Celiac 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 diarrhea, unexplained iron deficiency anemia, or a skin rash consistent with dermatitis herpetiformis should be tested for celiac 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 normalize 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 serologic tests for celiac 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 celiac 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, since 2% of patients with celiac disease may not have circulating tTG at the time of diagnosis (seronegative celiac disease).
Pediatric patients with symptoms consistent with celiac disease and a high IgA-tTG titer (above 10 times normal range for laboratory) may go on to have confirmatory EMA testing. If EMA is positive, celiac disease may be diagnosed without a small intestinal biopsy.
Some experts advise that adult patients with very high IgA-tTG titers (above 10 times normal range for laboratory), and positive EMA in a second blood sample, may be diagnosed without duodenal biopsy.
Duodenal biopsy changes in celiac disease are typically graded by the Marsh classification, from 0 to 4. To diagnose celiac disease, intraepithelial 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 celiac 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. Human leukocyte antigen (HLA) typing
May be used to rule out celiac disease in patients already on a gluten-free diet or in patients with an idiopathic celiac-like enteropathy, but is not helpful for diagnosis.
HLA typing may be used as a first-line screening test to rule out celiac disease among first-degree relatives. However, the availability and cost of this test may be prohibitive.
Atrophy and scalloping of mucosal folds; nodularity and mosaic pattern of mucosa may be seen, but these findings are not sensitive for celiac disease diagnosis.
People with celiac 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 wheat bread), with serologic tests and small bowel histology assessed after 2 to 8 weeks on the gluten-containing diet.
Patients who have used a home-testing kit, or are considering using one, should be counseled to discuss their symptoms with their healthcare professional, irrespective of the test outcome.
Commercially available tests for the assessment of individual risk for celiac disease detect the presence of HLA-DQ2 and HLA-DQ8 genes in saliva.
Healthcare professionals should be aware that patients who test positive for tTG antibodies using self-administered blood tests (finger-prick tests) may begin a gluten-free diet before being evaluated by their healthcare professional.
Tests for detection of tTG antibodies in saliva are being investigated, but there is insufficient evidence to recommend their use.
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