Studies in other pediatric autoimmune diseases are smaller, with antecedent infection and short-term exposure to ultraviolet radiation prior to diagnosis as emerging risk factors for subgroups of patients with JDM. Air pollution may increase disease activity in pediatric SLE and other systemic autoimmune diseases, but such findings need to be confirmed.
You Might Also Like
Explore This IssueMarch 2017
Future investigations in this area will require adequately powered and controlled studies, examination of well-defined subgroups of patients whose risk factors may differ from the disease overall and confirmation of exposures through medical record review or validated biomarkers. Challenges include difficulties in assessing environmental exposures outside traditional medical system reporting and reporting biases in questionnaire studies. Also, the timing of exposures in relation to disease onset, the effects of intensity vs. duration of exposures, potential gender and age differences, interactions of multiple exposures and genetic factors and assessing mechanisms are all important areas for future investigations.
Many environmental exposures have not yet been investigated as possible risk factors for autoimmunity in children and should be prioritized based on animal model and in vitro data and identified risk factors in the adult-onset systemic autoimmune diseases. In addition, study designs that include populations with high levels of exposures in certain geographic regions or after accidental exposures may be productive.
Uncovering modifiable environmental factors for pediatric systemic autoimmune diseases will not only help with our understanding of disease mechanisms, but also help guide treatments and even potentially aide in the prevention of these diseases.
Lisa G. Rider, MD, is a pediatric rheumatologist and deputy chief of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, National Institutes of Health at the Clinical Research Center in Bethesda, Maryland. Her research has focused on juvenile myositis, including studies on environmental risk factors.
Frederick W. Miller, MD, PhD, is an adult rheumatologist and immunologist and is chief of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, National Institutes of Health at the Clinical Research Center in Bethesda, Maryland. He has focused on adult myositis and systemic rheumatic diseases, leading studies and working groups on environmental and genetic risk factors for these diseases in adults and children.
- Li YR, Zhao SD, Li J, et al. Genetic sharing and heritability of paediatric age of onset autoimmune diseases. Nat Commun. 2015 Oct 9;6:8442.
- Li YR, Li J, Zhao SD, et al. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. Nat Med. 2015 Sep;21(9):1018–1027.
- Feldman BM, Birdi N, Boone JE, et al. Seasonal onset of systemic-onset juvenile rheumatoid arthritis. J Pediatr. 1996 Oct;129(4):513–518.
- Berkun Y, Lewy H, Padeh S, Laron Z. Seasonality of birth of patients with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2015 Jan–Feb;33(1):122–126.
- Nielsen HE, Dorup J, Herlin T, et al. Epidemiology of juvenile chronic arthritis: Risk dependent on sibship, parental income, and housing. J Rheumatol. 1999 Jul;26(7):1600–1605.
- Vegosen LJ, Weinberg CR, O’Hanlon TP, et al. Seasonal birth patterns in myositis subgroups suggest an etiologic role of early environmental exposures. Arthritis Rheum. 2007 Aug;56(8):2719–2728.
- Burns JC, Herzog L, Fabri O, et al. Seasonality of Kawasaki disease: A global perspective. PLoS One. 2013 Sep 18;8(9):e74529.
- Kao AS, Getis A, Brodine S, Burns JC. Spatial and temporal clustering of Kawasaki syndrome cases. Pediatr Infect Dis J. 2008 Nov;27(11):981–985.
- Rodo X, Curcoll R, Robinson M, et al. Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):7952–7957.
- Rodo X, Ballester J, Cayan D, et al. Association of Kawasaki disease with tropospheric wind patterns. Sci Rep. 2011;1:152.
- Rigante D, Bosco A, Esposito S. The etiology of juvenile idiopathic arthritis. Clin Rev Allergy Immunol. 2015 Oct;49(2):253–261.
- Berkun Y, Padeh S. Environmental factors and the geoepidemiology of juvenile idiopathic arthritis. Autoimmun Rev. 2010 Mar;9(5):A319–A324.
