Initial high-dose corticosteroids and renal impairment are risk factors for early severe infections in elderly patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: A retrospective observational study

Abstract

Recent large observational studies of antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) show that severe infection is a major cause of death and that the majority of infections occur during the early phase of initiating remission-induction therapy. Many risk factors for severe infection have been suggested, but these have been inconsistent. Nevertheless, infectious risk factors in elderly patients with AAV have not been adequately investigated in previous studies.In this retrospective observational study, we examined potential predictors of severe infection within 90 days (early severe infections) after remission-induction therapy in patients with AAV aged 65 years or older. We included 167 consecutive elderly patients with AAV admitted to our hospital. Data from medical history and remission-induction therapy were analyzed for predictive risk factors associated with early severe infections. The relationship between initial doses of corticosteroids and cumulative incidence of severe infections was also analyzed. A multivariate analysis of risk factors for early severe infections was performed using logistic regression analysis. The Kaplan-Meier method was used to estimate the overall survival, and the log-rank test was used to evaluate the differences between patients with and without early severe infections. Gray method was used to compare the cumulative incidence of severe infections in patients who did and did not receive initial high-dose corticosteroids.Logistic regression analysis showed that initial high-dose corticosteroid administration (prednisolone ≥0.8 mg/kg/d) (odds ratio [OR] 3.86, P = .030) and serum creatinine levels at diagnosis ≥1.5 mg/dL (OR 5.13, P = .003) were independent predictors of early severe infection although administration of cyclophosphamide or rituximab was not. The cumulative incidence of severe infections was also significantly higher in patients who received initial high-dose corticosteroids (P = .042), and patients with early severe infections exhibited a high mortality rate within 6 months (P < .001).Our findings suggest that initial high-dose corticosteroids and renal impairment at diagnosis are associated with a higher risk of early severe infections and early death in elderly patients with AAV.

Figure 1

Flow diagram of patient selection. Patients were selected retrospectively based on the International Classification of Diseases diagnostic codes assigned during their inpatient stay at our hospital. In total, 146 patients were excluded due to lack of data, inadequate inclusion criteria, early death, incorrect diagnosis, or if younger than 65 years old. Finally, 167 patients were included and categorized into 2 groups, according to the occurrence of severe infections within 90 days of starting treatment.

Figure 2

Cumulative incidences of severe infections in patients who received initial high-dose corticosteroids and those who did not. Cumulative incidences of severe infections were significantly higher in patients who received initial high-dose corticosteroids, considering death without severe infections as a competing risk (P = .042).

Figure 3

Overall survival rates within 6 months for patients with and without early severe infections. Kaplan–Meier curve showing an association between survival and early severe infections (P < .001).