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THU0218 Cow's Milk Allergy in Infancy and Later Development of Juvenile Idiopathic Arthritis: A Register-Based Case-Control Study
  1. P. Vähäsalo1,2,
  2. M. Arvonen1,2,3,
  3. T. Pokka2,4,
  4. L. Kröger3,
  5. L. Virta5
  1. 1Department of Pediatrics, Medical Research Center Oulu, Oulu University Hospital and University of Oulu
  2. 2PEDEGO Research Unit, University of Oulu, Oulu
  3. 3Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland, Kuopio
  4. 4Department of Pediatrics, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland, Oulu
  5. 5Research Department, Social Insurance Institution, Turku, Finland


Background There is discursive information about the incidence of food allergies in juvenile idiopathic arthritis (JIA). In rheumatoid arthritis antibodies from proximal gut secretions against nutritional proteins including cow's milk have been detected (1). We have earlier found a low-grade mucosal inflammatory activation in JIA patients, which resembled the findings of delayed type food allergy (2–3). Also in some case reports, JIA has been linked to food allergy. In our earlier study, we found that exposure to antibiotics was associated with later diagnosis of JIA (4).

Objectives Since there is discursive information about the relation between cow's milk allergy (CMA) and JIA, we wanted to study the association.

Methods The material was collected from national registers (Special Reimbursement Register, Drug Purchase Register and Population Register Center) containing all children born between 2000 and 2010 in Finland and diagnosed with JIA (N=1,298) and age-, gender- and place of birth-matched controls (N=5,179). Altogether 235 children with CMA were identified and 66 of them had JIA. A conditional logistic regression analysis was performed to evaluate the association between CMA and JIA. Additive interaction between CMA and antibiotics for JIA was evaluated by relative excess risk due to interaction (RERI), the attributable proportion due to interaction and synergy index.

Results In boys, a diagnosis of CMA and usage of hypoallergenic formula in infancy associated with later development of JIA (OR 2.4, 95% CI 1.6 to 3.6) whereas in girls with CMA such an association was not found (OR 1.1, 95% CI 0.7 to 1.7). Additionally, every 10-liter purchase of hypoallergenic formula increased the risk of JIA by 2% in boys (OR 1.02, 95% CI 1.01 to 1.03), but there was no increase in girls.

The association was most evident in those boys with diagnosis of JIA at less than three years of age (OR 3.8, 95% CI 1.9 to 7.6) and in those boys who had CMA with gastrointestinal symptoms (OR 4.4, 95% CI 1.9 to 9.9). In boys with both CMA and antibiotic exposure the risk of JIA was fourfold (OR 4.0, 95% CI 2.3 to 6.9) when compared to those without any such exposure. Nevertheless, no statistically significant additive interaction between CMA and antibiotic exposure was detected.

Conclusions Current associations may reflect difficulty in the maturation of intestinal immunity in boys at risk of JIA. Environmental factors related to JIA pathogenesis seem to have sex disparity.

  1. Kanerud L, Hällgren R, Brandtzaeg P. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut. 2006;55(9):1240–7

  2. Arvonen M, Vähäsalo P, Turunen S, Salo HM, Mäki M, Laurila K, et al. Altered expression of intestinal human leucocyte antigen D-related and immune signaling molecules in juvenile idiopathic arthritis. Clin Exp Immunol 2012;170:266–73

  3. Arvonen M, Alho L, Augustin M, Karttunen TJ, Vähäsalo P. Increase of duodenal and ileal mucosal cytotoxic lymphocytes in juvenile idiopathic arthritis. Clin Exp Rheumatol 2010;28(1):128–34

  4. Arvonen M, Virta LJ, Pokka T, Kröger L, Vähäsalo P. 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;42(3):521–6

Disclosure of Interest None declared

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