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Celiac disease and juvenile idiopathic arthritis: a still enigmatic crossover

The coexistence of celiac disease (CD) with autoimmune diseases is largely documented and there is increasing evidence that CD shares many predisposing susceptibility loci with juvenile idiopathic arthritis (JIA) [1]. The authors present a 13-year-old boy hospitalized for left tibiotarsal arthritis and metacarpophalangeal joint arthritis of all fingers of the hands. The boy had a past history of recurrent abdominal pain and irregular bowel movements. His staturoponderal growth was normal. Blood tests showed mild hypochromic normocytic anemia (hemoglobin (Hb) 9 g/dl), low ferritin level (9 ng/ml, n.v. 12–68) and positive IgA anti-tissue transglutaminase antibodies (above 100 U/ml, reference value <16). Small intestinal histology was consistent with CD and gluten-free elimination diet consented to improve both gastrointestinal complaint and CD-related arthritis. One year later, while gluten-free diet was maintained, the boy presented fever of 2 weeks’ duration combined with diffuse erythematosus rash, bilateral distention of the carpometacarpal region and hepatomegaly. Liver function test was normal; blood tests revealed neutrophil leukocytosis (white blood cells (WBC) 14.240/mm, N 80%), C-reactive protein (CRP) 151 mg/l (n.v. <5), erythrocyte sedimentation rate (ESR) 82, ferritin 738 ng/ml and D-dimer 2260 ng/ml (n.v. 0–270). Serology for hepatotropic viruses and autoimmunity tests were negative, with the exception of anti-thyroglobulin antibodies (283.3 IU/l, n.v. <28). Despite therapy with indomethacin (2 m/kg/day), fever persisted with occasional spikes, evanescent macular rash on the trunk and hands and arthralgias. Due to this picture suggesting the diagnosis of systemic JIA, fulldosage methylprednisolone was started after bone marrow evaluation. Fever and joint symptoms completely disappeared after 1 week, but required methotrexate (10 mg/m/week) to maintain a stable clinical remission. The proportion of children with JIA diagnosed according to International League of Associations for Rheumatology (ILAR) criteria having CD was 0.14% in a large cohort of Brazilian patients [2], but no data exist about the occurrence of the systemic variant of JIA in celiac patients. The resolution of CD-related arthritis with a gluten-free diet and the subsequent onset of systemic JIA in this boy demonstrate a still enigmatic relationship between the two diseases. Lymphocyte cytotoxicity may be abnormally increased in the intestinal mucosa of patients with JIA [3], but further studies are needed to evaluate the role of environmental factors other than gluten in the pathogenesis of the articular disease. Recent insight into molecular biology has hypothesized that different immune-mediated diseases of the gastrointestinal tract might be a “continuum” with genetic disorders of innate immunity, displaying abnormally disrupted cytokine production, as systemic JIA, which is now considered an autoinflammatory