- Ellis JA, Munro JE, Ponsonby AL. Possible environmental determinants of juvenile idiopathic arthritis. Rheumatology (Oxford). 2010 Mar;49(3):411–425.
- Oen K, Fast M, Postl B. Epidemiology of juvenile rheumatoid arthritis in Manitoba, Canada, 1975–92: Cycles in incidence. J Rheumatol. 1995 Apr;22:745–750.
- Gonzalez B, Larranaga C, Leon O, et al. Parvovirus B19 may have a role in the pathogenesis of juvenile idiopathic arthritis. J Rheumatol. 2007 Jun;34(6):1336–1340.
- Lehmann HW, Knoll A, Kuster RM, Modrow S. Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood. Arthritis Rheum. 2003 Jun;48(6):1631–1638.
- Horton DB, Scott FI, Haynes K, et al. Antibiotic exposure and juvenile idiopathic arthritis: A case-control study. Pediatrics. 2015 Aug;136(2):e333–e343.
- Arvonen M, Virta LJ, Pokka T, et al. Repeated exposure to antibiotics in infancy: A predisposing factor for juvenile idiopathic arthritis or a sign of this group’s greater susceptibility to infections? J Rheumatol. 2015 Mar;42(3):521–526.
- Tejesvi MV, Arvonen M, Kangas SM, et al. Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis. 2016 Mar;35(3):363–370.
- Lange L, Thiele GM, McCracken C, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016 Feb 9;14(1):8.
- Carlens C, Jacobsson L, Brandt L, et al. Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis. Ann Rheum Dis. 2009 Jul;68(7):1159–1164.
- Shenoi S, Shaffer ML, Wallace CA. Environmental risk factors and early-life exposures in juvenile idiopathic arthritis: A case-control study. Arthritis Care Res (Hoboken). 2016 Aug;68(8):1186–1194.
- Miller J, Ponsonby AL, Pezic A, et al. Sibling exposure and risk of juvenile idiopathic arthritis. Arthritis Rheumatol. 2015 Jul;67(7):1951–1958.
- Shenoi S, Bell S, Wallace CA, Mueller BA. Juvenile idiopathic arthritis in relation to maternal prenatal smoking. Arthritis Care Res (Hoboken). 2015 May;67(5):725–730.
- Radon K, Windstetter D, Poluda D, et al. Exposure to animals and risk of oligoarticular juvenile idiopathic arthritis: A multicenter case-control study. BMC Musculoskelet Disord. 2010 Apr 20;11:73.
- Principi N, Rigante D, Esposito S. The role of infection in Kawasaki syndrome. J Infect. 2013 Jul;67(1):1–10.
- Pachman LM, Hayford JR, Hochberg MC, et al. New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis. Arthritis Rheum. 1997 Aug;40(8):1526–1533.
- Pachman LM, Lipton R, Ramsey-Goldman R, et al. History of infection before the onset of juvenile dermatomyositis: Results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry. Arthritis Rheum. 2005 Apr 15;53(2):166–172.
- Rider LG, Wu L, Mamyrova G, et al. Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies. Rheumatology (Oxford). 2010 Dec;49(12):2381–2390.
- Habers GE, Huber AM, Mamyrova G, et al. Brief report: Association of myositis autoantibodies, clinical features, and environmental exposures at illness onset with disease course in juvenile myositis. Arthritis Rheumatol. 2016 Mar;68(3):761–768.
- Mamyrova G, Rider LG, Haagenson L, et al. Parvovirus B19 and onset of juvenile dermatomyositis. JAMA. 2005 Nov 2;294(17):2170–2171.
- Pachman LM, Litt DL, Rowley AH, et al. Lack of detection of enteroviral RNA or bacterial DNA in magnetic resonance imaging-directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis. Arthritis Rheum. 1995 Oct;38(10):1513–1518.
