Elsevier

The Journal of Pediatrics

Volume 157, Issue 3, September 2010, Pages 373-380.e1
The Journal of Pediatrics

Original Article
Celiac Disease without Villous Atrophy in Children: A Prospective Study

https://doi.org/10.1016/j.jpeds.2010.02.070Get rights and content

Objective

To establish whether children who are endomysial antibody (EmA) positive and have normal small-bowel mucosal villous morphology are truly gluten-sensitive and may benefit from early treatment with a gluten-free diet.

Study design

Children who were EmA positive with normal small-bowel mucosal villi were compared with children who were seropositive with villous atrophy by using several markers of untreated celiac disease. Thereafter, children with normal villous structure either continued on a normal diet or were placed on a gluten-free diet and re-investigated after 1 year. Seventeen children who were seronegative served as control subjects for baseline investigations.

Results

Normal villous morphology was noted in 17 children who were EmA positive, and villous atrophy was noted in 42 children who were EmA positive. These children were comparable in all measured variables regardless of the degree of enteropathy, but differed significantly from the seronegative control subjects. During the dietary intervention, in children who were EmA positive with normal villi, the disease was exacerbated in children who continued gluten consumption, whereas in all children who started the gluten-free diet, both the gastrointestinal symptoms and abnormal antibodies disappeared.

Conclusions

The study provided evidence that children who are EmA positive have a celiac-type disorder and benefit from early treatment despite normal mucosal structure, indicating that the diagnostic criteria for celiac disease should be re-evaluated.

Section snippets

Methods

The open study was performed at the Departments of Pediatrics and Gastroenterology and Alimentary Tract Surgery in Tampere University Hospital. The study protocol was approved by the ethical committee of Tampere University Hospital, and all the families gave written informed consent. The EmA-positive patient group comprised 59 consecutive children who were referred from primary health care because of suspicion of celiac disease (Figure 1; available at www.jpeds.com). After baseline

Results

Of the total 59 children who were EmA positive, 17 had normal small-bowel mucosal villous stucture (study group). Of these 17 children, 3 (18%) had Marsh 0 lesions, and 14 (82%) had Marsh I lesions; none had Marsh II lesions. The remaining 42 patients had small-bowel mucosal villous atrophy and crypt hyperplasia (Marsh III) and comprised the celiac group (Figure 1). The EmA-positive study and celiac groups and the seronegative non-celiac group were comparable in age, sex, main symptoms,

Discussion

The results of this trial strengthen the conception that all children who are EmA positive have a gluten-dependent disorder, irrespective of the small-bowel mucosal morphology. There was no difference in the duration or severity of the clinical symptoms in the subjects who were EmA positive with or without villous atrophy, and despite normal mucosal morphology, several celiac disease-related histological markers were detectable in children who were EmA positive. The density of CD3+ IELs in the

References (48)

  • M. Mäki et al.

    Prevalence of celiac disease among children in Finland

    N Engl J Med

    (2003)
  • S. Walker-Smith et al.

    Revised criteria for diagnosis of celiac disease

    Arch Dis Child

    (1990)
  • I. Hill et al.

    Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

    J Pediatr Gastroenterol Nutr

    (2005)
  • M. Mäki et al.

    Normal small bowel biopsy followed by coeliac disease

    Arch Dis Child

    (1990)
  • S. Iltanen et al.

    Changing jejunal γδ T cell receptor (TCR)-bearing intraepithelial lymphocyte density in coeliac disease

    Clin Exp Immunol

    (1999)
  • A. Fasano 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)
  • F. Paparo et al.

    Clinical, HLA and small bowel immunohistochemical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa

    Am J Gastroenterol

    (2005)
  • M. Mäki et al.

    Seroconversion of reticulin autoantibodies predicts coeliac disease in insulin dependent diabetes mellitus

    Gut

    (1995)
  • R. Troncone

    Latent coeliac disease in Italy. The SIGEP working group on latent coeliac disease. Italian Society for Paediatric Gastroenterology and Hepatology

    Acta Paediatr

    (1995)
  • M. Lähdeaho et al.

    Celiac disease: from inflammation to atrophy: a long-term follow-up study

    J Pediatr Gastroenterol Nutr

    (2005)
  • L. Tumer et al.

    Endomysium antibodies in the diagnosis of celiac disease in short-statured children with no gastrointestinal symptoms

    Pediatr Intern

    (2001)
  • L. Aine et al.

    Dental enamel defects in celiac disease

    J Oral Pathol Med

    (1990)
  • D.C. Weir et al.

    Variability of histopathological changes in childhood celiac disease

    Am J Gastroenterol

    (2009)
  • P. Kuitunen et al.

    Morphometric study of the jejunal mucosa in various childhood enteropathies with special reference to intraepithelial lymphocytes

    J Pediatr Gastroenterol Nutr

    (1982)
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    Supported by the Academy of Finland Research Council for Health, the Competitive Research Funding of the Pirkanmaa Hospital District, the Sigrid Juselius Foundation, the Foundation for Paediatric Research, the EU Commission Marie Curie Excellence Grant (FP6 contract MEXT-CT-2005-025270), Marie Curie Mobility Grant (MRTNCT-2006-036032; TRACKS), the National Graduate School of Clinical Investigation, the Ehrnrooth Foundation, and the Finnish Coeliac Society. The study sponsors had no role in the study design or collection, analysis and interpretation of the data, writing of the article or the decision to submit the manuscript for publication. The authors declare no conflicts of interest.

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