Reference [1,2,3,4,5,6]
Risk factor |
Comment |
Female sex |
- The prevalence in women is 2 - 3 times higher than that in men
|
First-degree relative with disease |
- The disease is prevalent in 10 - 15% of people who have a first-degree relative with the disease
|
Type 1 diabetes |
- Celiac disease is present in 3 - 16% of patients with type 1 diabetes
|
HLA-DQ2 and HLA-DQ8 haplotypes |
- The HLA-DQ2 haplotype (alleles A1*05 and B1*02) is present in 90% of patients with celiac disease
- One of two HLA-DQ2 alleles (A1*05 or B1*02) is present in 5% of patients
- The HLA-DQ8 haplotype is present in 5% of patients with celiac disease
- See labs below for more
|
IgA deficiency |
- IgA deficiency is present in 2 - 3% of patients with celiac disease
- IgA deficiency may affect laboratory diagnosis of celiac disease
- See labs below for more
|
Timing of gluten introduction into the diet |
- Observational studies have found that the timing of gluten introduction into the diet is associated with celiac disease
- Some studies have suggested that the introduction of gluten between 4 - 6 months of age may decrease the risk, while introducing gluten before 4 months and after 7 months may increase the risk
- Recent randomized trials have evaluated this hypothesis and found no effect - see studies for more
|
Rotavirus |
- In some observational studies, rotavirus infection in infancy has been associated with an increased risk of celiac disease
|
Breastfeeding |
- In some observational studies, the introduction of gluten while breastfeeding has been associated with a lower risk of celiac disease
- A recent randomized controlled trial did not confirm this finding - see studies for more
|
Other autoimmune disease |
- Celiac disease is more prevalent in patients with other autoimmune diseases (e.g. Hashimoto's thyroiditis, Sjögren's, autoimmune liver disease, IgA nephropathy, peripheral neuropathy)
|
Down's syndrome |
- Celiac disease is present in up to 5% of patients with Down's syndrome
|
Turner's syndrome |
- Celiac disease is present in up to 3% of patients with Turner's syndrome
|
ANTIBODY TESTS |
Tissue transglutaminase IgA antibodies (TTG IgA)
- TTG IgA is the preferred screening test in adults. In children < 2 years old, TTG Abs are less sensitive, therefore a combination of TTG IgA + DGP (IgA and IgG)
is the preferred screening method.
- IgA deficiency is more common in patients with celiac disease (2 - 3%), so if suspicion for celiac disease is high, total IgA levels should also be drawn
- Sensitivity: > 95%
- Specificity: > 95%
- Gluten-free diet - TTG IgA levels will return to normal in patients consuming a gluten-free diet. Weakly positive patients may return to normal within weeks of starting a gluten-free
diet. After 6 - 12 months, 80% of patients will have normal levels. By 5 years, > 90% of patients will have normal levels. TTG IgA levels may also be used to monitor compliance with a gluten-free diet.
- Studies: a cohort study found that TTG IgA levels ≥ 10 X ULN in adults were almost 100% specific for celiac disease (confirmed with biopsy) and had a positive predictive value of 95 - 100%. [PMID 33139268]
|
Tissue transglutaminase IgG antibodies (TTG IgG)
- TTG IgG are useful in patients who have suspected IgA deficiency. The sensitivity and specificity of TTG IgG is highly variable, therefore it is not as accurate as
TTG IgA.
- Sensitivity: widely variable
- Specificity: 86 - 100%
- Gluten-free diet - TTG IgG levels will return to normal in patients consuming a gluten-free diet. Weakly positive patients may return to normal within weeks of starting a gluten-free
diet. After 6 - 12 months, 80% of patients will have normal levels. By 5 years, > 90% of patients will have normal levels.
|
Deamidated gliadin peptide IgA and IgG antibodies (DGP Abs)
- DGP IgG antibody is useful in patients who have suspected IgA deficiency
- When screening children younger than 2 years of age for celiac disease, TTG IgA + DGP (IgA and IgG) are the recommended screening tests
- Sensitivity (IgG): > 90%
- Specificity (IgG): > 90%
- Gluten-free diet - DPG Ab levels (IgG and IgA) will return to normal in patients consuming a gluten-free diet. Weakly positive patients may return to normal within weeks of starting a gluten-free
diet. After 6 - 12 months, 80% of patients will have normal levels. By 5 years, > 90% of patients will have normal levels. DGP Ab levels may also be used to monitor compliance with a gluten-free diet.
|
Endomysial IgA antibody
- Endomysial antibodies are antibodies to the connective tissue inside muscle. TTG IgA antibody is the target antigen for endomysial antibodies.
