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Celiac Disease - Initial Diagnosis

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Overview

Celiac disease (CD) may present at any age following the introduction of gluten-containing foods into the diet. A definitive diagnosis should be made before beginning a gluten-free diet – testing for celiac disease while on a gluten-free diet may be inconclusive. Generally, the diagnosis is made on the basis of positive serology and small bowel histologic changes that meet the Marsh grading criteria. [Oberhuber: 1999] Observation of clinical response to gluten restriction and reintroduction may be useful in cases where serology and histology are equivocal. Once dietary gluten has been restricted, the child's symptoms should resolve, weight gain and growth should resume, endomysial and gliadin IgA antibodies should return to normal, and the intestinal mucosa should normalize with regeneration of the villi, reduction in crypt mitotic activity, and clearance of intraepithelial lymphocytes. Gluten reintroduction should result in recurrence of disease symptoms.

Presentations

At presentation, signs and symptoms of CD may be dramatic, but are more often subtle or insidious in onset. Many individuals present asymptomatically; they are identified as having celiac disease on the basis on positive screening results. See [Telega: 2008] and [Garampazzi: 2007].

Diagnostic Criteria

Definite diagnosis of CD
History and clinical presentation compatible with CD:
  • Serological screening compatible with CD: antigliadin antibody (AGA) anti-endomysial antibody (AEA), tissue transglutaminase (tTG) antibody
  • Histological findings compatible with CD: villous atrophy
  • Obvious clinical and serological response to a gluten-free diet (GFD)
  • Subject >2 years old
  • Rule out other clinical conditions mimicking CD
[Hill: 2005] [Fasano: 2008] and [Fasano: 2001]

Pearls And Alerts

Because false positives in children with failure-to-thrive are fairly common, assuring adequate calorie intake should precede testing for celiac disease to avoid unnecessary small bowel biopsies.

Evaluation and treatment decisions are made difficult by the silent celiac disease found in relatives of children with CD. See [Telega: 2008] , [Garampazzi: 2007], and [Bardella: 2007].

Celiac crisis, when gluten exposure causes a severe systemic reaction with hypoalbuminemia and hypoglycemia, occurs rarely. Although steroid treatment may be helpful, there are no published guidelines for management. [Mones: 2007]

Despite claims in the lay literature, there is no link between celiac disease and autism. Children with autism may have celiac disease and vice versa, but no cause-effect relationship exists. See [Black: 2002], [Pavone: 1997], and [Bushara: 2005].

Practice Guidelines

Fasano A, Araya M, Bhatnagar S, Cameron D, Catassi C, Dirks M, Mearin ML, Ortigosa L, Phillips A.
Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition consensus report on celiac disease.
J Pediatr Gastroenterol Nutr. 2008;47(2):214-9. PubMed abstract

Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, Hoffenberg EJ, Horvath K, Murray JA, Pivor M, Seidman EG.
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;40(1):1-19. PubMed abstract / Full Text

Elson, CO.
NIH Consensus Statement regarding the diagnosis and treatment of celiac disease.
NIH Consensus Development Conference on Celiac Disease, 2004; Bethesda, MD. / http://consensus.nih.gov/2004/2004CeliacDisease118html.htm
Diagnostic and management information for celiac disease from the NIH.

Differential Diagnosis

  • cystic fibrosis - An autosomal recessive disorder resulting in dysfunction in exocrine (mucus) glands of the lungs, liver, pancreas, and intestines. The sweat chloride test is positive in cystic fibrosis, negative in children with celiac disease. Gene testing is available.
  • Shwachman syndrome - a malabsorptive syndrome caused by pancreatic insufficiency. Bone marrow hypoplasia and frequent respiratory and skin infections are also observed.
  • giardiasis - due to infection with Giardia lamblia, a flagellated protozoan parasite. Diagnosed by stool sample.
  • abetalipoproteinemia – or Bassen-Kornzweig syndrome – a rare autosomal recessive disorder that interferes with absorption of fat and fat-soluble vitamins from food. Differentiated by the absence of beta-lipoproteins such as LDL, VLDL, and chylomicrons in this disorder. See Abetalipoproteinemia (Genetics Home Reference).
  • intestinal lymphangiectasia - (idiopathic hypoproteinemia), a disorder in which the lymph vessels draining the lining of the small intestine become enlarged and obstructed. Differentiated from CD by small-bowel biopsy showing marked dilation/ectasia of the mucosal and submucosal lymphatic vessels. [Vignes: 2008]
  • Crohn's disease - an autoimmune disorder leading to inflammation of any part of the digestive system, but usually the small intestine. There is some hereditary component. Crohn's disease usually has symptoms of abdominal pain and rectal bleeding. Celiac disease antibodies aren't elevated in patients with Crohn's disease and the inflammation doesn't respond to gluten restriction. See Crohn's disease (NDDIC).