- McClain MT, Poole BD, Bruner BF, et al. An altered immune response to Epstein-Barr nuclear antigen 1 in pediatric systemic lupus erythematosus. Arthritis Rheum. 2006 Jan;54(1):360–368.
- Mason T, Rabinovich CE, Fredrickson DD, et al. Breast feeding and the development of juvenile rheumatoid arthritis. J Rheumatol. 1995 Jun;22(6):1166–1170.
- Rosenberg AM. Evaluation of associations between breast feeding and subsequent development of juvenile rheumatoid arthritis. J Rheumatol. 1996 Jun;23(6):1080–1082.
- Ellis JA, Ponsonby AL, Pezic A, et al. CLARITY-Childhood arthritis risk factor identification study. Pediatr Rheumatol Online J. 2012 Nov 15;10(1):37.
- Young KA, Parrish LA, Zerbe GO, et al. Perinatal and early childhood risk factors associated with rheumatoid factor positivity in a healthy paediatric population. Ann Rheum Dis. 2007 Feb;66(2):179–183.
- Hyrich KL, Baildam E, Pickford H, et al. Influence of past breast feeding on pattern and severity of presentation of juvenile idiopathic arthritis. Arch Dis Child. 2016 Apr;101(4):348–351.
- Orione MA, Silva CA, Sallum AM, et al. Risk factors for juvenile dermatomyositis: Exposure to tobacco and air pollutants during pregnancy. Arthritis Care Res (Hoboken). 2014 Oct;66(10):1571–1575.
- Jaakkola JJ, Gissler M. Maternal smoking in pregnancy as a determinant of rheumatoid arthritis and other inflammatory polyarthropathies during the first 7 years of life. Int J Epidemiol. 2005 Jun;34(3):664–671.
- Butz AM, Rosenstein BJ. Passive smoking among children with chronic respiratory disease. J Asthma. 1992;29(4):265–272.
- Zeft AS, Prahalad S, Lefevre S, et al. Juvenile idiopathic arthritis and exposure to fine particulate air pollution. Clin Exp Rheumatol. 2009 Sep–Oct;27(5):877–884.
- Zeft AS, Prahalad S, Schneider R, et al. Systemic onset juvenile idiopathic arthritis and exposure to fine particulate air pollution. Clin Exp Rheumatol. 2016 Sep–Oct;34(5):946–952.
- Zeft AS, Burns JC, Yeung RS, et al. Kawasaki disease and exposure to fine particulate air pollution. J Pediatr. 2016 Oct;177:179–183.
- Vidotto JP, Pereira LA, Braga AL, et al. Atmospheric pollution: Influence on hospital admissions in paediatric rheumatic diseases. Lupus. 2012 Apr;21(5):526–533.
- Fernandes EC, Silva CA, Braga AL, et al. Exposure to air pollutants and disease activity in juvenile-onset systemic lupus erythematosus patients. Arthritis Care Res (Hoboken). 2015 Nov;67(11):1609–1614.
- Neufeld KM, Karunanayake CP, Maenz LY, Rosenberg AM. Stressful life events antedating chronic childhood arthritis. J Rheumatol. 2013 Oct;40(10):1756–1765.
- Shah M, Targoff IN, Rice MM, et al. Brief report: Ultraviolet radiation exposure is associated with clinical and autoantibody phenotypes in juvenile myositis. Arthritis Rheum. 2013 Jul;65(7):1934–1941.
- Miller FW, Alfredsson L, Costenbader KH, et al. Epidemiology of environmental exposures and human autoimmune diseases: Findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. J Autoimmun. 2012 Dec;39(4):259–271.
- Sparks JA, Costenbader KH. Genetics, environment, and gene-environment interactions in the development of systemic rheumatic diseases. Rheum Dis Clin North Am. 2014 Nov;40(4):637–657.
- Karlson EW, Deane K. Environmental and gene-environment interactions and risk of rheumatoid arthritis. Rheum Dis Clin North Am. 2012 May;38(2):405–426.
This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.