- Endomysial IgA antibodies are highly specific (low false-positives) but less sensitive than other tests. The test is also expensive and typically only recommended when
there is concern over a possible false-positive TTG Ab test.
- Endomysial IgG antibody tests are not widely available
- Sensitivity: > 90%
- Specificity: 98%
|
Other
- Anti-gliadin antibodies are antibodies to native gliadin (undeamidated). This test is no longer recommended because newer tests are more sensitive.
- Anti-reticulin antibodies are antibodies to reticulin, a connective tissue. This test is no longer recommended because newer tests are more sensitive.
|
GENOTYPE |
HLA DQ2/DQ8 genotype
- The HLA-DQ2 haplotype (alleles A1*05 and B1*02) is present in 90% of patients with celiac disease, and one of two HLA-DQ2 alleles (A1*05 or B1*02) is present in
5% of patients. The HLA-DQ8 haplotype is present in the remaining 5% of patients with celiac disease.
- This means a person who tests negative for both HLA-DQ2 and HLA-DQ8 is very unlikely to have celiac disease with a negative predictive value of > 99%
- The HLA-DQ2 haplotype is present in 25 - 30% of the general population, therefore a positive test has little meaning in screening situations
- The ACG states that haplotype testing may be useful in the following situations:
- Equivocal small-bowel histological finding (Marsh I-II) in seronegative patients
- Evaluation of patients on a gluten-free diet in whom no testing for celiac disease was done before gluten-free diet
- Patients with discrepant celiac-specific serology and histology
- Patients with suspicion of refractory celiac disease where the original diagnosis of celiac remains in question
- Patients with Down's syndrome
|
Reference [1,2,3]
OTHER CONDITIONS WITH CELIAC-LIKE SYMPTOMS |
Disease |
Comment |
Irritable bowel syndrome (IBS) |
- Many patients with celiac disease are initially diagnosed with IBS
|
Non-celiac gluten sensitivity |
- Diagnosis of exclusion
- Condition where patients have symptoms of celiac disease when they consume gluten, but they do not meet the serologic or histopathologic criteria for celiac disease
|
Wheat allergy |
- May be diagnosed with skin prick tests or blood tests
|
Lactose intolerance |
- May be diagnosed with dietary challenge/removal or lactose breath hydrogen test
|
Pancreatic insufficiency |
- Often difficult to diagnose
- Pancreatic calcifications may be seen on radiographs
|
Reference [1,3]
POTENTIAL CAUSES OF DUODENAL VILLOUS ATROPHY |
Disease |
Comment |
Tropical sprue |
- Tropical sprue is a chronic diarrheal disease of unknown etiology that occurs in tropical regions along the equator
|
Small bowel bacterial overgrowth |
- A condition marked by overgrowth of non-native bacteria in the small bowel
- Typically occurs in the setting of bowel abnormalities (structural, decreased motility, etc.)
|
Autoimmune enteropathy |
- Rare disease caused by autoantibodies to enterocytes
|
Drug-induced enteropathy |
|
Whipple disease |
- Syndrome of chronic diarrhea, joint pain, and malabsorption caused by T. whipplei infection
|
Collagenous sprue |
- Rare disease marked by excessive subepithelial collagen deposition in the small bowel
|
Crohn's disease |
|
Eosinophilic enteritis |
- Disease is marked by eosinophilic infiltration into the stomach and duodenum
|
Intestinal lymphoma |
- Intestinal lymphoma may cause villous atrophy
- Celiac disease increases the risk of enteropathy-associated T-cell lymphoma, but the disease is still very rare among celiac patients (see cancers below)
|
Intestinal tuberculosis |
- Although rare, tuberculosis may infect the gastrointestinal tract
|
Infectious enteritis |
|
Graft vs host disease |
|
AIDS enteropathy |
- Syndrome of chronic diarrhea and wasting in AIDS patients
- Infectious and neoplastic causes should be ruled out before making diagnosis
|