Coeliac disease can present in many varied ways and requires a high degree of clinical suspicion.
Patients with unexplained gastrointestinal symptoms (including those diagnosed with irritable bowel syndrome and/or dyspepsia), chronic diarrhoea, unexplained iron deficiency anaemia, or a skin rash consistent with dermatitis herpetiformis should be tested for coeliac disease.    Other situations that may prompt testing include failure to thrive, short stature, vitamin deficiency (B12, D, or folate), recurrent severe aphthous stomatitis, recurrent spontaneous abortion, and infertility. 
Before testing, it is crucial to ensure that the patient is ingesting gluten, because all diagnostic tests will normalise on a gluten-free diet.
Endomysial antibody (EMA) is a more expensive alternative to IgA-tTG, with greater specificity but lower sensitivity, which may be used if IgA-tTG is unavailable.  Unlike tTG, which is an enzyme-linked immunosorbent assay, EMA is based on immunofluorescence and thus is operator dependent.
In patients with IgA deficiency, request IgG-deamidated gliadin peptide (DGP) serology, although the diagnostic accuracy of this test is somewhat less than that of IgA-tTG.   Patients with an elevated IgA-tTG level should be advised to remain on a gluten-containing diet and referred for duodenal biopsy. It is also reasonable to proceed to duodenal biopsy in patients with IgA deficiency. IgG-tTG was previously one of the common serological tests for coeliac disease in individuals with known or suspected IgA deficiency. However, this test has been largely replaced by the newer and more accurate IgG DGP or IgA/IgG DGP.
A normal IgA-tTG and total IgA test result are adequate to exclude a diagnosis in patients with a low clinical index of suspicion for coeliac disease.
Patients with an elevated IgA-tTG level should be advised to remain on a gluten-containing diet and referred for duodenal biopsy.
Small intestinal biopsies should be obtained regardless of the IgA-tTG result in patients with a high clinical index of suspicion. However, paediatric patients with symptoms consistent with coeliac disease and a high IgA-tTG titre (above 10 times normal range for laboratory) may go on to have confirmatory EMA and human leukocyte antigen (HLA)-DQ2/-DQ8 testing. If both are positive, coeliac disease may be diagnosed without a small intestinal biopsy. 
Duodenal biopsy changes in coeliac disease are typically graded by the Marsh classification, from 0 to 4.  To diagnose coeliac disease, intra-epithelial lymphocytes should be increased and the villous-to-crypt ratio decreased. The presence of only one of these changes raises the possibility of a different diagnosis.
The presence of typical coeliac changes on duodenal histology with clinical improvement on a gluten-free diet confirms the diagnosis. A repeat duodenal biopsy after gluten withdrawal is no longer routinely necessary for verification.
3. HLA testing
May be used to rule out coeliac disease in patients already on a gluten-free diet or in patients with an idiopathic coeliac-like enteropathy, but is not helpful for diagnosis.
Atrophy and scalloping of mucosal folds; nodularity and mosaic pattern of mucosa may be seen, but these findings are not sensitive for coeliac disease diagnosis.
People with coeliac disease on a gluten-free diet prior to evaluation cannot be differentiated from healthy controls. In these patients, gluten challenge is necessary. In a gluten challenge, the person is placed back on a gluten-containing diet, containing 3 to 10 grams of gluten per day (2-5 slices of bread), with serological tests and small bowel histology assessed after 2 to 8 weeks on the gluten-containing diet. 
Some commercial kits offer an assessment of individual risk for coeliac disease through genetic tests using saliva. These tests can show the presence of the HLA-DQ2 or HLA-DQ8 genes. However, it is important to counsel patients that having these genes is not equivalent to having coeliac disease, and having these genes alone does not have any known prognostic value. If the test is negative, a person's risk for coeliac disease is extremely low.
Other tests detect the presence of gluten immunogenic peptides in stool or urine, indicating recent gluten exposure. These tests are not diagnostic tests for coeliac disease, because gluten peptides are normally excreted in the stools and urine of any individual.
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