CELIAC DISEASE
















Illustration of celiac disease pathology






  • Reference [7]
Celiac disease in children
Presenting symptom % of patients
Abdominal pain 44%
Diarrhea 33%
Iron-deficiency anemia 32%
Poor weight gain 25%
Bloating 23%
Nausea and vomiting 16%
Asymptomatic
(found during screening)
14%
Lethargy 14%
Weight loss 10%
Micronutrient deficiency
(iron, folate, zinc, etc.)
10%
Constipation 6%
Poor health/recurrent infections 5%
Short stature 4%
Irritability 4%
Headaches 2%
Puberty delay 1%
Poor sleep 1%


  • Other includes abdominal pain, constipation, weight loss, neurologic symptoms, dermatitis herpetiformis, macroamylasemia, hypoproteinemia, elevated sedimentation rate, insulin-dependent diabetes mellitus, increased thyroid hormone replacement requirement, and liver disease (elevated serum aminotransferase levels)
  • Reference [8]
Celiac disease in adults
Presenting symptom % of patients
Diarrhea 37%
Other 26%
Anemia 13%
Screening
(affected family member)
12%
Bone disease 8%
Childhood celiac disease 8%
Malignancy 5%
Incidental diagnosis
(found during EGD for other condition)
5%






  • References [1,2,3,4,5,6]
ANTIBODY TESTS
Tissue transglutaminase IgA (TTG IgA) antibodies
  • Screening
    • TTG IgA antibodies are the preferred screening test in adults and children > 2 years. In children < 2 years, TTG antibodies are less sensitive, and a combination of TTG IgA + DGP (IgA and IgG) is recommended.
    • IgA deficiency is seen in 2 - 3% of celiac disease patients, so if suspicion for celiac disease is high, total IgA levels should be measured
  • Accuracy
    • Sensitivity: > 95%
    • Specificity: > 95%
  • Effects of a 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, and by 5 years, > 90% of patients will be normal. TTG IgA levels may also be used to monitor gluten-free diet compliance.
  • 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 (TTG IgG) antibodies
  • Screening
    • TTG IgG antibodies are useful in patients who have suspected IgA deficiency. The sensitivity and specificity of TTG IgG is variable, therefore, it is not as accurate as TTG IgA.
  • Accuracy
    • Sensitivity: widely variable
    • Specificity: 86 - 100%
  • Effects of a 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, and by 5 years, > 90% of patients will be normal.
Deamidated gliadin peptide IgA and IgG antibodies (DGP Abs)
  • Screening
    • The preferred screening test in children < 2 years is a combination of TTG IgA and DGP (IgG and IgA)
    • DGP IgG antibody is useful in patients who have suspected IgA deficiency
  • Accuracy
    • Sensitivity (IgG): > 90%
    • Specificity (IgG): > 90%
  • Effects of a 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, and by 5 years, > 90% of patients will be normal. DGP Ab levels may also be used to monitor gluten-free diet compliance.
Endomysial antibodies (IgA and IgG)
  • Screening
    • The endomysium is connective tissue that lines muscle fibers, and it contains a form of TTG. Antibodies that bind TTG in endomysial tissue are called endomysial antibodies, and they are highly specific for celiac disease.
    • Endomysial antibody testing may be helpful in cases where small bowel biopsies are undesirable (e.g. children with failure to thrive) or when there is concern for a false-positive TTG test.
  • Accuracy
    • 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
  • HLA-DQ2 (alleles A1*05 and B1*02) is found in ∼ 95% of patients with celiac disease, and HLA-DQ8 (alleles A1*03 and B1*0302) is present in the remaining 5%.
  • Patients who test negative for both HLA-DQ2 and HLA-DQ8 have a less than 1% chance of having celiac disease (NPV > 99%). Positive testing is less useful, as HLA-DQ2 is present in 25 - 30% of the general population.

  • 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