Risk factors for infectious complications of ANCA-associated vasculitis: a cohort study

Abstract

BackgroundSevere infections are common complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal involvement. We investigated the clinical characteristics and risk factors of severe infection in Chinese patients with AAV after immunosuppressive therapy.MethodsA total of 248 patients with a new diagnosis of ANCA-associated vasculitis were included in this study. The incidence, time, site, and risk factors of severe infection by the induction therapies were analysed. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI).ResultsA total of 103 episodes of severe infection were identified in 86 (34.7%, 86/248) patients during a median follow-up of 15 months. The incidence of infection during induction therapy was 38.5% for corticosteroids (CS), 39.0% for CS+ intravenous cyclophosphamide (IV-CYC), 33.8% for CS+ mycophenolate mofetil and 22.5% for CS + tripterygium glycosides, 76 (73.8%) infection episodes occurred within 6 months, while 66 (64.1%) occurred within 3 months. Pneumonia (71.8%, 74/103) was the most frequent type of infection, and the main pathogenic spectrum included bacteria (78.6%), fungi (12.6%), and viruses (8.7%). The risk factors associated with infection were age at the time of diagnosis (HR = 1.003, 95% CI = 1.000–1.006), smoking (HR = 2.338, 95% CI = 1.236–4.424), baseline secrum creatinine (SCr) ≥5.74 mg/dl (HR = 2.153, 95% CI = 1.323–3.502), CD4+ T cell< 281 μl (HR = 1.813, 95% CI = 1.133–2.900), and intravenous cyclophosphamide regimen (HR = 1.951, 95% CI =1.520–2.740). Twelve (13.9%) patients died of severe pneumonia.ConclusionThe infection rate during induction therapy was high in patients with AAV. Bacterial pneumonia was the main type of infection encountered. Age at the time of diagnosis, smoking, baseline SCr ≥5.74 mg/dl, CD4+ T cell< 281 μl, and IV-CYC therapy were identified as risk factors for infection.

Risk of opportunistic infections in patients with antineutrophil cytoplasmic antibody‐associated vasculitis, using a Japanese health insurance database

“…In this study, older age, high dosages of CS, and CS pulse therapy were identified as significant risk factors for OIs. The findings of previous studies were in line with our results, and showed that older age and CS use were associated with serious infections, including OIs, in patients with AAV . Elderly patients are generally vulnerable to infections, and CS use increases the risk of infections .…”

“…There are several reports showing that patients with AAV have a high risk of infection. About 20%‐60% of patients with AAV developed infections, and respiratory infection was the most frequent . An observational cohort study conducted in Japan also revealed that serious infections occurred in about 27% of patients with AAV during remission‐induction therapy .…”

“…However, details on risk of OIs in patients with AAV are limited to date, due to the small numbers of events and affected patients with OIs. Although patients with AAV receiving immunosuppressive treatments are always at risk of serious infections, including OIs, they are most vulnerable during remission‐induction therapy where intensive treatments are provided . Our previous studies reported that the risk of infections was highest during the first 3 months after initiation of remission‐induction therapy in patients with AAV, and in patients with connective tissue diseases including vasculitis …”

The Importance of Demographic and Geographical Factors on the Incidence and Outcome of Systemic Small Vessel Vasculitis Associated with Anti-Neutrophil Cytoplasmic Antibodies

“…Compared to population controls, the rate ratio for serious infections was 4.5 in a study from southern Sweden [275] and the risk of hospitalization due to infections was increased almost ten times in a study from Denmark [276]. Although the aim of Paper IV was not to study infections, we did find that it was the most common cause of both death and readmission, in line with the increased risk of infections in AAV, seen especially with higher age and renal impairment [269,272,275,277].…”

Severe infections following rituximab treatment in antineutrophil cytoplasmic antibody-associated vasculitis

“…The incidence of infection during induction therapy was 36.0% (41/114) in CYCLOPS study [5] and was 39.0% for glucocorticoids in combination with intravenous cyclophosphamide (IV-CYC) in a Chinese cohort [8].…”