Celiac disease (CD) or gluten-sensitive enteropathy is a complex autoimmune disorder characterized by intestinal and extraintestinal manifestations that occur in genetically susceptible individuals after exposure to gluten-containing foods. The disease is associated with human leukocyte antigen DQ2 and DQ8 haplotypes. The prevalence of CD is estimated to be 4.54% among first-degree relatives of patients with CD and 0.5% to 1% in the general population (1,2). Classic CD presents in children with failure to thrive and malabsorption. CD is also diagnosed after screening high-risk groups such as children with diabetes (4.5%), Down syndrome (4.6%), and thyroid disorders (3.3%) (3–5).
Obesity is the most prevalent nutritional disorder among children and adolescents in the United States. The prevalence of overweight and obesity has doubled in a single generation, and approximately 1 in 3 American children and adolescents are overweight, with nearly 15% being obese (6). Almost half of all adult patients with CD have BMI ≥25 at diagnosis. Only 4 isolated pediatric case reports of CD and obesity have been reported. We hypothesize that obesity is more common in pediatric CD than previously suspected. The aim of our study was to estimate the prevalence of obesity at diagnosis in children with CD and describe the clinical characteristics of this group.
PATIENTS AND METHODS
We reviewed the charts of all of the patients diagnosed with CD in a 17-year period, 1986 through 2003, at Children's Hospital of Wisconsin as previously reported (7). Data collected from the medical records included age, sex, ethnicity, presenting signs and symptoms, body mass index (BMI), celiac antibody titers, small-intestinal biopsy results, and follow-up weight 1 year after starting on a gluten-free diet (GFD) following the diagnosis of CD. Biopsies were reviewed by a pediatric pathologist and were graded according to the Marsh criteria (8). Antibody tests including antigliadin antibody, anti-endomysial antibodies, tissue transglutaminase-IgA, and total immunoglobulin (Ig)A were done by commercial laboratories. The diagnosis of CD was considered if there was histological evidence of Marsh 2 or greater abnormality in an appropriate clinical setting or in the presence of elevated celiac antibodies. A BMI >95th percentile was considered obese. Symptoms and compliance were monitored and follow-up BMI was recorded at 1 year after GFD. All of the information was entered into a Microsoft Excel spreadsheet for analysis. This study was approved by the Human Rights Review Committee of the Children's Hospital of Wisconsin.
Seven of the 143 (5%) patients with CD identified during the study period had BMI >95th percentile. The mean age at presentation was 11.2 years (9.9–16 years) for obese patients versus 8.3 years (1–17 years) in all of the patients with CD (Table 1). Of those 7 patients, 4 were female, 3 were male, and 6 were white. The most common indications for biopsy among obese patients were abdominal pain (4), type 1 diabetes mellitus (2), diarrhea (2), and Down syndrome (1). All of the 5 patients tested for transglutaminase-IgA were positive, 4 of the 7 were positive for anti-endomysial antibodies, and 1 of the 7 was positive for IgA and IgG anti-gliadin antibody. All of the patients had abnormal biopsies consistent with CD. Lactase deficiency was present in 28% of the patients. Symptoms improved in all of the patients on a GFD. Follow-up BMI decreased in 4 (57%) and increased in 2 (28%) patients, and 1 patient was lost to follow-up (Fig. 1).
There are multiple studies in the adult literature reporting the association of CD and obesity. Dickey et al (9) conducted a 10-year study to analyze the prevalence of increased BMI in CD and described that almost 39% of adult patients with CD were overweight at diagnosis, with 13% being obese. Nearly 82% of the overweight patients gained weight after 2 years on GFD. The authors attributed the weight gain and increase in body fat stores to improved intestinal absorption after gluten exclusion (9). In contrast, Murray et al (10) showed that 6% of 215 adult patients with CD were obese at diagnosis and 60% of these patients had a decrease in BMI after 6 months of GFD. The authors hypothesized that iron and micronutrient deficiency seen in patients with CD results in increased food craving leading to obesity, similar to increased intake seen in patients experiencing pica (10). West et al (11) found that 3.9% of 3590 patients with CD were obese and 17% were overweight. A 14-year follow-up study on compliance and quality of life of patients with CD conducted by Viljamaa et al (12) stated that 15% of 50 patients were in the obese category.
Only 4 children with CD and obesity have been reported. Nibali et al (13) reported a 5-year-old obese girl with CD whose recurrent abdominal pain improved after GFD. The patient gained excessive weight after starting on a GFD. Semeraro et al (14) described a 14-year-old girl with CD who gained excessive weight after starting on a GFD, and speculated that the parental urge to improve her previous undernourishment led to increased caloric consumption and obesity (14). Oso et al (15) reported on a 14-year-old boy with diarrhea and obesity. On a GFD his BMI increased from 37 to 42. The authors noted that patients on GFD take excessive energy in the form of fats and high-energy drinks because of the expense and unpalatability of GFD (15). Czaja-Bulsa et al (16) described an 18-year-old obese boy with increased obesity after GFD for 6 months. The weight gain stabilized after reintroduction of gluten in the diet.
