year of disease. Furthermore, reported causes of death (COD) and risk factors for mortality vary between studies, which indicate the need of further investigation.

Objectives To investigate the COD and risk factors for mortality in patients with AAV.

Methods A retrospective study was conducted in 44 patients with microscopic polyangiitis (MPA) and 12 granulomatosis with polyangiitis (GPA) from January 1999 to December 2011. All patients fulfilled the Chapel Hill Consensus Conference 1992 definition and Sorensen's diagnostic criteria for MPA and GPA. We reviewed medical records of patients including basic demographic characteristics, cumulative clinical features, treatment agents, and causes of death. The primary COD was defined as the main clinical and pathological process directly responsible for death and then categorized into 3 groups: vasculitis-related, vasculitis-unrelated, and unknown.

Results Renal involvement and DAH were observed in 73.2% (41/56), and 30.4 (17/56), respectively, in all the patients with MPA or GPA. The mortality rate was 41.1% (23/56) with 5 deaths (41.6%) in patients with GPA and 18 (40.9%) with MPA. Among the significant risk factors for mortality on univariate analysis, which include DAH, renal involvement, ≥4 organ involvements, ≥2 FFS scores, and ≥4 treatment modalities, a multivariate regression analysis identified DAH as an independent predicting factor (HR, 10.28; 95% CI, 2.58–40.56; p<0.001). In an analysis of COD, two deaths (8.6%) were related to vasculitis, while 19 (82.6%) were related to infection. The most common COD was pneumonia (17/23, 73.9%) which, in turn, was associated with DAH (OR, 27.18; 95% CI, 4.30 - 171.80; p <0.001) and ≥4 organ involvement (OR, 7.62; 95% CI, 1.54 - 37.71; p =0.013) as independent risk factors. Bacteria were the most frequent microorganisms causing pneumonia (n=43, 68.2%), followed by fungi (n=8, 12.7%) and Pneumocyctis jirovecii (n=7, 11.1%). Most frequently isolated bacteria were Acinetobacter baumanii (6 cases), and Staphylococcus aureus (MRSA, 6 cases). The mean number of isolated pathogens in patients with pneumonia was 3.33 ±2.11. There were no significant difference in the mean number of pathogens between patients who survived and dead (3.00±0.00 vs. 3.37±2.24).

Conclusions The result of present study implicated that early intervention of pulmonary infection may be critical to increase survival rates in AAV patients with DAH and or severe disease.

1. Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. 2010;69:1036–43.

Disclosure of Interest None declared