Celiac Disease in Juvenile Idiopathic Arthritis and Other Pediatric Rheumatic Disorders

Abstract

Celiac Disease (CD) is an immune-mediated and gluten-related disorder whose prevalence is higher in children affected with other autoimmune disorders, including diabetes mellitus type 1, autoimmune thyroiditis, and others. As regards Juvenile Idiopathic Arthritis (JIA) and other pediatric rheumatic disorders, there is no clear recommendation for CD serological screening. In this review, we analyze all the available clinical studies investigating CD among children with JIA (and other rheumatic diseases), in order to provide objective data to better understand the necessity of CD serological screening during the follow-up. Based on the present literature review and analysis, >2.5% patients with JIA were diagnosed with CD; however, the CD prevalence in JIA patients may be even higher (>3–3.5%) due to several study limitations that could have underestimated CD diagnosis to a variable extent. Therefore, serological screening for CD in children affected with JIA could be recommended due to the increased CD prevalence in these patients (compared to the general pediatric population), and because these JIA patients diagnosed with CD were mostly asymptomatic. However, further research is needed to establish a cost-effective approach in terms of CD screening frequency and modalities during the follow-up for JIA patients. Conversely, at the moment, there is no evidence supporting a periodical CD screening in children affected with other rheumatic diseases (including pediatric systemic lupus erythematosus, juvenile dermatomyositis, and systemic sclerosis).

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study

“…The epidemiological relationship between CD and JIA has been explored for decades (9,40,41), but most studies to date have consisted of single-center cohort studies or case series. A recent review found that the combined prevalence of CD in patients with JIA across multiple previous cohort studies was 2.6% (30 CD cases of 1174 patients with JIA), but acknowledged significant limitations in estimating prevalence due to small sample sizes, lack of robust control groups, variability in serological screening assays for CD, and infrequent confirmation of CD with intestinal biopsy (42). Larger studies of CD in patients with JIA, meanwhile, have had conflicting results.…”

Screening for celiac disease in juvenile idiopathic arthritis

“…Very recently, our group reviewed all the available clinical studies investigating CD among children affected with rheumatic disorders, including JIA. Notably, we retrieved 30 CD cases in a pooled population consisting of 1174 JIA patients, which corresponds to a 2.6% prevalence of CD in JIA population [ 2 ]. This estimation is very similar to that emerging from the study by Naddei et al…”

“…Moreover, we suggested that such a prevalence might be even underestimated, because some JIA patients positive for anti-tissue transglutaminase IgA (anti-tTG IgA) and/or anti-endomysium (EmA) antibodies, did not undergo or declined the upper gastrointestinal endoscopy (and related duodenal biopsy), which may have led to some additional CD diagnoses. We also noticed that the CD serological screening approach was quite heterogeneous across the 14 clinical studies that we analyzed and pooled, which may have further impacted on the identification of a few additional CD cases in JIA patients [ 2 ]. Indeed, as emphasized by Naddei et al too, most patients were diagnosed with CD after the JIA onset and, thus, were “asymptomatic” (for CD), which further highlights the importance of the serological screening in patients previously diagnosed with JIA [ 1 , 2 ].…”

“…We also noticed that the CD serological screening approach was quite heterogeneous across the 14 clinical studies that we analyzed and pooled, which may have further impacted on the identification of a few additional CD cases in JIA patients [ 2 ]. Indeed, as emphasized by Naddei et al too, most patients were diagnosed with CD after the JIA onset and, thus, were “asymptomatic” (for CD), which further highlights the importance of the serological screening in patients previously diagnosed with JIA [ 1 , 2 ]. These authors clearly described their follow-up strategy in JIA patients: “CD screening was systematically carried out by measuring serum anti-tTG IgA antibodies at the time of JIA diagnosis and thereafter annually.…”

“…Total IgA levels were assessed at diagnosis to exclude IgA deficiency” [ 1 ]. However, as mentioned in our review, there is no (clear) recommendation for CD screening in JIA patients according to the recently updated ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology and Nutrition) guidelines for CD diagnosis and management [ 2 , 3 ].…”