Outcomes of lupus and rheumatoid arthritis patients with primary dengue infection: A seven-year report from Brazil

https://doi.org/10.1016/j.semarthrit.2017.09.001Get rights and content

Abstract

Objective

We described the clinical profile and outcomes of patients with SLE and RA diseases reported to the Brazilian Health Information System with primary dengue infection.

Methods

Databases from the Brazilian Public Health Informatics System (SUS) were linked as the source of information. Three databases comprising different longitudinal information of lupus or rheumatoid arthritis (RA) patients under treatment and care through the Brazilian Health System were linked. Patients who had lupus ICD-9 code or RA ICD-9 code and their treatment approved by SUS were included in the study. In Study 1, we described the clinical characteristics of RA/lupus patients who had dengue infection. In Study 2, we compared RA/lupus patients with or without dengue for hospitalization rates after index dengue diagnosis for dengue-exposed or matching date for dengue-unexposed.

Results

We included 69 SLE and 301 RA patients with dengue. In the RA/lupus with dengue case series, hospitalization was found in 24.6% of lupus subjects and of 11.2% of RA subjects. It differed by geographic region (p = 0.03), gender (p = 0.05) and the use of azathioprine (p = 0.02). Dengue was the most frequent reason for hospitalization reported (43.0%). Hospitalization due to dengue was noted in 12 (42.9%) dengue-exposed patients (p = 0.02), while rheumatoid arthritis was reported as the cause of hospitalization in 22.2% of dengue-unexposed (p = 0.005). Five deaths were reported among the dengue-exposed and none among dengue-unexposed. Bacterial infection was the most frequent cause of death. We found that the dengue exposure was associated with an increased risk of hospitalization outcome in RA and lupus patients (RR = 6.2; 95% CI: 2.99–12.94).

Summary

We found that when comparing RA/lupus patients with or without dengue, dengue-exposed patients had an increased rates of hospitalization and death.

Introduction

Dengue is an arbovirus that presents clinical symptoms similar to those in rheumatic diseases. Myalgia, arthralgia, and thrombocytopenia are found in this mosquito-borne illness, with increasing prevalence [1]. Along with other arboviruses transmitted by Aedes aegypti, dengue is currently one of the most important emerging infectious diseases in the world. It has increased fourfold over the past 3 decades and has been reported in more than 100 countries across Latin America, Africa, Asia and continues to spread in many developed countries [2]. An estimated 390-million dengue cases occur globally each year. However, its precise burden is still difficult to determine because of under-reporting in many mild-to-moderate dengue cases [3].

The typical incubation period for dengue is 3–7 days, followed by a disease period of 7–10 days [4]. In 2009, the World Health Organization (WHO) reclassified the case definition of dengue clinical syndromes into classical dengue and severe dengue, with hospitalization due to dengue defined as an indicator of severity [5].

In Brazilian general population, according to the Annual Bulletin of Ministry of Health, there were 1,587,680 new dengue cases in 2015. The majority of them were found in the Southeast region (62%). Severe dengue (hospitalization) was reported in 1529 of these dengue cases (0.09%); among them, death was found in 839 dengue cases. Similar distribution was found in 2014 and previous years [6].

The occurrence of hospitalization due to dengue is a concern in adult patients with comorbidities, even in primary dengue that is less severe when compared to repeated infections [7], [8]. Rheumatic diseases may contribute to severe outcome of dengue, although their contribution has not been previously characterized. Therefore, we described the clinical profile and outcomes of patients with SLE and RA diseases reported to the Brazilian Health Information System with primary dengue infection [9].

Section snippets

Data sources

This study was based on the national administrative databases of Brazilian Health Information System. A linkage between two databases from DATASUS, the outpatient and inpatient databases, with the surveillance database, called SINAN was constructed [10]. These databases comprise different longitudinal information of SLE and RA patients treated at the Brazilian Public Health System (Sistema Único de Saúde, SUS). We received anonymized information from 2008 to 2014 for this analysis. Details on

Study 1: RA/SLE with dengue case series study

There were 882 subjects in the dengue database. Among them, 3380 (38.4%) patients were excluded because outpatient observations about them started after the date of dengue infection and 5032 (93.15%) had ICD codes for diseases other than SLE or RA (Fig. 1).

From a total of 370 patients who fulfilled the eligibility criteria, 69 had SLE and 301 had RA. The mean (±SD) age for SLE was 38.6 (±12.4) years and for RA was 50.3 (±14.0) years, as presented in Table 1. Most of the sample was female:

Discussion

The use of more potent immunosuppressive drugs has become common in rheumatology and so have vector-borne illnesses [12]. We analyzed the outcomes of the primary dengue infection in 370 patients with SLE or RA (Study 1, RA/SLE+ dengue case series) reported in the Brazilian public health system database. We found that 13.5% of the dengue infection among SLE or RA patients required hospitalization, having dengue fever as the most frequent reason reported for it (43.0%), which differed according

Acknowledgment

Dr. Abreu received support from the Brazilian Research Council (CNPq-2014.4004.678/80) and Pan American League of Associations for Rheumatology under award (PANLAR Award 2014); Dr. Solomon receives support from NIH for mentoring under award (NIH-AR-K24-AR055989); K.Y. receives tuition support jointly from Japan Student Services Organization (JASSO) and Harvard T.H. Chan School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer, and PhRMA).

DATASUS department

References (34)

  • R.C.G. Fares et al.

    Epidemiological scenario of dengue in Brazil

    Biomed Res Int

    (2015)
  • Dengue outbreak—Federated States of Micronesia, 2012–2013

    MMWR Morb Mortal Wkly Rep

    (2013)
  • M.K. Nisar et al.

    Chikungunya and bilateral sacroiliitis–is there a link?

    Ann Rheum Dis

    (2015)
  • BRAZIL. Ministry of Health. Successful Brazilian experiences in the field of health information. Final Report,...
  • M.M. Silva

    Accuracy of dengue reporting by National Surveillance System, Brazil

    Emerg Infect Dis

    (2016)
  • Nathan MB, Dayal-Drager R. Recent epidemiological trends, the global strategy and public health advances in dengue....
  • D.C. Kajeguka et al.

    Prevalence of dengue and Chikungunya virus infections in north-eastern Tanzania: a cross-sectional study among participants presenting with malaria-like symptoms

    BMC Infect Dis

    (2016)
  • View full text