Diagnosing celiac disease

  1. Dr. Schär Institute
  2. Diagnosing celiac disease
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Diagnosis of celiac disease is based on four elements. It is essential that patients follow a gluten-containing diet both before and during the diagnostic procedure.

The four key elements of  a diagnosis of celiac disease, are:

  1. Clinical history
  2. Serology
  3. Histology
  4. Improvement of symptoms and antibody response to a gluten-free diet

1. Clinical history

Clinical history includes both individual and family medical and dietary history. The diet history should include typical eating patterns, cultural traditions and food preferences. Clinical symptoms are also assessed in this step including, bowel habits, weight loss, abdominal bloating, abdominal pain, nausea and growth disorders in children. Extraintestinal symptoms such as fatigue, skin manifestations bone/joint pain and headaches/migraine are also important factors to consider here.

2. Serological tests

Serological testing for celiac disease involves the identification of immunoglobulin A tissue transglutaminase (IgA tTG) antibodies and specific endomysial antibodies (EMA). Total IgA should be determined in order to rule out IgA deficiency and reduce the risk of a false negative result. In patients with known IgA deficiency, immunoglobulin G (IgG) EMA, IgG deaminated gliadin peptide (DGP) or IgG tTG may be used in order to support the diagnosis [1,2]. It is essential that patients consume a gluten containing diet prior to and during diagnostic investigation to avoid a potential false negative result.

HLA typing

Human leukocyte antigen (HLA) DQ2/DQ8 testing may be considered as part of the diagnostic work-up. The diagnostic value of HLA genotyping revolves around it’s high negative predictive value – a negative result indicating that a patient is highly unlikely to have celiac disease (less than 1% of patients with celiac disease do not carry these alleles [3]). However, the positive predictive value of value of HLA genotyping is very low, since up to 40% of the general population also carry genes encoding HLA DQ2/DQ8 [4]. HLA testing may therefore be useful for patients where the diagnosis is equivocal, or for those who have already embarked on a gluten free diet and choose not to undergo a gluten challenge.

3. Histological tests

Patients with positive serological test results should be referred to a gastrointestinal for endoscopic intestinal biopsy to confirm or exclude celiac disease [2]. Villous atrophy may be patchy in celiac disease, therefore a minimum of four biopsy specimens should be obtained, including a duodenal bulb biopsy [1]. The histological changes observed in these samples are classified according to the Marsh classification. Evidence of villous atrophy and increased intraepithelial lymphocytes are typical features of a celiac-positive histology (Marsh 3a-c).

Marsh classificationhistological findings
Stage 0Normal duodenal mucosa
Stage 1Increased intraepithelial lymphocytes (IELs) >25 IELs/100 enterocytes (non-specific finding)
Stage 2Stage 1 plus crypt hyperplasia (non-specific finding)
Stage 3aIncreased IELs, crypt hyperplasia, and partial villous atrophy
Stage 3bIncreased IELs, crypt hyperplasia, and subtotal villous atrophy
Stage 3cIncreased IELs, crypt hyperplasia, and total villous atrophy

5. Response to a gluten-free diet

The diagnosis of celiac disease is considered to be confirmed if symptoms improve and repeat serological testing indicates that the antibodies are responding to the gluten-free diet. Current NICE guidelines on the Recognition, Assessment and Management of Celiac Disease [2] recommend that patients with persistently high serological titres or persistent symptoms after 12 months (where the possibility of continued gluten exposure has been excluded) should be considered for repeat intestinal biopsy and review by a specialist gastroenterology team.

Regular follow-up examinations

Guidelines from the Primary Care Society for Gastroenterology (PCSG) [8] recommend that newly diagnosed patients should be reviewed after 3-6 months and annually thereafter in order to  monitor compliance with and response to treatment, and evidence of disease complications. Patients should be offered access to specialist dietetic and nutritional advice as part of this review, during which symptoms may be reviewed alongside dietary adherence, nutritional adequacy, and collection of anthropometrical data [2]. Repeat serological testing may be used in conjunction with dietetic review in order to assess adherence. Follow-up biopsies are not routinely used in the review of patients with coeliac disease but may be useful for patients whose condition does not respond to a gluten free diet [1].

References

  1. Ludvigsson JF, Bai JC, Biagi F et al. Diagnosis and management of adult coeliac disease : guidelines from the British Society of Gastroenterology. Gut 2014; 63(8):1210-28
  2. NICE Clinical Guideline 86: Recognition, Assessment & Management of Coeliac Disease. National Institute of Clinical Excellence 2015.
  3. Polvi A, Arranz E, Fernandez-Arquero M et al. HLA-DQ2-negative celiac disease in Finland and Spain. Hum Immunol 1998;59:169-75
  4. Abadie V, Sollid LM, Barreiro LB et al. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu Rev Immunol 2011; 29:493-525
  5. Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 1999; 11:1185-94
  6. Husby S, Koletzko S, Korponay-Szabó IR et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54: 136-160
  7. Evaluation of the ESPGHAN Celiac Guidelines in a North American Pediatric Population. Gidrewicz D, Potter K, Trevenen CL, Lyon M, Butzner JD. Am J Gastroenterol. 2015 May;110(5):760-7. doi: 10.1038/ajg.2015.87.
  8. Fasano, A., Catassi, C. (2012). Clinical practice. Celiac disease. N Engl J Med.;     20; 367(25):2419-26. doi: 10.1056/NEJMcp1113994.
  9. Celiac disease: past, present, and future challenges: dedicated to the memory of our friend and colleague, Prof David Branski (1944-2013). Heyman MB. J Pediatr Gastroenterol Nutr. 2014 Jul;59 Suppl 1:S1. doi:10.1097/01.mpg.0000450390.38403.22
Biopsies for children?

Recently, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) proposed new guidance regarding the diagnosis of celiac disease in children [6,7]. ESPGHAN suggest that in symptomatic children, in whom the IgA tTG level exceeds 10 times the upper limit of normal, EMA antibodies are positive on a separately taken blood sample, and HLA-DQ2 or HLA-DQ8 are positive, then biopsies do not need to be performed to confirm a diagnosis of coeliac disease. Although this approach remains controversial, the North American Society of Pediatric Gastroentrology, Heaptology and Nutriton (NASPGHAN) published a guideline supporting ESPGHAN’s approach to the diagnosis of celiac disease in children [7].

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