In other pediatric systemic autoimmune diseases, however, including JDM, pediatric SLE and Kawasaki disease, a variety of infections have been temporally associated with disease onset (reviewed in reference 26), but few case-control studies have corroborated these. A case-control epidemiologic study of 80 newly diagnosed cases compared JDM with JIA and healthy controls and reported a greater number of infectious illnesses antecedent to diagnosis in JDM patients, based on structured interviews.27
In a five-year U.S. registry study of 286 incident JDM patients, children younger than 6 years of age more frequently had respiratory symptoms within three months of disease onset than older children, based on responses in questionnaires and structured interviews. JDM patients with constitutional or gastrointestinal symptoms at diagnosis were also more likely to have contact with sick animals prior to diagnosis.28
A second U.S. juvenile myositis registry study, using physician questionnaire and medical record review, found differences in exposures by subgroup, with more frequent antecedent infections in older children and those who did not have myositis autoantibodies.29 Another study using this same registry also found antecedent infections within six months of illness onset to be associated with a chronic or polycyclic course of illness.30
Some studies have utilized biospecimens to assess exposure to infectious organisms. However, a case-control study of recent-onset JDM vs. matched healthy controls found no difference in the detection of parvovirus antibodies or DNA in the peripheral blood or muscle tissue.31 In studies of newly diagnosed JDM patients, antibody titers to coxsackievirus B, herpes simplex virus or Toxoplasma gondii did not differ compared with controls, and no enteroviral RNA or bacterial DNA was detected in the affected muscle tissue from 20 JDM patients.27,32 In pediatric SLE, a small case-control study detected uniform seroreactivity to EBNA-1, an Epstein-Barr virus–associated nuclear protein, in SLE patients, but not as frequently in healthy controls.33
Early Life Factors
The role of early life factors has been examined in several case-control studies (see Table 2, Early Life Factors). The effects of breastfeeding, as ascertained by questionnaire data, on the development of JIA are unclear, but breastfeeding may decrease risk and severity. One U.S. case-control study found that longer breastfeeding (for more than three months) was protective against the development of JIA, particularly in the pauciarticular subgroup,34 but a German study suggested increased risk of JIA with breastfeeding,25 and three other case-control studies showed no effect (see Table 2, Breastfeeding).22,35,36
A longitudinal cohort study of healthy children found that breastfeeding for more than three months is protective against the development of rheumatoid factor in those without the RA susceptibility factor, HLA-DR-4.37
