Patients hospitalized for rotavirus more likely to develop childhood autoimmune disease
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Key takeaways:
- Children hospitalized due to rotavirus had an increased risk for autoimmune disease.
- Clinicians should be aware of the predisposition for autoimmune disease in these patients, the researchers wrote.
Children who are hospitalized for rotavirus demonstrate a higher risk for developing juvenile-onset autoimmune diseases, including inflammatory arthritis and vasculitis, according to data published in JAMA Network Open.
“Rotavirus infection is a leading cause of mortality and morbidity in infants and young children, and these infections are also linked to autoimmunity,” Eun Kyo Ha, MD, of Hallym University Kangnam Sacred Heart Hospital, in Seoul, South Korea, and colleagues wrote. “... Several lines of evidence suggest that rotavirus infection can trigger autoimmune diseases.
“However, previous studies had limitations in terms of controls, small sample sizes, and study design,” they added. “While there is supporting evidence from humans and animals, clinical epidemiology studies have only provided limited support.”
To investigate the relationship between rotavirus and subsequent autoimmune disease, Ha and colleagues conducted a population cohort study of patients born in South Korea between 2002 and 2005. Included patients were aged younger than 19 years on the date of hospitalization for rotavirus, while those who exhibited other autoimmune diseases or had conflicting information in their records were excluded. The researchers additionally conducted a literature review to find any current associations that might exist with rotavirus.
The main exposure variable was hospitalization for rotavirus during the first or second documented infection. The date of hospitalization was the index date for each case. The researchers followed all included patients from the index date through their first diagnosed autoimmune disease, death or the end of the study on Dec. 31, 2017. Ha and colleagues considered 41 autoimmune diseases due to the nature of their relationships with rotavirus as reported in the literature review.
The analysis included 86,517 patients who were exposed to rotavirus, and 86,517 individuals who were not exposed. Median age at the time of hospitalization for rotavirus was 1.5 years (95% CI, 0.9-2.7). According to the researchers, the HR among patients who were hospitalized for rotavirus to develop an autoimmune disease was 1.24 (95% CI, 1.19-1.28). The researchers also found that additional hospitalizations due to rotavirus increased patients’ chances for autoimmune disease. This was true in single hospitalizations (HR = 1.2; 95% CI, 1.16-1.24) and multiple hospitalizations (HR = 1.6; 95% CI, 1.49-1.72).
Regarding specific autoimmune diseases, the researchers, following the population-matched analysis, found “notable” associations between rotavirus hospitalization and the development of inflammatory arthritis (HR = 1.36; 95% CI, 1.25-1.48), connective tissue disease (HR = 1.29; 95% CI, 1.08-1.55), nervous system diseases (HR = 1.29; 95% CI, 1.04-1.6), endocrine diseases (HR = 1.28; 95% CI, 1.17-1.4) and vasculitis (HR = 1.2; 95% CI, 1.12-1.29), they wrote.
“In this nationwide cohort study, rotavirus-associated hospitalization was associated with an increased risk for childhood autoimmune disease overall and multiple specific autoimmune diseases,” Ha and colleagues wrote. “Clinicians should be aware of the increased predisposition for autoimmune disease in individuals who experienced rotavirus-associated hospitalization.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Autoimmune disorders were once thought to be uncommon, but they currently impact 3% to 21% of the world’s population — from widely varying estimations — with autoimmune thyroid disease and type 1 diabetes mellitus being the most common. There are almost 100 autoimmune diseases.
The connection between infectious agents and autoimmunity is not new, and has in fact been discussed for decades, as illustrated 20 years ago with Epstein-Barr virus. Considering that autoimmune diseases are influenced by environmental, epigenetic, hormonal and genetic factors, this means that the inherent traits of a population could impact the onset of an autoimmune disease when they encounter an infection.
Some of the mechanisms involved include molecular mimicry, epitope spreading, bystander activation and superantigens. Infectious agents cause infections and disease but can also be protective against subsequent disease development. For instance, in places where there is a low prevalence of parasite infections, the prevalence of autoimmune diseases is rising.
Many inverse associations have been reported between parasitic infections and protection from autoimmune diseases. The present study finds a link between rotavirus infection and subsequent autoimmune disease. We know the pathway from infection to autoimmune disease is complex and variable, but this is an important area of study.
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