by Dr. Sylvia van den Berg (Ampath)
PATHCHAT Edition No. 3
Please contact your local Ampath pathologist for more information.
Endorsed by the Infectious Diseases Peer Group
Overview of Coeliac Disease
Coeliac disease (CD) is an immune-mediated inflammatory disease triggered by the gliadin component of gluten in genetically predisposed individuals.
Pathogenesis
The disease results from a complex interplay between:
- Genetic factors (Strong association with HLA-DQ2 and/or HLA-DQ8 gene loci).
- Serum auto-antibodies (Tissue transglutaminase IgA and Endomysium IgA).
- Innate immune response to gliadin-reactive T cells.
Tissue transglutaminase (TTG) is released in response to inflammation and modifies gluten peptides, increasing their affinity for HLA-DQ2 and/or DQ8, which then triggers an immune response.
This results in villous atrophy and crypt hyperplasia, leading to malabsorption and nutrient deficiencies.
Epidemiology of Coeliac Disease
Coeliac disease is most common in individuals of North European descent, with a prevalence of 1:70 to 1:300. However, cases have also been reported in:
- Middle East
- Asia
- South America
- North Africa
Studies suggest that many cases remain undiagnosed.
Clinical Presentation of Coeliac Disease
Previously thought to be a disease of infancy, CD now more commonly presents between the ages of 10 and 40 with milder symptoms.
Gastrointestinal Manifestations
- Steatorrhea (fatty stools) and excessive gas.
- Malabsorption complications, including:
- Growth failure
- Weight loss
- Severe anemia
- Neurological symptoms (due to Vitamin B deficiency)
- Osteopenia (Vitamin D and calcium malabsorption)
Subclinical Disease
- Fatigue
- Unexplained elevation of liver enzymes (aminotransferases)
- Mild iron-deficiency anemia
Why is early detection important?
- Higher risk of malignancy
- Nutritional deficiencies
- Pregnancy complications (low birth weight infants, recurrent miscarriages)
- Association with other autoimmune diseases
Conditions Associated with Coeliac Disease
Coeliac disease is linked to several autoimmune and genetic disorders, including:
- Dermatitis herpetiformis
- Down syndrome
- Selective IgA deficiency
- Type 1 diabetes mellitus (T1DM)
- Autoimmune thyroid disease
- Autoimmune liver disease
- Increased risk of lymphoma (especially non-Hodgkin’s lymphoma)
- Gastrointestinal tract cancers
- Neuropsychiatric disorders
- Hyposplenism
- Idiopathic pulmonary hemosiderosis
Coeliac Disease and Women's Reproductive Health
Women with untreated CD may experience:
- Delayed menarche
- Secondary amenorrhea
- Infertility
- Recurrent first-trimester miscarriages
- Earlier menopause
Studies show that 5% of women with recurrent miscarriages have undiagnosed coeliac disease, and treatment with a gluten-free diet (GFD) may prevent pregnancy loss.
Who Should Be Tested for Coeliac Disease?
Individuals with Unexplained Symptoms:
- Chronic diarrhea or constipation
- Weight loss
- Iron-deficiency anemia
- Nausea or vomiting
- Chronic abdominal pain or bloating
- Fatigue
- Dermatitis herpetiformis
- Osteopenia or osteoporosis
- Abnormal liver enzymes
- Growth delay, delayed puberty, or amenorrhea in children
High-Risk Individuals (Even if Asymptomatic):
- Type 1 diabetes mellitus (T1DM)
- Down syndrome
- Autoimmune thyroid disease
- Turner syndrome
- William’s syndrome
- Selective IgA deficiency
- Autoimmune liver disease
- First-degree relatives of coeliac patients
Diagnostic Approach to Coeliac Disease
1. Coeliac-Specific Antibody Testing
Common antibody tests:
- Tissue transglutaminase IgA (TTG-IgA)
- Endomysial antibodies (EMA-IgA)
- Deamidated gliadin peptide (DGP-IgA/IgG)
Key Testing Recommendations:
- IgA anti-TTG or EMA → First-line test (patient must be on a gluten-containing diet).
- IgA levels should be measured to rule out IgA deficiency (low IgA can cause false negatives).
- IgG-based tests (IgG anti-TTG, IgG EMA, IgG DGP) are useful in IgA-deficient patients.
- Children under 2 years should be tested for IgG DGP, as TTG may be less reliable.
If antibodies are positive: A gastroenterologist should evaluate further.
2. HLA-DQ2 and HLA-DQ8 Genetic Testing
- HLA-DQ2/DQ8 positivity suggests genetic susceptibility.
- HLA-DQ2/DQ8 negativity rules out coeliac disease in most cases.
Who should get HLA testing?
- High-risk but asymptomatic individuals before antibody testing.
- Patients with uncertain diagnosis (negative antibodies but persistent symptoms).
- Children with high antibodies where a biopsy is not planned.
3. Duodenal Biopsy (Endoscopy)
A small bowel biopsy is the gold standard for confirming coeliac disease in many cases.
When is a biopsy recommended?
- Antibody levels are low or borderline.
- Strong clinical suspicion but negative antibodies.
- Assessing villous atrophy severity.
Marsh-Oberhuber Classification is used to grade biopsy findings.
Follow-Up and Management
Treatment: A Gluten-Free Diet (GFD)
The only effective treatment is strict lifelong gluten avoidance.
Monitoring After Diagnosis
- Follow-up testing of coeliac antibodies (anti-TTG, EMA) should show normalization within 12 months.
- Symptom improvement and weight stabilization confirm adherence to GFD.
Conclusion
A diagnosis of coeliac disease is confirmed by:
- Gluten-dependent symptoms
- Coeliac-specific antibodies (positive TTG, EMA, or DGP tests)
- HLA-DQ2 or HLA-DQ8 positivity
- Small bowel biopsy showing villous atrophy (if needed)
High TTG-IgA levels (>10x upper limit of normal) strongly suggest CD and may allow a biopsy-free diagnosis.
If a gluten-free diet results in symptom resolution and declining antibody levels, this further confirms the diagnosis.
References
- Green PH, Cellier C. Celiac disease. N Engl J Med 2007; 357:1731.
- Snyder MR, Murray JA. Clinical Laboratory News: Celiac Disease. Clin Chem 2010; 36.
- Husby S, Koletzko S, et al. European Society for Pediatric Gastroenterology Guidelines for the Diagnosis of Coeliac Disease. JPGN 2012; 136-160.