Incidence and clinical predictors of infections in patients treated with severe systemic ANCA-associated vasculitis

Immunosuppressive therapy has improved the outcome of ANCA-associated vasculitis (AAV), but infectious morbidity and mortality remained high. Recognizing its risk factors seems crucial for prevention, aiming to increase survival of these patients.

We investigated the incidence and types of infections and assessed predictive factors in 132 patients with severe systemic AAV.

Patients with lower than median incidence of total infections/patient-year during induction had lower baseline serum creatinine, dialysis requirement and Charlson comorbidity index (CCI), compared to those with higher than median incidence (P = 0.037; P = 0.024; P = 0.001; respectively). In subgroups with below and above than median number of severe infections/patient-year during induction, differences were found in baseline creatinine (P = 0.002) and dialysis requirement (P = 0.001); comparing the same cohorts during maintenance immunosuppression, baseline dialysis requirement, diabetes, CCI, and dose of cyclophosphamide (CYC) administered as induction therapy differed significantly (P = 0.019; P = 0.015; P = 0.001; P = 0.015, respectively). Severe infections were predicted by baseline serum creatinine (OR 1.002 [CI 1.001-1.003]) and pulmonary manifestation (OR 2.153 [CI 1.017-4.560]) during induction immunosuppression. In multivariable Cox regression model all-cause mortality was independently predicted by severe infection (HR 1.998 [CI 1.214-3.287]). Among the 168 positive cultures Gram-negative bacteria were responsible for blood stream infections in 33%, and respiratory tract infections in 72%.

Advanced renal failure, pulmonary involvement and high degree of comorbidities increase the risk of infection in AAV. Those who suffer infection during induction immunosuppression have worse long-term survival. Our findings indicate the need for high vigilance for infections and close follow-up of comorbidities when treating AAV.