Celiac disease was once considered rare in North America. However, a recent study conducted by Fasano et al.(2003) revealed biopsy-proven prevalence rates of 1 in 133 asymptomatic subjects. These rates are similar to those reported in Europe where, in a recent study from Sweden, it was estimated that 8 out of 10 cases of celiac disease have not been diagnosed.
In Canada, present research shows the prevalence of celiac disease to be 1 in 100-200; however, based on statistics in Europe it is likely that this rate is under-representative of the number of celiac sufferers in Canada.
In Canada, the average length of time between the onset of symptoms and the diagnosis of celiac disease is typically between 9 – 11 years. Studies have shown that the diagnostic delay is physician related. Undiagnosed and untreated celiac disease is linked to osteoporosis, anemia, infertility and in severe cases lymphoma. The longer a person goes undiagnosed and untreated, the greater the chance of developing malnutrition and other complications.
Screening for celiac disease involves testing blood to measure levels of tissue transglutaminase and endomysial IgA antibodies. If these tests and symptoms suggest celiac disease, then an individual should be sent for a small bowel biopsy to make the diagnosis.
Diagnosis Details – Blood Tests
Routine hemogram, urinalysis and electrolytes, liver function tests, serum iron or ferritin, folate or red blood cell folate and B12 should be measured. Liver function tests may be mildly abnormal in patients with celiac disease, even when associated hepatic disorders are absent. Specific deficiencies of iron and folic acid should be therapeutically corrected, although they will not normally be required long-term after introduction of a gluten-free diet. B12 levels usually normalize without specific therapy.
Screening in patients with celiac disease should consist of:
- IgA endomysial antibodies (EMA)
- IgA tissue transglutaminase antibodies (TTG)
- Total IgA level (If 1 and 2 are negative but IgA level is low, then celiac disease is strongly suspected)
For an individual with suggestive symptoms, four scenarios are possible:
- The individual might have selective IgA defi ciency.
- The other serological test could be conducted and/or a small bowel biopsy could be performed.
- The patient may not have celiac disease.
- The patient may be on a self-imposed gluten-free diet which can result in false negative tests.
Selective IgA deficiency (SIgA deficiency)
SIgA deficiency occurs 10 to 15 times more commonly among people with celiac disease compared to the general population (2 – 3% of persons with celiac disease are IgA deficient). Patients with SIgA deficiency will lack IgA antibodies including endomysial antibody andTTG. To detect celiac disease in patients with SIgA deficiency a small bowel biopsy should be performed.
Seronegative celiac disease
Both the TTG and the EMA titers correlate with the severity of villous atrophy. As a result, in the presence of partial villous atrophy either or both antibodies may be negative. In addition the mode of presentation of the celiac disease, i.e. presence of silent or subclinical celiac disease may be associated with a negative EMA. Clinically seronegative celiac disease is similar to sero-positive celiac disease. Several studies have demonstrated that reliance on either TTG or endomysial antibody as a single test will underestimate the prevalence of celiac disease. The key is to biopsy early and if in doubt.
Causes of false positive celiac serologic tests
The endomysial antibody test is virtually 100% specific for celiac disease. However TTG has been reported to be positive in the presence of liver disease, especially cirrhosis, inflammatory bowel disease (Crohn’s and ulcerative colitis), irritable bowel syndrome, diabetes and severe heart failure, as well as arthritis and various autoimmune disorders.
Positive serologic tests in the presence of a normal biopsy
This situation occasionally arises. The presence of a positive EMA with a normal biopsy indicates either the presence of celiac disease that was not detected in the biopsy, either because of too few pieces being taken or misinterpretation. The biopsy should be reviewed by an expert gastrointestinal pathologist. If it is considered to be truly a normal biopsy the patient may well have latent celiac disease and will probably develop the disease at a later date
Diagnosis Details – Biopsy
The mainstay of diagnosis of celiac disease is a small intestinal biopsy specimen, which is taken at endoscopy. 4-6 biopsy specimens are preferable. They should be taken with standard size forceps from the descending duodenum.
In 4-6 months, if there has been no improvement in the small intestinal mucosal morphology and lab tests dictate no change, the original diagnosis should be questioned and the biopsy repeated. Testing for certain genetic markers (HLA haplotypes) can stratify individuals to a high or low risk for celiac disease. Greater than 97 percent of celiac disease individuals have the DQ2 and/or DQ8 marker, compared to about 40 percent of the general population. These tests are not easily available yet.
A single best approach cannot be prescribed when there is a positive celiac disease serology and a normal biopsy result. The best option should consider the patient preferences. Some choices for approach are: additional small bowel biopsies, periodic monitoring with celiac disease serology tests, or a trial of gluten-free diet. (NIH Consensus Development Conference Statement on Celiac Disease, 2004).