Celiac Autoimmunity, Celiac Disease and Growth

The objective of this study was to evaluate growth and clinical features of children who tested positive for antibodies associated with celiac disease (CD). A cohort of HLA-DRB1*03-characterized newborns from 1234 families in Denver, Colorado were prospectively followed since birth for the development of IgA autoimmune transglutaminase antibodies (TG). Clinical evaluation, growth, anthropometry and biochemical assessments, as well as small bowel biopsies were performed. There were 33 children who tested positive to TG; 18 of them completed the studies, underwent repeated testing and were compared with 100 pair-matched controls. The TG-positive children had antibodies detected at a mean age of 4.4 (+ 1.2) years and the mean age at clinical evaluation was 5.3 (+ 1.5) years. They had significantly lower z-scores for height, weight and BMI (–0.3 + 0.7), but not for weight- or height-for-age. They also had decreased mid-arm circumference and mid-arm muscle mass area. TG-positive children experienced more symptoms which increased over time, including abdominal pain, constipation and irritability/lethargy and these were independently associated with decreased weight gain. Thirteen (72%) of the 18 TG children had small intestinal mucosa evidence of CD (Marsh 2-3), 2 showed increased intraepithelial lymphocytes (Marsh 1), and 3 had normal biopsies. No relationship was found between copies of HLA-DRB1*03 and biopsy scores. The authors concluded that screening for CD identified TG-positive children who demonstrated mild alterations in weight and body composition and reported more symptoms than control subjects. They also had intestinal mucosa evidence of CD.

Hoffenberg EJ, Emery LM, Barriga KJ, et al. Clinical features of children with screening-identified evidence of celiac disease. Pediatrics 2004;113:1254-1259.

Editor’s Comment: This prospective study provided important data of the natural history of CD autoimmunity in a genetically susceptible population. It also discerned the clinical findings of TG-positive children and the small intestinal mucosa alterations. However, the response to a gluten-free diet was not reported; expert consensus panels require the assessment of the response to dietary therapy as important evidential data for the diagnosis of CD. Additionally, the nutrient intake or fecal-fat excretion was not reported. It is possible that children decreased food ingestion to minimize the discomfort of malabsorption, thus contributing to decreased weight and body composition. The prevalence of CD in children ranges between 0.4% to 1.0%,^1,2 whereas the prevalence of CD autoimmunity was close to 3% in this genetically susceptible population. TG-positive children presented few if any symptoms, and the autoimmune markers had a lower predictive value (75%) of detecting small bowel evidence of CD.³ Symptomatic CD patients are at risk of long-term consequences, including osteoporosis, lymphoma and other autoimmune processes,^4,5 though no data are available on the risks of patients with CD autoimmunity and silent disease. However, CD screening of at-risk patients is increasingly being done by pediatric endocrinologists in patients with T1DM, short stature, Turner or Down syndromes who have shown a prevalence of CD autoimmunity of up to 15%. Screening for CD is best accomplished by measurements of TG and endomysial antibody immunoflorecence IgA. Both have a high sensibility and sensitivity, whereas antigliadin antibodies do not. However, the case finding efforts need to be tempered with the cost of labeling children with CD, with the realization that this disease is difficult to prove and that only half of the patients follow a strict gluten-free diet.⁶ The benefits from early diagnosis and treatment of silent patients have not been demonstrated. Thus more research is warranted along with careful monitoring of height and weight progression of children with CD autoimmunity.

Fima Lifshitz, MD

References - (linked to )

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