Diagnosis of celiac disease combines a blood test that detects the immune reaction and a biopsy that shows its effect on the small-bowel mucosa. The two are used together because serology can be positive without enteropathy, and enteropathy can have causes other than celiac disease.
Who should be tested
Testing is directed at people with a higher probability of disease rather than at the whole population. It is recommended for people with suggestive symptoms, for first-degree relatives of patients with celiac disease, and for people with associated conditions that raise the pretest probability, such as type 1 diabetes or autoimmune thyroid disease. Testing must be done while the patient is still eating gluten: a gluten-free diet before testing suppresses both the serology and the biopsy.
Serology
The most reliable tests for the diagnosis of celiac disease are specific serology and intestinal biopsy. The single most reliable and useful serological test for the diagnosis, for monitoring adherence to therapy and for screening of celiac disease is IgA tTG (IgA against tissue transglutaminase). The sensitivity of these serological tests depends on the severity of the condition, especially for the anti-EMA (anti-endomysial antibody) test.
There are some patients with confirmed CD who are not positive for IgA anti-tTG but are positive on the test for DGP (deaminated gliadin protein). This has led to the inclusion of anti-DGP serological tests in the diagnostic panel of CD. IgA tTG and IgA/IgG DGP levels decrease in patients months after the initiation of a gluten-free diet (GFD), so their levels can be used for monitoring adherence to the gluten-free diet.
The false results are predictable in direction. False-positive IgA tTG results are more common in subjects younger than 2 years of age and in mild celiac enteropathy. IgA deficiency, by contrast, is a cause of false-negative IgA tTG results rather than false-positive ones: IgA-based assays cannot detect the antibody, so IgG-based tests are used instead in these patients.
No-biopsy criteria in children
In the European guideline for the diagnosis of CD in children, criteria to avoid a duodenal biopsy for diagnosis were proposed in 2012. Children who meet all 4 of these criteria are excluded from diagnostic duodenal biopsy:
- presence of symptoms
- IgA tTG level more than 10 times above the ULN (upper limit of normal)
- positive anti-EMA
- compatible HLA haplotype
HLA typing
HLA-DQ2/DQ8 are almost positive in all patients with CD, and almost all subjects of European ancestry are positive for DQ2. HLA typing is therefore not a useful test for initial diagnosis, but thanks to its high negative predictive value it is very useful for the exclusion of CD in patients suspected of CD who are on the borderline of diagnosis, such as patients with borderline biopsy and serological evidence, or patients whose serological values do not decrease after adherence to the GFD.
Endoscopy and biopsy
The definitive diagnosis of CD is endoscopic biopsy and histological study. The main problem is that in a vast majority of patients with CD the endoscopic appearance is normal, while the histological findings are pathological; so in any case, even if the endoscopic appearance is normal, a biopsy has to be performed. The common findings of endoscopy in CD patients are scalloping of the duodenum, nodular findings, and flattening of the mucosa, with loss of the finger-like projections, the villi.
Gluten challenge
In the past a test was done for confirmation of CD, called the gluten challenge test. After a period of adherence to the GFD, the patient was challenged with gluten to show the histological changes. This test is not done nowadays and is reserved only for patients with suspected CD who are already adhering to gluten, and for adults diagnosed with biopsy confirmation without serological testing in childhood, because there are many pediatric conditions in which the same histological pattern of CD is seen.
Imaging
CT and MRI of the abdomen are useful for the detection of complications of CD, which can be mesenteric lymphadenopathy, enteropathy-associated lymphoma, stricture, jejunitis and carcinoma. They do not make the diagnosis; they answer a different question once the diagnosis is established.