Association Between a History of Dengue Fever and the Risk of Systemic Autoimmune Rheumatic Diseases: A Nationwide, Population-Based Case-Control Study

Yun-Wen Chen,Chi-Chien Lin,Hsian-Min Chen,Ching-Heng Lin,Tsu-Yi Hsieh,Hsin-Hua Chen

doi:10.3389/fmed.2021.738291

Abstract

Purpose: To determine the association between a history of clinically diagnosed dengue infection and the risk of systemic autoimmune rheumatic diseases (SARDs).Methods: Using claims data from the 1997–2013 Taiwanese National Health Insurance Research Database, we included 74,422 patients who were diagnosed with SARDs and 297,688 patients without SARDs who were matched (in a 1:4 ratio) for age, sex, year of SARDs index date, and city of residence. The associations between the development of SARDs and a history of dengue infection (International Classification of Diseases, Ninth Revision, Clinical Modification code 061) were investigated using conditional logistic regression analysis shown as odds ratios (ORs) with 95% confidence intervals (CIs) after adjusting for potential confounders.Results: We included 17,126 patients with systemic lupus erythematosus (SLE), 15,531 patients with Sjogren's syndrome (SS), 37,685 patients with rheumatoid arthritis (RA), 1,911 patients with systemic sclerosis (SSc), 1,277 patients with dermatomyositis (DM), and 892 patients with polymyositis (PM). SLE (OR, 4.55; 95% CI, 2.77–7.46; p <0.001) risk was significantly associated with a history of dengue infection. However, no statistically significant association was found between dengue infection and SS (OR, 1.41; 95% CI, 0.88–2.26; p = 0.155), RA (OR, 1.03; 95% CI, 0.70–1.50; p = 0.888), SSc (OR, 1.97; 95% CI, 0.38–10.29; p = 0.420), DM (OR, 0.54; 95% CI, 0.04–7.27; p = 0.641), or PM (OR, 2.08; 95% CI, 0.23–18.79; p = 0.513).Conclusion: This study revealed that a history of dengue infection was significantly associated with the risk of SLE, but not SS, RA, SSc, DM, or PM.

Highlights

Systemic autoimmune rheumatic diseases (SARDs) develop when the immune system is dysregulated such that its tolerance to self-antigens is lost
systemic lupus erythematosus (SLE) (OR, 4.55; 95% confidence intervals (CIs), 2.77–7.46; p < 0.001) risk was significantly associated with a history of dengue infection
No statistically significant association was found between dengue infection and s syndrome (SS) (OR, 1.41; 95% CI, 0.88–2.26; p = 0.155), rheumatoid arthritis (RA) (OR, 1.03; 95% CI, 0.70–1.50; p = 0.888), Dengue and systemic autoimmune rheumatic disease (SARD) Risk

Summary

Introduction

Systemic autoimmune rheumatic diseases (SARDs) develop when the immune system is dysregulated such that its tolerance to self-antigens is lost. DENV infection triggers several pathways, including DENV nonstructural protein 1 (NS1) antibody-induced autophagy, the activation of the complement pathway, the dysregulation of B and T cells, elevated levels of cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ, which were considered to be associated with the development of autoimmunity in dengue patients [4,5,6,7,8]. The exact pathophysiology of autoimmune manifestations in patients with dengue infection and the risk of autoimmune diseases are not fully elucidated [9]. To the best of our knowledge, no population-based, case-control study assessed the association between dengue infection and the risk of SARDs. Because the incidences of some SARDs were quite low (for example, polymyositis/dermatomyositis: 0.6–0.7 per 105 person-years) in Taiwan, we are unlikely to identify a sufficient number of patients with a SARD with a very low incidence using a cohort study design [12]

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Discussion

Conclusion