Because classic CD presents as failure to thrive and malabsorption during infancy and school age, most physicians include CD in the differential diagnosis of such children but not in those with obesity. Recent studies have described a changing pattern in the presentation of CD, which includes asymptomatic disease to atypical presentations including fatigue, seizures, behavioral problems, and dermatitis herpetiformis (7,17,18). Increasing number of asymptomatic patients are diagnosed after serologic screening performed in conditions associated with CD (ie, Down syndrome, type I diabetes mellitus). We describe yet another important subgroup of children, those who are obese, that may be missed if the diagnosis is not suspected.
We analyzed the prevalence of obesity in pediatric patients with CD during a 17-year period at a major tertiary center. We found that 5% of patients CD are obese with a BMI >95th percentile. BMI decreased in 57% of patients after institution of GFD. The most common presentation of patients with CD and obesity included abdominal pain and diarrhea. These patients presented at a later age compared with a nonobese cohort.
One of the limitations of our study was that only a small group of children were identified and a prospective multicenter study involving a large group of children with long-term follow-up is required to identify the true association, prevalence, and outcome of CD and obesity.
Obesity is more common in children with CD than previously recognized. In the appropriate clinical setting CD must be considered even in obese children because CD can be easily missed if the diagnosis is not considered in this population subset. The treatment of CD in obese children may reduce BMI.
1. Hoffenberg EJ, MacKenzie T, Barriga KJ, et al
. A prospective study of the incidence of childhood celiac disease. J Pediatr 2003; 143:308–314.
2. Fasano A, Berti I, Gerarduzzi T, et al
. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003; 163:286–292.
3. Holmes GK. Screening for coeliac disease in type 1 diabetes. Arch Dis Child 2002; 87:495–498.
4. Bonamico M, Mariani P, Danesi HM, et al
. Prevalence and clinical picture of celiac disease in Italian Down syndrome patients: a multicenter study. J Pediatr Gastroenterol Nutr 2001; 33:139–143.
5. Valentino R, Savastano S, Tommaselli AP, et al
. Prevalence of coeliac disease in patients with thyroid autoimmunity. Horm Res 1999; 51:124–127.
6. Ogden CL, Carroll MD, Curtin LR. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006; 295:1549–1555.
7. Telega G, Bennet TR, Werlin S. Emerging new clinical patterns in the presentation of celiac disease. Arch Pediatr Adolesc Med 2008; 162:164–168.
8. Marsh MN. Grains of truth: evolutionary changes in small intestinal mucosa in response to environmental antigen challenge. Gut 1990; 31:111–114.
9. Dickey W, Kearney N. Overweight in celiac disease: prevalence, clinical characteristics, and effect of a gluten-free diet
. Am J Gastroenterol 2006; 101:2356–2359.
10. Murray JA, Watson T, Clearman B, et al
. Effect of a gluten-free diet
on gastrointestinal symptoms in celiac disease. Am J Clin Nutr 2004; 79:669–673.
11. West J, Logan RF, Card TR, et al
. Risk of vascular disease in adults with diagnosed coeliac disease: a population-based study. Aliment Pharmacol Ther 2004; 20:73–79.
12. Viljamaa M, Collin P, Huhtala H, et al
. Is coeliac disease screening in risk groups justified? A fourteen-year follow-up with special focus on compliance and quality of life. Aliment Pharmacol Ther 2005; 22:317–324.
13. Conti Nibali S, Magazzu G, De Luca F. Obesity in a child with untreated coeliac disease. Helv Paediatr Acta 1987; 42:45–48.
14. Lucille A, Semeraro MD, Kenneth W, et al
. Gryboski obesity in celiac sprue. J Clin Gastroenterol 1986; 8:177–180.
15. Oso O, Fraser NC. A boy with coeliac disease and obesity. Acta Paediatr 2006; 95:618–619.
16. Czaja-Bulsa G, Garanty-Bogacka B, Syrenicz M, et al
. Obesity in an 18-year-old boy with untreated celiac disease. J Pediatr Gastroenterol Nutr 2001; 32:226.
17. Hull CM, Liddle M, Hansen N, et al
. Elevation of IgA anti-epidermal transglutaminase antibodies in dermatitis herpetiformis. Br J Dermatol 2008; 159:120–124.
18. Brow JR, Parker F, Weinstein WM, et al
. The small intestinal mucosa in dermatitis herpetiformis. I. Severity and distribution of the small intestinal lesion and associated malabsorption. Gastroenterology 1971; 60:355–361.