History And Examination

Family History

The likelihood of celiac disease being the cause of the presenting symptoms is greater when there is a family history of:
  • celiac disease in first or second degree relatives
  • autoimmune thyroiditis or other autoimmune diseases
  • grain or wheat intolerance
  • type I diabetes mellitus
  • short stature
  • early osteoporosis
  • miscarriage

Medical History

Celiac disease is more common in children with Down syndrome, diabetes mellitus type I, Turner syndrome, Williams syndrome, selective IgA deficiency, and dermatitis herpetiformis. Look for symptoms beginning any time after introduction of wheat, barley, rye or oats into the infant's diet. Symptoms that are primarily gastrointestinal and growth related include:
  • chronic diarrhea
  • flatulence
  • distention
  • weight loss, or failure to gain expected weight
  • deceleration in linear growth or unexplained short stature
  • constipation
  • abdominal pain
  • indigestion or nausea and/or vomiting
  • bloating or distention
  • anorexia
Celiac disease is a multi-system disorder, often involving non-gastrointestinal symptoms/signs. These can vary considerably, some being related to secondary nutrient deficiencies, and may include:
  • unexplained iron deficiency anemia (a common presenting sign);
  • delayed puberty, infertility;
  • fatigue;
  • protein-calorie malnutrition;
  • recurrent aphthous stomatitis;
  • defects in dental enamel;
  • vitamin deficiencies;
  • osteoporosis;
  • other autoimmune endocrine disorders, such as thyroiditis; and
  • neurological symptoms, including ataxia and peripheral neuropathy. [Hadjivassiliou: 2003] [Hadjivassiliou: 2003] [Hadjivassiliou: 2006]

Social and Family History

Family history may be positive for celiac disease, but presence or lack of a family history should not sway decisions about testing.

Physical Exam

Growth Parameters

Look for low weight for age, low height for age, low weight for height or low BMI.

Skin

dermatitis herpetiformis: symmetric, grouped, small, tense, erythematous, stinging, pruritic papules or vesicles (see Celiac disease: DH pictures).

Abdomen

abdominal distention

Extremities

clubbing, edema

HEENT

enamel hypoplasia

Testing

Laboratory Testing

Blood: Individuals with celiac disease may have elevated serum transaminases, low albumin or iron deficiency anemia.

Serologic: (Note that IgA deficiency is thought to be prevalent in CD and that interpretation of some of the tests below will vary with IgA levels.)
  • Children under two: Test only if clinically very suspicious. Measure anti-gliadin IgA and IgG and tissue transglutaminase (tTG) IgA and IgG antibodies. Some clinicians so not use anti-gliadin antibodies in this age group.
  • Children older than two: First test for quantitative IgA - if it is sufficient, then measure anti-tTG IgA; if IgA is not sufficient, measure anti-tTG IgG.
Because false positives serologic tests are fairly common in children with failure to thrive, assuring adequate calorie intake should be considered before testing for celiac disease to avoid unnecessary small bowel biopsies.

Genetic Testing

Celiac disease is polygenic. Associated genes include the HLA-DQ2 heterodimer in 90% of patients with the condition and the HLA-DQ8 heterodimer in 10%. These markers may have valid negative predictive value if absent in a symptomatic patient. A minority of people with these genotypes ever develop celiac disease, so the predictive value is poor. DQ2 testing is also quite expensive.

Other Testing

Radiologic: Upper gastrointestinal barium study may reveal flocculation or separation of the barium stream with a "wet" appearance, but this is of little diagnostic value.

Histologic: Definitive diagnosis after serological testing is based on small bowel biopsy and the Oberhuber-modified Marsh Classification [Oberhuber: 1999]:
  • Type I - normal mucosa infiltrated with intraepithelial lymphocytes > 30/100 epithelial cells.
  • Type II - additional feature of elongated or deeper crypts with increased mitoses consistent with crypt hyperplastic response.
  • Type III subtypes A-C - additional features of increasing atrophy of the villi from blunt to flat.
  • Type IV - total villous atrophy but no inflammation or crypt hyperplasia.

Subspecialist Collaborations and Other Resources

Pediatric Gastroenterology (see Services below for relevant providers)

Referral to pediatric gastroenterology is important to confirm the diagnosis through small bowel biopsy and to advise on long-term management.

Resources

Information & Support

For Professionals

Celiac disease (GeneReviews)
Detailed overview of celiac disease, testing, genetics, resources, reviews, and research; hosted by NCBI (National Center for Biotechnology Information).

For Parents and Patients

Support

Celiac Disease Foundation
Provides support, information and assistance to people affected by Celiac Disease/Dermatitis Herpetiformis (CD/DH).

General

Celiac disease (MedLinePlus)
Brief description and links to many reliable sources of information, compiled and maintained by the National Library of Medicine.

Celiac disease (NDDIC)
General information and links to a lot more, from the National Digestive Diseases Information Clearinghouse, National Institutes of Health.

