Diagnosis

The four pillars underpinning a diagnosis of coeliac disease, are:

1. Clinical history

Clinical history includes both personal and family medical history in addition to a dietary history that specifically focuses on foods that contain gluten. Clinical symptoms are also monitored in this step, for example bowel habits, weight loss, abdominal bloating, abdominal pain, nausea and growth disorders in children. Extraintestinal symptoms such as fatigue, bone/joint pain and headaches/migraine are also important factors to consider here.

2. Serological tests

Serological testing for coeliac 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 as results may normalise on a gluten-free diet.

HLA typing

Human leukocyte antigen (HLA) DQ2/DQ8 testing may be considered within the diagnostic work-up for patients within specialist settings. The diagnostic value of HLA genotyping within this patient group, revolves around it’s high negative predictive value – a negative result indicating that a patient is highly unlikely to have coeliac disease (less than 1% of patients with coeliac disease do not carry these alleles [3]). However, the positive predictive value of value of HLA genotyping is very low, since a 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 have a gluten challenge.

3. Histological tests

Patients with positive serological test results should be referred to a gastrointestinal specialist for endoscopic intestinal biopsy to confirm or exclude coeliac disease [2]. Villous atrophy may be patchy in coeliac 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 coeliac-positive histology (Marsh 3a-c).

4. Response to a gluten-free diet

The diagnosis of coeliac 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 Coeliac 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].