The celiac iceberg: from the clinical spectrum to serology and histopathology in children and adolescents with type 1 diabetes mellitus and Down syndrome

Abstract

Objective: The objective of this study is to investigate the occurrence of gastrointestinal (GI) and extraintestinal symptoms in children and adolescents with type 1 diabetes mellitus (DM1) and Down syndrome (DS) and their association with specific antibodies and histopathology of celiac disease (CelD), representing its clinical forms in the iceberg. Material and methods: Cross-sectional study (November 2009–December 2012) conducted at an outpatient care facility in Northeast Brazil including patients [DM1 (n = 111); DS (n = 77)] aged 10 months–18 years old. Measurement of anti-endomysial (EmA) and anti-tissue transglutaminase (anti-tTG) IgA antibodies was performed, as was that of anti-tTG-IgG in the cases with low serum IgA. The patients with antibody positivity were subjected to small intestine biopsy. Results: GI symptoms occurred in 53.7% of the sample, extraintestinal symptoms in 4.3%, and antibody positivity in 28.2% (n = 53). Of those who underwent biopsy (n = 40), histopathological findings of CelD were found in 37.5% [DM1 = 5/111 (4.5%), DS = 10/77 (13.0%)]. GI symptoms were associated with antibody positivity, but not with the histopathology. The GI (32.5%), silent (5.0%), and potential (62.5%) forms of disease were detected. Conclusions: The prevalence of GI symptoms was high in groups DM1 and DS, and the occurrence of such symptoms was associated with antibody positivity. The lack of association between the symptoms and histopatholological findings points to the inconsistency of the former as indicators of CelD. Although the GI form predominated among the cases with active CelD, its contribution to the celiac iceberg was smaller compared with the potential form, which determined the large and submerged base of the iceberg representing the high-risk groups investigated.

Prevalence of celiac disease in a large cohort of young patients with type 1 diabetes

“…Studies from different Brazilian regions have shown a wide frequency range of GI manifestations in patients with T1DM and CD (38.3%‐80.0%) . In the present study, almost two‐thirds of patients (71.4%) with biopsy‐proven CD reported unspecific GI symptoms, predominantly abdominal pain and distension.…”

“…In our study, which is the largest cohort in Brazil to date, the prevalence was 5.6%. This frequency is higher than that observed in most studies carried out in different regions of Brazil (Table ) . The only Brazilian study showing a higher prevalence (15.8%) of biopsy‐proven CD was based in a very small sample (19 patients with T1DM) .…”

“…However, this meta‐analysis considered the presence of CD in a heterogeneous population, including 801 patients with positive immunoglobulin A anti‐tissue transglutaminase (IgA‐tTG) antibodies or IgA antiendomysial antibodies (IgA‐EMA) and 454 with positive antibodies and intestinal biopsies . In other studies conducted in different Brazilian regions, the prevalence of biopsy‐proven CD in individuals with T1DM ranged from 2.5% to 4.8% …”

Prevalence of celiac disease in patients with Down syndrome: a meta-analysis

“…Compared to the general population, literature has provided evidence that CD is more frequent in patients with some genetic and autoimmunological diseases, these diseases include type 1 diabetes [ 5 , 6 ], autoimmune thyroid disease [ 7 , 8 ], autoimmune hepatitis [ 9 ] and Down syndrome (DS) [ 10 ]. Although the prevalence of CD in those diseases varied substantially among studies, a systematic review with meta-analysis showed that 6 % of patients with type 1 diabetes have biopsy-confirmed celiac disease [ 11 ].…”

Coeliac disease: review of diagnosis and management

“…The pooled prevalence of coeliac disease among first degree relatives is 7.5% 19 . Recent studies show that children with diabetes mellitus type 1 and Down syndrome have a high prevalence of coeliac disease, which may present with abdominal pain and constipation rather than classical diarrhoea 20 — also pointing to case finding in this group. Although current evidence is not sufficient to support mass screening for coeliac disease, active case finding is appropriate in high risk groups 12 …”