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Parvovirus B19 and Onset of Juvenile Dermatomyositis
To the Editor: Juvenile dermatomyositis (JDM) is a systemic autoimmune disease characterized by chronic muscle and cutaneous inflammation of unknown cause; however, some studies have suggested that infectious agents may trigger the onset of JDM and other childhood systemic autoimmune diseases.1 Several studies have described the detection of parvovirus B19 DNA in skin or muscle of patients with JDM, adult dermatomyositis, and other systemic rheumatic diseases.2 Given the similarity of the disease presentation of JDM and parvovirus B19 infection, we performed a case-control study to determine if parvovirus B19 infection is associated with the onset of JDM.
Methods
A plasma sample and clinical questionnaire were obtained from 62 patients with JDM (45 girls, mean [SD] age, 9.7 [4.6] years) meeting probable or definite Bohan and Peter criteria3 as part of the Childhood Myositis Heterogeneity Study, a North American registry of patients with juvenile idiopathic inflammatory myopathies. All patients in our study were within 6 months of diagnosis (mean [SD] time after diagnosis, 1.8 [1.6] months), and 86% of the patients were diagnosed between 1995 and 1998. An equal number of healthy control children, matched by age, sex, and race, were enrolled at the National Institutes of Health Clinical Center in Bethesda, Md, from 1995 to 1997 and resided in the area. All patients and parents signed written informed consent for an institutional review board–approved study.
Muscle biopsies were obtained at diagnosis before initiation of therapy from 4 patients with JDM (mean [SD] age, 6.0 [2.9] years), 2 of whom also provided plasma samples, and from a second group of 4 control patients with a history of muscle weakness without a defined myopathy on histological examination (mean [SD] age, 10.0 [3.2] years); these control patients did not provide a plasma sample. Five 5-µm sections from each biopsy were used for DNA extraction. Plasma and biopsy specimens were stored at –80°C before assay in 2004.
Parvovirus B19 IgM and IgG antibodies were detected by commercial enzyme-linked immunosorbent assay (Biotrin International, Dublin, Ireland). Parvovirus B19 DNA was detected by dotblot hybridization (sensitivity >106 genome equivalents [gEq]/mL) and 2 different polymerase chain reaction (PCR) assays (sensitivity <1 gEq/µL).4 The PCR results were confirmed by real-time PCR and sequencing. All laboratory studies were performed blinded to clinical information or patient status. Comparisons were made using the McNemar test. The power to detect a difference of 0.17 in the odds ratio, using a 2-tailed test, was estimated to be 0.60. All statistical analyses were performed using nQuery Advisor 5.0 (Statistical Solutions, Cork, Ireland). Statistical significance was set at P<.05.
Results
Only 1 plasma sample from a control patient had detectable parvovirus B19 IgM (Table 1). Parvovirus B19 IgG was detected in the plasma of 25 patients (40.3%) with JDM and 36 age-matched healthy controls (58.1%) (P = .04) (Table 2). All samples were negative for parvovirus B19 DNA by dotblot hybridization, and 2 patients with JDM and 2 control patients had detectable parvovirus B19 DNA in plasma by PCR (Table 1). The titer was low in all (each <1-5 gEq/µL plasma) and sequences were genotype 1.
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Table 1. Plasma and Muscle Biopsy Results for Patients With Juvenile Dermatomyositis and Controls Tested for Parvovirus B19 Serology and DNA
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Table 2. Frequency of Parvovirus B19 IgG in Plasma Samples From Patients With Juvenile Dermatomyositis and Their Matched Controls*
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Parvovirus B19 genotype 1 DNA was detected in low titer (<1 gEq/µL extracted DNA) in the muscle tissue of 1 of 4 patients with JDM and in 0 of 4 control patients. The patient with positive parvovirus B19 genome in the muscle also had parvovirus B19 IgG antibody detected in a plasma sample obtained 31 months after diagnosis, but was parvovirus B19 IgM negative.
Comment
In our case-control study, parvovirus B19 infection was not positively associated with the onset of JDM, with no increased prevalence of parvovirus B19 DNA in the plasma or muscle of patients with JDM compared with age-matched controls. The rate of parvovirus B19 seropositivity in patients with JDM is similar to that published for healthy children,5 and the higher seroprevalence in controls may be related to geographical differences in patient recruitment (nationwide for patients with JDM vs Washington, DC, metro area for controls). These results indicate that previous anecdotal data suggesting a role for parvovirus B19 in the onset of JDM and other systemic autoimmune diseases may be misleading.
Author Contributions: Dr Rider had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Rider, Brown.
Acquisition of data: Rider, Haagenson, Wong, Brown.
Analysis and interpretation of data: Mamyrova, Rider, Brown.
Drafting of the manuscript: Mamyrova, Rider, Haagenson, Brown.
Critical revision of the manuscript for important intellectual content: Mamyrova, Rider, Wong, Brown.
Statistical analysis: Mamyrova, Rider.
Obtained funding: Rider, Brown.
Administrative, technical, or material support: Haagenson, Wong.
Study supervision: Rider, Brown.
Financial Disclosures: None reported.
Funding/Support: This study was completely funded by the Intramural Research Divisions of the National Heart, Lung, and Blood Institute and the National Institute of Environmental Health Sciences. Dr Mamyrova is a research fellow who is supported by The Myositis Association.
Role of the Sponsor: The funding agencies played no role in the design and conduct of the study, or in the collection, management, analysis, and interpretation of the data. Both institutes approved the submission of the manuscript.
Acknowledgment: We thank members of the Childhood Myositis Heterogeneity Collaborative Group who contributed materials to this study, and especially thank Kathleen Patterson, MD, for muscle biopsy material, and Peter Lachenbruch, PhD, for guidance in the analysis.
Gulnara Mamyrova, MD, PhD;
Lisa G. Rider, MD
Environmental Autoimmunity Group
National Institute of Environmental Health Sciences
Laura Haagenson;
Susan Wong, BS;
Kevin E. Brown, MD
brownk{at}nhlbi.nih.gov
Hematology Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
Department of Health and Human Services
Bethesda, Md
1. Finkel TH, Torok TJ, Ferguson PJ, et al. Chronic parvovirus B19 infection and systemic necrotising vasculitis: opportunistic infection or aetiological agent? Lancet. 1994;343:1255-1258.
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2. Crowson AN, Magro CM, Dawood MR. A causal role for parvovirus B19 infection in adult dermatomyositis and other autoimmune syndromes. J Cutan Pathol. 2000;27:505-515.
FULL TEXT
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3. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine. 1977;56:255-286.
PUBMED
4. Nguyen QT, Wong S, Heegaard ED, Brown KE. Identification and characterization of a second novel human erythrovirus variant, A6. Virology. 2002;301:374-380.
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5. Cohen BJ, Buckley MM. The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol. 1988;25:151-153.
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Letters Section Editor: Robert M. Golub, MD, Senior Editor.
JAMA. 2005;294:2170-2171.
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