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:
- Clinical history
- 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.
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 ). 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 . 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 . Villous atrophy may be patchy in celiac disease, therefore a minimum of four biopsy specimens should be obtained, including a duodenal bulb biopsy . 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 classification||histological findings|
|Stage 0||Normal duodenal mucosa|
|Stage 1||Increased intraepithelial lymphocytes (IELs) >25 IELs/100 enterocytes (non-specific finding)|
|Stage 2||Stage 1 plus crypt hyperplasia (non-specific finding)|
|Stage 3a||Increased IELs, crypt hyperplasia, and partial villous atrophy|
|Stage 3b||Increased IELs, crypt hyperplasia, and subtotal villous atrophy|
|Stage 3c||Increased 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  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)  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 . 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 .
- 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
- NICE Clinical Guideline 86: Recognition, Assessment & Management of Coeliac Disease. National Institute of Clinical Excellence 2015.
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