Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus

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Abstract

Objectives

To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort.

Methods

All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection.

Results

A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6–30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009–1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539–3.005), corticosteroids (≥10 mg/day) (HR = 1.271, 95% CI: 1.034–1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079–1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905–3.459), Katz severity index (HR = 1.160, 95% CI: 1.105–1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031–1.108), and smoking (HR = 1.332, 95% CI: 1.121–1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997–0.999).

Conclusions

Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.

Introduction

Infection remains an important cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE). Severe infection occurred in 11–45% of SLE patients depending on case definition, study population, observation period, etc. [1], [2], [3], [4], [5], [6], [7]. Although several centers reported their incidence of infection, specific studies on severe infection from large, multicenter SLE cohorts are lacking. Roughly 30% of deaths in SLE patients are related to infections and recent data from a multicenter French registry suggest that overall mortality for infectious diseases in SLE is higher than thought [8]. Additionally, severe infections account for 11–23% of all hospitalization in SLE patients [3], [9], [10], with hospitalization rates for serious infections 12 times higher than that in patients without SLE [11], thus forming a significant part of the direct health-related costs associated with SLE [12].

Several factors are associated with a predisposition to infection in SLE patients, including disease-related factors, immunosuppressant and corticosteroid use, and intrinsic immune deregulations [13], [14], [15]. However, the relative contribution of each is not well known and comprehensive infection risk factor analysis is lacking. To determine the density of incidence of severe infection, delineate any associated factors and explore its clinical impact, we analyzed cumulative infection data from the RELESSER-T registry (Spanish Society of Rheumatology Lupus Registry—retrospective phase), a very large, non-selected multicenter and well-characterized SLE patient cohort containing abundant data on comorbidities [16].

Section snippets

Methods

Patients from the RELESSER-T registry who met at least 4 ACR-97 SLE criteria were included. The variables, definitions, processes, and methodological characteristics of the registry have been previously described in detail [17], [18]. In short, RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health

Results

A total of 3658 SLE patients were included, 90% female, median age 32.9 years, and interquartile range (IQR): 19.4. Regarding ethnic distribution, 93% were Caucasian, 5% Hispanic (Latin-American: Amerindian or Mestizo) (N = 185) and less than 1% other ethnic groups. Mean follow-up (months) was 120.2 (SD = ±87.6, range: 508).

The main clinical characteristic of the cohort has been extensively described elsewhere [15]. The ACR97 SLE criteria distribution are shown in Table 1. The median S-SLEDAI

Discussion

The incidence of severe infection in SLE patients in the RELESSER registry (19.3%) was not very different than previous reports involving other large cohorts [4], [9], [21], [22], although certainly lower than in previous studies from monocentric cohorts in Spain, ranging from 29% to 38% [23], [24], or than was recently reported by Feldman et al. [25] in a study involving an extensive administrative SLE database from the United States. Differences in patient selection and/or time of follow-up

Conclusions

Our results need to be confirmed in prospective studies; specifically, with a more exhaustive inclusion of variables related to infection. Nonetheless, several remarkable conclusions can be drawn from our data:

  • (1)

    Severe infection is associated with severity and damage in SLE patients. There are ethnic differences in the prevalence of infection in SLE, with rates appearing to be higher in Latin-Americans.

  • (2)

    Respiratory bacterial infections are the most commonly found severe infection in SLE, although

Acknowledgments

We are grateful to all of the employees of the Spanish Rheumatology Society Research Unit for their commitment and professionalism.

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  • Cited by (0)

    Financial supporters: Spanish Foundation of Rheumatology. FIS/ISCIII (Grant no. PI11/02857). Dr. Pego-Reigosa is supported by Grant 316265 (BIOCAPS) from the European Union 7th Framework Programe (FP7/REGPOT-2012–2013.1).

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