Practice Guidelines

Elson, CO.
NIH Consensus Statement regarding the diagnosis and treatment of celiac disease.
NIH Consensus Development Conference on Celiac Disease, 2004; Bethesda, MD. / http://consensus.nih.gov/2004/2004CeliacDisease118html.htm
Diagnostic and management information for celiac disease from the NIH.

Fasano A, Araya M, Bhatnagar S, Cameron D, Catassi C, Dirks M, Mearin ML, Ortigosa L, Phillips A.
Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition consensus report on celiac disease.
J Pediatr Gastroenterol Nutr. 2008;47(2):214-9. PubMed abstract

Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, Hoffenberg EJ, Horvath K, Murray JA, Pivor M, Seidman EG.
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;40(1):1-19. PubMed abstract / Full Text
Recommendations for the diagnosis and treatment of celiac disease in children from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Services

Pediatric Gastroenterology

See all Pediatric Gastroenterology services providers (2) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed Search on Celiac Disease in children for last 2 years.

McGowan KE, Castiglione DA, Butzner JD.
The changing face of childhood celiac disease in north america: impact of serological testing.
Pediatrics. 2009;124(6):1572-8. PubMed abstract

Green PH, Cellier C.
Celiac disease.
N Engl J Med. 2007;357(17):1731-43. PubMed abstract
Excellent and extensive review article, not focused on children.

Authors

Authors: Lynne M Kerr MD, PhD, 3/2009
Daniel Jackson M.D., 6/2008
Content Last Updated: 3/2009

Page Bibliography

Bardella MT, Elli L, Velio P, Fredella C, Prampolini L, Cesana B.
Silent celiac disease is frequent in the siblings of newly diagnosed celiac patients.
Digestion. 2007;75(4):182-7. PubMed abstract

Black C, Kaye JA, Jick H.
Relation of childhood gastrointestinal disorders to autism: nested case-control study using data from the UK General Practice Research Database.
BMJ. 2002;325(7361). PubMed abstract / Full Text
Children diagnosed with autism were not more likely to have presented with celiac disease than controls.

Bushara KO.
Neurologic presentation of celiac disease.
Gastroenterology. 2005;128(4 Suppl 1):S92-7. PubMed abstract

Fasano A, Araya M, Bhatnagar S, Cameron D, Catassi C, Dirks M, Mearin ML, Ortigosa L, Phillips A.
Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition consensus report on celiac disease.
J Pediatr Gastroenterol Nutr. 2008;47(2):214-9. PubMed abstract

Fasano A, Catassi C.
Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum.
Gastroenterology. 2001;120(3):636-51. PubMed abstract
Guidelines for diagnosis and treatment of celiac disease.

Garampazzi A, Rapa A, Mura S, Capelli A, Valori A, Boldorini R, Oderda G.
Clinical pattern of celiac disease is still changing.
J Pediatr Gastroenterol Nutr. 2007;45(5):611-4. PubMed abstract

Hadjivassiliou M, Davies-Jones GA, Sanders DS, Grunewald RA.
Dietary treatment of gluten ataxia.
J Neurol Neurosurg Psychiatry. 2003;74(9):1221-4. PubMed abstract / Full Text

Hadjivassiliou M, Grunewald R, Sharrack B, Sanders D, Lobo A, Williamson C, Woodroofe N, Wood N, Davies-Jones A.
Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics.
Brain. 2003;126(Pt 3):685-91. PubMed abstract

Hadjivassiliou M, Grunewald RA, Kandler RH, Chattopadhyay AK, Jarratt JA, Sanders DS, Sharrack B, Wharton SB, Davies-Jones GA.
Neuropathy associated with gluten sensitivity.
J Neurol Neurosurg Psychiatry. 2006;77(11):1262-6. PubMed abstract

Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, Hoffenberg EJ, Horvath K, Murray JA, Pivor M, Seidman EG.
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;40(1):1-19. PubMed abstract / Full Text
Recommendations for the diagnosis and treatment of celiac disease in children from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Mones RL, Atienza KV, Youssef NN, Verga B, Mercer GO, Rosh JR.
Celiac crisis in the modern era.
J Pediatr Gastroenterol Nutr. 2007;45(4):480-3. PubMed abstract

Oberhuber G, Granditsch G, Vogelsang H.
The histopathology of coeliac disease: time for a standardized report scheme for pathologists.
Eur J Gastroenterol Hepatol. 1999;11(10):1185-94. PubMed abstract

Pavone L, Fiumara A, Bottaro G, Mazzone D, Coleman M.
Autism and celiac disease: failure to validate the hypothesis that a link might exist.
Biol Psychiatry. 1997;42(1):72-5. PubMed abstract

Telega G, Bennet TR, Werlin S.
Emerging new clinical patterns in the presentation of celiac disease.
Arch Pediatr Adolesc Med. 2008;162(2):164-8. PubMed abstract

Vignes S, Bellanger J.
Primary intestinal lymphangiectasia (Waldmann's disease).
Orphanet J Rare Dis. 2008;3:5. PubMed abstract / Full Text